Individual Differences in Eye-Movements During Reading: Working Memory and Speed-of-Processing Effects

Mathematical models of eye-movement control do not yet incorporate individual differences as a source of variation in reading. These models nonetheless provide an excellent foundation for describing and explaining how and why patterns of eye-movements differ across readers (e.g., Rayner et al., 2006). We focus in this article on two aspects of individual variation: global processing speed (e.g., Salthouse, 1996) and working-memory capacity (e.g., Just & Carpenter, 1992). Using Hierarchical Linear Modeling (HLM) (Raudenbush & Bryk, 2001), we tested the extent to which overall reading speed and working-memory capacity moderate the degree to which syntactic and semantic information affect fixation times. We found that working-memory capacity interacted with sentence-characteristic variables only when processing speed was not included in the model

Memory availability and referential access

Most theories of coreference specify linguistic factors that modulate antecedent accessibility in memory; however, whether non-linguistic factors also affect coreferential access is unknown. Here we examined the impact of a non-linguistic generation task (letter transposition) on the repeated-name penalty, a processing difficulty observed when coreferential repeated names refer to syntactically prominent (and thus more accessible) antecedents. In Experiment 1, generation improved online (event-related potentials) and offline (recognition memory) accessibility of names in word lists. In Experiment 2, we manipulated generation and syntactic prominence of antecedent names in sentences; both improved online and offline accessibility, but only syntactic prominence elicited a repeated-name penalty. Our results have three important implications: first, the form of a referential expression interacts with an antecedent’s status in the discourse model during coreference; second, availability in memory and referential accessibility are separable; and finally, theories of coreference must better integrate known properties of the human memory system

The Lantern Vol. 53, No. 1, Fall 1986

• Living In-Sanity • Sentence of Dawn • Addict • Where Do They Come From? • Midnight Hags Astride • Escape • Here I Sit • A Minor Key • To Picasso\u27s Old Guitarist • Nothing More • Love or Futility • A Few Inches • My Only Gift • Reserved • A Message to a Disillusioned Friend • Doing it the Hard Way • The Wall • A Look Ahead at a Look Behind • Fantasy Secret • Lisa • Caesar\u27s Last Words • There\u27s a Grouse in My House • If You Want Me • The Education of a Samaritan • Death of Illusion • I Walked and Pondered • A Woman Walked Past Him and He Smiled • Betrayal • Blindness • Innocence Unveiled • Amandahttps://digitalcommons.ursinus.edu/lantern/1129/thumbnail.jp

A Hypermorphic Missense Mutation in PLCG2, Encoding Phospholipase Cγ2, Causes a Dominantly Inherited Autoinflammatory Disease with Immunodeficiency

Whole-exome sequencing was performed in a family affected by dominantly inherited inflammatory disease characterized by recurrent blistering skin lesions, bronchiolitis, arthralgia, ocular inflammation, enterocolitis, absence of autoantibodies, and mild immunodeficiency. Exome data from three samples, including the affected father and daughter and unaffected mother, were filtered for the exclusion of reported variants, along with benign variants, as determined by PolyPhen-2. A total of eight transcripts were identified as possible candidate genes. We confirmed a variant, c.2120C>A (p.Ser707Tyr), within PLCG2 as the only de novo variant that was present in two affected family members and not present in four unaffected members. PLCG2 encodes phospholipase Cγ2 (PLCγ2), an enzyme with a critical regulatory role in various immune and inflammatory pathways. The p.Ser707Tyr substitution is located in an autoinhibitory SH2 domain that is crucial for PLCγ2 activation. Overexpression of the altered p.Ser707Tyr protein and ex vivo experiments using affected individuals’ leukocytes showed clearly enhanced PLCγ2 activity, suggesting increased intracellular signaling in the PLCγ2-mediated pathway. Recently, our laboratory identified in individuals with cold-induced urticaria and immune dysregulation PLCG2 exon-skipping mutations resulting in protein products with constitutive phospholipase activity but with reduced intracellular signaling at physiological temperatures. In contrast, the p.Ser707Tyr substitution in PLCγ2 causes a distinct inflammatory phenotype that is not provoked by cold temperatures and that has different end-organ involvement and increased intracellular signaling at physiological temperatures. Our results highlight the utility of exome-sequencing technology in finding causal mutations in nuclear families with dominantly inherited traits otherwise intractable by linkage analysis

The Lantern Vol. 52, No. 2, Spring 1986

• The Cartoonist • Balance • Haiku • Moment of Truth • There Was a Man • Mad Song / Cassandra\u27s Song • Part I - The Descent • Political Thought • Beast • Questions Yet Unanswered • Aphrodite: A Lover\u27s Lament • The Most Limber Boy • Style And • Thoughts From My Confusion • Andy • Momma Wake Up • In The Suburbs • Tommy • When the Phone Rings • There\u27s Something Soothing • Starting Over • A Day in the Life of a Flower • Pretension • It Seems Like So Long Ago • I Walk Along • Insignificant Man • Variations on a Latin Theme • The Riddle • Roll the Dice - Its Your Turn • This Is Your Day • One Night Stand • Make My Day • You Really Can\u27t Expect • Medusa • Don\u27t Think • Broken Chain • Life...A Hammock? • To My Friend • Ode On a Grecian Keghttps://digitalcommons.ursinus.edu/lantern/1128/thumbnail.jp

Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis

Background: Impaired signaling in the IFN-g/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis. Objective: We sought to identify the molecular defect in patients with disseminated dimorphic yeast infections. Methods: PBMCs, EBV-transformed B cells, and transfected U3A cell lines were studied for IFN-g/IL-12 pathway function. STAT1 was sequenced in probands and available relatives. Interferon-induced STAT1 phosphorylation, transcriptional responses, protein-protein interactions, target gene activation, and function were investigated. Results: We identified 5 patients with disseminated Coccidioides immitis or Histoplasma capsulatum with heterozygous missense mutations in the STAT1 coiled-coil or DNA-binding domains. These are dominant gain-of-function mutations causing enhanced STAT1 phosphorylation, delayed dephosphorylation, enhanced DNA binding and transactivation, and enhanced interaction with protein inhibitor of activated STAT1. The mutations caused enhanced IFN-g–induced gene expression, but we found impaired responses to IFN-g restimulation. Conclusion: Gain-of-function mutations in STAT1 predispose to invasive, severe, disseminated dimorphic yeast infections, likely through aberrant regulation of IFN-g–mediated inflammationFil: Sampaio, Elizabeth P.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos. Instituto Oswaldo Cruz. Laboratorio de Leprologia; BrasilFil: Hsu, Amy P.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Pechacek, Joseph. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Hannelore I.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos. Erasmus Medical Center. Department of Medical Microbiology and Infectious Disease; Países BajosFil: Dias, Dalton L.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Paulson, Michelle L.. Clinical Research Directorate/CMRP; Estados UnidosFil: Chandrasekaran, Prabha. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Rosen, Lindsey B.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Carvalho, Daniel S.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos. Instituto Oswaldo Cruz, Laboratorio de Leprologia; BrasilFil: Ding, Li. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Vinh, Donald C.. McGill University Health Centre. Division of Infectious Diseases; CanadáFil: Browne, Sarah K.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Datta, Shrimati. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Allergic Diseases. Allergic Inflammation Unit; Estados UnidosFil: Milner, Joshua D.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Allergic Diseases. Allergic Inflammation Unit; Estados UnidosFil: Kuhns, Douglas B.. Clinical Services Program; Estados UnidosFil: Long Priel, Debra A.. Clinical Services Program; Estados UnidosFil: Sadat, Mohammed A.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Host Defenses. Infectious Diseases Susceptibility Unit; Estados UnidosFil: Shiloh, Michael. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados UnidosFil: De Marco, Brendan. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados UnidosFil: Alvares, Michael. University of Texas. Southwestern Medical Center. Division of Allergy and Immunology; Estados UnidosFil: Gillman, Jason W.. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados UnidosFil: Ramarathnam, Vivek. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados UnidosFil: de la Morena, Maite. University of Texas. Southwestern Medical Center. Division of Allergy and Immunology; Estados UnidosFil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moreira, Ileana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; ArgentinaFil: Uzel, Gulbu. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Johnson, Daniel. University of Chicago. Comer Children; Estados UnidosFil: Spalding, Christine. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Zerbe, Christa S.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados UnidosFil: Wiley, Henry. National Eye Institute. Clinical Trials Branch; Estados UnidosFil: Greenberg, David E.. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados UnidosFil: Hoover, Susan E.. University of Arizona. College of Medicine. Valley Fever Center for Excellence; Estados UnidosFil: Rosenzweig, Sergio D.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Host Defenses Infectious Diseases Susceptibility Unit; Estados Unidos. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Primary Immunodeficiency Clinic; Estados UnidosFil: Galgiani, John N.. University of Arizona. College of Medicine. Valley Fever Center for Excellence; Estados UnidosFil: Holland, Steven M.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unido

Atomic Resonance and Scattering

Contains reports on two research projects.National Science Foundation (Grant PHY 87-06560)Joint Services Electronics Program (Contract DAAL03-86-K-O002)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0695)National Science Foundation (Grant PHY 86-05893

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN