Digital Commons Network^™

Stress Granules And Rna Processing Bodies Are Novel Autoantibody Targets In Systemic Sclerosis, Michael E. Johnson, Andrew V. Grassetti, Jaclyn N. Taroni, Shawn M. Lyons, Devin Schweppe, Jessica K. Gordon, Robert F. Speira, Robert Lafyatis, Paul J. Anderson, Scott A. Gerber, Michael L. Whitfield

Dartmouth Scholarship

Autoantibody profiles represent important patient stratification markers in systemic sclerosis (SSc). Here, we performed serum-immunoprecipitations with patient antibodies followed by mass spectrometry (LC-MS/MS) to obtain an unbiased view of all possible autoantibody targets and their associated molecular complexes recognized by SSc.

Comparative Study Of Ethics In Librarianship And The Bible, Japheth Abdulazeez Yaya

The Christian Librarian

This paper is a comparative study that discusses ethical issues in librarianship and the Bible. Such issues include: Laws in librarianship vs. laws in the Bible; censorship in librarianship vs. censorship in the Bible; Bible teachings on access to information and access to information in librarianship; purification (i.e., book binding), conservation and preservation practices in the library and in the Bible; weeding of library collections and weeding practices in the Bible; privacy and confidentiality in the library and in the Bible; orderliness of the library collections and the Bible; consortium building of library collections and in the Bible; and consequences …

Why Animal Welfarism Continues To Fail, Lori Marino

Animal Sentience

Welfarism prioritizes human interests over the needs of nonhuman animals. Despite decades of welfare efforts other animals are mostly worse off than ever before, being subjected to increasingly invasive and harmful treatments, especially in the factory farming and biomedical research areas. A legal rights-based approach is essential in order for other animals to be protected from the varying ethical whims of our species.

Functional Mechanisms Underlying Pleiotropic Risk Alleles At The 19p13.1 Breast–Ovarian Cancer Susceptibility Locus, Kate Lawrenson, Siddhartha Kar, Karen Mccue, Karoline Kuchenbaeker, Kyriaki Michailidou, Jonathan Tyrer, Jonathan Beesley, Susan J. Ramus, Qiyuan Li, Melissa K. Delgado, Janet M. Lee, Kristiina Aittomäki, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Banu K. Arun, Brita Arver, Elisa V. Bandera, Monica Barile, Rosa B. Barkardottir, Daniel Barrowdale, Matthias W. Beckmann, Javier Benitez, Andrew Berchuck, Maria Bisogna, Line Bjorge, Carl Blomqvist, William Blot, Natalie Bogdanova, Anders Bojesen, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Anne-Lise Børresen-Dale, Hiltrud Brauch, Paul Brennan, Hermann Brenner, Fionna Bruinsma, Joan Brunet, Shaik Ahmad Buhari, Barbara Burwinkel, Ralf Butzow, Sandra S. Buys, Qiuyin Cai, Trinidad Caldes, Ian Campbell, Rikki Canniotto, Jenny Chang-Claude, Jocelyne Chiquette, Ji-Yeob Choi, Kathleen B.M Claes, Gemo Study Collaborators, Linda S. Cook, Angela Cox, Daniel W. Cramer, Simon S. Cross, Cezary Cybulski, Kamila Czene, Mary B. Daly, Francesca Damiola, Agnieszka Dansonka-Mieszkowska, Hatef Darabi, Joe Dennis, Peter Devilee, Orland Diaz, Jennifer A. Doherty

Dartmouth Scholarship

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 X 10^-20), ER-negative BC (P = 1.1 X 10^-13), BRCA1 -associated BC (P = 7.7 X 10^-16) and triple negative BC (P-diff = 2 X 10^-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 X 10^{-3 …}

Which Matters More? Effects Of Surface- And Deep- Level Diversity On Team Processes And Performance, Mai P. Trinh

Management Faculty Publications

This chapter reviews what we know about the effects of surface-level diversity (age, sex, and ethnicity) and deep-level diversity (personality characteristics such as conscientiousness, openness to experience, extraversion, emotional stability, and agreeableness) in organizational teams. It also outlines challenges to today’s diversity management and Human Resource (HR) practices, such as the lack of definite conclusions from research results, the mismatch between team diversity research designs and organizations’ needs, and the lack of research examining simultaneously different aspects of diversity. Drawing from analysis results of team data from 55 teams of volunteers from Shanghai, the author recommends that HR training and …

Experimenting With Sex: Four Approaches To The Genetics Of Sex Reversal Before 1950, Michael Dietrich

Dartmouth Scholarship

In the early twentieth century, Tatsuo Aida in Japan, jvind Winge in Denmark, Richard Goldschmidt in Germany, and Calvin Bridges in the United States all developed different experimental systems to study the genetics of sex reversal. These locally specific experimental systems grounded these experimenters' understanding of sex reversal as well as their interpretation of claims regarding experimental results and theories. The comparison of four researchers and their experimental systems reveals how those different systems mediated their understanding of genetic phenomena, and influenced their interpretations of sex reversal.

Energy Partisanship, Hari M. Osofsky

Emory Law Journal

Whether the topic is the Paris Agreement on climate change, greenhouse gas emissions from power plants, the Keystone XL pipeline, hydraulic fracturing, offshore drilling, or renewable energy, much of the U.S. policy dialogue about energy and climate change is deeply partisan. This Article provides a novel analysis of how to make progress on energy and climate change issues by translating this emerging psychological research into a framework for action. It proposes two interconnected strategies¿ substantive and structural¿for moving past imbedded partisanship and political dysfunction. Substantively, the Article argues for refocusing regulatory efforts on areas where a greater degree of consensus …

G-Cpt Symmetry Of Quantum Emergence And Submergence -- An Information Conservational Multiagent Cellular Automata Unification Of Cpt Symmetry And Cp Violation For Equilibrium-Based Many-World Causal Analysis Of Quantum Coherence And Decoherence, Wen-Ran Zhang

Computer Science: Faculty Publications

An equilibrium-based YinYang bipolar dynamic Generalization of CPT (G -CPT) symmetry is introduced based on energy/information conservational quantum emergence-submergence. As a bottleneck of quantum computing, quantum decoherence or collapse has been plaguing quantum mechanics for decades. It is suggested that the crux of the problem can trace its origin back to the incompleteness of CPT symmetry due to the lack of holistic representation for equilibrium-based bipolar coexistence. In this work, the notion of quantum emergence-submergence is coined as two opposite processes with bipolar energy/information conservation. The new notion leads to G-CPT symmetry supported by a Bipolar Quantum Cellular Automata (BQCA) …

Internal Funding Newsletter, Academic Year 2015-2016, Uno Office Of Research And Creative Activity

Internal Funding Newsletters

This newsletter features: a letter from Scott Snyder, Chief Research Officer, Office of Research and Creative Activity; UNIVERSITY COMMITTEE ON RESEARCH AND CREATIVE ACTIVITY (UCRCA) Faculty Awards; FACULTY AWARD: ADROCA; 2015-2016 Internal Funding Awardees Student Awards; 2015-2016 FACULTY MENTORS; and Internal Funding Opportunities and Summary.

Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong

Bioelectrics Publications

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In …

Genetic And Cellular Studies Highlight That A Disintegrin And Metalloproteinase 19 Is A Protective Biomarker In Human Prostate Cancer, Gerard F. Hoyne, Caoline Rudnicka, Qing-Xiang Sang, Mark Roycik, Sarah Howarth, Peter Leedman, Markus Schlaich, Patrick Candy, Vance Matthews

Health Sciences Papers and Journal Articles

Background: Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group …

Maturity, Physical Ability, Technical Skill And Coaches' Perception Of Semi-Elite Adolescent Australian Footballers, A Cripps, L Hopper, C Joyce

Health Sciences Papers and Journal Articles

Purpose: To confirm the effect of maturational differences on anthropometric and physical testing and explore the effect of maturation on technical skill and coaches’ perceptions of skill in adolescent Australian footballers.

Methods: Athletes were recruited from a semi-elite under 16 competition (n = 94, age 15.7 ± 0.3 years) and completed anthropometric, physical, and technical skill tests. Coaches from each team provided subjective ratings of athletes’ technical skills. Maturation groups were derived from years from peak height velocity estimates, with classifications either later, average or earlier maturing.

Results: Effect size comparisons revealed very large to moderate effects between groups for …

Male And Female Differences In Health Benefits Derived From Physical Activity: Implications For Exercise Prescription, Beth P. Hands, Helen Parker, Dawne Larkin, Marja Cantell, Elizabeth Rose

Health Sciences Papers and Journal Articles

Abstract:

Males are consistently reported as more physically active than females regardless of age or measure. Often, this difference results in females identified as under active and at risk of longterm poor health outcomes. In this paper a different perspective drawing on evidence from many sources is offered. Males and females gain different health benefits according to the level, mode and intensity of the physical activity. Some potential ramifications of these gender differences in health benefits are evident in the prevalence of hypokinetic diseases across the life span and the interpretation of measured physical activity levels and intensities. By focusing …

Dual Energy X-Ray Absorptiometry Compared With Anthropometry In Relation To Cardio-Metabolic Risk Factors In A Young Adult Population: Is The ‘Gold Standard’ Tarnished?, D Demmer, L Beilin, B Hands, S Burrows, C Pennell, S Lye, J Mountain, T Mori

Health Sciences Papers and Journal Articles

Background and Aims: Assessment of adiposity using dual energy x-ray absorptiometry (DXA) has been considered more advantageous in comparison to anthropometryfor predicting cardio-metabolic risk in the older population, by virtue of its ability to distinguish total and regional fat. Nonetheless, there is increasing uncertainty regarding the relative superiority of DXA and little comparative data exist in young adults. This study aimed to identify which measure of adiposity determined by either DXA or anthropometry is optimal within a range of cardio-metabolic risk factors in young adults.

Methods and Results: 1138 adults aged 20 years were assessed by DXA and standard …

Student Perceptions To Teaching Undergraduate Anatomy In Health Sciences, R Anderton, L Chiu, S Aulfrey

Health Sciences Papers and Journal Articles

Anatomy and physiology teaching has undergone significant changes to keep up with advances in technology and to cater for a wide array of student specific learning approaches. This paper examines perceptions towards a variety of teaching instruments, techniques, and innovations used in the delivery and teaching of anatomy and physiology for health science students, and asks whether active learning through more progressive methods of teaching is beneficial for students across health science disciplines. In total, 138 health science students consisting of 32 biomedical science students, 52 exercise and sports science students, and 54 health and physical education students completed the …

The Pathology Of Command And Control: A Formal Synthesis, Michael Cox

Dartmouth Scholarship

One of the most important theories in the study of environmental governance and policy is the pathology of command and control, which describes the negative consequences of top-down, technocratic governance of social and ecological systems. However, to date, this theory has been expressed somewhat inconsistently and informally in the literature, even by the seminal works that have established its importance and popularized it. This presents a problem for the sustainability science community if it cannot be sure of the precise details of one of its most important theories. Without such precision, applications and tests of various elements of the theory …

An Analysis Of Plasticity In The Rat Respiratory System Following Cervical Spinal Cord Injury And The Application Of Nanotechnology To Induce Or Enhance Recovery Of Diaphragm Function, Janelle Lorien Walker

Wayne State University Dissertations

Second cervical segment spinal cord hemisection (C2Hx) results in ipsilateral hemidiaphragm paralysis. However, the intact latent crossed phrenic pathway can restore function spontaneously over time or immediately following drug administration.

WGA bound fluorochromes were administered to identify nuclei associated with diaphragm function in both the acute and chronic C2Hx models. WGA is unique in that it undergoes receptor mediated endocytosis and is transsynaptically transported across select physiologically active synapses. Comparison of labeling in the acutely injured to the chronically injured rat provided an anatomical map of spinal and supraspinal injury induced synaptic plasticity. The plasticity occurs over time in the …

Exploration Of Cancer Proliferative Signaling In Chemotherapy Drug Resistance And Mdig-Induced Tumorigenesis, Kai Wu

Wayne State University Dissertations

ABSTRACT

EXPLORATION OF CANCER PROLIFERATIVE SIGNALING IN CHEMOTHERAPY DRUG RESISTANCE AND MDIG-INDUCED TUMORIGENESIS

by

KAI WU

August 2016

Advisor: Dr. Fei Chen

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Aberrant intracellular signaling pathway is one of the major driving forces of malignancy through multiple stages of human cancers. Our study demonstrates that in cancer cells, the signaling pathways are profoundly and actively intertwined with each other so they can synergistically affect cell biology, including promoting development of malignancy and compensating the loss of proliferation or survival signals in responses to anti-tumor drug. Moreover, cancer cells can also adopt “non-canonical” mechanisms …

Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model, Bing Xu

Wayne State University Dissertations

The aim of this study was to elucidate the expression and functions of interleukin (IL)-24 and suppressor of cytokine signaling 3 (SOCS3), and their regulatory relationship in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by the infection, and this upregulation was dampened by flagellin pretreatment. Time course studies revealed that IL-24 expression was markedly elevated, followed by a subsidence and second elevation, a pattern shared with SOCS3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression, and suppressed SOCS3, IL-1β, IL-1RN, and …

Novel Regulatory Mechanisms Of Inositol Biosynthesis In Saccharomyces Cerevisiae And Mammalian Cells, And Implications For The Mechanism Underlying Vpa-Induced Glucose 6-Phosphate Depletion, Wenxi Yu

Wayne State University Dissertations

Myo-inositol is the precursor of all inositol containing molecules, including inositol phosphates, phosphoinositides and glycosylphosphatidylinositols, which are signaling molecules involved in many critical cellular functions. Perturbation of inositol metabolism has been linked to neurological disorders. Although several widely-used anticonvulsants and mood-stabilizing drugs have been shown to exert inositol depletion effects, the mechanisms of action of the drugs and the role of inositol in these diseases are not understood. Elucidation of the molecular control of inositol synthesis will shed light on the pathologies of inositol related illnesses.

In Saccharomyces cerevisiae, deletion of the four glycogen synthase kinase-3 genes, MCK1, MRK1, MDS1, …

After The Clinic: Gendered Pathology In Modernist Literature, Alisa Allkins

Wayne State University Dissertations

ABSTRACT

AFTER THE CLINIC: GENDERED PATHOLOGY IN MODERNIST LITERATURE

By

ALISA ALLKINS

December 2016

Advisor: Dr. Barrett Watten

Major: English (Literature)

Degree: Doctor of Philosophy

After the Clinic: Gendered Pathology in Modernist Literature demonstrates the ways in which formal innovations of modernism construct a relationship between sexual pathology and modernity. I read a selection of canonical and lesser known modernist works through their investments in overturning hierarchical relationships constructed through the clinical institution, focusing on their depiction of clinical types such as the traumatized male veteran, the hysterical woman, and the often-patriarchal figure of the doctor. Modernist prose and hybrid …

Essays On Healthy Aging From The Perspective Of A Health Production Function, Nasim Baghban Ferdows

Wayne State University Dissertations

This dissertation examines the determinants of healthy aging among older adults using Grossman’s framework of a health production function. Healthy aging is produced using a variety of inputs, including some determined in early life, such as health and socioeconomic status as a child, others determined in young adulthood, such as education, others determined in mid-life, such as household wealth, and still others determined in later-life, such as current health habits. A production function for healthy aging is estimated using nationally representative data from the 2010 Health and Retirement Study on non-institutionalized seniors, and positing a simultaneous equations mediation model, recognizing …

