Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Signaling In Effector Lymphocytes: Insights Toward Safer Immunotherapy, Kamalakannan Rajasekaran, Matthew J. Riese, Sridhar Rao, Li Wang, Monica Thakar, Charles Sentman, Subramaniam Malarkannan

Dartmouth Scholarship

Receptors on T and NK cells systematically propagate highly complex signaling cascades that direct immune effector functions, leading to protective immunity. While extensive studies have delineated hundreds of signaling events that take place upon receptor engagement, the precise molecular mechanism that differentially regulates the induction or repression of a unique effector function is yet to be fully defined. Such knowledge can potentiate the tailoring of signal transductions and transform cancer immunotherapies. Targeted manipulations of signaling cascades can augment one effector function such as antitumor cytotoxicity while contain the overt generation of pro-inflammatory cytokines that contribute to treatment-related toxicity such as …

The Influence Of Mir-99a On Mtor Signaling Regulation In Colorectal Cancer Cell Lines., Jonathan Rice

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. These are staggering statistics for a disease that can essentially be cured if caught early and the pathology is favorable to therapeutic intervention. There is currently a drastic decrease in five year survival as the cancer stage increases from locally confined disease to metastatic disease. These statistics suggest that although some strides have been made with colon cancer screening and early intervention, there is still much room for improvement in both screening and treatment of CRC. One of the pathways that have …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Factors Influencing Uptake Of Risk-Reducing Salpingo-Oophorectomy By Brca1 And Brca2 Mutation Carriers, Victoria E. Breen

Dissertations and Theses (Open Access)

Germline mutations in the BRCA1 and BRCA2 genes are associated with significantly increased risks for ovarian cancer. The National Comprehensive Cancer Network (NCCN) currently recommends that female BRCA mutation carriers undergo risk-reducing salpingo-oophorectomy (RRSO) after age 35; however, not all women elect this option. The purpose of this study was to prospectively survey women with BRCA mutations currently undergoing ovarian cancer screening about their intention to have an RRSO and the various factors influencing their decision. Of the 26 women who completed our survey, 26 (100%, CI: 86.8-100) plan to undergo an RRSO in their lifetime. The average woman reported …

1st Place Contest Entry: The Effectiveness Of Yoga Therapy On An Adult, Post-Stroke Population: A Systematic Review, Baylor E. Hogan

Kevin and Tam Ross Undergraduate Research Prize

This is Baylor Hogan's submission for the 2016 Kevin and Tam Ross Undergraduate Research Prize, which won first place. She wrote about the effects of yoga therapy on the physical and mental wellbeing of stroke patients. You can read the final essay that came out of her research here.

Baylor is a senior at Chapman University, majoring in Kinesiology. Her faculty mentor is Dr. Elizabeth DeBaets.

Volume Averaging Of Spectral-Domain Optical Coherence Tomography Impacts Retinal Segmentation In Children, Carmelina Trimboli-Heidler, Kelly Vogt, Robert A. Avery

GW Research Days 2016 - 2020

Purpose: To determine the influence of volume averaging on retinal layer thickness measures acquired with spectral-domain optical coherence tomography (SD-OCT) in children.

Methods: Macular SD-OCT images were acquired using three different volume acquisition settings (i.e., ART 1, 3, and 9 volumes) in children enrolled in a prospective OCT study. Total retinal, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer thicknesses were measured around an ETDRS grid using beta version automated segmentation software for the Spectralis. The magnitude of manual segmentation required to correct the automated segmentation was classified as …

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8⁺ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …

Role Of Serum Biomarkers In Early Detection Of Diabetic Cardiomyopathy In The West Virginian Population, Adam Shaver, Alexandra Nichols, Ellen A. Thompson, Amrita Mallick, Nandini Manne, Shanmuga Sundaram, Joseph I. Shapiro Md, Komal Sodhi

Biochemistry and Microbiology

Objectives: Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.

Methods: The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.

Results: …

Stability Of Metabolic Factor Before And After Bariatric Surgery, Brandon Davis, Joseph Indelicato

The School of Health Sciences Publications and Research

No abstract provided.

