Medicine and Health Sciences Commons^™

The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …

Diet And Toenail Arsenic Concentrations In A New Hampshire Population With Arsenic-Containing Water, Kathryn L. Cottingham, Roxanne Karimi, Joann F. Gruber, M Scot Zens, Vicki Sayarath, Carol L. Folt, Tracy Punshon, J. Steven Morris, Margaret R. Karagas

Dartmouth Scholarship

Background: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest.

Methods: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) …

Evidence For Finely-Regulated Asynchronous Growth Of Toxoplasma Gondii Cysts Based On Data-Driven Model Selection, Adam M. Sullivan, Xiaopeng Zhao, Yasuhiro Suzuki, Eri Ochiai, Stephen Crutcher, Michael A. Gilchrist

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe …

Innovative University Partnership Meets Neonatal Nurse Practitioner Program Need Amid Faculty Shortage, Rebecca Siewert, L. Rasmussen, Maria Lofgren, Patricia Clinton

Maria A Lofgren

This nation is facing a significant nursing faculty shortage not only at the undergraduate but also at the graduate level. As nursing faculty, we must be innovative in considering ways of consolidating resources in this time of demand for advanced practice nurses. With the apparent need for qualified neonatal nurse practitioners in Iowa, the University of Iowa understood the importance of starting a neonatal nurse practitioners program. The University of Iowa College of Nursing and the University of Missouri-Kansas City formed a partnership to educate neonatal nurse practitioners. Although this partnership concentrates on a specific subspecialty population, it can serve …

The Stability Of Patient Subgroups Identified Using Cluster Analysis, Stephanie Gilbertson-White, C. Miaskowski, K. Lee, M. Dodd, C. West, B. Cooper

Stephanie Gilbertson-White

No abstract provided.

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Local Tobacco Control: Application Of The Essential Public Health Services Model In A County Health Department’S Efforts To Put It Out Rockland, Lisa D. Lieberman, Una Diffley, Sandy King, Shelley Chanler, Maryanne Ferrera, Oscar Alleyne, Joan Facelle

Department of Public Health Scholarship and Creative Works

In 2000, Rockland County, a small suburban county north of New York City, dedicated $1 million of its Master Settlement Agreement funds to a comprehensive tobacco control program, Put It Out Rockland. Developed and implemented by the county health department, this program used an essential public health services model and an ongoing financial investment, within the context of strong statewide tobacco control efforts, to lower adult smoking rates to 9.7% and to reduce both smoking among youths and exposure to secondhand smoke over the ensuing decade. By combining state funds and local dollars for a total of $6.75 cost per …

Multi-Criteria Decision Analysis As An Innovative Approach To Managing Zoonoses: Results From A Study On Lyme Disease In Canada, Cécile Aenishaenslin, Valérie Hongoh, Hassane D. Cissé, Anne Gatewood Hoen

Dartmouth Scholarship

ackground: Zoonoses are a growing international threat interacting at the human-animal-environment interface and call for transdisciplinary and multi-sectoral approaches in order to achieve effective disease management. The recent emergence of Lyme disease in Quebec, Canada is a good example of a complex health issue for which the public health sector must find protective interventions. Traditional preventive and control interventions can have important environmental, social and economic impacts and as a result, decision-making requires a systems approach capable of integrating these multiple aspects of interventions. This paper presents the results from a study of a multi-criteria decision analysis (MCDA) approach for …

Impact Of Treatment Response Metrics On Photodynamic Therapy Planning And Outcomes In A Three-Dimensional Model Of Ovarian Cancer, Sriram Anbil, Imran Rizvi, Jonathan P. Celli, Nermina Alagic, Brian W. Pogue, Tayyaba Hasan