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …

Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish

Wayne State University Dissertations

Breast cancer is the most common cancer and the second leading

cause of cancer death in women. While ER-positive breast cancer subtypes are initially

well-managed by targeted therapies targeting estrogen signaling, many women are

suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients

who were previously successfully treated with anti-estrogen therapies worsens

overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of

a tumor may allow for the possibility …

Molecular Regulation Of Trophoblast Survival During Placentation And Pathologies Of Placental Insufficiency, Chandni V. Jain

Wayne State University Dissertations

HBEGF, is present in the uterus at the time of embryo implantation and protects first

trimester TB cells from apoptosis and promotes their invasion. The hypertensive disease, PE, in

which TB invasion of the uterine arteries is reduced and TB apoptosis is elevated, is

characterized by a reduction in HBEGF expression. In this study using a first trimester cell line

and villous explant culture key components involved in HBEGF survival signaling pathway were

identified. Specific MMP inhibitors established the requirement for MMP2 in HBEGF shedding

and upregulation. NGS identified a HIF regulated gene, HSPA6 (HSP70B’) and using specific

inhibitors it …

Calponin And Cytoskeleton Dynamics In Macrophage Functions And The Pathogenesis Of Atherosclerosis, Rong Liu

Wayne State University Dissertations

Arterial atherosclerosis is an inflammatory disease. Macrophages play a major role in the pathogenesis and progression of atherosclerotic lesions. Modulation of macrophage function is a therapeutic target for the treatment of atherosclerosis. Calponin is an actin-filament-associated regulatory protein that inhibits the activity of myosin-ATPase and dynamics of the actin cytoskeleton. Encoded by the Cnn2 gene, calponin isoform 2 is expressed at significant levels in macrophages. Deletion of calponin 2 increases macrophage migration and phagocytosis. In the present study, we investigated the effect of deletion of calponin 2 in macrophages on the pathogenesis and development of atherosclerosis. The results showed that …

Cardiolipin Is Required For Optimal Acetyl-Coa Metabolism, Vaishnavi Raja

Wayne State University Dissertations

The phospholipid cardiolipin (CL) is crucial for many cellular functions and signaling pathways, both inside and outside of mitochondria. My thesis focuses on the role of CL in energy metabolism. Many reactions of electron transport and oxidative phosphorylation, the transport of metabolites needed for these processes, and the stabilization of electron transport chain supercomplexes, require CL. Recent studies indicate that CL is required for the synthesis of iron-sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways. Activation of carnitine-acetylcarnitine translocase, which transports acetyl-CoA into the mitochondria, is CL dependent. The presence of substantial amounts of CL in the peroxisomal …

Navigating The Transition Into Motherhood: Women's Experiences Of Control, Emotions, And Social Ideals, Jody Sue Sauer-Sargent

Wayne State University Dissertations

In this dissertation, I sought to give postpartum women their own voices so that they could help define the postpartum experience on their own terms. It fills important gaps within the literature on new mothers’ experiences. A phenomenological approach was used, emphasizing the lived experiences of the women, with an overlay of autoethnography, where the personal experience of the researcher becomes important primarily in how it illuminates the phenomenon being studied. Thus, my personal experience of pregnancy into early motherhood is interwoven throughout this dissertation. Forty-two women participated in the in-depth, face-to-face interview, followed by a questionnaire. The qualitative data …

Loss Of Rap1gap: A Driver In The Progression From Dcis Of The Breast To Idc, Seema Shah

Wayne State University Dissertations

The purpose of this study is to determine the role of Rap1Gap in the progression of DCIS (ductal carcinoma in situ) to IDC (invasive ductal cancer). We employed an in-vitro three-dimensional (3D) overlay model that provides a physiologically relevant microenvironment to study mechanisms of malignant progression. Previous studies from this laboratory aimed to determine specific gene expression changes common to three models of DCIS- MCF10.DCIS, SUM 102 and SUM 225 in comparison to MCF10A cells, a model of non-transformed human mammary epithelium. The expression of 295 genes was found to be significantly altered, with 63 being increased in expression in …

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …