Digital Commons Network^™

Division Of Research And Economic Development Monthly Report For October-November 2011, Uri Division Of Research And Economic Development

Reports (Research and Economic Development)

The monthly reports include statistics for project proposals and awards received by individual academic and administrative departments at the University of Rhode Island.

Division Of Research And Economic Development Monthly Report For July-September 2011, Uri Division Of Research And Economic Development

Reports (Research and Economic Development)

The monthly reports include statistics for project proposals and awards received by individual academic and administrative departments at the University of Rhode Island.

Coupling Sensitive In Vitro And In Silico Techniques To Assess Cross-Reactive Cd4+ T Cells Against The Swine-Origin H1n1 Influenza Virus, Brian C. Schanen, Anne S. De Groot, Leonard Moise, Matt Ardito, Elizabeth Mcclaine, William Martin, Vaughan Wittman, William L. Warren, Donald R. Drake Iii

Institute for Immunology and Informatics Faculty Publications

The outbreak of the novel swine-origin H1N1 influenza in the spring of 2009 took epidemiologists, immunologists, and vaccinologists by surprise and galvanized a massive worldwide effort to produce millions of vaccine doses to protect against this single virus strain. Of particular concern was the apparent lack of pre-existing antibody capable of eliciting cross-protective immunity against this novel virus, which fueled fears this strain would trigger a particularly far-reaching and lethal pandemic. Given that disease caused by the swine-origin virus was far less severe than expected, we hypothesized cellular immunity to cross-conserved T cell epitopes might have played a significant role …

Helicovax: Epitope-Based Therapeutic Helicobacter Pylori Vaccination In A Mouse Model, Steven F. Moss, Leonard Moise, Dong Soo Lee, Woojin Kim, Songhua Zhang, Jinhee Lee, Arlin B. Rogers, William Martin, Anne S. De Groot

Institute for Immunology and Informatics Faculty Publications

Helicobacter pylori is the leading cause of gastritis, peptic ulcer disease and gastric adenocarcinoma and lymphoma in humans. Due to the decreasing efficacy of anti-H. pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-H. pylori vaccines. In this study an in silico-based approach was utilized to develop a multi-epitope DNA-prime/peptide-boost immunization strategy using informatics tools. The efficacy of this construct was then assessed as a therapeutic vaccine in a mouse model of gastric cancer induced by chronic H. pylori infection. The multi-epitope vaccine administered intranasally induced a broad immune response as determined …

Harnessing The Power Of Genomics And Immunoinformatics To Produce Improved Vaccines, Leonard Moise, Leslie Cousens, Joanna Fueyo, Anne S. De Groot

Institute for Immunology and Informatics Faculty Publications

The role of cellular immunity as a mediator of protection against disease is gaining recognition, particularly with regard to the many pathogens for which we presently lack effective vaccines. As a result, there is an ever-increasing need to understand the T-cell populations induced by vaccination and, therefore, T-cell epitopes responsible for triggering their activation. Although the characterization and harnessing of cellular immunity for vaccine development is an active area of research interest, the field still needs to rigorously define T-cell epitope specificities, above all, on a genomic level. New immunoinformatic epitope mapping tools now make it possible to identify pathogen …

Tryptophan Degradation In Women With Breast Cancer: A Pilot Study, Debra E. Lyon, Jeanne M. Walter, Angela R. Starkweather, Christine M. Schubert, Nancy L. Mccain

School of Nursing Publications

Background

Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy. …

Semen Quality And Chemical Oxidative Stress; Quantification And Remediation, Saleem Ali Bani-Hani

ETD Archive

The necessary multi-step process to prepare human semen for assisted reproduction (AR) such as in vitro fertilization (IVF) is known to induce oxidative stress in human spermatozoa and subsequent damage to the integrity of their cell components and, thus, to their function. Literature reports have viewed this as a potential link with the high frequency of birth defects among the IVF babies. In this work, we studied the effect of incubation and centrifugation on human sperm quality using established AR protocols. We found that in vitro incubation and centrifugation (20 min at 220g) of sperm generally degrade sperm quality in …

Wireless Signals And Male Fertility, Rand Mouradi

ETD Archive

Rapid advances in wireless technology have increased the number of users of mobile devices. As of 2011, the number of cell phone subscribers have reached 5.3 billion worldwide. Mobile devices have saturated our environment with radio frequency (RF) signals. This situation has created public concern over the effect of such signals on human health. This dissertation focuses on the correlation of RF signals emitted by cell phones with male infertility. A thorough discussion is provided on the effects of RF signals on the development of central nervous system (CNS) neoplasm, the design of these mobile devices, the range of the …

Quantitative And Qualitative Mass Spectrometric Analysis Of Anticancer Agents, Drugs Of Abuse And Enzyme-Inhibitor Complexes, Keri M. Smith

ETD Archive

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 …

How Is Encystment Regulated In Giardia Intestinalis, Iryna G. Tsarukyanova

ETD Archive

Giardia intestinalis is a protozoan parasite causing one of the most widely spread water-born intestinal infections: named giardiasis. The parasite has two life forms: trophozoite, responsible for the symptoms, and a transmittable cyst. Cysts are protected from the environment by a cyst wall build up from protein and a complex polysaccharide. The initiation and the key for cyst wall biosynthesis is amination of fructose 6-phosphate by glucosamine 6-phosphate deaminase (GNP). Fructose 6-phosphate is also an intermediate in glycolysis, the main energy producing pathway in trophozoites. The alternative energy source is the arginine dihydrolase pathway (ADHP), which is upregulated upon encystment. …

One-Dimensional Radial Diffusion Of Small Molecules (376 Da) In Bone Tissue, Kurt W. Farrell

ETD Archive

The flow of nutrients through any biological tissue is important to maintain homeostasis. If the transport process is understood, medical research teams can better design medications, prosthetic implants, and tissue scaffolds. Additionally, transport rates help physicians to better understand disease states and wound healing, including minor injuries such as breaks and sprains, which will aid in better diagnoses. We developed a novel method that measures the rate of diffusion in vitro, of fluorescein sodium salt. Samples were incubated at 37°C in a 5 CO2 atmosphere for various periods of time. Samples were sliced and analyzed using Image-Pro Plus and MATLAB …

Modification, Expression, And Purification Of Hyperactive Antifreeze Proteins From Insect Tenebrio Molitor, Sen Bu

ETD Archive

Antifreeze proteins (AFPs), also known as thermal hysteresis proteins, can protect organisms from damage caused by freezing by lowering the freezing point of fluids. AFPs can bind to small ice crystals, inhibit ice growth, and change the morphology of ice crystals. The difference between the freezing temperature and the melting temperature is termed thermal hysteresis (TH). There are different types of AFPs, such as fish AFPs (type I, II, III, and IV) and insect AFPs. These AFPs can also be classified by their thermal hysteresis activity: moderately active AFPs and hyperactive AFPs. Previous research groups successfully constructed AFP (type I, …

Characterization Of Elastin-Like Polypeptides Using Viscometry, Hamdan Noman Alanazi

ETD Archive

Elastin-like polypeptides (ELPs) are a class of polypeptide polymers that are gaining interest in various potential applications. These polymers are responsive to the changes in their environment by exhibiting conformational changes and aggregation. Monodisperse elastin-like polypeptides, (GVGVP)40, (GVGVP)40-foldon, and (GVGVP)60-foldon are made in bacterial expression system. An Ubbelohde capillary viscometer was set up to characterize the structural changes of these ELPs in phosphate buffered saline (PBS) solution. For the ELP-foldon, the relative viscosity measurements were utilized to calculate the intrinsic viscosities using Kraemer and Huggins equations. The known molecular weights of the ELPs and the experimentally determined intrinsic viscosities facilitated …

Insect Signature Indicating Corpse Movement From Urban To Rural Areas Of Northeast Ohio, Krystal R. Hans

ETD Archive

The distribution of insects geographically may provide evidence that indicates the movement of human remains from one location to another. The aims of this study were: (1) to observe insect succession in an urban and rural area in northeastern Ohio to document differences in the entomofaunal succession, and (2) to determine if there is an insect signature associated with a body moved from an urban to a rural area. It was hypothesized that there would be a difference in species composition between the urban and rural sites and the body moved would retain insect evidence indicating initial exposure to an …

Targeting Expression Of An Oncogene By Splicing Interference (Splicei) In Human Mammary Carcinoma Cell Culture Model, Chaucola K. Pleasant

ETD Archive

In nuclear pre-mRNA splicing, introns are removed through cooperative interactions of small nuclear RNAs (snRNAs). Many human genes are interrupted by two types of nuclear pre-mRNA introns. Major class or the U2-dependent type introns are spliced by U1, U2, U4, U5 and U6 snRNAs. The minor class or U12-dependent type introns are spliced by U11, U12, U4atac, U5, and U6atac snRNAs. It has been shown that over expression of minor class spliceosomal snRNAs can have an inhibitory effect on the splicing of major class introns. To further test the concept, we targeted HER-2/Neu proto-oncogene, which is over-expressed in 20-30 of …

Novel Thermal Analytical Techniques To Characterize Drugs And Drug Delivery, Lakshmi Swetha Kaza

