Rita Dove: 03-06-1985

Dove discusses her fascination with the unseen and insignificant details of historical events and individual lives. This interest in the less celebrated moments of experience shaped Museum and Thomas and Beulah. Her careful attention to language, form, structure, and organization in her work is revealed throughout the interview. She talks about the crafting of Parsley as well as the organization of the Museum. Dove says she doesn\u27t want the reader to know what is coming in a book. She says the worst thing that can happen to a poet is to be self-conscious because it interferes with the creative process. She tries not to clutter her head with too much literary critique and theory, particularly when she is composing. Work(s) Discussed: The Yellow House on the Corner Museum Thomas and Beulah Work(s) Read: Parsley Delft Anti-Father Dusting Variation on Painhttps://digitalcommons.brockport.edu/writers_videos/1040/thumbnail.jp

FGCUScholars: Using Undergraduate Research as a Tool to Enhance Student Writing, Critical Thinking, and Information Literacy

This presentation will overview FGCUScholars, a university-wide program at Florida Gulf Coast University that integrates undergraduate research across the university as a means of teaching and assessing writing, critical thinking, and information literacy. We will overview the development and learning outcomes of FGCUScholars and the implementation across the campus, highlighting examples of curricular changes in engineering that engage students throughout their career at FGCU, the role of problem/project-based learning (PBL) in business classes, the development of research assignments that use digital media in literature courses, and the creation of disciplinary-specific sections of Composition II

E5501: phase II study of topotecan sequenced with etoposide/cisplatin, and irinotecan/cisplatin sequenced with etoposide for extensive-stage small-cell lung cancer.

PURPOSE: Sequence-dependent improved efficacy of topoisomerase I followed by topoisomerase 2 inhibitors was assessed in a randomized phase II study in extensive-stage small-cell lung cancer (SCLC). METHODS: Patients with previously untreated extensive-stage SCLC with measurable disease, ECOG performance status of 0-3 and stable brain metastases were eligible. Arm A consisted of topotecan (0.75 mg/m(2)) on days 1, 2 and 3, etoposide (70 mg/m(2)) and cisplatin (20 mg/m(2)) (PET) on days 8, 9 and 10 in a 3-week cycle. Arm B consisted of irinotecan (50 mg/m(2)) and cisplatin (20 mg/m(2)) on days 1 and 8 followed by etoposide (85 mg/m(2) PO bid) on days 3 and 10 (PIE) in a 3-week cycle. RESULTS: We enrolled 140 patients and randomized 66 eligible patients to each arm. Only 54.5 % of all patients completed the planned maximum 6 cycles. There were grade ≥3 treatment-related adverse events in approximately 70 % of the patients on both arms including 6 treatment-related grade 5 events. The overall response rates (CR + PR) were 69.7 % (90 % CI 59.1-78.9, 95 % CI 57.1-80.4 %) for arm A and 57.6 % (90 % CI 46.7-67.9, 95 % CI 44.8-69.7 %) for arm B. The median progression-free survival and overall survival were 6.4 months (95 % CI 5.4-7.5 months) and 11.9 months (95 % CI 9.6-13.7 months) for arm A and 6.0 months (95 % CI 5.4-7.0 months) and 11.0 months (95 % CI 8.6-13.1 months) for arm B. CONCLUSION: Sequential administration of topoisomerase inhibitors did not improve on the historical efficacy of standard platinum-doublet chemotherapy for extensive-stage SCLC

The JAK2V617F mutation disrupts the regulated association between calreticulin and the glucocorticoid receptor observed in normal erythroid cells

Calreticulin (CALR) is a multifunctional protein normally found within the lumen of the endoplasmic reticulum that mediates the cellular response to Ca2+ by chaperoning other proteins to their acting sites. Somatic loss-of-function mutations in the CALR gene were recently discovered in 70% of patients with the Philadelphia-negative myeloproliferative neoplasm (MPN) primary myelofibrosis (PMF) who did not harbor gain-of-function mutations of JAK21,2. Nevertheless, the JAK2 pathway is constitutively activated also in patients carrying CALR mutation and treatments with JAK2 inhibitors are effective not only in MPN patients (PMF and polycythemia vera, PV) harboring JAK2 mutations but also in PMF patients harboring mutations in CALR3. We have previously reported that erythroid cells from PV and PMF patients express abnormal activity of the glucocorticoid receptor (GR), a nuclear receptor whose transcriptional activity plays an important role in the regulation of stress erythropoiesis4,5. Since GR is one of the numerous proteins regulated by CALR6, we hypothesized that in human erythroid cells CALR regulates GR functions and that this regulation is disrupted both by CALR and JAK2 mutations in MPN. In this study we tested this hypothesis by determining whether GR and CALR are associated in normal erythroid cells and whether this association is impaired in those from MPN patients. First, biochemical studies determined that human erythroblasts (Erys) expanded ex-vivo from normal stem cell sources [cord blood (CB) and adult blood (AB)] and from MPN patients contain similar levels of CALR and GR. Analyses of cell fractions indicated that in normal Erys, CALR was constitutively localized in the cytoplasm while GR was detected either in the cytoplasm or in the nucleus, depending on the growth factor (the glucocorticoid receptor agonist dexamethasone, erythropoietin or stem cell factor) to which they had been exposed. Second, robust levels of CALR and GR expression were also detected by confocal microscopy. In addition, this analyses revealed that in Erys expanded from normal sources CALR and GR are co-localized in the cytoplasm and that the cytoplasmic association between the two proteins is increased by growth factor deprivation and further enhanced by stimulation with growth factors that activate the JAK2/STAT5 signaling (dexamethasone and/or erythropoietin) while it is inhibited by stimulation with factors that do not use this pathway (stem cell factor). By contrast, in Erys expanded from MPN carrying either CALR or JAK2 mutations, CALR and GR are not associated and remain not associated when the cells are exposed to dexamethasone or erythropoietin. However, in Erys from JAK2V17F-positive MPN patients, association between CALR and GR in the cytoplasm is restored by exposing the cells to the JAK2 inhibitor ruxolitinib. These results suggest that CALR/GR association is a downstream event induced by the JAK2/STAT5 pathway and identify for the first time that CALR functions are impaired in erythroid cells from MPN patients carrying JAK2 mutations

Ancient coins: cluster analysis applied to find a correlation between corrosion process and burial soil characteristics

Although it is well known that any material degrades faster when exposed to an aggressive environment as well as that "aggressive" cannot be univocally defined as depending also on the chemical-physical characteristics of material, few researches on the identification of the most significant parameters influencing the corrosion of metallic object are available

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

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

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

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment