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Key Role Of T Cell Defects In Age-Related Vulnerability To West Nile Virus, James D. Brien, Jennifer L. Uhrlaub, Alec Hirsch, Clayton A. Wiley, Janko Nikolich-Zugich

Open Access Publications

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40-50x more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level …

Quality Improvement In Small Office Settings: An Examination Of Successful Practices., Daniel Wolfson, Elizabeth Bernabeo, Brian Leas, Shoshanna Sofaer, Gregory Pawlson, Donna Pillittere

College of Population Health Faculty Papers

BACKGROUND: Physicians in small to moderate primary care practices in the United States (U.S.) (<25 >physicians) face unique challenges in implementing quality improvement (QI) initiatives, including limited resources, small staffs, and inadequate information technology systems 23,36. This qualitative study sought to identify and understand the characteristics and organizational cultures of physicians working in smaller practices who are actively engaged in measurement and quality improvement initiatives.

METHODS: We undertook a qualitative study, based on semi-structured, open-ended interviews conducted with practices (N = 39) that used performance data to drive quality improvement activities.

RESULTS: Physicians indicated that benefits to performing measurement and …

Mitochondrial Mislocalization Underlies Abeta42-Induced Neuronal Dysfunction In A Drosophila Model Of Alzheimer's Disease., Kanae Iijima-Ando, Stephen A Hearn, Christopher Shenton, Anthony Gatt, Lijuan Zhao, Koichi Iijima

Department of Biochemistry and Molecular Biology Faculty Papers

The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial …

Hematologic Effects Of Placental Pathology On Very Low Birthweight Infants Born To Mothers With Preeclampsia., Kelly J. Zook, Md, Amy B. Mackley, Rnc, Jennifer Kern, David A. Paul. Md

Department of Pediatrics Faculty Papers

OBJECTIVE: To investigate the effect of placental pathology on neonatal neutrophils, platelets, hematocrit and nucleated red blood cells in very low birthweight (VLBW) infants born to mothers with preeclampsia. STUDY DESIGN: Retrospective cohort study of infants with birthweight < 1500 g born to mothers with preeclampsia from july, 2002 to july, 2006 at a single level III neonatal intensive care unit. Placental pathology was reviewed for the presence of placental infarction and vasculopathy. Hematologic parameters from day of life 0, 1 and 2 were obtained. Statistical analysis included repeated-measures analysis of variance and multivariable analysis using logistic regression. RESULT: The study sample included 203 infants with estimated gestational age of 28+/-3 weeks; 45% had placental infarctions and 26% placental vasculopathy. Infants with neutropenia and thrombocytopenia did not have an increased occurrence of placental infarction or maternal vasculopathy but were more likely to be of small gestational age (SGA) and of lower gestational age compared with infants without neutropenia or thrombocytopenia. After multivariable analysis, gestational age and SGA remained associated with both neutropenia and thrombocytopenia whereas placental infarction and vasculopathy did not remain in the models. CONCLUSION: In our population of VLBW infants born to mothers with preeclampsia, placental pathology was common. There was no association of placental infarction or vasculopathy with neonatal neutropenia and thrombocytopenia. The data suggest that neonatal hematologic effects of maternal preeclampsia, if related to the placenta, are associated with factors other than placental histology.

The Root Of Dental Anatomy: A Case For Naming Eustachius The "Father Of Dental Anatomy"., Gregory W. Bennett

Journal Articles: College of Dentistry

When one considers the names of those whose affect on dentistry reached far beyond their lifetimes, one may think of Fauchard, Wells, Morton and Black. One name that deserves to be called among the pantheon of the greats is Bartholomaeus Eustachius. Eustachius was not the first to study the anatomy of the teeth and jaws, having been preceded by Da Vinci; however, he was the first to publish a treatise devoted entirely to this subject, Libellus de Dentibus, in 1563. As Sir William Osler, the father of modern medicine, stated: "In Science, the credit goes to the man who convinces …

Micrornas: Key Modulators Of Posttranscriptional Gene Expression., Steven P. O'Hara, Justin L. Mott, Patrick L. Splinter, Gregory J. Gores, Nicholas F. Larusso

Journal Articles: Biochemistry & Molecular Biology

No abstract provided.

Elevated Expression Of L-Selectin Ligand In Lymph Node-Derived Human Prostate Cancer Cells Correlates With Increased Tumorigenicity., Prakash Radhakrishnan, Ming-Fong Lin, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Human prostate cancer LNCaP cells including C-33 and C-81 cells were originally derived from the lymph nodes of a patient with metastatic prostate cancer. These two cells were employed for characterization of L-selectin ligand and in vitro tumorigenicity, because they mimic the clinical conditions of early and late-stage human prostate cancer. C-81 cells exhibit higher in vitro migratory and invasive properties as compared with C-33 cells. We find that the L-selectin ligand and mucin glycan-associated MECA-79 epitope were elevated in C-81 cells. An increase of these glycotopes positively correlates with elevated tumorigenicity and expression of key glycosyl- and sulfotransferase genes. …

Effector Memory T Cell Responses Are Associated With Protection Of Rhesus Monkeys From Mucosal Simian Immunodeficiency Virus Challenge., Scott G. Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Michael K. Axthelm, Kelli Oswald, Charles M. Trubey, Michael Piatak, Jeffrey D. Lifson, Jay A. Nelson, Michael A. Jarvis, Louis J. Picker

School of Biomedical Sciences

The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion and differentiation. We hypothesized that vaccines designed to maintain differentiated effector memory T cell (TEM cell) responses at viral entry sites might improve efficacy by impairing viral replication at its earliest stage, and we have therefore developed SIV protein-encoding vectors based on rhesus cytomegalovirus (RhCMV), the prototypical inducer of life-long TEM cell responses. RhCMV vectors expressing SIV Gag, …

A National Survey Investigating Uk Prescribers' Opinions On Chemotherapy Dosing And 'Dose-Banding'., Sa Kaestner, Gj Sewell

School of Health Professions

AIMS: The primary purpose of dose-banding for cancer chemotherapy is to reduce patient waiting times, but dose-banding also has additional benefits, such as reduced drug wastage, reduced stress for staff, and prospective quality control of infusions. However, the uptake of dose-banding seems fairly low. Possible reasons for this are a reluctance to use dose-banding for clinical reasons or a lack of awareness. Despite the seemingly minor change from established practice of dose preparation, dose-banding has the potential to alter patient chemotherapy exposure. The aim of this study was to investigate prescribers' awareness of dose-banding and their opinions on the scope …

The Interaction Of Hab18g/Cd147 With Integrin Alpha6beta1 And Its Implications For The Invasion Potential Of Human Hepatoma Cells., Jing-Yao Dai, Ke-Feng Dou, Cong-Hua Wang, Pu Zhao, Wayne Bond Lau, Ling Tao, Ya-Mei Wu, Juan Tang, Jian-Li Jiang, Zhi-Nan Chen

Department of Emergency Medicine Faculty Papers

BACKGROUND: HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin alpha3beta1. However, it has never been investigated whether alpha3beta1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. METHODS: Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine …

Small Individual Loans And Mental Health: A Randomized Controlled Trial Among South African Adults, Lia C. H. Fernald, Rita Hamad, Dean Karlan, Emily J. Ozer, Jonathan Zinman

Dartmouth Scholarship

Background: In the developing world, access to small, individual loans has been variously hailed as a poverty-alleviation tool – in the context of "microcredit" – but has also been criticized as "usury" and harmful to vulnerable borrowers. Prior studies have assessed effects of access to credit on traditional economic outcomes for poor borrowers, but effects on mental health have been largely ignored.

Methods: Applicants who had previously been rejected (n = 257) for a loan (200% annual percentage rate – APR) from a lender in South Africa were randomly assigned to a "second-look" that encouraged loan officers to approve their …

Denaturation And Unfolding Of Human Anaphylatoxin C3a: An Unusually Low Covalent Stability Of Its Native Disulfide Bonds, Jui-Yoa Chang, Curtis C-J Lin, Silvia Salamanca, Michael K Pangburn, Rick A Wetsel

Faculty, Staff and Student Publications

The complement C3a anaphylatoxin is a major molecular mediator of innate immunity. It is a potent activator of mast cells, basophils and eosinophils and causes smooth muscle contraction. Structurally, C3a is a relatively small protein (77 amino acids) comprising a N-terminal domain connected by 3 native disulfide bonds and a helical C-terminal segment. The structural stability of C3a has been investigated here using three different methods: Disulfide scrambling; Differential CD spectroscopy; and Reductive unfolding. Two uncommon features regarding the stability of C3a and the structure of denatured C3a have been observed in this study. (a) There is an unusual disconnection …

Gender Specific Differences In The Pros And Cons Of Smoking Among Current Smokers In Eastern Kentucky: Implications For Future Smoking Cessation Interventions, Dana A. Hazen, David M. Mannino, Richard Clayton

Preventive Medicine and Environmental Health Faculty Publications

This study investigated gender differences in the perceived “pros” and “cons” of smoking using the constructs of decisional balance (DB) and stage of change from the Transtheoretical Model. The population distribution for stage of change among a population-based, cross-sectional survey of 155 current smokers over 40 years was: precontemplation (22.6%), contemplation (41.9%), preparation (35.5%). Results of stepwise regression models indicated significant gender differences in DB were in the preparation stage of change; scores on the DB measure increased 3.94 points (95% CI: 1.94, 5.93) for male smokers. Interventions targeting the “pros” and “cons” of smoking may need to be gender …

Scan-Rescan And Intra-Observer Variability Of Magnetic Resonance Imaging Of Carotid Atherosclerosis At 1.5 T And 3.0 T, Arvin Vidal, Yves Bureau, Trevor Wade, J David Spence, Brian K Rutt, Aaron Fenster, Grace Parraga

Medical Biophysics Publications

Carotid atherosclerosis measurements for eight subjects at baseline and 14 +/- 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using …

Down-Regulation Of Ppargamma1 Suppresses Cell Growth And Induces Apoptosis In Mcf-7 Breast Cancer Cells, Yekaterina Y. Zaytseva, Xin Wang, R. Chase Southard, Natalie K. Wallis, Michael W. Kilgore

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARgamma has been identified as a potential target for breast cancer therapy based on the fact that its activation by synthetic ligands affects the differentiation, proliferation, and apoptosis of cancer cells. However, the controversial nature of current studies and disappointing results from clinical trials raise questions about the contribution of PPARgamma signaling in breast cancer development in the absence of stimulation by exogenous ligands. Recent reports from both in vitro and in vivo studies …

Evaluation Of The Stability And Validity Of Participant Samples Recruited Over The Internet., Daniel Z Lieberman

Psychiatry and Behavioral Sciences Faculty Publications

Research conducted via the Internet has the potential to reach important clinical populations of participants who would not participate in traditional studies. Concerns exist, however, about the validity of samples recruited in this manner, especially when participants are anonymous and never have contact with study staff. This study evaluated two anonymous samples that were recruited over the Internet to test an online program designed to help problem drinkers. The two studies were conducted 3 years apart, and different recruitment strategies were utilized. Despite these differences, the two samples were highly similar in demographic and clinical features. Correlations that have been …

Genomic Rna Profiling And The Programme Controlling Preimplantation Mammalian Development., Christine E Bell, Michele D Calder, Andrew J Watson

Obstetrics & Gynaecology Publications

Preimplantation development shifts from a maternal to embryonic programme rapidly after fertilization. Although the majority of oogenetic products are lost during the maternal to embryonic transition (MET), several do survive this interval to contribute directly to supporting preimplantation development. Embryonic genome activation (EGA) is characterized by the transient expression of several genes that are necessary for MET, and while EGA represents the first major wave of gene expression, a second mid-preimplantation wave of transcription that supports development to the blastocyst stage has been discovered. The application of genomic approaches has greatly assisted in the discovery of stage specific gene expression …

Consistency Check Of Planned Adaptive Option On Helical Tomotherapy., M Schirm, S Yartsev, G Bauman, Jerry J. Battista Dr., Jacob Van Dyk

Oncology Publications

This study aims to evaluate a new Planned Adaptive software (TomoTherapy Inc., Madison, WI) of the helical tomotherapy system by retrospective verification and adaptive re-planning of radiation treatment. Four patients with different disease sites (brain, nasal cavity, lungs, prostate) were planned in duplicate using the diagnostic planning kVCT data set and MVCT studies of the first treatment fraction with the same optimization parameters for both plan types. The dosimetric characteristics of minimum, maximum, and mean dose to the targets as well as to organs at risk were compared. Both sets of plans were used for calculation of dose distributions in …

Borderline Personality Disorder: An Overview Of History, Diagnosis And Treatment In Adolescents, Linah Al-Alem, Hatim A. Omar

Pharmacology and Nutritional Sciences Faculty Publications

Borderline personality disorder (BPD) is a cluster B personality disorder. It is characterized by erratic behaviors, emotional instability and one of its hallmarks is self injurious behavior, which starts in adolescence. Patients with BPD are difficult to treat, most have a history of child sexual abuse, about a quarter present with sexual abuse from a caretaker. Although personality disorders are diagnosed only in adults, BPD manifests itself in adolescence in the form of uncontrollable anger, self mutilations, dissociation and other such behaviors. Hence, there is a growing number of scientists discussing the possibility of diagnosing BPD in adolescents. Here, we …

Meeting Report: Methylmercury In Marine Ecosystems—From Sources To Seafood Consumers, Celia Y. Chen, Nancy Serrell, David C. Evers, Bethany J. Fleishman, Kathleen F. Lambert, Jeri Weiss, Robert P. Mason, Michael S. Bank

Dartmouth Scholarship

Mercury and other contaminants in coastal and open-ocean ecosystems are an issue of great concern globally and in the United States, where consumption of marine fish and shellfish is a major route of human exposure to methylmercury (MeHg). A recent National Institute of Environmental Health Sciences–Superfund Basic Research Program workshop titled “Fate and Bioavailability of Mercury in Aquatic Ecosystems and Effects on Human Exposure,” convened by the Dartmouth Toxic Metals Research Program on 15–16 November 2006 in Durham, New Hampshire, brought together human health experts, marine scientists, and ecotoxicologists to encourage cross-disciplinary discussion between ecosystem and human health scientists and …

Young People's Blood Alcohol Concentration And The Alcohol Consumption City Law, Brazil, Raquel De Boni, Carl G. Leukefeld, Flavio Pechansky

Center on Drug and Alcohol Research Faculty Publications

The paper assesses blood alcohol concentration and risk behaviors for traffic accidents before and after the implementation of a law which prohibits the use of alcoholic beverages on city gas stations. In Porto Alegre, Southern Brazil, young people go out at night and drive to gas station convenience stores to buy alcoholic beverages which are consumed on the premises of parking lots in gas stations. Data were obtained from self-administered questionnaires and breath analyzers in two cross-sectional collections with purposive samples of youngsters in May and July 2006 (n=62, and n=50, respectively). There were no significant differences between the groups …

Manufactured Aluminum Oxide Nanoparticles Decrease Expression Of Tight Junction Proteins In Brain Vasculature, Lei Chen, Robert A. Yokel, Bernhard Hennig, Michal Toborek

Pharmaceutical Sciences Faculty Publications

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular …

Intracerebral Hemorrhage For The Palliative Care Provider: What You Need To Know., B Brent Simmons, Susan M Parks

Department of Family & Community Medicine Faculty Papers

Intracerebral hemorrhage (ICH) makes up 10%-30% of all strokes. Palliative care providers are often asked to get involved with ICH cases to aid with development of short-term and long-term goals. Prognosis can be calculated using the ICH score (based on Glasgow Coma Score score, ICH volume, presence of intraventricular hemorrhage, age, and location of origin) or the Essen score (based on age, NIH Stroke Scale [NIHSS], and level of consciousness). Do-not-resuscitate (DNR) status is important to discuss with families. Expert consensus states DNR is appropriate if the patient has two of the following: severe stroke, life-threatening brain damage, or significant …

Retinoid X Receptor And Peroxisome Proliferator-Activated Receptor-Gamma Agonists Cooperate To Inhibit Matrix Metalloproteinase Gene Expression, Peter S. Burrage, Adam C. Schmucker, Yanqing Ren, Michael B. Sporn, Constance E. Brinckerhoff

Dartmouth Scholarship

We recently described the ability of retinoid X receptor (RXR) ligand LG100268 (LG268) to inhibit interleukin-1-beta (IL-1-β)-driven matrix metalloproteinase-1 (MMP-1) and MMP-13 gene expression in SW-1353 chondrosarcoma cells. Other investigators have demonstrated similar effects in chondrocytes treated with rosiglitazone, a ligand for peroxisome proliferator-activated receptor-gamma (PPARγ), for which RXR is an obligate dimerization partner. The goals of this study were to evaluate the inhibition of IL-1--induced expression of MMP-1andMMP-13 by combinatorial treatment with RXR and PPAR  ligands and to investigate the molecular mechanisms of this inhibition.

Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu

Faculty, Staff and Student Publications

Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and …

Stromal Gene Signatures In Large-B-Cell Lymphomas., G Lenz, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, Javeed Iqbal, Julie M. Vose, M Bast, Kai Fu, D D. Weisenburger, T C Greiner, James O. Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C. Chan, L M Staudt

Journal Articles: Pathology and Microbiology

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.

METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.

RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted …

Medial Temporal Lobe Bold Activity At Rest Predicts Individual Differences In Memory Ability In Hhealthy Young Adults, Gagan S. Wig, Scott T. Grafton, Kathryn E. Demos, George L. Wolford, Steven E. Petersen, William M. Kelley

Dartmouth Scholarship

Human beings differ in their ability to form and retrieve lasting long-term memories. To explore the source of these individual differences, we used functional magnetic resonance imaging to measure blood-oxygen-level-dependent (BOLD) activity in healthy young adults (n = 50) during periods of resting fixation that were interleaved with periods of simple cognitive tasks. We report that medial temporal lobe BOLD activity during periods of rest predicts individual differences in memory ability. Specifically, individuals who exhibited greater magnitudes of task-induced deactivations in medial temporal lobe BOLD signal (as compared to periods of rest) demonstrated superior memory during offline testing. This relationship …

Androgen-Independent Prostate Cancer Cells Acquire The Complete Steroidogenic Potential Of Synthesizing Testosterone From Cholesterol., Paulette R. Dillard, Ming-Fong Lin, Shafiq A. Khan

Journal Articles: Biochemistry & Molecular Biology

The proliferation and differentiation of normal prostate epithelial cells depends upon the action of androgens produced by the testis. Prostate cancers retain the ability to respond to androgens in the initial stages of cancer development, but progressively become independent of exogenous androgens in advanced stages of the disease while maintaining the expression of functional androgen receptor (AR). In the present study, we have determined the potential of prostate cancer cells to synthesize androgens from cholesterol which may be involved in intracrine regulation of AR in advanced stages of the disease. Established androgen-independent prostate cancer cell lines, PC3 and DU145 cells, …

Pgrmc1: A New Biomarker For The Estrogen Receptor In Breast Cancer, Rolf J. Craven

Pharmacology and Nutritional Sciences Faculty Publications

Estrogen receptor (ER) status is a critical biomarker in breast cancer, in large part because the ER is the target of tamoxifen and similar drugs. In the previous issue of Breast Cancer Research, Neubauer and colleagues used a proteomic approach to identify proteins that are differentially regulated by ER in breast tumors. The authors showed that ER-negative tumors have elevated levels of PGRMC1 (progesterone receptor membrane component-1), a hormone receptor component and binding partner for P450 proteins. In contrast, PGRMC1 was phosphorylated in ER-positive tumors. The staining patterns of ER and PGRMC1 were mutually exclusive in breast tumor sections, and …

Extended Kalman Filter For Estimation Of Parameters In Nonlinear State-Space Models Of Biochemical Networks, Xiaodian Sun, Li Jin, Momiao Xiong

Faculty, Staff and Student Publications

It is system dynamics that determines the function of cells, tissues and organisms. to develop mathematical models and estimate their parameters are an essential issue for studying dynamic behaviors of biological systems which include metabolic networks, genetic regulatory networks and signal transduction pathways, under perturbation of external stimuli. In general, biological dynamic systems are partially observed. Therefore, a natural way to model dynamic biological systems is to employ nonlinear state-space equations. Although statistical methods for parameter estimation of linear models in biological dynamic systems have been developed intensively in the recent years, the estimation of both states and parameters of …