ETD Archive

This thesis encompasses three significant projects. The study includes the characterization and evaluation of the properties of a commercial contraceptive transdermal patch, Ortho Evra® by Dielectric Analysis and Differential Scanning Calorimetry (DSC). This study helps in monitoring the mobility of the drug and transport properties by Isothermal and Scanning Dielectric Analysis as a function of temperature and frequency. The drugs in this product are norelgestromin and ethinyl estradiol. DSC was used to detect any crystalline character of the drugs by their fusion properties. Having no melting endotherm and detecting a glass transition temperature suggested that the drugs in the patches …

Producing Governable Subjects: Images Of Childhood Old And New, Karen Smith

Articles

Conceptions of childhood in terms of ‘evil’ and ‘innocence’ transcend time and culture. These conflicting images are deployed by Chris Jenks as the Dionysian and Apollonian models of childhood to symbolize external and internal forms of control. Drawing on the literature on governmentality this paper revisits these models and introduces a third model, the ‘Athenian’ child, analogous and supplementary to those developed by Jenks. This model is necessary in order to take account of relatively recent strategies in the government of childhood, which, predicated on understandings of children in terms of competence and agency, operate via responsibility and reflexivity.

Bound Water At Protein-Protein Interfaces: Partners, Roles And Hydrophobic Bubbles As A Conserved Motif, Mostafa H. Ahmed, Francesca Spyrakis, Pietro Cozzini, Parijat K. Tripathi, Andrea Mozzarelli, J. Neel Scarsdale, Martin A. Safo, Glen E. Kellogg

Medicinal Chemistry Publications

Background

There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region.

Methodology

A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed …

First-Passage Time Analysis Of A One-Dimensional Diffusion-Reaction Model: Application To Protein Transport Along Dna, Michael L. Mayo, Edward J. Perkins, Preetam Ghosh

Computer Science Publications

Background

Proteins search along the DNA for targets, such as transcription initiation sequences, according to one-dimensional diffusion, which is interrupted by micro- and macro-hopping events and intersegmental transfers that occur under close packing conditions.

Results

A one-dimensional diffusion-reaction model in the form of difference-differential equations is proposed to analyze the nonequilibrium protein sliding kinetics along a segment of bacterial DNA. A renormalization approach is used to derive an expression for the mean first-passage time to arrive at sites downstream of the origin from the occupation probabilities given by the individual transport equations. Monte Carlo simulations are employed to assess the …

A Modified Stokes-Einstein Equation For Aβ Aggregation, Srisairam Achuthan, Bon Jae Chung, Preetam Ghosh, Vijayaraghavan Rangachari, Ashwin Vaidya

Computer Science Publications

Background

In all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a …

Fracture Detection In Traumatic Pelvic Ct Images, Jie Wu, Pavani Davuluri, Kevin R. Ward, Charles Cockrell, Rosalyn Hobson, Kayvan Najarian

Computer Science Publications

Fracture detection in pelvic bones is vital for patient diagnostic decisions and treatment planning in traumatic pelvic injuries. Manual detection of bone fracture from computed tomography (CT) images is very challenging due to low resolution of the images and the complex pelvic structures. Automated fracture detection from segmented bones can significantly help physicians analyze pelvic CT images and detect the severity of injuries in a very short period. This paper presents an automated hierarchical algorithm for bone fracture detection in pelvic CT scans using adaptive windowing, boundary tracing, and wavelet transform while incorporating anatomical information. Fracture detection is performed on …

Superhalogen Properties Of Cumcln Clusters: Theory And Experiment, Y. J. Ko, H. Wang, K. Pradhan, P. Koirala, A. K. Kandalam, K. H. Bowen, P. Jena

Physics Publications

Using a combination of density functional theory and anion photoelectron spectroscopy experiment, we have studied the structure and electronic properties of CuCl _n ⁻ (n = 1–5) and Cu₂Cl _n ⁻ (n = 2–5) clusters. Prominent peaks in the mass spectrum of these clusters occurring at n = 2, 3, and 4 in CuCl _n ⁻ and at n = 3, 4, and 5 in Cu₂Cl _n ⁻ are shown to be associated with the large electron affinities of their neutral clusters that far exceed the value of Cl. While CuCl _n(n …

Fractalkine/Cx3cl1 Protects Striatal Neurons From Synergistic Morphine And Hiv-1 Tat-Induced Dendritic Losses And Death, Masami Suzuki, Nazira El-Hage, Shiping Zou, Yun-Kyung Hahn, Mary Sorrell, Jamie Sturgill, Daniel H. Conrad, Pamela E. Knapp, Kurt F. Hauser

Pharmacology and Toxicology Publications

Background Fractalkine/CX3CL1 and its cognate receptor CX3CR1 are abundantly expressed in the CNS. Fractalkine is an unusual C-X3-C motif chemokine that is important in neuron-microglial communication, a co-receptor for HIV infection, and can be neuroprotective. To assess the effects of fractalkine on opiate-HIV interactive neurotoxicity, wild-type murine striatal neurons were co-cultured with mixed glia from the striata of wild-type or Cx3cr1 knockout mice ± HIV-1 Tat and/or morphine. Time-lapse digital images were continuously recorded at 20 min intervals for up to 72 h using computer-aided microscopy to track the same cells repeatedly.

Results Co-exposure to Tat and morphine caused synergistic …

Electrospun Collagen: A Tissue Engineering Scaffold With Unique Functional Properties In A Wide Variety Of Applications, Balendu Shekhar Jha, Chantal E. Ayres, James R. Bowman, Todd A. Telemeco, Scott A. Sell, Gary L. Bowlin, David G. Simpson

Anatomy and Neurobiology Publications

Type I collagen and gelatin, a derivative of Type I collagen that has been denatured, can each be electrospun into tissue engineering scaffolds composed of nano- to micron-scale diameter fibers. We characterize the biological activity of these materials in a variety of tissue engineering applications, including endothelial cell-scaffold interactions, the onset of bone mineralization, dermal reconstruction, and the fabrication of skeletal muscle prosthetics. Electrospun collgen (esC) consistently exhibited unique biological properties in these functional assays. Even though gelatin can be spun into fibrillar scaffolds that resemble scaffolds of esC, our assays reveal that electrospun gelatin (esG) lacks intact α chains …

Combinatorial Effect Of Non-Steroidal Anti-Inflammatory Drugs And Nf-Κb Inhibitors In Ovarian Cancer Therapy, Luiz F. Zerbini, Rodrigo E. Tamura, Ricardo G. Correa, Akos Czibere, Jason Coideiro, Manoj Bhasin, Fernando M. Simabuco, Yihong Wang, Xuesong Gu, Linglin Li, Devanand Sarkar, Jin-Rong Zhou, Paul B. Fisher, Towia A. Libermann

Human and Molecular Genetics Publications

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor …

Comprehensive Gene-Based Association Study Of A Chromosome 20 Linked Region Implicates Novel Risk Loci For Depressive Symptoms In Psychotic Illness, T. Bernard Bigdeli, Brion S. Maher, Zhongming Zhao, Edwin J. C. G. Van Den Oord, Dawn L. Thiselton, Jingchun Sun, Bradley T. Webb, Richard L. Amdur, Brandon Wormley, Francis A. O'Neill, Dermot Walsh, Brien P. Riley, Kenneth S. Kendler, Ayman H. Fanous

Human and Molecular Genetics Publications

Background

Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.

Methods

We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs) in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects). These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted …

An Immunologic Portrait Of Cancer, Maria-Libera Ascierto, Valeria De Giorgi, Qiuzhen Liu, Davide Bedognetti, Tara L. Spivey, Daniela Murtas, Lorenzo Uccellini, Ben D. Ayotte, David F. Stroncek, Lofti Chouchane, Masoud H. Manjili, Ena Wang, Francesco M. Marincola

Microbiology and Immunology Publications

The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns …

Pseudomonas Aeruginosa Elastase Provides An Escape From Phagocytosis By Degrading The Pulmonary Surfactant Protein-A, Zhizhou Kuang, Yonghua Hao, Brent E. Walling, Jayme L. Jeffries, Dennis E. Ohman, Gee W. Lau

Microbiology and Immunology Publications

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB), an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs …

Identification And Phylogenetic Analysis Of Heme Synthesis Genes In Trypanosomatids And Their Bacterial Endosymbionts, João M. P. Alves, Logan Voegtly, Andrey V. Matveyev, Ana M. Lara, Flávia Maia Da Silva, Myrna G. Serrano, Gregory A. Buck, Marta M. G. Teixeira, Erney P. Camargo

Microbiology and Immunology Publications

It has been known for decades that some insect-infecting trypanosomatids can survive in culture without heme supplementation while others cannot, and that this capability is associated with the presence of a betaproteobacterial endosymbiont in the flagellate's cytoplasm. However, the specific mechanisms involved in this process remained obscure. In this work, we sequence and phylogenetically analyze the heme pathway genes from the symbionts and from their hosts, as well as from a number of heme synthesis-deficient Kinetoplastida. Our results show that the enzymes responsible for synthesis of heme are encoded on the symbiont genomes and produced in close cooperation with the …

Fetal Erap2 Variation Is Associated With Preeclampsia In African Americans In A Case-Control Study, Lori D. Hill, Dashaunda D. Hilliard, Timothy P. York, Sindhu Srinivas, Juan P. Kusanovic, Ricardo Gomez, Michal A. Elovitz, Roberto Romero, Jerome F. Strauss

Obstetrics and Gynecology Publications

Background Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate …