Digital Commons Network^™

The Speciation Of Metals In Mammals Influences Their Toxicokinetics And Toxicodynamics And Therefore Human Health Risk Assessment, Robert A. Yokel, Stephen M. Lasley, David C. Dorman

Pharmaceutical Sciences Faculty Publications

Chemical form (i.e., species) can influence metal toxicokinetics and toxicodynamics and should be considered to improve human health risk assessment. Factors that influence metal speciation (and examples) include: (1) carrier-mediated processes for specific metal species (arsenic, chromium, lead and manganese), (2) valence state (arsenic, chromium, manganese and mercury), (3) particle size (lead and manganese), (4) the nature of metal binding ligands (aluminum, arsenic, chromium, lead, and manganese), (5) whether the metal is an organic versus inorganic species (arsenic, lead, and mercury), and (6) biotransformation of metal species (aluminum, arsenic, chromium, lead, manganese and mercury). The influence of speciation on metal …

Never Let Me Clone? Countering An Ethical Argument Against The Reproductive Cloning Of Humans, Yvette Pearson

Philosophy Faculty Publications

In the March 2006 issue of EMBO reports, Christof Tannert, a bioethicist at the Max Delbrück Research Centre in Berlin, Germany, presented a moral argument against human reproductive cloning on the basis of Immanuel Kant’s categorical imperative (Tannert, 2006). In this article, I address some problems with Tannert’s views and show that our concerns about this prospective procedure should prompt us to scrutinize carefully the conventional procreative practices and attitudes. Indeed, if we set aside objections that are grounded in genetic determinism, many of the offensive features of human cloning are identical to problems with procreation by more conventional means, …

Spatiotemporal Dynamics Of Networks Of Excitable Nodes, Aaron J. Steele, Mark Tinsley, Kenneth Showalter

Faculty & Staff Scholarship

No abstract provided.

Modification Of Human Immunodeficiency Virus Type 1 Reverse Transcriptase To Target Cells With Elevated Cellular Dntp Concentrations, Varuni K. Jamburuthugoda, Pauline Chugh, Baek Kim

Biology

Retroviruses and DNA viruses utilize cellular dNTPs as substrates for their DNA polymerases during viral replication in infected cells. However, because of S phase-dependent dNTP biosynthesis, the availability of cellular dNTPs significantly varies among cell types (e.g. dividing versus nondividing cells and normal versus tumor cells). Here we tested whether alterations in the dNTP utilization efficiency and dNTP binding affinity of viral DNA polymerases can switch viral infection specificity to cell types with different dNTP concentrations. We employed an HIV-1 reverse transcriptase (RT) mutant (Q151N), which is catalytically active only at high dNTP concentrations because of its reduced dNTP binding …

Identification Of The Heparin-Binding Determinants Within Fibronectin Repeat Iii1: Role In Cell Spreading And Growth, Liqiong Gui, Katherine Wojciechowski, Candace D. Gildner, Hristina Nedelkovska, Denise C. Hocking

Biology

Fibronectins are high molecular mass glycoproteins that circulate as soluble molecules in the blood, and are also found in an insoluble, multimeric form in extracellular matrices throughout the body. Soluble fibronectins are polymerized into insoluble extracellular matrix (ECM) fibrils via a cell-dependent process. Recent studies indicate that the interaction of cells with the ECM form of fibronectin promotes actin organization and cell contractility, increases cell growth and migration, and enhances the tensile strength of artificial tissue constructs; ligation of integrins alone is insufficient to trigger these responses. Evidence suggests that the effect of ECM fibronectin on cell function is mediated …

Classification And Risk Stratification Of Invasive Breast Carcinomas Using A Real-Time Quantitative Rt-Pcr Assay., Laurent Perreard, Cheng Fan, John F Quackenbush, Michael Mullins, Nicholas P Gauthier, Edward Nelson, Mary Mone, Heidi Hansen, Saundra S Buys, Karen Rasmussen, Alejandra Ruiz Orrico, Donna Dreher, Rhonda Walters, Joel Parker, Zhiyuan Hu, Xiaping He, Juan P Palazzo, Olufunmilayo I Olopade, Aniko Szabo, Charles M Perou, Philip S Bernard

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

INTRODUCTION: Predicting the clinical course of breast cancer is often difficult because it is a diverse disease comprised of many biological subtypes. Gene expression profiling by microarray analysis has identified breast cancer signatures that are important for prognosis and treatment. In the current article, we use microarray analysis and a real-time quantitative reverse-transcription (qRT)-PCR assay to risk-stratify breast cancers based on biological 'intrinsic' subtypes and proliferation. METHODS: Gene sets were selected from microarray data to assess proliferation and to classify breast cancers into four different molecular subtypes, designated Luminal, Normal-like, HER2+/ER-, and Basal-like. One-hundred and twenty-three breast samples (117 invasive …

Cutaneous And Presumed Visceral Leishmaniasis In A Soldier Deployed To Afghanistan, James P. Woodrow, Joshua D. Hartzell, Jim Czarnik, David Brett-Major, Glenn Wortmann

Journal Articles: Epidemiology

Leishmaniasis has been frequently diagnosed in US military personnel returning from duty in Southwest Asia. The majority of cases have demonstrated cutaneous disease, although a few cases of visceral disease have been documented. We present the case of an immunocompetent, HIV-negative, US Army soldier who suffered both visceral and cutaneous manifestations of leishmaniasis after returning from deployment in Afghanistan. Overlap of cutaneous and visceral involvement is rare and has not been reported in our cohort. Latent Plasmodium vivax infection may have been an exacerbating cofactor. We discuss this case and present a review of the literature.

Interdependency Of Pharmacokinetic Parameters: A Chicken-And-Egg Problem? Not!, Reza Mehvar

Pharmacy Faculty Articles and Research

Pharmacokinetic (PK) software packages are widely used by scientists in different disciplines to estimate PK parameters. However, their use without a clear understanding of physiological parameters affecting the PK parameters and how different PK parameters are related to each other may result in erroneous interpretation of data. Often, mathematical relationships used for the estimation of PK parameters obscure the true physiological relationships among these parameters, prompting a discussion of which parameter came first and giving the appearance of the-chicken-and-the-egg dilemma. In this article, the author attempts to show how different PK parameters are related to physiological parameters and each other …

The Need For Tobacco Education: Studies Of Collegiate Dental Hygiene Patients And Faculty, Joan M. Davis Rdh, Ms, Margaret S Stockdale, Martha Cropper

Journal Articles

The need for inclusion of comprehensive tobacco control education/training for health care providers continues to be stressed in publications addressing cessation services. The dental appointment presents an excellent opportunity to provide tobacco interventions to basically healthy people on regular intervals. The purpose of this study was twofold: 1) to assess the need (stage of change and concomitant need for tobacco cessation intervention) of dental hygiene patients at a Midwest dental hygiene clinic, and 2) to assess and compare the level of tobacco intervention education currently being offered by dental hygiene educators in a Midwestern state. Patients (n=426) of a collegiate …

Principal Component Analysis For Predicting Transcription-Factor Binding Motifs From Array-Derived Data, Yunlong Liu, Matthew P Vincenti, Hiroki Yokota

Dartmouth Scholarship

The responses to interleukin 1 (IL-1) in human chondrocytes constitute a complex regulatory mechanism, where multiple transcription factors interact combinatorially to transcription-factor binding motifs (TFBMs). In order to select a critical set of TFBMs from genomic DNA information and an array-derived data, an efficient algorithm to solve a combinatorial optimization problem is required. Although computational approaches based on evolutionary algorithms are commonly employed, an analytical algorithm would be useful to predict TFBMs at nearly no computational cost and evaluate varying modelling conditions. Singular value decomposition (SVD) is a powerful method to derive primary components of a given matrix. Applying SVD …

Evaluation Of Stature Development During Childhood And Adolescence In Individuals With Familial Hypophosphatemic Rickets, Mauro M. S. Borghi, Verônica Coates, Hatim A. Omar

Pediatrics Faculty Publications

This review was conducted to study the diagnosis, treatment, and growth progression in infants and adolescents with familial hypophosphatemic rickets. The bibliographic search was carried out utilizing the electronic databases MEDLINE, OVID, and LILACS and by direct research within the last 15 years using the keywords rickets, familial hypophosphatemia, vitamin D deficiency, stature growth, childhood, and adolescence. Article selection was done by comparing the evaluation of the growth in patients with familial hypophosphatemic rickets, including the variables that might affect them, for possible future therapeutic proposals. It is concluded that the most significant fact in the treatment of familial hypophosphatemic …

Near-Infrared Characterization Of Breast Tumors In Vivo Using Spectrally-Constrained Reconstruction, Subhadra Srinivasan, Brian W. Pogue, Ben Brooksby, Shudong Jiang, Hamid Dehghani, Christine Kogel, Wendy A. Wells, Steven P. Poplack, Keith D. Paulsen

Dartmouth Scholarship

Multi-wavelength Near-Infrared (NIR) Tomography was utilized in this study to non-invasively quantify physiological parameters of breast tumors using direct spectral reconstruction. Frequency domain NIR measurements were incorporated with a new spectrally constrained direct chromophore and scattering image reconstruction algorithm, which was validated in simulations and experimental phantoms. Images of total hemoglobin, oxygen saturation, water, and scatter parameters were obtained with higher accuracy than previously reported. Using this spectral approach, in vivo NIR images are presented and interpreted through a series of case studies (n=6 subjects) having differing abnormalities. The corresponding mammograms and ultrasound images are also evaluated. Three of six …

Experts Recommend Strategies For Strengthening The Use Of Advanced Practice Nurses In Nursing Homes., Mathy Mezey, Sarah Greene Burger, Harrison G Bloom, Alice Bonner, Mary Bourbonniere, Barbara Bowers, Jeffrey B Burl, Elizabeth Capezuti, Diane Carter, Jacob Dimant, Sarah A Jerro, Susan C Reinhard, Marilyn Ter Maat

College of Nursing Faculty Papers & Presentations

In 2003, The John A. Hartford Foundation Institute for Geriatric Nursing, New York University Division of Nursing, convened an expert panel to explore the potential for developing recommendations for the caseloads of advanced practice nurses (APNs) in nursing homes and to provide substantive and detailed strategies to strengthen the use of APNs in nursing homes. The panel, consisting of nationally recognized experts in geriatric practice, education, research, public policy, and long-term care, developed six recommendations related to caseloads for APNs in nursing homes. The recommendations address educational preparation of APNs; average reimbursable APN visits per day; factors affecting APNs caseload …

Towards Semantic Service Request Of Web Service Composition, Qianhui Althea Liang, Jen-Yao Chung, Steven M. Miller

Research Collection School Of Computing and Information Systems

When meeting the challenges in automatic and semi-automatic Web service composition, capturing the user's service demand and preferences is as important as knowing what the services can do. This paper discusses the idea of semantic service requests for composite services, and presents a way to model the elements of a composite service request as user preferences and constraints. The model is based on an interactive and iterative strategy meant to obtain the exact requirements from potential service consumers. The markup vocabularies and associated inference mechanism of OWL-S are used as a means to bring semantics to service requests. Language constructs …

Taxol-Stabilized Microtubules Can Position The Cytokinetic Furrow In Mammalian Cells, Katie Shannon, Julie C. Canman, C. Ben Moree, Jennifer S. Tirnauer, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

How microtubules act to position the plane of cell division during cytokinesis is a topic of much debate. Recently, we showed that a subpopulation of stable microtubules extends past chromosomes and interacts with the cell cortex at the site of furrowing, suggesting that these stabilized microtubules may stimulate contractility. To test the hypothesis that stable microtubules can position furrows, we used taxol to rapidly suppress microtubule dynamics during various stages of mitosis in PtK1 cells. Cells with stabilized prometaphase or metaphase microtubule arrays were able to initiate furrowing when induced into anaphase by inhibition of the spindle checkpoint. In these …

Does The Choice Of Bottle Nipple Affect The Oral Feeding Performance Of Very-Low-Birthweight (Vlbw) Infants?, C E. Scheel, Richard J. Schanler, Chantal Lau

Faculty, Staff and Students Publications

BACKGROUND: There is a continuous debate regarding the best bottle nipple to be used to enhance the bottle-feeding performance of a preterm infant. Aim: To verify that feeding performance can be improved by using the bottle nipple with the physical characteristics that enhance infants' sucking skills. METHODS: Ten "healthy" VLBW infants (941+/-273 g) were recruited. Feeding performance was monitored at two time periods, when taking 1-2 and 6-8 oral feedings/d. At each time and within 24 h, performance was monitored using three different bottle nipples offered in a randomized order. Rate of milk transfer (ml/min) was the primary outcome measure. …

Ergonomics: Implications On Computer End-Users, Maheen Ghauri, Dr. Arshad Siddiqi

International Conference on Information and Communication Technologies

Ergonomics is the application of scientific information related to humans to the design of objects, systems and environment for human use. The objective is to apply human characteristics to the design of computer-based work environments to reduce problems of people at work. Lack of ergonomics has serious repercussions on end-users, including physical and mental illnesses. Using ergonomics to design computer-intensive environments would maximize efficiency, productivity and job satisfaction of employees. Unfortunately, in the Government Sector in Pakistan, there is no application of ergonomics in computer-based environments, and this leads to inefficiencies, errors, and safety and health issues. The purpose of …

Basal Endothelial Nitric Oxide Release Is Preserved In Overweight And Obese Adults, Christopher A Desouza, Gary P. Van Guilder, Jared J Greiner, Derek T Smith, Greta L Hoetzer, Brian L Stauffer

Health and Nutritional Sciences Faculty Publications

OBJECTIVE: Impaired basal nitric oxide release is associated with a number of cardiovascular disorders including hypertension, arterial spasm, and myocardial infarction. We determined whether basal endothelial nitric oxide release is reduced in otherwise healthy overweight and obese adult humans.
RESEARCH METHODS AND PROCEDURES: Seventy sedentary adults were studied: 32 normal weight (BMI/m(2)), 24 overweight (BMI > or = 25 < 30 kg/m(2)), and 14 obese (BMI > or = 30 kg/m(2)). Forearm blood flow (FBF) responses to intra-arterial infusions of N(g)-monomethyl-L-arginine (5 mg/min), a nitric oxide synthase inhibitor, were used as an index of basal nitric oxide release.
RESULTS: N(g)-monomethyl-L-arginine elicited significant reductions in FBF in the normal weight …

Tcpf Is A Soluble Colonization Factor And Protective Antigen Secreted By El Tor And Classical O1 And O139 Vibrio Cholerae Serogroups, Thomas J. Kirn, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae causes diarrhea by colonizing the human small bowel and intoxicating epithelial cells. Colonization is a required step in pathogenesis, and strains defective for colonization are significantly attenuated. The best-characterized V. cholerae colonization factor is the toxin-coregulated pilus (TCP). It has been demonstrated that TCP is required for V. cholerae colonization in both humans and mice. TCP enhances bacterial interactions that allow microcolony formation and thereby promotes survival in the intestine. We have recently discovered that the TCP biogenesis apparatus also serves as a secretion system, mediating the terminal step in the extracellular secretion pathway of TcpF. TcpF was …

The Human Paf Complex Coordinates Transcription With Events Downstream Of Rna Synthesis., Bing Zhu, Subhrangsu S. Mandal, Anh-Dung Pham, Yong Zheng, Hediye Erdjument-Bromage, Surinder K. Batra, Paul Tempst, Danny Reinberg

Journal Articles: Biochemistry & Molecular Biology

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates …

Pathways To Ptsd, Part Ii: Sexually Abused Children, Julie B Kaplow, Kenneth A Dodge, Lisa Amaya-Jackson, Glenn N Saxe

Faculty, Staff and Students Publications

OBJECTIVE: The goal of this research was to develop and test a prospective model of posttraumatic stress symptoms in sexually abused children that includes pretrauma, trauma, and disclosure-related pathways.

METHOD: At time 1, several measures were used to assess pretrauma variables, trauma variables, and stress reactions upon disclosure for 156 sexually abused children ages 8 to 13 years. At the time 2 follow-up (7 to 36 months following the initial interview), the children were assessed for posttraumatic stress disorder (PTSD) symptoms.

RESULTS: A path analysis involving a series of hierarchically nested ordinary least squares multiple regression analyses indicated three direct …

Erythroid Cell-Specific Α-Globin Gene Regulation By The Cp2 Transcription Factor Family, Ho C. Kang, Jui Hyung Chae, Yeon H. Lee, Mi-Ae Park, June Ho Shin, Sung-Hyun Kim, Sang-Kyu Ye, Yoon Shin Cho, Steven Fiering, Chul Geun Kim

Dartmouth Scholarship

We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of …

Effect Of Non-Metabolized Sweeteners On Health Parameters In Humans, Matthew Alan Leonhardt

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The demand for functional foods is on the rise. These are food products that, besides providing energy and nutrients for life, provide additional health benefits. Xylitol, a five-carbon sugar alcohol, is a possible functional food, as well as a sugar replacement. The cost of xylitol has led manufacturers to add inulin, a nondigestible oligosaccharide, as an extender. Both xylitol and inulin have been suggested to provide added health benefits beyond being a reduced calorie replacement for sugar. We tested their impact on several human health parameters (fecal weight, fecal pH, fecal % moisture, blood lipids, blood glucose, and fecal micro …

Cart: An Hrs/Actinin-4/Berp/Myosin V Protein Complex Required For Efficient Receptor Recycling, Qing Yan, Wei Sun, Pekka Kujala, Yasmin Lotfi, Thomas A Vida, Andrew J Bean

Faculty, Staff and Student Publications

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The …

Quadratic Regression Analysis For Gene Discovery And Pattern Recognition For Non-Cyclic Short Time-Course Microarray Experiments, Hua Liu, Sergey Tarima, Aaron S. Borders, Thomas V. Getchell, Marilyn L. Getchell, Arnold J. Stromberg

Statistics Faculty Publications

BACKGROUND: Cluster analyses are used to analyze microarray time-course data for gene discovery and pattern recognition. However, in general, these methods do not take advantage of the fact that time is a continuous variable, and existing clustering methods often group biologically unrelated genes together.

RESULTS: We propose a quadratic regression method for identification of differentially expressed genes and classification of genes based on their temporal expression profiles for non-cyclic short time-course microarray data. This method treats time as a continuous variable, therefore preserves actual time information. We applied this method to a microarray time-course study of gene expression at short …

Ocular Surface Epithelia Contain Abcg2-Dependent Side Population Cells Exhibiting Features Associated With Stem Cells., Murat T Budak, Onder S Alpdogan, Mingyuan Zhou, Robert M Lavker, M A Murat Akinci, J Mario Wolosin

Department of Medical Oncology Faculty Papers

When cell populations are incubated with the DNA-binding dye Hoechst 33342 and subjected to flow cytometry analysis for Hoechst 33342 emissions, active efflux of the dye by the ABCG2/BCRP1 transporter causes certain cells to appear as a segregated cohort, known as a side population (SP). Stem cells from several tissues have been shown to possess the SP phenotype. As the lack of specific surface markers has hindered the isolation and subsequent biochemical characterization of epithelial stem cells this study sought to determine the existence of SP cells and expression of ABCG2 in the epithelia of the ocular surface and evaluate …

A Short History Of Medical Dictionaries, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

No abstract provided.

Bench-To-Bedside Review: Rhabdomyolysis -- An Overview For Clinicians., Ana L Huerta-Alardín, Joseph Varon, Paul E Marik

Jefferson Hospital Staff Papers and Presentations

Rhabdomyolysis ranges from an asymptomatic illness with elevation in the creatine kinase level to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure and disseminated intravascular coagulation. Muscular trauma is the most common cause of rhabdomyolysis. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, drugs, toxins and endocrinopathies. Weakness, myalgia and tea-colored urine are the main clinical manifestations. The most sensitive laboratory finding of muscle injury is an elevated plasma creatine kinase level. The management of patients with rhabdomyolysis includes early vigorous hydration.

The Meaning Of Computers To A Group Of Men Who Are Homeless., Kathleen Swenson Miller, Stacey Bunch-Harrison, Brett Brumbaugh, Rekha Sankaran Kutty, Kathleen Fitzgerald

Department of Occupational Therapy Faculty Papers

The purpose of this pilot study was to explore the experience with computers and the meaning of computers to a group of homeless men living in a long-term shelter. This descriptive exploratory study used semistructured interviews with seven men who had been given access to computers and had participated in individually tailored occupation based interventions through a Work Readiness Program. Three themes emerged from analyzing the interviews: access to computers, computers as a bridge to life-skill development, and changed self-perceptions as a result of connecting to technology. Because they lacked computer knowledge and feared failure, the majority of study participants …

Yos1p Is A Novel Subunit Of The Yip1p–Yif1p Complex And Is Required For Transport Between The Endoplasmic Reticulum And The Golgi Complex, Matthew Heidtman, Catherine Z. Chen, Ruth N. Collins, Charles Barlowe

Dartmouth Scholarship

Yeast Yip1p is a member of a conserved family of transmembrane proteins that interact with Rab GTPases. Previous studies also have indicated a role for Yip1p in the biogenesis of endoplasmic reticulum (ER)-derived COPII transport vesicles. In this report, we describe the identification and characterization of the uncharacterized open reading frame YER074W-A as a novel multicopy suppressor of the thermosensitive yip1-4 strain. We have termed this gene Yip One Suppressor 1 (YOS1). Yos1p is essential for growth and for function of the secretory pathway; depletion or inactivation of Yos1p blocks transport between the ER and …