Crispr/Cas9 As A Therapeutic Approach To Duchenne Muscular Dystrophy, Abraham Daniel Levitman

The Science Journal of the Lander College of Arts and Sciences

Transhumanism, designer babies, gene therapy, and super-soldiers are founded upon the same concept—genetic engineering. Clustered Regularly-Interspersed Short Palindromic Repeats (CRISPR) is a natural bacterial immune response method that takes advantage of gene manipulation to prevent an infection from mobile genetic elements. Since Mojica et al. (2005) first suggested the relationship between the CRISPR/Cas system and prokaryotic immunity, significant advancements have been made in understanding the mechanism and subsequent applications of CRISPR. CRISPR, has three main subtypes based on unique proteins and interference pathways and serves as an accurate and effective method for gene editing. Its mechanism consists of spacer acquisition, …

Initial Development Of A Patient-Reported Instrument Assessing Harm, Efficacy, And Misuse Of Long-Term Opioid Therapy, William C. Becker, David A. Fiellin, Anne C. Black, Carol T. Kostovich, Robert D. Kerns, Liana Fraenkel

Nursing: School of Nursing Faculty Publications and Other Works

Guidelines on long-term opioid therapy recommend frequent reassessment of harm, efficacy, and misuse of these potentially harmful and sometimes ineffective medications. In primary care, there is a need for a brief, patient-reported instrument. This report details the initial steps in the development of such an instrument. An interdisciplinary team of clinician-scientists performed four discrete steps in this study: (1) conceptualization of the purpose and function of the instrument, (2) assembly of an item pool, (3) expert rating on which items were most important to include in the instrument, and (4) modification of expert-selected items based on a reading level check …

A Urinary Metabolic Signature For Multiple Sclerosis And Neuromyelitis Optica, Teklab Gebregiworgis, Helle H. Nielsen, Chandirasegara Massilamany, Arunakumar Gangaplara, Jay Reddy, Zsolt Illes, Robert Powers

Jay Reddy Publications

Urine is a metabolite-rich biofluid that reflects the body’s effort to maintain chemical and osmotic homeostasis. Clinical diagnosis routinely relies on urine samples because the collection process is easy and noninvasive. Despite these advantages, urine is an under-investigated source of biomarkers for multiple sclerosis (MS). Nuclear magnetic resonance spectroscopy (NMR) has become a common approach for analyzing urinary metabolites for disease diagnosis and biomarker discovery. For illustration of the potential of urinary metabolites for diagnosing and treating MS patients, and for differentiating between MS and other illnesses, 38 urine samples were collected from healthy controls, MS patients, and neuromyelitis optica-spectrum …

Micrornas Are Involved In The Development Of Morphine-Induced Analgesic Tolerance And Regulate Functionally Relevant Changes In Serpini1., Jenica D. Tapocik, Kristin Ceniccola, Cheryl L. Mayo, Melanie L. Schwandt, Matthew Solomon, Bi-Dar Wang, Truong V. Luu, Jacqueline Olender, Thomas Harrigan, Thomas M. Maynard, Greg I. Elmer, Norman H. Lee

Pharmacology and Physiology Faculty Publications

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The …

Choosing An Allograft Or Autograft In Orthopedic Surgeries For Athletes, Cassandra M. Izzo

Honors Theses and Capstones

Athletes and their doctors have the choice of using an allograft or autograft in reconstruction surgeries. The purpose of this study is to see if there is a difference in the healing mechanism and surgical outcome in using an allograft or autograft during orthopedic surgical procedures, as well as to analyze graft rejection and disease transmission through donor tissue.

Doctors and athletic trainers were interviewed in order to learn about the healing mechanisms and advantages and disadvantages of allografts and autografts in order to conclude if one was better than the other. College level athletes on different sports teams were …

Interaction Of Alu Polymorphisms And Novel Measures Of Discrimination In Association With Blood Pressure In African Americans Living In Tallahassee, Alexis C. Boulter, Jackyn Quinlan, Aida T. Miró-Herrans, Laurel N. Pearson, Nubiana L. Todd, Clarence C. Gravlee, Connie J. Mulligan

Human Biology Open Access Pre-Prints

African Americans are 40% more likely to be afflicted with hypertension in comparison to non-Hispanic, white Americans, resulting in a 30% higher instance of mortality due to cardiovascular disease. There is debate about the relative contributions of genetic and sociocultural risk factors to the racial disparity in hypertension.

We assayed three Alu insertion polymorphisms located in the angiotensin-1-converting enzyme (ACE), tissue plasminogen activator (PLAT), and with no-lysine kinase 1 (WNK1) genes. We also estimated West African genetic ancestry and developed novel measures of perceived discrimination to create a biocultural model of blood pressure among …

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Journal of Patient-Centered Research and Reviews

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs.

Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

We Are… Bridging Medicine And Science, Vol. 1, Issue 4, Fall 2015, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

The Tri-State Experience: Outcome Analysis Of Patients With Triple Negative Breast Cancer Treated At Marshall University, Laurie Matt Md, Mph, Mohammad Mozayen Md, Todd W. Gress Md, Maria Tria Tirona Md

Internal Medicine

Breast cancer is the most frequently diagnosed malignancy in women in the United States. It is the second most common malignancy to cause death, with approximately 39,000 women dying of breast cancer in the United States in 2013. Triple negative breast cancer is defined as the absence of estrogen, progesterone and human epidermal growth factor receptor 2 receptors. It has been associated with a higher incidence in African American women, a younger age and a more advanced stage at diagnosis, and an inferior overall survival. To recognize the differences of our West Virginia community population when compared to the national …

Adverse Effects Of Asparaginase In Pediatric Patients With Acute Lymphoblastic Leukemia, Chengcheng Liu

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Asparaginase is a critical treatment component for ALL. However, its use is complicated by adverse effects, such as hypersensitivity, osteonecrosis and pancreatitis.

Hypersensitivity to asparaginase typically requires discontinuation of current formulation and substitution with other formulations, but the differential diagnosis can be challenging, and the diagnostic utility of antibody tests is unclear. We comprehensively analyzed anti-Elspar (native E.coli asparaginase) IgG antibodies in 410 pediatric patients treated on an asparaginaseintensive front-line clinical trial. Of 169 patients (41.2%) who exhibited clinical allergy, 147 (87.0%) were positive for anti-Elspar antibody. Of …

Functional Analysis Of The Molluscum Contagiosum Virus Mc160 Death Effector Domain-Containing Protein Rxdl Motif, Sarah Weber

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum contagiosum virus (MCV) is a member of the Poxviridae family that causes benign skin lesions. MCV lesions persist on average for 8-12 months in otherwise healthy individuals. MCV lesions are characterized by reduced inflammation. The persistence and reduction of inflammation at the site of MCV lesions have been attributed to MCV immune evasion genes. MCV encodes two death effector domain (DED) containing proteins, MC159 and MC160. DEDs are found in cellular proteins such as FADD and procaspase-8. These cellular proteins are involved in several innate immune responses such as apoptosis and activation of interferon (IFN). Presumably, MC159 and …

A Novel Caspase 8 Selective Small Molecule Potentiates Trail-Induced Cell Death, Octavian Bucur, Gabriel Gaidos, Achani Yatawara, Bodvael Pennarun, Chamila Rupasinghe, Jérémie Roux, Stefan Andrei, Bingqian Guo, Alexandra Panaitiu, Maria Pellegrini, Dale Mierke, Roya Khosravi-Far

Dartmouth Scholarship

Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations and Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Live Imaging Of The Ependymal Cilia In The Lateral Ventricles Of The Mouse Brain, Alzahra J. Al Omran, Hannah C. Saternos, Tongyu Liu, Surya M. Nauli, Wissam A. Aboualaiwi

Pharmacy Faculty Articles and Research

Multiciliated ependymal cells line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia is associated with various neurological deficits. The current ex vivo live imaging of motile ependymal cilia technique allows for a detailed study of ciliary dynamics following several steps. These steps include: mice euthanasia with carbon dioxide according to protocols of The University of Toledo’s Institutional Animal Care and Use Committee (IACUC); craniectomy followed by brain removal and sagittal brain dissection with a vibratome or sharp blade to obtain very thin sections through the brain lateral ventricles, where the ependymal cilia can be visualized. …

The Preparatory Set: A Novel Approach To Understanding Stress, Trauma, And The Bodymind Therapies, Peter Payne, Mardi A. Crane-Godreau

Dartmouth Scholarship

Basic to all motile life is a differential approach/avoid response to perceived features of environment. The stages of response are initial reflexive noticing and orienting to the stimulus, preparation, and execution of response. Preparation involves a coordination of many aspects of the organism: muscle tone, posture, breathing, autonomic functions, motivational/emotional state, attentional orientation, and expectations. The organism organizes itself in relation to the challenge. We propose to call this the "preparatory set" (PS). We suggest that the concept of the PS can offer a more nuanced and flexible perspective on the stress response than do current theories. We also hypothesize …

Breast Cancer Screening: Early Detection Is Not Enough, Judy A. Tjoe

Journal of Patient-Centered Research and Reviews

N/A