Dartmouth Scholarship

Common methods to characterize treatment efficacy based on morphological imaging may misrepresent outcomes and exclude effective therapies. Using a three-dimensional model of ovarian cancer, two functional treatment response metrics are used to evaluate photodynamic therapy (PDT) efficacy: total volume, calculated from viable and nonviable cells, and live volume, calculated from viable cells. The utility of these volume-based metrics is corroborated using independent reporters of photodynamic activity: viability, a common fluorescence-based ratiometric analysis, and photosensitizer photobleaching, which is characterized by a loss of fluorescence due in part to the production of reactive species during PDT. Live volume correlated with both photobleaching …

Patchy ‘Coherence’: Using Normalization Process Theory To Evaluate A Multi-Faceted Shared Decision Making Implementation Program (Magic), Amy Lloyd, Natalie Joseph-Williams, Adrian Edwards, Andrew Rix, Glyn Elwyn

Dartmouth Scholarship

Implementing shared decision making into routine practice is proving difficult, despite considerable interest from policy-makers, and is far more complex than merely making decision support interventions available to patients. Few have reported successful implementation beyond research studies. MAking Good Decisions In Collaboration (MAGIC) is a multi-faceted implementation program, commissioned by The Health Foundation (UK), to examine how best to put shared decision making into routine practice. In this paper, we investigate healthcare professionals' perspectives on implementing shared decision making during the MAGIC program, to examine the work required to implement shared decision making and to inform future efforts. The MAGIC …

Crystal Structure Of 3wj Core Revealing Divalent Ion-Promoted Thermostability And Assembly Of The Phi29 Hexameric Motor Prna., Hui Zhang, James A. Endrizzi, Yi Shu, Farzin Haque, Claude Sauter, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, Peixuan Guo, Young-In Chi

Journal Articles: Pharmaceutical Sciences

The bacteriophage phi29 DNA packaging motor, one of the strongest biological motors characterized to date, is geared by a packaging RNA (pRNA) ring. When assembled from three RNA fragments, its three-way junction (3WJ) motif is highly thermostable, is resistant to 8 M urea, and remains associated at extremely low concentrations in vitro and in vivo. To elucidate the structural basis for its unusual stability, we solved the crystal structure of this pRNA 3WJ motif at 3.05 Å. The structure revealed two divalent metal ions that coordinate 4 nt of the RNA fragments. Single-molecule fluorescence resonance energy transfer (smFRET) analysis confirmed …

Conservation Of Structure And Mechanism By Trm5 Enzymes., Thomas Christian, Howard Gamper, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Enzymes of the Trm5 family catalyze methyl transfer from S-adenosyl methionine (AdoMet) to the N¹ of G37 to synthesize m¹ G37-tRNA as a critical determinant to prevent ribosome frameshift errors. Trm5 is specific to eukaryotes and archaea, and it is unrelated in evolution from the bacterial counterpart TrmD, which is a leading anti-bacterial target. The successful targeting of TrmD requires detailed information on Trm5 to avoid cross-species inhibition. However, most information on Trm5 is derived from studies of the archaeal enzyme Methanococcus jannaschii (MjTrm5), whereas little information is available for eukaryotic enzymes. Here we use human Trm5 (Homo sapiens; HsTrm5) …

A Multivariate Method To Determine The Dimensionality Of Neural Representation From Population Activity., Jörn Diedrichsen, Tobias Wiestler, Naveed Ejaz

Brain and Mind Institute Researchers' Publications

How do populations of neurons represent a variable of interest? The notion of feature spaces is a useful concept to approach this question: According to this model, the activation patterns across a neuronal population are composed of different pattern components. The strength of each of these components varies with one latent feature, which together are the dimensions along which the population represents the variable. Here we propose a new method to determine the number of feature dimensions that best describes the activation patterns. The method is based on Gaussian linear classifiers that use only the first d most important pattern …

Friends Of Nursing: A Community Of Caring To Promote Excellence In Nursing Practice, Education, And Research, Kim S. Hitchings Msn, Rn, Nea-Bc, Terry Capuano Rn, Svp, Clinical Services, Mary Ellen Herzog Med, Cfre, Cgms

Terry A Capuano MBA, MSN, RN, FACHE, NE-BC

More than 25 years ago, the name "Friends of Nursing" was adopted by an academic, community Magnet(®) hospital to signify a model for community support of nursing. From inception, the intent was to recruit philanthropic dollars to promote recognition of and excellence in nursing practice, education, and research. Although philanthropy in health care settings is common, what is unique about this program is the long-standing, dedicated conceptual framework for nursing philanthropy and the very significant number of philanthropic dollars from literally thousands of donors to support a diverse range of activities to affect and advance the professional excellence of nurses …

A Joint Matrix Completion And Filtering Model For Influenza Serological Data Integration., Xiao-Tong Yuan, Tong Zhang, Xiu-Feng Wan

College of Veterinary Medicine Publications and Scholarship

Antigenic characterization based on serological data, such as Hemagglutination Inhibition (HI) assay, is one of the routine procedures for influenza vaccine strain selection. In many cases, it would be impossible to measure all pairwise antigenic correlations between testing antigens and reference antisera in each individual experiment. Thus, we have to combine and integrate the HI tables from a number of individual experiments. Measurements from different experiments may be inconsistent due to different experimental conditions. Consequently we will observe a matrix with missing data and possibly inconsistent measurements. In this paper, we develop a new mathematical model, which we refer to …

Chymase Inhibition Prevents Fibronectin And Myofibrillar Loss And Improves Cardiomyocyte Function And Lv Torsion Angle In Dogs With Isolated Mitral Regurgitation., Betty Pat, Yuanwen Chen, Cheryl Killingsworth, James D Gladden, Ke Shi, Junying Zheng, Pamela C Powell, Greg Walcott, Mustafa I Ahmed, Himanshu Gupta, Ravi Desai, Chih-Chang Wei, Naoki Hase, Tsunefumi Kobayashi, Abdelkarim Sabri, Henk Granzier, Thomas Denney, Michael Tillson, A Ray Dillon, Ahsan Husain, Louis J Dell'italia

Ravi V Desai MD

BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR.

METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with …

An Mll-Dependent Network Sustains Hematopoiesis, Erika L. Artinger, Bibhu P. Mishra, Kristin M. Zaffuto, Bin E. Li, Elaine K. Y. Chung, Adrian W. Moore, Yufei Chen, Chao Cheng, Patricia Ernst

Dartmouth Scholarship

The histone methyltransferase Mixed Lineage Leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene. Although clustered homeobox genes are well-characterized targets of MLL and MLL fusion oncoproteins, the range of Mll-regulated genes in normal hematopoietic cells remains unknown. Here, we identify and characterize part of the Mll-dependent transcriptional network in hematopoietic stem cells with an integrated approach by using conditional loss-of-function models, genomewide expression analyses, chromatin immunoprecipitation, and functional rescue assays. The Mll-dependent transcriptional network extends well beyond the previously appreciated Hox targets, is comprised of many characterized regulators of self-renewal, and contains target genes …

Impaired Expression Of Protein Phosphatase 2a Subunits Enhances Metastatic Potential Of Human Prostate Cancer Cells Through Activation Of Akt Pathway., P Pandey, Parthasarathy Seshacharyulu, Srustidhar Das, Satyanarayana Rachagani, Moorthy P. Ponnusamy, Y Yan, Sonny L. Johansson, K Datta, Ming-Fong Lin, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Protein phosphatase 2A (PP2A) is a dephosphorylating enzyme, loss of which can contribute to prostate cancer (PCa) pathogenesis. The aim of this study was to analyse the transcriptional and translational expression patterns of individual subunits of the PP2A holoenzyme during PCa progression.

METHODS: Immunohistochemistry (IHC), western blot, and real-time PCR was performed on androgen-dependent (AD) and androgen-independent (AI) PCa cells, and benign and malignant prostate tissues for all the three PP2A (scaffold, regulatory, and catalytic) subunits. Mechanistic and functional studies were performed using various biochemical and cellular techniques.

RESULTS: Through immunohistochemical analysis we observed significantly reduced levels of PP2A-A …

The Effect Of Music Therapy On Patients' Perception And Manifestation Of Pain, Anxiety, And Patient Satisfaction, T. Richards, J. Johnson, Amy Sparks, H. Emerson

Amy E.T. Sparks

An extensive review and synthesis of current research was completed to identify the clinical benefit of using music therapy in the hospital setting. It demonstrated that music therapy has the potential to improve the hospital experience of patients.

Computational Models For Prediction Of Ivf/Icsi Outcomes With Surgically Retrieved Spermatozoa, M. Wald, Amy Sparks, J. Sandlow, Bradley Van Voorhis, Craig Syrop, C. Niederberger

Amy E.T. Sparks

IVF/intracytoplasmic sperm injection (ICSI) using surgically retrieved spermatozoa (SRS) is a key option in the treatment of severe male infertility. It was aimed to develop a computational model for the prediction of this modality's outcome. A dataset of 113 exemplars, derived from patients who underwent IVF/ICSI with SRS, was retrospectively analysed. The dataset, containing input features maternal age, sperm retrieval technique, type of spermatozoa used, type of male factor and output intrauterine pregnancy, was randomized into a modelling ('training') set of 83 and cross-validation ('test') set of 30. neUROn++, a set of C++ programs, was used to model the dataset …

Comparison Of Hyperbaric Oxygen And Medical Ozone Therapies In A Rat Model Of Experimental Distal Colitis, O. Altinel, S. Demirbas, E. Cakir, H. Yaman, I. Ozerhan, Eyup Duran, T. Cayci, E. Akgul, N. Ersoz, B. Uysal, B. Kurt, M. Yasar, S. Oter, Y. Peker

Eyup Hakan Duran

No abstract provided.

A Logistic Regression Model Including Dna Status And Morphology Of Spermatozoa For Prediction Of Fertilization In Vitro, Eyup Duran, T. Gurgan, S. Gunalp, M. Enginsu, H. Yarali, A. Ayhan

Eyup Hakan Duran

To determine predictive values of routine semen analysis, sperm morphology evaluation using strict criteria and DNA status for in-vitro fertilization (IVF), 66 consecutive couples undergoing IVF in a university hospital IVF programme were prospectively investigated. Semen samples from 66 men were evaluated by routine semen analysis, morphology evaluation using strict criteria and acridine orange staining for determination of DNA status. A new technique is described for acridine orange scoring which consisted of evaluation of two smears per case, with and without heat treatment. Resistance to heat-provoked denaturation was determined by the difference between two evaluations. A logistic regression model was …

The Older Patient, The Doctor And The Trainee: Patients' Attitudes And Implications For Models Of Care, Andrew Bonney, Sandra Jones, Donald Iverson

Sandra Jones

Aims & rationale/Objectives Population ageing poses major challenges for health systems. Additionally, training future general practitioners in the management of older and chronically ill patients is potentially hampered by the reluctance of these patients to consult trainees for chronic care. This paper reports a cross-sectional study investigating the attitudes of older patients to trainees, to inform strategies to improve older patient-trainee interaction. Methods The survey instrument was distributed to 1900 patients aged 60 and over from 38 training practices from five Australian states using a stratified, randomised cluster sampling process. Generalised estimating equation models were used for analysis. Principal findings …

Are Pre-Adolescent Girls' Magazines Providing Age-Appropriate Role Models?, Belinda S. Fabrianesi, Sandra C. Jones, Amanda Reid

Sandra Jones

Purpose – Repeated exposure to unrealistic notions of female beauty and body shapes, and limited gender stereotypes, may result in the internalization of those standards by pre-adolescent girls. The purpose of this content analysis is to examine the celebrity role models to whom young girls are exposed via magazines specifically targeted at the “tween” audience. Female celebrities are contrasted with those in magazines targeted at older adolescent girls. Design/methodology/approach – Two pre-adolescent girls’ magazines, Total Girl and Barbie, and two adolescent girls’ magazines, Dolly and Girlfriend, were analyzed for the first six months of 2005. All photos (including advertising images) …

Computational Models For Prediction Of Ivf/Icsi Outcomes With Surgically Retrieved Spermatozoa, M. Wald, Amy Sparks, J. Sandlow, Bradley Van Voorhis, Craig Syrop, C. Niederberger

Bradley J Van Voorhis

IVF/intracytoplasmic sperm injection (ICSI) using surgically retrieved spermatozoa (SRS) is a key option in the treatment of severe male infertility. It was aimed to develop a computational model for the prediction of this modality's outcome. A dataset of 113 exemplars, derived from patients who underwent IVF/ICSI with SRS, was retrospectively analysed. The dataset, containing input features maternal age, sperm retrieval technique, type of spermatozoa used, type of male factor and output intrauterine pregnancy, was randomized into a modelling ('training') set of 83 and cross-validation ('test') set of 30. neUROn++, a set of C++ programs, was used to model the dataset …

The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …

Protective Immunization In Mice Against Group B Streptococci Using Encapsulated C5a Peptidase, Donna Santillan, M. Andracki, Stephen Hunter

Stephen K. Hunter

OBJECTIVE: The purpose of the study was to test whether C5a peptidase encapsulated within a biodegradable polymer can act as a vaccine and elicit an immune response to prevent group B streptococci (GBS) infection in mice and provide protection to pups. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-co-glycolide). Female ICR mice were immunized with encapsulated C5a peptidase, free C5a peptidase, or empty microparticles. Booster doses were given at days 21 and 42. Antibody responses were measured by enzyme-linked immunosorbent assay. Challenge with GBS type III was performed 4 days after the final booster in the vaginal …

Theoretical Prediction Of Induction Period From Transient Pore Evolvement In Polyester-Based Microparticles, A. Zhao, Stephen Hunter, V. Rodgers

Stephen K. Hunter

A model was developed and compared to experimental results for prediction of the induction period during drug delivery from various compositions of biodegradable copolymer PLGA microparticles. The uniqueness of this model is that it considers transient pore evolvement and uses the kinetic parameters of polymer degradation, which are independent of experimental measurements of microparticle erosion, in its analysis. Delivery data from PLGA microparticles (50:50, 75:25, and 85:15) releasing ovalbumin (OVA, 46 kDa) and bovine serum albumin (BSA, 66 kDa) were determined and used as the model systems. Experimental measurements were carried out from 85 to 150 days depending on the …

Mathematical Modeling Of Myoglobin Facilitated Transport Of Oxygen In Devices Containing Myoglobin-Expressing Cells, H. Tilakaratne, Stephen Hunter, V. Rodgers

Stephen K. Hunter

Low pO(2) is perhaps the most significant factor in artificial pancreas failure. In these environments, not only is the beta cell production of insulin reduced, but the cell death rate is also significantly higher. Mathematical models are developed to test the feasibility of facilitated oxygen transport in enhancing O(2) flux to genetically engineered cells in a bioartificial device such as a pancreas. For this device, it is proposed that beta cells be genetically engineered to express myoglobin throughout the cell. In addition, the significance of including myoglobin throughout the alginate matrix present to provide immuno-protection for the transplanted cells is …

A Perspective On Multiple Waves Of Influenza Pandemics, Anna Mummert, Howard Weiss, Li-Ping Long, José M. Amigó, Xiu-Feng Wan

College of Veterinary Medicine Publications and Scholarship

BACKGROUND: A striking characteristic of the past four influenza pandemic outbreaks in the United States has been the multiple waves of infections. However, the mechanisms responsible for the multiple waves of influenza or other acute infectious diseases are uncertain. Understanding these mechanisms could provide knowledge for health authorities to develop and implement prevention and control strategies. MATERIALS AND METHODS: We exhibit five distinct mechanisms, each of which can generate two waves of infections for an acute infectious disease. The first two mechanisms capture changes in virus transmissibility and behavioral changes. The third mechanism involves population heterogeneity (e.g., demography, geography), where …