Digital Commons Network^™

Backward Position Shift In Apparent Motion, Hsin-Hung Li, Won Mok Shim, Patrick Cavanagh

Dartmouth Scholarship

We investigated the perceived position of visual targets in apparent motion. A disc moved horizontally through three positions from -10° to +10° in the far periphery (20° above fixation), generating a compelling impression of apparent motion. In the first experiment, observers compared the position of the middle of the three discs to a subsequently presented reference. Unexpectedly, observers judged its position to be shifted backward, in the direction opposite that of the motion. We then tested the middle disc in sequences of 3, 5, and 7 discs, each covering the same spatial and temporal extents (similar speeds). The backwards shift …

Investigating The Early Stages Of Person Perception: The Asymmetry Of Social Categorization By Sex Vs. Age, Jasmin Cloutier, Jonathan B. Freeman, Nalini Ambady

Dartmouth Scholarship

The wealth of information provided by facial cues presents challenges to our understanding of these early stages of person perception. The current study aimed to uncover the dynamics of processing multiply categorizable faces, notably as a function of their gender and age. Using a modified four-choice version of a mouse-tracking paradigm (which assesses the relative dominance of two categorical dimensions), the relative influence that sex and age have on each other during categorization of infant, younger adult, and older adult faces was investigated. Results of these experiments demonstrate that when sex and age dimensions are simultaneously categorized, only for infant …

Response Of An Aggressive Periosteal Aneurysmal Bone Cyst (Abc) Of The Radius To Denosumab Therapy., Chantal Pauli, Bruno Fuchs, Christian Pfirrmann, Julia A. Bridge, Silvia Hofer, Beata Bode

Journal Articles: Pathology and Microbiology

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the …

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

The Rak/Frk Tyrosine Kinase Associates With And Internalizes The Epidermal Growth Factor Receptor, Ling Jin, Rolf J. Craven

Pharmacology and Nutritional Sciences Faculty Publications

Src is the founding member of a diverse family of intracellular tyrosine kinases, and Src has a key role in promoting cancer growth, in part, through its association with receptor tyrosine kinases. However, some Src-related proteins have widely divergent physiological roles, and these proteins include the Rak/Frk tyrosine kinase (Frk stands for Fyn-related kinase), which inhibits cancer cell growth and suppresses tumorigenesis. Rak/Frk phosphorylates and stabilizes the Pten tumor suppressor, protecting it from degradation, and Rak/Frk associates with the retinoblastoma (Rb) tumor suppressor. However, the role of Rak/Frk in receptor-mediated signaling is largely unknown. Here, we demonstrate that Rak/Frk associates …

Axl/Gas6/Nfκb Signalling In Schwannoma Pathological Proliferation, Adhesion And Survival., S. Ammoun, L. Provenzano, L. Zhou, M. Barczyk, K. Evans, D. A. Hilton, S. Hafizi, C. O. Hanemann

Peninsula Medical School

TAM family receptor tyrosine kinases comprising Tyro3 (Sky), Axl, and Mer are overexpressed in some cancers, correlate with multidrug resistance and contribute to tumourigenesis by regulating invasion, angiogenesis, cell survival and tumour growth. Mutations in the gene coding for a tumour suppressor merlin cause development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas occurring spontaneously or as part of a hereditary disease neurofibromatosis type 2. The benign character of merlin-deficient tumours makes them less responsive to chemotherapy. We previously showed that, amongst other growth factor receptors, TAM family receptors (Tyro3, Axl and Mer) are significantly …

Bihemispheric Transcranial Direct Current Stimulation Enhances Effector-Independent Representations Of Motor Synergy And Sequence Learning., Sheena Waters-Metenier, Masud Husain, Tobias Wiestler, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Complex manual tasks-everything from buttoning up a shirt to playing the piano-fundamentally involve two components: (1) generating specific patterns of muscle activity (here, termed "synergies"); and (2) stringing these into purposeful sequences. Although transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) has been found to increase the learning of motor sequences, it is unknown whether it can similarly facilitate motor synergy learning. Here, we determined the effects of tDCS on the learning of motor synergies using a novel hand configuration task that required the production of difficult muscular activation patterns. Bihemispheric tDCS was applied to M1 of …

Effect Of Age On The Hemodynamic And Sympathetic Responses At The Onset Of Isometric Handgrip Exercise., Sophie Lalande, Carolyn P Sawicki, Jacquie R Baker, Kevin Shoemaker

Kinesiology Publications

Cardiac and peripheral vasomotor factors contribute to the rapid pressor response at the onset of isometric handgrip exercise. We tested the hypothesis that age enhances the sympathetic and vasoconstrictor response at the onset of isometric handgrip exercise so that the pressor response is maintained, despite a diminished cardiac function. Twelve young and twelve older (24 ± 3 and 63 ± 8 yr) individuals performed 20-s isometric handgrip exercise at 30, 40, or 50% of maximal voluntary contraction force. Muscle sympathetic nerve activity (MSNA) was measured using microneurography. Mean arterial pressure (MAP) and cardiac output (Q) were assessed continuously by finger …

Identification Of A Developmental Gene Expression Signature, Including Hox Genes, For The Normal Human Colonic Crypt Stem Cell Niche: Overexpression Of The Signature Parallels Stem Cell Overpopulation During Colon Tumorigenesis., Seema Bhatlekar, Sankar Addya, Moreh Salunek, Christopher R Orr, Saul Surrey, Steven E. Mckenzie, Jeremy Z Fields, Bruce M Boman

Kimmel Cancer Center Faculty Papers

Our goal was to identify a unique gene expression signature for human colonic stem cells (SCs). Accordingly, we determined the gene expression pattern for a known SC-enriched region--the crypt bottom. Colonic crypts and isolated crypt subsections (top, middle, and bottom) were purified from fresh, normal, human, surgical specimens. We then used an innovative strategy that used two-color microarrays (∼18,500 genes) to compare gene expression in the crypt bottom with expression in the other crypt subsections (middle or top). Array results were validated by PCR and immunostaining. About 25% of genes analyzed were expressed in crypts: 88 preferentially in the bottom, …

Then And Now: The Progress In Hepatitis B Treatment Over The Past 20 Years., Dina Halegoua-De Marzio, Hie-Won Hann

Department of Medicine Faculty Papers

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this …

Development Of A Personalized Decision Aid For Breast Cancer Risk Reduction And Management, Elissa M. Ozanne, Rebecca Howe, Zehra Omer, Laura J. Esserman

Dartmouth Scholarship

Background: Breast cancer risk reduction has the potential to decrease the incidence of the disease, yet remains underused. We report on the development a web-based tool that provides automated risk assessment and personalized decision support designed for collaborative use between patients and clinicians. Methods: Under Institutional Review Board approval, we evaluated the decision tool through a patient focus group, usability testing, and provider interviews (including breast specialists, primary care physicians, genetic counselors). This included demonstrations and data collection at two scientific conferences (2009 International Shared Decision Making Conference, 2009 San Antonio Breast Cancer Symposium). Results: Overall, the evaluations were favorable. …

Assessments Of Empathy In Medical School Admissions: What Additional Evidence Is Needed?, Mohammadreza Hojat

Department of Psychiatry and Human Behavior Faculty Papers

The Association for the Study of Medical Education (ASME) sponsored a symposium on the theme of Examin-ing the Evidence with Regard to Character, Personality and Values in Medical School Selection which was held on October 14, 2013 at the University of Sheffield Medical School in the United Kingdom. I was invited to speak about credibility issues related to personality assessments in health profession educations. To my pleasant surprise, I found the European audience receptive (more than their counterparts in the United States) to the idea of using personality assess-ments in admission decisions. There seems to be a hesita-tion among leaders …

The Evolutionary Young Mir-1290 Favors Mitotic Exit And Differentiation Of Human Neural Progenitors Through Altering The Cell Cycle Proteins., Sowmya V. Yelamanchili, Brenda M. Morsey, Emily B. Harrison, D. A. Rennard, Kathleen M. Emanuel, I Thapa, D. R. Bastola, H. S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

Regulation of cellular proliferation and differentiation during brain development results from processes requiring several regulatory networks to function in synchrony. MicroRNAs are part of this regulatory system. Although many microRNAs are evolutionarily conserved, recent evolution of such regulatory molecules can enable the acquisition of new means of attaining specialized functions. Here we identify and report the novel expression and functions of a human and higher primate-specific microRNA, miR-1290, in neurons. Using human fetal-derived neural progenitors, SH-SY5Y neuroblastoma cell line and H9-ESC-derived neural progenitors (H9-NPC), we found miR-1290 to be upregulated during neuronal differentiation, using microarray, northern blotting and qRT-PCR. We …

Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee

Dartmouth Scholarship

We previously identified a Drosophila maternal effect-lethal mutant named ‘no poles’ (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of …

Prognosis Of Differentiated Thyroid Cancer In Relation To Serum Thyrotropin And Thyroglobulin Antibody Status At Time Of Diagnosis, Donald S. A. Mcleod, David S. Cooper, Paul W. Ladenson, Kenneth B. Ain, James D. Brierley, Henry G. Fein, Bryan R. Haugen, Jacqueline Jonklaas, James Magner, Douglas S. Ross, Monica C. Skarulis, David L. Steward, Harry R. Maxon, Steven I. Sherman

Internal Medicine Faculty Publications

BACKGROUND: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis.

OBJECTIVE: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry.

METHODS: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) …

Resveratrol Induces Vascular Smooth Muscle Cell Differentiation Through Stimulation Of Sirt1 And Ampk, Anne Marie Thompson, Kathleen A. Martin, Eva M. Rzucidlo

Dartmouth Scholarship

Phenotypic plasticity in vascular smooth muscle cells (VSMC) is necessary for vessel maintenance, repair and adaptation to vascular changes associated with aging. De-differentiated VSMC contribute to pathologies including atherosclerosis and intimal hyperplasia. As resveratrol has been reported to have cardio- protective effects, we investigated its role in VSMC phenotypic modulation. We demonstrated the novel finding that resveratrol promoted VSMC differentiation as measured by contractile protein expression, contractile morphology and contraction in collagen gels. Resveratrol induced VSMC differentiation through stimulation of SirT1 and AMPK. We made the novel finding that low or high dose resveratrol had an initially different mechanism on …

Revealing Variations In Perception Of Mental States From Dynamic Facial Expressions: A Cautionary Note, Elisa Back, Timothy R. Jordan

All Works

Although a great deal of research has been conducted on the recognition of basic facial emotions (e.g., anger, happiness, sadness), much less research has been carried out on the more subtle facial expressions of an individual's mental state (e.g., anxiety, disinterest, relief). Of particular concern is that these mental state expressions provide a crucial source of communication in everyday life but little is known about the accuracy with which natural dynamic facial expressions of mental states are identified and, in particular, the variability in mental state perception that is produced. Here we report the findings of two studies that investigated …

Redox Pioneer: Professor Joe M. Mccord, David M. Schnell, Daret K. St Clair

Graduate Center for Nutritional Sciences Faculty Publications

Dr. Joe McCord (Ph.D. 1970) is recognized here as a Redox Pioneer because he has published at least three articles on antioxidant/redox biology as first/last author that have been cited over 1000 times and has published at least 37 articles each cited over 100 times. Dr. McCord is known for the monumental discovery of the antioxidant superoxide dismutase (SOD) while a graduate student under fellow redox pioneer Irwin Fridovich and demonstrating its necessity to aerobic life. Beyond this, McCord's career is distinguished for bridging the gap from basic science to clinical relevance by showing the application of SOD and superoxide …

Spatial Frequency Analysis Of Anisotropic Drug Transport In Tumor Samples, Stewart Russell, Kimberley S. Samkoe, Jason R. Gunn, P Jack Hoopes, Thienan A. Nguyen, Milo J. Russell, Robert R. Alfano, Brian W. Pogue

Dartmouth Scholarship

Directional Fourier spatial frequency analysis was used on standard histological sections to identify salient directional bias in the spatial frequencies of stromal and epithelial patterns within tumor tissue. This directional bias is shown to be correlated to the pathway of reduced fluorescent tracer transport. Optical images of tumor specimens contain a complex distribution of randomly oriented aperiodic features used for neoplastic grading that varies with tumor type, size, and morphology. The internal organization of these patterns in frequency space is shown to provide a precise fingerprint of the extracellular matrix complexity, which is well known to be related to the …

The Mammalian Neocortex New Pyramidal Neuron: A New Conception, Miguel Marín-Padilla

Dartmouth Scholarship

The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex …

Relationship Between Altitude And Lithium In Groundwater In The United States Of America: Results Of A 1992–2003 Study, Rebekah S. Huber, Namkug Kim, Carl E. Renshaw, Perry F. Renshaw, Douglas Kondo

Dartmouth Scholarship

Therapeutic dosages of lithium are known to reduce suicide rates, which has led to investigations of confounding environmental risk factors for suicide such as lithium in groundwater. It has been speculated that this might play a role in the potential relationship between suicide and altitude. A recent study in Austria involving geospatial analysis of lithium in groundwater and suicide found lower levels of lithium at higher altitudes. Since there is no reason to suspect this correlation is universal given variation in geology, the current study set out to investigate the relationship between altitude and lithium in groundwater in the United …

Cardiac Calcium Handling On Trial: Targeting The Failing Cardiomyocyte Signalosome., Sven T Pleger, Philip Raake, Hugo A Katus, Patrick Most

Center for Translational Medicine Faculty Papers

No abstract provided.

Aortic Aneurysms In Loeys-Dietz Syndrome - A Tale Of Two Pathways?, Frank Davis, Debra L. Rateri, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by skeletal abnormalities, craniofacial malformations, and a high predisposition for aortic aneurysm. In this issue of the JCI, Gallo et al. developed transgenic mouse strains harboring missense mutations in the genes encoding type I or II TGF-β receptors. These mice exhibited several LDS-associated phenotypes. Despite being functionally defective, the mutated receptors enhanced TGF-β signaling in vivo, inferred by detection of increased levels of phosphorylated Smad2. Aortic aneurysms in these LDS mice were ablated by treatment with the Ang II type 1 (AT1) receptor antagonist losartan. The results from this …

Images In Clinical Medicine. Rumpel-Leede Sign., Krystle Wang, Jason Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Multiple Epidural Steroid Injections And Body Mass Index Linked With Occurrence Of Epidural Lipomatosis: A Case Series., Rafael Jaimes, Angelo G. Rocco

Orthopaedic Surgery Faculty Publications

BACKGROUND:

Epidural lipomatosis (EL) is an increase of adipose tissue, normally occurring in the epidural space, sufficient to distort the thecal sac and compress neural elements. There is a lack of knowledge of risk factors, impact on patient's symptoms, and its possible association with epidural steroid injections.

METHODS:

History, physical examination, patient chart, and MRI were analyzed from 856 outpatients referred for epidural steroid injections. Seventy patients with signs of EL on MRI comprised the study group. Thirty-four randomly selected patients comprised the control group. The severity of EL was determined by the MRI assessment. The impact of EL was …

Acute Cranial Neuropathies Heralding Neurosyphilis In Human Immunodeficiency Virus-Infected Patient., Saeed Alqahtani

Neurology Faculty Publications

No abstract provided.

Whole Exome Sequencing Identifies Novel Genes For Fetal Hemoglobin Response To Hydroxyurea In Children With Sickle Cell Anemia., V. A. Sheehan, J. R. Crosby, A. Sabo, N. A. Mortier, T. A. Howard, D. M. Muzny, S. Dugan-Perez, Banu Aygun, K. A. Nottage, J. M. Flanagan, +3 Additional Authors

Journal Articles

Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final …

Proposed Guidelines For The Diagnosis And Management Of Methylmalonic And Propionic Acidemia., Matthias R Baumgartner, Friederike Hörster, Carlo Dionisi-Vici, Goknur Haliloglu, Daniela Karall, Kimberly A. Chapman, +19 Additional Authors

Pediatrics Faculty Publications

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~ 1:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA and late complications include chronic kidney disease almost exclusively in MMA …

Aspirin Use And Knowledge In The Community: A Population- And Health Facility Based Survey For Measuring Local Health System Performance., Gregory A Roth, Catherine W. Gillespie, Ali A Mokdad, Danny D Shen, David W Fleming, Andy Stergachis, Christopher J L Murray, Ali H Mokdad

Pediatrics Faculty Publications

BACKGROUND: Little is known about the relationship between cardiovascular risk, disease and actual use of aspirin in the community.

METHODS: The Measuring Disparities in Chronic Conditions (MDCC) study is a community and health facility-based survey designed to track disparities in the delivery of health interventions for common chronic diseases. MDCC includes a survey instrument designed to collect detailed information about aspirin use. In King County, WA between 2011 and 2012, we surveyed 4633 white, African American, or Hispanic adults (45% home address-based sample, 55% health facility sample). We examined self-reported counseling on, frequency of use and risks of aspirin for …

Stationary Wavelet Transform For Under-Sampled Mri Reconstruction., Mohammad H Kayvanrad, A Jonathan Mcleod, John S H Baxter, Charles A Mckenzie, Terry M Peters

Robarts Imaging Publications

In addition to coil sensitivity data (parallel imaging), sparsity constraints are often used as an additional lp-penalty for under-sampled MRI reconstruction (compressed sensing). Penalizing the traditional decimated wavelet transform (DWT) coefficients, however, results in visual pseudo-Gibbs artifacts, some of which are attributed to the lack of translation invariance of the wavelet basis. We show that these artifacts can be greatly reduced by penalizing the translation-invariant stationary wavelet transform (SWT) coefficients. This holds with various additional reconstruction constraints, including coil sensitivity profiles and total variation. Additionally, SWT reconstructions result in lower error values and faster convergence compared to DWT. These concepts …