Digital Commons Network^™

Therapeutic Targeting Of Atp7b In Ovarian Carcinoma, Lingegowda S Mangala, Vesna Zuzel, Rosemarie Schmandt, Erik S Leshane, Jyotsna B Halder, Guillermo N Armaiz-Pena, Whitney A Spannuth, Takemi Tanaka, Mian M K Shahzad, Yvonne G Lin, Alpa M Nick, Christopher G Danes, Jeong-Won Lee, Nicholas B Jennings, Pablo E Vivas-Mejia, Judith K Wolf, Robert L Coleman, Zahid H Siddik, Gabriel Lopez-Berestein, Svetlana Lutsenko, Anil K Sood

Faculty, Staff and Student Publications

PURPOSE: Resistance to platinum chemotherapy remains a significant problem in ovarian carcinoma. Here, we examined the biological mechanisms and therapeutic potential of targeting a critical platinum resistance gene, ATP7B, using both in vitro and in vivo models.

EXPERIMENTAL DESIGN: Expression of ATP7A and ATP7B was examined in ovarian cancer cell lines by real-time reverse transcription-PCR and Western blot analysis. ATP7A and ATP7B gene silencing was achieved with targeted small interfering RNA (siRNA) and its effects on cell viability and DNA adduct formation were examined. For in vivo therapy experiments, siRNA was incorporated into the neutral nanoliposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC).

RESULTS: ATP7A …

Revisiting Histidine-Dependent Acid Phosphatases: A Distinct Group Of Tyrosine Phosphatases., Suresh Veeramani, Ming-Shyue Lee, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

Although classical protein tyrosine phosphatase (PTP) superfamily members are cysteine-dependent, emerging evidence shows that many acid phosphatases (AcPs) function as histidine-dependent PTPs in vivo. These AcPs dephosphorylate phospho-tyrosine substrates intracellularly and could have roles in development and disease. In contrast to cysteine-dependent PTPs, they utilize histidine, rather than cysteine, for substrate dephosphorylation. Structural analyses reveal that active site histidine, but not cysteine, faces towards the substrate and functions as the phosphate acceptor. Nonetheless, during dephosphorylation, both histidine-dependent and cysteine-dependent PTPs use their active site arginine and aspartate for substrate binding and proton donation, respectively. Thus, we propose that they should …

Interaction With Lc8 Is Required For Pak1 Nuclear Import And Is Indispensable For Zebrafish Development., Christine M Lightcap, Gabor Kari, Luis E Arias-Romero, Jonathan Chernoff, Ulrich Rodeck, John C Williams

Department of Biochemistry and Molecular Biology Faculty Papers

Pak1 (p21 activated kinase 1) is a serine/threonine kinase implicated in regulation of cell motility and survival and in malignant transformation of mammary epithelial cells. In addition, the dynein light chain, LC8, has been described to cooperate with Pak1 in malignant transformation of breast cancer cells. Pak1 itself may aid breast cancer development by phosphorylating nuclear proteins, including estrogen receptor alpha. Recently, we showed that the LC8 binding site on Pak1 is adjacent to the nuclear localization sequence (NLS) required for Pak1 nuclear import. Here, we demonstrate that the LC8-Pak1 interaction is necessary for epidermal growth factor (EGF)-induced nuclear import …

Hiv Policy: The Path Forward--A Joint Position Paper Of The Hiv Medicine Association Of The Infectious Diseases Society Of America And The American College Of Physicians., Christine Lubinski, Judith Aberg, Arlene D Bardeguez, Richard Elion, Patricia Emmanuel, Daniel Kuritzkes, Michael Saag, Kathleen E Squires, Andrea Weddle, Jennifer Rainey, M Renee Zerehi, J Fred Ralston, David A Fleming, David Bronson, Molly Cooke, Charles Cutler, Yul Ejnes, Robert Gluckman, Mark Liebow, Kenneth Musana, Mark E Mayer, Mark W Purtle, P Preston Reynolds, Lavanya Viswanathan, Kevin B Weiss, Baligh Yehia

Department of Medicine Faculty Papers

Executive Summary

The American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA) have jointly published 3 policy statements on AIDS, the first in 1986 [1], the second in 1988 [2], and the third in 1994 [3]. In 2001, the IDSA created the HIV Medicine Association (HIVMA), and this updated policy paper is a collaboration between the ACP and the HIVMA of the IDSA. Since the last statement, many new developments call for the need to reexamine and update our policies relating to HIV infection. First, there have been major advances …

A Gene Expression Predictor Of Response To Egfr-Targeted Therapy Stratifies Progression-Free Survival To Cetuximab In Kras Wild-Type Metastatic Colorectal Cancer, Justin M. Balko, Esther P. Black

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC), and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy.

METHODS: Microarray data from 80 metastatic CRC patients subsequently …

Memory Functioning In Developmental Dyslexia: An Analysis Using Two Clinical Memory Measures., Michelle Y. Kibby

Publications

The goals of this project were threefold: to determine the nature of the memory deficit in children/adolescents with dyslexia, to utilize clinical memory measures in this endeavor, and to determine the extent to which semantic short-term memory (STM) is related to basic reading performance. Two studies were conducted using different samples, one incorporating the Wide Range Assessment of Memory and Learning and the other incorporating the California Verbal Learning Test-Children's Version. Results suggest that phonological STM is deficient in children with dyslexia, but semantic STM and visual-spatial STM are intact. Long-term memory (LTM) for both visual and verbal material also …

Human Cerebral Neuropathology Of Type 2 Diabetes Mellitus, Peter T. Nelson, Charles D. Smith, Erin L. Abner, Frederick A. Schmitt, Stephen W. Scheff, Gregory J. Davis, Jeffrey N. Keller, Gregory A. Jicha, Daron Davis, Wang-Xia Wang, Adria Hartman, Douglas G. Katz, William R. Markesbery

Pathology and Laboratory Medicine Faculty Publications

The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the ‘Pubmed Era’. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met …

The Physician's Response To Climate Change., Mona Sarfaty, Safiya Abouzaid

Department of Family & Community Medicine Faculty Papers

Climate change will have an effect on the health and well-being of the populations cared for by practicing physicians. The anticipated medical effects include heat- and cold-related deaths, cardiovascular illnesses, injuries and mental harms from extreme weather events, respiratory illnesses caused by poor air quality, infectious diseases that emanate from contaminated food, water, or spread of disease vectors, the injuries caused by natural disasters, and the mental harm associated with social disruption. Within several years, such medical problems are likely to reach the doorsteps of many physicians. In the face of this reality, physicians should assume their traditional roles as …

State Infant Mortality: An Ecologic Study To Determine Modifiable Risks And Adjusted Infant Mortality Rates., David A. Paul. Md, Amy Mackley, Rnc, Robert G. Locke, Do, John L. Stefano, Md, Charlan Kroelinger, Phd

Department of Pediatrics Faculty Papers

OBJECTIVE: To determine factors contributing to state infant mortality rates (IMR) and develop an adjusted IMR in the United States for 2001 and 2002. DESIGN/METHODS: Ecologic study of factors contributing to state IMR. State IMR for 2001 and 2002 were obtained from the United States linked death and birth certificate data from the National Center for Health Statistics. Factors investigated using multivariable linear regression included state racial demographics, ethnicity, state population, median income, education, teen birth rate, proportion of obesity, smoking during pregnancy, diabetes, hypertension, cesarean delivery, prenatal care, health insurance, self-report of mental illness, and number of in-vitro fertilization …

Differences In Responses Of Platelets To Fluid Shear Stress In Patients With Peripheral Artery Disease (Pad) And Coronary Artery Disease (Cad)., Vijay Nambi, Kay T Kimball, Paul Bray, Angela L Bergeron, Shawna L Johnson, Joel D Morrisett, Changyi Chen, Peter H Lin, Alan B Lumsden, Christie M Ballantyne, Jing-Fei Dong

Cardeza Foundation for Hematologic Research

Information on differences in platelet function between patients with peripheral arterial disease (PAD) and patients with coronary artery disease (CAD) is limited. We sought to examine the differences in the platelets response to shear stress in patients with PAD compared to those with CAD. Men with symptomatic PAD (ankle brachial index [ABI] < 0.9; n = 29) were compared with similarly aged men with CAD (post coronary artery bypass grafting; n = 40) but without PAD. All participants were on aspirin, and none were on clopidogrel. We measured changes in shear-induced platelet aggregation (SIPA) and shear-induced P-selectin expression (SIPE) under fluid shear rates of 5000 and 10,000 s(-1)which are typically found in arterioles and stenosed arteries, respectively. Aggregation was also induced by a combined stimulation of collagen, fluid shear stress, and adenosine diphosphate (ADP) or epinephrine using a platelet function analyzer (PFA-100) as well as optical aggregometry (arachidonic acid, collagen and epinephrine). Analyses of covariance adjusted for age, aspirin dose, and statin use were used to estimate differences between the groups. Values of SIPA at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in the PAD group, while there were no differences between the PAD and CAD groups in SIPE at both fluid shear rates. However, baseline shear-induced P-selectin expression was higher in patients with PAD than CAD (mean fluorescence intensity [MFI] = 2.93 +/- 1.37 vs.1.94 +/- 0.67; p = 0.01), while the percentage increases in SIPA and SIPE at fluid shear rates of 5000 and 10,000 s(-1) were significantly higher in patients with CAD when compared to PAD (p < 0.001 for all comparisons). Although there were several similarities in platelet function between men with PAD and men with CAD, significant differences in platelet responses to shear stress were observed in men with PAD when compared to those with CAD. Although the mechanism for these observed differences are not clear, we hypothesize that in vivo platelet activation in PAD patients may contribute to the differences and will need to be further investigated.

Genome Based Cell Population Heterogeneity Promotes Tumorigenicity: The Evolutionary Mechanism Of Cancer., Christine J. Ye, Joshua B. Stevens, Guo Liu, Steven W. Bremer, Aruna S. Jaiswal, Karen J. Ye, Ming-Fong Lin, Lesley Lawrenson, Wayne D. Lancaster, Markku Kurkinen, Joshua D. Liao, C. Gary Gairola, Malathy P. V. Shekhar, Satya Narayan, Fred R. Miller, Henry H. Q. Heng

Journal Articles: Biochemistry & Molecular Biology

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal …

How Tagging Helps Bridge The Gap Between Social And Technical Aspects In Software Development, Christoph Treude, Margaret-Anne Storey

Research Collection School Of Computing and Information Systems

Empirical research on collaborative software development practices indicates that technical and social aspects of software development are often intertwined. The processes followed are tacit and constantly evolving, thus not all of them are amenable to formal tool support. In this paper, we explore how ldquotaggingrdquo, a lightweight social computing mechanism, is used to bridge the gap between technical and social aspects of managing work items. We present the results from an empirical study on how tagging has been adopted and adapted over the past two years of a large project with 175 developers. Our research shows that the tagging mechanism …

Hand Hygiene Compliance Rates In The United States--A One-Year Multicenter Collaboration Using Product/Volume Usage Measurement And Feedback., Maryanne Mcguckin, Richard Waterman, John Govednik

College of Population Health Faculty Papers

Hand hygiene (HH) is the single most important factor in the prevention of health care-acquired infections. The 3 most frequently reported methods of measuring HH compliance are: (1) direct observation, (2) self-reporting by health care workers (HCWs), and (3) indirect calculation based on HH product usage. This article presents the results of a 12-month multicenter collaboration assessing HH compliance rates at US health care facilities by measuring product usage and providing feedback about HH compliance. Our results show that HH compliance at baseline was 26% for intensive care units (ICUs) and 36% for non-ICUs. After 12 months of measuring product …

Imaging Of Glioma Tumor With Endogenous Fluorescence Tomography, Dax S. Kepshire, Summer L. Gibbs-Strauss, Julia A. O'Hara, Michael Hutchins, Niculae Mincu, Frederic Leblond, Mario Khayat, Hamid Dehghani, Subhadra Srinivasan, Brian W. Pogue

Dartmouth Scholarship

Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a noncontact single-photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX (PpIX) was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single-photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid (ALA) and provides the first in vivo demonstration of deep tissue tomographic imaging …

Automated Identification Of Tumor Microscopic Morphology Based On Macroscopically Measured Scatter Signatures, Pilar Beatriz Garcia-Allende, Venkataramanan Krishnaswamy, P Jack Hoopes, Kimberley S. Samkoe, Olga M. Conde, Brian W. Pogue

Dartmouth Scholarship

An automated algorithm and methodology is presented to identify tumor-tissue morphologies based on broadband scatter data measured by raster scan imaging of the samples. A quasi-confocal reflectance imaging system was used to directly measure the tissue scatter reflectance in situ, and the spectrum was used to identify the scattering power, amplitude, and total wavelength-integrated intensity. Pancreatic tumor and normal samples were characterized using the instrument, and subtle changes in the scatter signal were encountered within regions of each sample. Discrimination between normal versus tumor tissue was readily performed using a K-nearest neighbor classifier algorithm. A similar approach worked …

Plant Vaccines: An Immunological Perspective., Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective.

Upregulation Of Pip3-Dependent Rac Exchanger 1 (P-Rex1) Promotes Prostate Cancer Metastasis., Jianbing Qin, Yan Xie, Bo Wang, Mikio Hoshino, Dennis W. Wolff, Jing Zhao, Margaret A. Scofield, Frank J. Dowd, Ming-Fong Lin, Yaping Tu

Journal Articles: Biochemistry & Molecular Biology

Excessive activation of G-protein-coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation by guanine nucleotide exchange factors (GEFs) plays an important role in directional cell migration, a critical step of tumor metastasis cascades. We found that the upregulation of P-Rex1, a Rac-selective GEF synergistically activated by Gbetagamma freed during GPCR signaling, and PIP3, generated during either RTK or GPCR signaling, strongly correlates with metastatic phenotypes in both prostate cancer cell lines and human prostate cancer specimens. Silencing endogenous P-Rex1 in metastatic prostate cancer PC-3 cells selectively inhibited Rac activity and reduced …

Depression And Resilience During The First Six-Months Of Internship, Rachel Laff

Yale Medicine Thesis Digital Library

Consistent with prior studies, the prevalence of depression in interns is significantly higher than the general population. There is a significant amount of suicidal ideation among interns during the first three-months of internship. It appears that international medical graduates are significantly less depressed than U.S. medical graduates during the first six-months of internship. A prior history of depression, longer work hours, female gender, and a lack of confidence in coping with challenges are associated with the development of depression during the first six-months of internship. Of greatest concern, very few interns with clinically significant levels of depression are seeking treatment. …

Anatomy, Physiology And Management Of Patients With Diffuse Pulmonary Arteriovenous Malformations, Tamara Lazic

Yale Medicine Thesis Digital Library

Diffuse pulmonary vascular malformations (PAVMs) are a small and understudied, but nevertheless important subset of the PAVM population of patients, associated with significant mortality and morbidity. A review of literature was undertaken to investigate the current understanding of diffuse PAVMs. This review demonstrated that no additional attempts to define diffuse PAVMs and describe their natural history was made before or after the in 2000 report by Faughnan et al {{51 Faughnan,M.E. 2000; }}. To further expand the findings from 2000, we performed a retrospective review of 36 patients (21 female, 15 male) with diffuse PAVMs from a cohort of 821 …

Differences In The Central Neural Activation Under Emotional Stress Across The Menstrual Cycle, Nayalya Lopushnyan

Yale Medicine Thesis Digital Library

The present study had several goals. First, we aimed to investigate the potential differences in the activation of the corticolimbic structures during emotional stress in healthy women across the menstrual cycle using stress imagery. Second, we searched for differences in the subjective anxiety under emotional stress across the menstrual cycle and tried to correlate the perceived level of anxiety to activation of the specific corticolimbic structures. Third, we attempted to compare central neural activation of women in follicular and in luteal phases of the menstrual cycle separately to that of men during emotional stress to investigate potential differences in neural …

Efficacy Of Formal Screening For Depression In Pediatric Type 1 Diabetes Clinic, Jeffrey Winer

Yale Medicine Thesis Digital Library

This study was undertaken to examine the efficacy of screening for depression in a pediatric diabetes clinic and how the yield of such screening compares with established screening protocols aimed at identifying early microvascular complications and associated autoimmune diseases. Two-hundred-fifteen children and adolescents 8-18 years old in the Yale Pediatric Diabetes Center were screened for depression using the Children's Depression Inventory (CDI), with information including gender, age, duration of diabetes, HbA1C, and results of other screening protocols compiled. A total of 8.4% of our cohort had CDI scores ≥13 indicative of clinically-significant depressive symptoms, with a range of 0-34. Depression …

Microsaccade Rate Varies With Subjective Visibility During Motion-Induced Blindness, Po-Jang Hsieh, Peter U. Tse

Dartmouth Scholarship

Motion-induced blindness (MIB) occurs when a dot embedded in a motion field subjectively vanishes. Here we report the first psychophysical data concerning effects of microsaccade/eyeblink rate upon perceptual switches during MIB. We find that the rate of microsaccades/eyeblink rises before and after perceptual transitions from not seeing to seeing the dot, and decreases before perceptual transitions from seeing it to not seeing it. In addition, event-related fMRI data reveal that, when a dot subjectively reappears during MIB, the blood oxygen-level dependent (BOLD) signal increases in V1v and V2v and decreases in contralateral hMT+. These BOLD signal changes observed upon perceptual …

Primary Cardiac Tumors., Suraj Maraj, Md, Gregg S. Pressman, Md, Vincent M. Figueredo, Md

Division of Cardiology Faculty Papers

Primary cardiac tumors are a rare entity compared to tumors that metastasize to the heart. Patients with such tumors may be asymptomatic. Many cases are found incidentally during evaluation of an unrelated medical condition. It is important for the clinician to have a high index of suspicion when evaluating a patient presenting with signs and systemic symptoms concerning possible malignancy, plus cardiac specific symptoms or complications. These can include new onset dyspnea, congestive heart failure, arrhythmias or murmurs varying with body positions. Imaging, particularly the use of echocardiography, remains the cornerstone of diagnosis, and may be combined with new imaging …

A Study Of Micrornas In Silico And In Vivo: Diagnostic And Therapeutic Applications In Cancer., Scott A Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

There is emerging evidence of the production in human tumors of abnormal levels of microRNAs (miRNAs), which have been assigned oncogenic and/or tumor-suppressor functions. While some miRNAs commonly exhibit altered amounts across tumors, more often, different tumor types produce unique patterns of miRNAs, related to their tissue of origin. The role of miRNAs in tumorigenesis underscores their value as mechanism-based therapeutic targets in cancer. Similarly, unique patterns of altered levels of miRNA production provide fingerprints that may serve as molecular biomarkers for tumor diagnosis, classification, prognosis of disease-specific outcomes and prediction of therapeutic responses.

The Relationship Between Cerebral Hemisphere Volume And Receptive Language Functioning In Dyslexia And Attention-Deficit Hyperactivity Disorder (Adhd)., Michelle Y. Kibby, Shital P. Pavawalla, Jill B. Fancher, Angela J. Naillon, George W. Hynd

Publications

Because poor comprehension has been associated with small cerebral volume and there is a high comorbidity between developmental dyslexia, attention-deficit hyperactivity disorder (ADHD), and specific language impairment, the goal of this study was to determine whether cerebral volume is reduced in dyslexia and attention-deficit hyperactivity disorder in general, as some suggest, or whether the reduction in volume corresponds to poor receptive language functioning, regardless of the diagnosis. Participants included 46 children with and without dyslexia and attention-deficit hyperactivity disorder, aged 8 to 12 years. Our results indicated that cerebral volume was comparable between those with and without dyslexia and attention-deficit …

Drug Abuse Treatment Beyond Prison Walls, Carl Leukefeld, Carrie B. Oser, Jennifer Havens, Michele Staton Tindall, Jennifer Mooney, Jamieson B. Duvall, Hannah Knudsen

Behavioral Science Faculty Publications

The period surrounding release from prison is a critical time for parolees, bearing the potential for a drug-free and crime-free life in the community but also high risks for recidivism and relapse to drugs. The authors describe two projects. The first illustrates the use of a formal Delphi process to elicit and combine the expertise of treatment providers, researchers, corrections personnel, and other stakeholders in a set of statewide guidelines for facilitating re-entry. The second project is a six-session intervention to enable women to protect themselves against acquiring or transmitting HIV in their intimate relationships.

Polyglutamine Disruption Of The Huntingtin Exon 1 N Terminus Triggers A Complex Aggregation Mechanism, Ashwani K. Thakur, Murali Jayaraman, Rakesh Mishra, Monika Thakur, Veronique M. Chellgren, In-Ja L Byeon, Dalaver H. Anjum, Ravindra Kodali, Trevor P. Creamer, James F. Conway, Angela M. Gronenborn, Ronald Wetzel

Molecular and Cellular Biochemistry Faculty Publications

Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17-amino-acid flanking sequence (HTT^NT) N-terminal to the polyQ in the toxic huntingtin exon 1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation, the HTT^NT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in HTT^NT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with HTT^NT cores and exposed polyQ. In a second …

Long-Term Survival After Multidisciplinary Management Of Resected Pancreatic Adenocarcinoma, Matthew H G Katz, Huamin Wang, Jason B Fleming, Charlotte C Sun, Rosa F Hwang, Robert A Wolff, Gauri Varadhachary, James L Abbruzzese, Christopher H Crane, Sunil Krishnan, Jean-Nicolas Vauthey, Eddie K Abdalla, Jeffrey E Lee, Peter W T Pisters, Douglas B Evans

Faculty, Staff and Student Publications

INTRODUCTION: Actual 5-year survival rates of 10-18% have been reported for patients with resected pancreatic adenocarcinoma (PC), but the use of multimodality therapy was uncommon in these series. We evaluated long-term survival and patterns of recurrence in patients treated for PC with contemporary staging and multimodality therapy.

METHODS: We analyzed 329 consecutive patients with PC evaluated between 1990 and 2002 who underwent resection. Each received a multidisciplinary evaluation and a standard operative approach. Pre- or postoperative chemotherapy and/or chemoradiation were routine. Surgical specimens of 5-year survivors were re-reviewed. A multivariate model of factors associated with long-term survival was constructed.

RESULTS: …

Pick1 Deficiency Causes Male Infertility In Mice By Disrupting Acrosome Formation, Nan (Tori) Xiao, Chuen Kam, Chong Shen, Wenying Jin, Junqi Wang, Kwong Man Lee, Liwen Jiang, Jun Xia

All Dugoni School of Dentistry Faculty Articles

Protein interacting with C kinase 1 (PICK1) is a peripheral membrane protein involved in protein trafficking, a function that has been well characterized in neurons. Here, we report that male mice deficient in PICK1 are infertile and have a phenotype resembling the human disease globozoospermia. The primary defect in the testes of Pick1-knockout mice was fragmentation of acrosomes in the early stages of spermiogenesis. This fragmentation was followed by defects in nuclear elongation and mitochondrial sheath formation, leading to round-headed sperm, reduced sperm count, and severely impaired sperm motility. We found that PICK1 interacted with Golgi-associated PDZ- and coiled-coil motif-containing …

Bias For Consonantal Information Over Vocalic Information In 30-Month-Olds: Cross-Linguistic Evidence From French And English., Thierry Nazzi, Caroline Floccia, Bérangère Moquet, Joseph Butler

School of Psychology

Using a name-based categorization task, Nazzi found in 2005 that French-learning 20-month-olds can make use of one-feature consonantal contrasts between new labels but fail to do so with one-feature vocalic contrasts. This asymmetry was interpreted as developmental evidence for the proposal that consonants play a more important role than vowels at the lexical level. In the current study using the same task, we first show that by 30 months French-learning infants can make use of one-feature vocalic contrasts (e.g., /pize/-/pyze/). Second, we show that in a situation where infants must neglect either a consonantal one-feature change or a vocalic one-feature …