cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Integrated analysis of RNA and DNA from the phase III trial CALGB 40601 identifies predictors of response to trastuzumab-based neoadjuvant chemotherapy in HER2-positive breast cancer
Creators: name: Mardis, E.R.
name: Tolaney, S.
name: Carey, L.A.
name: Fan, C.
name: Pitcher, B.N.
name: Harris, L.N.
name: Perou, C.M.
name: Spears, P.A.
name: Henry, L.N.
name: Hoadley, K.A.
name: Dang, C.T.
name: Parker, J.S.
name: Hu, Z.
name: Hyslop, T.M.
name: Li, Y.
name: Soloway, M.G.
name: Hudis, C.A.
name: Krop, I.E.
name: Winer, E.P.
name: Tanioka, M.
name: Berry, D.A.
Publisher: name: American Association for Cancer Research Inc.
Year: 2018

description: Purpose: Response to a complex trastuzumab-based regimen is affected by multiple features of the tumor and its microenvironment. Developing a predictive algorithm is key to optimizing HER2-targeting therapy. Experimental Design: We analyzed 137 pretreatment tumors with mRNA-seq and DNA exome sequencing from CALGB 40601, a neoadjuvant phase III trial of paclitaxel plus trastuzumab with or without lapatinib in stage II to III HER2-positive breast cancer. We adopted an Elastic Net regularized regression approach that controls for covarying features within high-dimensional data. First, we applied 517 known gene expression signatures to develop an Elastic Net model to predict pCR, which we validated on 143 samples from four independent trials. Next, we performed integrative analyses incorporating clinicopathologic information with somatic mutation status, DNA copy number alterations (CNA), and gene signatures. Results: The Elastic Net model using only gene signatures predicted pCR in the validation sets (AUC ¼ 0.76). Integrative analyses showed that models containing gene signatures, clinical features, and DNA information were better pCR predictors than models containing a single data type. Frequently selected variables from the multiplatform models included amplifications of chromosome 6p, TP53 mutation, HER2-enriched subtype, and immune signatures. Variables predicting resistance included Luminal/ERþ features. Conclusions: Models using RNA only, as well as integrated RNA and DNA models, can predict pCR with improved accuracy over clinical variables. Somatic DNA alterations (mutation, CNAs), tumor molecular subtype (HER2E, Luminal), and the microenvironment (immune cells) were independent predictors of response to trastuzumab and paclitaxel-based regimens. This highlights the complexity of predicting response in HER2-positive breast cancer.
CAPSTONE PROJECT ON ENHANCING THE COMPLETENESS OF MEDICAL RECORDS AT IN-PATIENT DEPARTMENTOF KARAT PRIMARY HOSPITAL, KONSOWOREDA, SNNPR, ETHIOPIA
Creators: name: KafitaKatusa Kaylote
Publisher: name: Zenodo
Year: 2018

description: Background: The completeness of medical records is key performance indicator that is related

with delivery of healthcare services in the hospital and assessed with minimum set of indictors

such as physician note, physician order sheet, Nursing care plan, medication administration

sheet, discharge summary, progress note and clinical pharmacist record form.

Objective: The objective of the study was to enhance the completeness of inpatient medical

records from 22% to 60% in time period from Feb to June, 2018 at In-patient department of

Karat Primary Hospital, KonsoWoreda,SNNPR

Design: before-after interventional study was carried from Feb to June, 2018 using document

review, observation, inpatient medical record review form and focus group discussions.
Gene expression-phenotype associations in adults with eosinophilic esophagitis
Creators: name: Genta, R.M.
name: Dellon, E.S.
name: Lash, R.H.
name: Parker, J.S.
name: Selitsky, S.R.
Publisher: name: Elsevier B.V.
Year: 2018

description: Background: Gene expression patterns have not been extensively examined in the context of clinical features of eosinophilic esophagitis (EoE). Aims: To assess whether gene expression is associated with clinically defined phenotypes in adults with EoE. Methods: This was an analysis of prospectively collected esophageal biopsies in newly diagnosed EoE patients. We determined differential gene expression with a 94 gene panel in relation to clinical features and phenotypes. These included: endoscopic findings of esophageal rings, stricture, narrowing, linear furrows, exudates, edema, and dilation; an allergic phenotype; an inflammatory phenotype, and a fibrostenotic phenotype. Results: In 89 EoE cases analyzed, patients with exudates on endoscopy had multiple differences in gene expression compared to patients without exudates, though patients with exudates also had higher eosinophil counts (172 vs 106 eos/hpf; p =.01). Genes associated with esophageal narrowing included CCL26 (q-value = 0.028), ALOX15 (q = 0.011), GRK5 (q = 0.029), CPA3 (q = 0.012), and TRIM2 (q = 0.0027). TRIM2 was also associated with the fibrostenotic phenotype (q = 0.0051). No genes were associated with the inflammatory or atopic phenotypes, or with dilation. Conclusions: Multiple genes are associated with exudates, possibly related to higher eosinophil counts. However, a number of genes, including those related to both inflammation and remodelling, are associated with esophageal narrowing. In particular, TRIM2 is associated with clinical fibrotic phenotypes.
The effects of CB1R activation on age-related cognitive decline and presynaptic calcium in the aged hippocampus
Creators: name: Pinder, Sophie C.
Publisher: name: University of Leicester
Year: 2023
Subjects: Uncategorized

description: Higher life expectancy has led to an increasingly ageing population. Healthy ageing is accompanied by a decline in hippocampus-dependent cognitive function, which has detrimental effects on mental health, well-being, and independent living in the elderly population. A recent study using a transgenic mouse line (SyG37) that expresses a calcium sensor at presynaptic terminals, showed an association between the agerelated cognitive decline and elevations in presynaptic calcium in the hippocampus. The endocannabinoid system inhibits presynaptic calcium influx and has recently been demonstrated as a target to reverse age-related hippocampus-dependent cognitive decline in rodents. The mechanism of cognitive function restoration in aged rodents, via activation of the cannabinoid one receptor (CB1R), is not well understood. This thesis aimed to investigate whether cognitive restoration induced by CB1R activation is associated with reversing elevated presynaptic calcium in the aged hippocampus. Using a combination of in vivo behavioural and pharmacological studies and ex vivo presynaptic calcium imaging in hippocampal slices, this thesis investigated whether chronic CB1R activation reversed cognitive decline and decreased presynaptic calcium levels in the hippocampus using SyG37 mice. Firstly, an altered version of the Barnes maze task was established as a sensitive behavioural paradigm to measure age-related cognitive decline in mice. Next, elevations of presynaptic calcium in the aged hippocampus were confirmed and reduced evoked presynaptic calcium in hippocampal slices were reported following cannabinoid agonist WIN55 application. Subsequently, adult and aged mice were chronically dosed with WIN55 and performed the Barnes maze and object location task. The treatment failed to restore cognitive function. Finally, hippocampal slices were prepared from these mice, and calcium imaging revealed that chronic CB1R activation reduced evoked presynaptic calcium in the aged hippocampus.These results provided evidence for chronic CB1R activation restoring calcium homeostasis in the aged brain, however, this was not associated with reversal of cognitive details.
Meta-analysis of airway epithelium gene expression in asthma
Creators: name: Parker, J.S.
name: Tsai, Y.-H.
name: Kelada, S.N.P.
name: Yang, I.V.
Publisher: name: European Respiratory Society
Year: 2018

description: Differential gene expression in the airway epithelium of patients with asthma versus controls has been reported in several studies. However, there is no consensus on which genes are reproducibly affected in asthma. We sought to identify a consensus list of differentially expressed genes (DEGs) using a meta-analysis approach. We identified eight studies with data that met defined inclusion criteria. These studies comprised 355 cases and 193 controls and involved sampling either bronchial or nasal epithelium. We conducted study-level analyses, followed by a meta-analysis. Likewise, we applied a meta-analysis framework to the results of study-level pathway enrichment. We identified 1273 DEGs, 431 of which had not been identified in previous studies. 450 DEGs exhibited large effect sizes and were robust to study population differences in age, sex, race/ethnicity, medication use, smoking status and exacerbations. The magnitude of differential expression of these 450 genes was highly similar in bronchial and nasal airway epithelia. Meta-analysis of pathway enrichment revealed a number of consistently dysregulated biological pathways, including putative transcriptional and post-transcriptional regulators. In total, we identified a set of genes that is consistently dysregulated in asthma, that links to known and novel biological pathways, and that will inform asthma subtype identification.
The Immune Landscape of Cancer
Creators: name: Liu, J.
name: Rao, A.
name: Malta, T.M.
name: Bortone, D.S.
name: Vincent, B.G.
name: Lazar, Alex J.
name: Holt, R.A.
name: Ojesina, A.I.
name: Eddy, J.A.
name: Noushmehr, H.
name: Serody, J.S.
name: Gentles, A.J.
name: Porta-Pardo, E.
name: The Cancer Genome Atlas Research Network
name: Rader, J.
name: Bowlby, R.
name: Thorsson, V.
name: Bullman, S.
name: Krasnitz, A.
name: Ou Yang, T.-H.
name: Ziv, E.
name: Dhankani, V.
name: Rabkin, C.E.
name: Wolf, D.
name: Pedamallu, C.S.
name: Bedognetti, D.
name: Gao, G.F.
name: Disis, M.L.
name: Chen, K.
name: Liu, Y.
name: Farshidfar, F.
name: Vo, N.S.
name: Demicco, E.G.
name: Cherniack, A.D.
name: Choueiri, T.K.
name: Shmulevich, L.
name: Zhou, W.
name: Paull, E.O.
name: Guinney, J.
name: Culhane, A.C.
name: Colaprico, A.
name: Plaisier, C.L.
name: Malhotra, R.
name: Califano, A.
name: Weinstein, J.N.
name: Hu, H.
name: Anastassiou, D.
name: Mose, L.E.
name: Lamb, A.
name: Brown, S.D.
name: Sivakumar, I.K.A.
name: Shen, H.
name: Reynolds, S.M.
name: Gibbs, D.L.
name: Saltz, J.
name: Parker, J.S.
Publisher: name: Cell Press
Year: 2018

description: We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field. Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy.
Integrated RNA and DNA sequencing reveals early drivers of metastatic breast cancer
Creators: name: Pearce, J.B.
name: Mardis, E.R.
name: Perou, C.M.
name: Hoadley, K.A.
name: Van Swearingen, A.E.D.
name: Siegel, M.B.
name: Gupta, G.P.
name: Kumar, S.
name: Carey, L.A.
name: Hoyle, A.
name: Marron, D.
name: Chen, M.
name: Moylan, V.J.
name: He, X.
name: Livasy, C.
name: Kieran, N.
name: Anders, C.K.
name: Thorne, L.B.
name: Parker, J.S.
name: Brady, C.M.
name: Garrett, A.L.
Publisher: name: American Society for Clinical Investigation
Year: 2018

description: Breast cancer metastasis remains a clinical challenge, even within a single patient across multiple sites of the disease. Genome-wide comparisons of both the DNA and gene expression of primary tumors and metastases in multiple patients could help elucidate the underlying mechanisms that cause breast cancer metastasis. To address this issue, we performed DNA exome and RNA sequencing of matched primary tumors and multiple metastases from 16 patients, totaling 83 distinct specimens. We identified tumor-specific drivers by integrating known protein-protein network information with RNA expression and somatic DNA alterations and found that genetic drivers were predominantly established in the primary tumor and maintained through metastatic spreading. In addition, our analyses revealed that most genetic drivers were DNA copy number changes, the TP53 mutation was a recurrent founding mutation regardless of subtype, and that multiclonal seeding of metastases was frequent and occurred in multiple subtypes. Genetic drivers unique to metastasis were identified as somatic mutations in the estrogen and androgen receptor genes. These results highlight the complexity of metastatic spreading, be it monoclonal or multiclonal, and suggest that most metastatic drivers are established in the primary tumor, despite the substantial heterogeneity seen in the metastases.
Convolutional LSTM Networks for Subcellular Localization of Proteins
Creators: name: Sønderby, Søren Kaae
name: Sønderby, Casper Kaae
name: Nielsen, Henrik
name: Winther, Ole
Publisher: name: arXiv
Year: 2015
Subjects: subject: Quantitative Methods (q-bio.QM)
subject: Neural and Evolutionary Computing (cs.NE)
subject: FOS: Biological sciences
subject: FOS: Computer and information sciences

description: Machine learning is widely used to analyze biological sequence data. Non-sequential models such as SVMs or feed-forward neural networks are often used although they have no natural way of handling sequences of varying length. Recurrent neural networks such as the long short term memory (LSTM) model on the other hand are designed to handle sequences. In this study we demonstrate that LSTM networks predict the subcellular location of proteins given only the protein sequence with high accuracy (0.902) outperforming current state of the art algorithms. We further improve the performance by introducing convolutional filters and experiment with an attention mechanism which lets the LSTM focus on specific parts of the protein. Lastly we introduce new visualizations of both the convolutional filters and the attention mechanisms and show how they can be used to extract biological relevant knowledge from the LSTM networks.
Compact Development Policy and Urban Resilience: A Critical Review
Creators: name: Dehghani, Alireza
name: Alidadi, Mehdi
name: Sharifi, Ayyoob
Publisher: name: figshare
Year: 2023
Subjects: classificationCode: 330499
subject: Urban and regional planning not elsewhere classified
classificationCode: 330410
subject: Urban analysis and development
classificationCode: 440612
subject: Urban geography
classificationCode: 330411
subject: Urban design

description: Sustainable development and urban resilience are dominant urban planning paradigms that have become buzzwords in urban planning and policy domains over the past 2–3 decades. While these two paradigms have been analyzed and scrutinized in different studies, the interconnection between them in policy realms is understudied. Compact development policy is expected to contribute to a variety of sustainability goals. However, these goals’ alignment with the principles and goals of urban resilience is under question. This research tries to shed some light on this issue. A critical review method is employed to understand how compactness as a sustainable urban development policy relates to different principles and dimensions of urban resilience. First, the conceptual and theoretical relationship between urban resilience and compact city is established. Next, the resulting framework is used to critically analyze 124 articles to understand how the compact city policy relates to urban resilience from different dimensions and principles. Densification and intensification, mixed land use and diversity, and spatial connectivity and public transportation are identified as principles of the compact city. Finally, the interconnection between compact city policy and urban resilience dimensions and principles is explored and assessed through examining the selected literature. The results of the review show some alignments between compact city policy outcomes and urban resilience. However, the level of alignment may vary depending on the context, scale, or dimension. In other words, while compact city in one scale/dimension can increase urban resilience to a specific adverse event or stressor, it might increase vulnerability to others in another scale/dimension. From the policy perspective, compact development policy and urban resilience principles should clearly be defined a priori to reach favorable outcomes.
Leaf beetle herbivory shapes the subsequent flower-visiting insect community and impacts plant reproduction
Creators: name: de Souza, Livia Aparecida
name: Souza, Brígida
name: Pereira, Ramom Vasconcelos
name: Morales, Mírian Nunes
name: Peñaflor, Maria Fernanda G. V.
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Medicine
subject: Ecology
subject: FOS: Biological sciences
subject: Plant Biology
subject: 60506 Virology

description: Herbivory can induce changes in flower traits influencing the community of flower-visiting insects and ultimately impacting the plant’s reproductive output. Here, we investigated how leaf herbivory on sweet pepper plants, Capsicum annuum L., by Diabrotica speciosa (Germar) adults influences the community of insect floral visitors and alters plant reproduction. In an experimental field, we found that flowers of herbivore-infested plants were less visited by insects than those of uninfested plants. A similar pattern was found for the abundance of the three most common species of floral visitors in the collections, Apis mellifera (Linnaeus), Toxomerus sp.1, and Trigona spinipes (Fabricius). The insect community associated with the flowers of herbivore-infested plants was distinct, less rich, and diverse than that of uninfested plants. Leaf herbivory also impacted flower abundance that likely influenced the visual attraction of insects. The changes in flower-visiting insect community associated with herbivore-infested plants coincided with a reduced number of fruits, which were smaller and contained fewer seeds than those from uninfested plants. Our results suggest that leaf herbivory by D. speciosa results in direct and indirect costs to the plants through modifications in abundance and composition of flower-visiting insect community.
Hamiltonian approach to modelling interfacial internal waves over variable bottom
Creators: name: Ivanov, Rossen I.
name: Martin, Calin I.
name: Todorov, Michail D.
Publisher: name: arXiv
Year: 2022
Subjects: subject: Pattern Formation and Solitons (nlin.PS)
subject: Mathematical Physics (math-ph)
subject: Fluid Dynamics (physics.flu-dyn)
subject: FOS: Physical sciences
subject: 76B55, 76B25, 37K10

description: We study the effects of an uneven bottom on the internal wave propagation in the presence of stratification and underlying non-uniform currents. Thus, the presented models incorporate vorticity (wave-current interactions), geophysical effects (Coriolis force) and a variable bathymetry. An example of the physical situation described above is well illustrated by the equatorial internal waves in the presence of the Equatorial Undercurrent (EUC). We find that the interface (physically coinciding with the thermocline and the pycnocline) satisfies in the long wave approximation a KdV-mKdV type equation with variable coefficients. The soliton propagation over variable depth leads to effects such as soliton fission, which is analysed and studied numerically as well.
description: LaTeX, 37 pages, 7 figures
Identification of Topological Surface State in PdTe2 Superconductor by Angle-Resolved Photoemission Spectroscopy
Creators: name: Liu, Yan
name: Zhao, Jianzhou
name: Yu, Li
name: Lin, Chengtian
name: Liang, Aiji
name: Hu, Cheng
name: Ding, Ying
name: Xu, Yu
name: He, Shaolong
name: Zhao, Lin
name: Liu, Guodong
name: Dong, Xiaoli
name: Zhang, Jun
name: Chen, Chuangtian
name: Xu, Zuyan
name: Weng, Hongming
name: Dai, Xi
name: Fang, Zhong
name: Zhou, X. J.
Publisher: name: arXiv
Year: 2015
Subjects: subject: Superconductivity (cond-mat.supr-con)
subject: Materials Science (cond-mat.mtrl-sci)
subject: Strongly Correlated Electrons (cond-mat.str-el)
subject: FOS: Physical sciences

description: High resolution angle-resolved photoemission measurements have been carried out on transition metal dichalcogenide PdTe2 that is a superconductor with a Tc at 1.7 K. Combined with theoretical calculations, we have discovered for the first time the existence of topologically nontrivial surface state with Dirac cone in PbTe2 superconductor. It is located at the Brillouin zone center and possesses helical spin texture. Distinct from the usual three-dimensional topological insulators where the Dirac cone of the surface state lies at the Fermi level, the Dirac point of the surface state in PdTe2 lies deep below the Fermi level at ~1.75 eV binding energy and is well separated from the bulk states. The identification of topological surface state in PdTe2 superconductor deep below the Fermi level provides a unique system to explore for new phenomena and properties and opens a door for finding new topological materials in transition metal chalcogenides.
description: 12 Pages, 4 Figures, Updated Figure 1
Identification of Germline Variants in Tumor Genomic Sequencing Analysis
Creators: name: Parker, J.S.
name: Weck, K.E.
name: Patel, N.M.
name: Montgomery, N.D.
name: Selitsky, S.R.
name: Hayes, D.N.
Publisher: name: Elsevier B.V.
Year: 2018

description: This Correspondence relates to the article by Li et al (Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and the College of American Pathologists. J Mol Diagn 2017, 19:4–23).
The mass of the white dwarf in GK Per
Creators: name: Álvarez-Hernández, A.
name: Torres, M. A. P.
name: Rodríguez-Gil, P.
name: Shahbaz, T.
name: Anupama, G. C.
name: Gazeas, K. D.
name: Pavana, M.
name: Raj, A.
name: Hakala, P.
name: Stone, G.
name: Gomez, S.
name: Jonker, P. G.
name: Ren, J.-J.
name: Cannizzaro, G.
name: Pastor-Marazuela, I.
name: Goff, W.
name: Corral-Santana, J. M.
name: Sabo, R.
Publisher: name: Zenodo
Year: 2022
Subjects: white dwarf
dynamical study
binary stars
cataclysmic variable
intermediate polar
X-ray

description: Poster contribution to the XV Scientific Meeting of the Sociedad Española de Astronomía (2022). We present a dynamical study of the cataclysmic variable GK Per, comparing our dynamical white dwarf mass with several estimates obtained from indirect methods.
A functional riboSNitch in the 3' untranslated region of FKBP5 alters MicroRNA-320a binding efficiency and mediates vulnerability to chronic post-traumatic pain
Creators: name: Tsai, Y.-H.
name: Domeier, R.
name: Linnstaedt, S.D.
name: Pearson, C.
name: Kaushik, S.
name: Lewandowski, C.
name: O'neil, B.
name: Laederach, A.
name: Lackey, L.
name: McLean, S.A.
name: McCarthy, K.R.
name: Kutchko, K.M.
name: Parker, J.S.
name: Hendry, P.L.
name: Rueckeis, C.A.
name: Riker, K.D.
name: Kurz, M.C.
name: Datner, E.
Publisher: name: Society for Neuroscience
Year: 2018

description: Previous studies have shown that common variants of the gene coding for FK506-binding protein 51 (FKBP5), a critical regulator of glucocorticoid sensitivity, affect vulnerability to stress-related disorders. In a previous report, FKBP5 rs1360780 was identified as a functional variant because of its effect on gene methylation. Here we report evidence for a novel functional FKBP5 allele, rs3800373. This study assessed the association between rs3800373 and post-traumatic chronic pain in 1607 women and men from two ethnically diverse human cohorts. The molecular mechanism through which rs3800373 affects adverse outcomes was established via in silico, in vivo, and in vitro analyses. The rs3800373 minor allele predicted worse adverse outcomes after trauma exposure, such that individuals with the minor (risk) allele developed more severe post-traumatic chronic musculoskeletal pain. Among these individuals, peritraumatic circulating FKBP5 expression levels increased as cortisol and glucocorticoid receptor (NR3C1) mRNA levels increased, consistent with increased glucocorticoid resistance. Bioinformatic, in vitro, and mutational analyses indicate that the rs3800373 minor allele reduces the binding of a stress-and pain-associated microRNA, miR-320a, to FKBP5 via altering the FKBP5 mRNA 3'UTR secondary structure (i.e., is a riboSNitch). This results in relatively greater FKBP5 translation, unchecked by miR-320a. Overall, these results identify an important gene–miRNA interaction influencing chronic pain risk in vulnerable individuals and suggest that exogenous methods to achieve targeted reduction in poststress FKBP5 mRNA expression may constitute useful therapeutic strategies.
Identification of gene expression levels in primary melanoma associated with clinically meaningful characteristics
Creators: name: Her, S.
name: Gorlov, I.
name: Cheng, C.
name: Orlow, I.
name: Amos, C.
name: Hernando, E.
name: Ringelberg, C.
name: Parker, J.S.
name: Gerstenblith, M.R.
name: Berwick, M.
name: Thompson, C.L.
name: Ernstoff, M.S.
Publisher: name: Lippincott Williams and Wilkins
Year: 2018

description: Factors influencing melanoma survival include sex, age, clinical stage, lymph node involvement, as well as Breslow thickness, presence of tumor-infiltrating lymphocytes based on histological analysis of primary melanoma, mitotic rate, and ulceration. Identification of genes whose expression in primary tumors is associated with these key tumor/patient characteristics can shed light on molecular mechanisms of melanoma survival. Here, we show results from a gene expression analysis of formalin-fixed paraffin-embedded primary melanomas with extensive clinical annotation. The Cancer Genome Atlas data on primary melanomas were used for validation of nominally significant associations. We identified five genes that were significantly associated with the presence of tumor-infiltrating lymphocytes in the joint analysis after adjustment for multiple testing: IL1R2, PPL, PLA2G3, RASAL1, and SGK2. We also identified two genes significantly associated with melanoma metastasis to the regional lymph nodes (PIK3CG and IL2RA), and two genes significantly associated with sex (KDM5C and KDM6A). We found that LEF1 was significantly associated with Breslow thickness and CCNA2 and UBE2T with mitosis. RAD50 was the gene most significantly associated with survival, with a higher level of expression associated with worse survival.
ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer
Creators: name: Lu, R.
name: Bareja, R.
name: Earp, H.S.
name: Whang, Y.E.
name: Zheng, D.
name: Wang, G.G.
name: Sboner, A.
name: Li, D.
name: Parker, J.S.
name: Fan, H.
name: Cai, L.
name: Wang, J.
name: Wang, P.
name: Wilson, E.M.
name: Zhao, Y.
name: Tsai, Y.-H.
Publisher: name: Cell Press
Year: 2018

description: Androgen receptor splice variant 7 (AR-V7) is crucial for prostate cancer progression and therapeutic resistance. We show that, independent of ligand, AR-V7 binds both androgen-responsive elements (AREs) and non-canonical sites distinct from full-length AR (AR-FL) targets. Consequently, AR-V7 not only recapitulates AR-FL's partial functions but also regulates an additional gene expression program uniquely via binding to gene promoters rather than ARE enhancers. AR-V7 binding and AR-V7-mediated activation at these unique targets do not require FOXA1 but rely on ZFX and BRD4. Knockdown of ZFX or select unique targets of AR-V7/ZFX, or BRD4 inhibition, suppresses growth of castration-resistant prostate cancer cells. We also define an AR-V7 direct target gene signature that correlates with AR-V7 expression in primary tumors, differentiates metastatic prostate cancer from normal, and predicts poor prognosis. Thus, AR-V7 has both ARE/FOXA1 canonical and ZFX-directed non-canonical regulatory functions in the evolution of anti-androgen therapeutic resistance, providing information to guide effective therapeutic strategies. By cistrome profiling of endogenous androgen receptor (AR) versus an AR splice variant, AR-V7, Cai et al. uncovered non-canonical pathways uniquely targeted by AR-V7 and ZFX, a previously unknown AR-V7 partner. Targeting cofactors (ZFX or BRD4) or non-canonical downstream pathways of AR-V7 provides potential therapeutic ways for treating prostate cancer.
Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
Creators: name: Parker, J.S.
name: Mose, L.E.
name: Dittmer, D.P.
name: Selitsky, S.R.
name: Marron, D.
Publisher: name: American Society for Microbiology
Year: 2018

description: Epstein-Barr virus (EBV) is convincingly associated with gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. To test the hypothesis that there are additional cancer types with high prevalence of EBV, we determined EBV viral expression in all the Cancer Genome Atlas Project (TCGA) mRNA sequencing (mRNA-seq) samples (n 10,396) from 32 different tumor types. We found that EBV was present in gastric adenocarcinoma and lymphoma, as expected, and was also present in 5% of samples in 10 additional tumor types. For most samples, EBV transcript levels were low, which suggests that EBV was likely present due to infected infiltrating B cells. In order to determine if there was a difference in the B-cell populations, we assembled B-cell receptors for each sample and found B-cell receptor abundance (P 1.4 1020) and diversity (P 8.3 1027) were significantly higher in EBV-positive samples. Moreover, diversity was independent of B-cell abundance, suggesting that the presence of EBV was associated with an increased and altered B-cell population. IMPORTANCE Around 20% of human cancers are associated with viruses. Epstein-Barr virus (EBV) contributes to gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. We assessed the prevalence of EBV in RNA-seq from 32 tumor types in the Cancer Genome Atlas Project (TCGA) and found EBV to be present in 5% of samples in 12 tumor types. EBV infects epithelial cells and B cells and in B cells causes proliferation. We hypothesized that the low expression of EBV in most of the tumor types was due to infiltration of B cells into the tumor. The increase in B-cell abundance and diversity in subjects where EBV was detected in the tumors strengthens this hypothesis. Overall, we found that EBV was associated with an increased and altered immune response. This result is not evidence of causality, but a potential novel biomarker for tumor immune status.
Nasonia vitripennis: An Insect Model for DNA Methylation
Creators: name: Thomas, Christian L.
Publisher: name: University of Leicester
Year: 2023
Subjects: Uncategorized

description: DNA methylation is an epigenetic mechanism that regulates gene expression and chromosomal organisation. Despite being a conserved phenomena across eukaryotes, the role and location of DNA methylation differs greatly across kingdoms. In the last decade, a new field exploring the role of DNA methylation in insect phenotypes has evolved. However, understanding the exact function of insect methylation has proven difficult. To elucidate this, what is needed is an insect model organism for DNA methylation studies. Nasonia vitripennis is a parasitoid wasp with a wide range of publications to its name. Unlike many insect species,Nasonia possess a fully functional DNA methylation system, displays observable methylation levels, and doesn’t exhibit social behaviour. The aim of this thesis is to expand on current Nasonia literature to establish Nasonia vitripennis at the forefront of insect methylomics. I investigate DNA methylation through metamorphosis and find a dynamic methylome through developmental stages. I explore the expression profile of Nasonia DNA methyltransferase enzymes in an attempt to characterise the functionality of the expanded Nasonia repertoire and find NvDnmt1c is a female and potentially ovary specific gene. Given the links between DNA methylation and ageing in mammals I investigate the link between gene expression and DNA methylation across time in adult Nasonia. Studying whole adult females, I find little evidence of DNA methylation correlating with ageing in Nasonia vitripennis. Finally, I attempt to alter loci specific methylation in Nasonia vitripennis using a deactivated version of Cas9 fused to DNMT3a. I failed to observe transient expression of dCas9-DNMT3a, but have created a plasmid which allows easy promoter replacement for future attempts. This thesis adds to the expanding field of Nasonia methylomics, and outlines strategies to truly make this jewel wasp the dominant force in arthropod epigenetics.
Acid-functionalized mesoporous silicate (KIT-5-Pr-SO3H) synthesized as an efficient and nanocatalyst for green multicomponent
Creators: name: Heravi, Majid Mommahed
Publisher: name: figshare
Year: 2020
Subjects: subject: 30302 Nanochemistry and Supramolecular Chemistry
subject: FOS: Chemical sciences
subject: 30502 Natural Products Chemistry
subject: 30205 Non-metal Chemistry
subject: Nuclear Chemistry
subject: 30303 Optical Properties of Materials
subject: 30503 Organic Chemical Synthesis
subject: 30599 Organic Chemistry not elsewhere classified
subject: Organic Chemistry
subject: 30504 Organic Green Chemistry

description: Aim and Objective: KIT-5 nanoporous silica was functionalized with sulfonic acid and SO3H group has been immobilized on nanoporous KIT-5 silica support via in situ method to produce novel nanocatalyst as “KIT-5-Pr-SO3H”. The catalyst was fully characterized by FT-IR, SEM, EDXs, TEM, BET and TGA techniques. The surface morphology images approved that the nanocatalyst particle sizes are around 7-15 nm. The prepared catalyst was efficiently used in the synthesis of benzimidazolo quinazolinones, imidazo[1,2- a]chromeno[4,3-d]pyrimidinone and imidazo[1,2-a]pyrimidine via a multicomponent reaction under green conditions. The easy synthesis condition, environmental compatibility, high specific surface area, reusability for 5 run without loses in any activity, high selectivity, availability of raw material, are the remarkable properties for this new catalyst. Materials and Methods: All reagents were purchased from Aldrich and Merck with high-grade quality and used as received. The structural characteristics of the KIT-5 which was obtained, using three-dimensional large cage type face-centered cubic Fm3m mesoporous silica materials (KIT-5) nanocages were obtained according to the procedure described by Kleitz et al. Results: The purpose of this study is developing a new acid-functionalized mesoporous catalyst. Initially, (KIT-5) nanocages were obtained according to the procedure described by Kleitz et al. Then, KIT-5-Pr-SH was prepared by Mercaptopropyltriethoxysilane as illustrated in Scheme 1. In the next step, the solid product was oxidized with H2O2. The full characterization for proving the structure of the nano-size particles was achieved using FT-IR, TGA, TEM, SEM, and EDX analysis. Conclusion: Acid-functionalized mesoporous silica has been proved to act as an effective catalyst in various organic reactions. In this project, for the first time, KIT-5 was functionalized by propyl-sulfonic acid as a heterogeneous solid acid catalyst. Sulfonic acid functionalized KIT-5 (KIT-5-Pr-SO3H) performs as an organicinorganic hybrid catalyst, whereas Brønsted acid sites have been selectively generated. In this regard, the catalytic activities of this novel heterogeneous catalyst were successfully examined by the one-pot multicomponent reaction
Drivers of extreme wildfire years in the 1965–2019 fire regime of the Tłı̨chǫ First Nation territory, Canada
Creators: name: Gaboriau, Dorian M.
name: Asselin, Hugo
name: Ali, Adam A.
name: Hély, Christelle
name: Girardin, Martin P.
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Space Science
subject: Medicine
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: Ecology
subject: FOS: Biological sciences
subject: 69999 Biological Sciences not elsewhere classified

description: Exceptionally large areas burned in 2014 in central Northwest Territories (Canada), leading members of the Tłı̨chǫ First Nation to characterize this year as ‘extreme’. Top-down climatic and bottom-up environmental drivers of fire behavior and areas burned in the boreal forest are relatively well understood, but not the drivers of extreme wildfire years (EWY). We investigated the temporal and spatial distributions of fire regime components (fire occurrence, size, cause, fire season length) on the Tłı̨chǫ territory from 1965 to 2019. We used BioSIM and data from weather stations to interpolate mean weather conditions, fuel moisture content and fire-weather indices for each fire season, and we described the environmental characteristics of burned areas. We identified and characterized EWY, i.e., years exceeding the 80th percentile of annual area burned for the study period. Temperature and fuel moisture were the main drivers of areas burned. Nine EWY occurred from 1965 to 2019, including 2014. Compared to non-EWY, EWY had significantly higher mean temperature (>14.7°C) and exceeded threshold values of Drought Code (>514), Initial Spread Index (>7), and Fire Weather Index (>19). Our results will help limit the effects of EWY on human safety, health and Indigenous livelihoods and lifestyles.
New definition of wormhole throat
Creators: name: Tomikawa, Yoshimune
name: Izumi, Keisuke
name: Shiromizu, Tetsuya
Publisher: name: arXiv
Year: 2015
Subjects: subject: General Relativity and Quantum Cosmology (gr-qc)
subject: FOS: Physical sciences

description: We present a new definition of the wormhole throat including the flare-out condition and the traversability for general dynamical spacetimes in terms of null geodesic congruences. We will examine our definition for some examples and see advantages compared to the others.
description: 7 pages
Enhancing Next-Generation Sequencing-Guided Cancer Care Through Cognitive Computing
Creators: name: Eberhard, D.A.
name: Salazar, A.H.
name: Sharpless, N.E.
name: Hayes, D.N.
name: Koyama, T.
name: Harvey, S.J.
name: Patel, N.M.
name: Utro, F.
name: Parida, L.
name: Hoyle, A.P.
name: Bilal, E.
name: Grilley-Olson, J.E.
name: Earp, H.S.
name: Kim, W.Y.
name: Huettner, C.S.
name: Snell, J.M.
name: Parker, J.S.
name: Royyuru, A.
name: Balu, S.
name: Hayward, M.C.
name: Norel, R.
name: Rhrissorrakrai, K.
name: Michelini, V.V.
name: McNeillie, P.
name: Xu, J.
Publisher: name: Wiley-Blackwell
Year: 2018

description: Background: Using next-generation sequencing (NGS) to guide cancer therapy has created challenges in analyzing and reporting large volumes of genomic data to patients and caregivers. Specifically, providing current, accurate information on newly approved therapies and open clinical trials requires considerable manual curation performed mainly by human “molecular tumor boards” (MTBs). The purpose of this study was to determine the utility of cognitive computing as performed by Watson for Genomics (WfG) compared with a human MTB. Materials and Methods: One thousand eighteen patient cases that previously underwent targeted exon sequencing at the University of North Carolina (UNC) and subsequent analysis by the UNCseq informatics pipeline and the UNC MTB between November 7, 2011, and May 12, 2015, were analyzed with WfG, a cognitive computing technology for genomic analysis. Results: Using a WfG-curated actionable gene list, we identified additional genomic events of potential significance (not discovered by traditional MTB curation) in 323 (32%) patients. The majority of these additional genomic events were considered actionable based upon their ability to qualify patients for biomarker-selected clinical trials. Indeed, the opening of a relevant clinical trial within 1 month prior to WfG analysis provided the rationale for identification of a new actionable event in nearly a quarter of the 323 patients. This automated analysis took <3 minutes per case. Conclusion: These results demonstrate that the interpretation and actionability of somatic NGS results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing could potentially improve patient care by providing a rapid, comprehensive approach for data analysis and consideration of up-to-date availability of clinical trials. Implications for Practice: The results of this study demonstrate that the interpretation and actionability of somatic next-generation sequencing results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing can significantly improve patient care by providing a fast, cost-effective, and comprehensive approach for data analysis in the delivery of precision medicine. Patients and physicians who are considering enrollment in clinical trials may benefit from the support of such tools applied to genomic data.
title: Born Across Grey Water
Creators: name: Novak, Dasha Dana
Publisher: name: Emily Carr University of Art and Design
Year: 2008
Subjects: subject: Liminality
valueUri: https://id.loc.gov/authorities/subjects/sh90003430
subject: Ethnology
valueUri: https://id.loc.gov/authorities/subjects/sh85045198
subject: Identity (Psychology) in art
valueUri: https://id.loc.gov/authorities/subjects/sh96011828
subject: Self perception in art
valueUri: https://id.loc.gov/authorities/subjects/sh97001426

description: I position my artistic inquiry at the edge of chaos. It is here that the dynamic space of possibilities opens up, from which a new worldview might be born. I am drawing from a sense of process; transgression of borders creates new ways of perceiving. The space between the borders, the liminal space, is constantly informed by transgressions of human thought processes and gestures toward new ways of seeing. Human existence is increasingly liminal. Mechanistic viewing caused by specialization in all spheres of human activity, including our language, has lead to an overall sense of fragmentation, automatic functioning of our thought, and division through of fields of experience. The modern “Machine” has cauterized our attachments to the natural world and brought us to proximity with major ecological shift. As an immigrant and mother, no stranger to liminal space, I have searched for a sense of connection to Canadian cultural and natural environment through the use of photographic and video media. My need to connect initiated the exploration of landscape and motherhood embodiment and, eventually, the scrutiny of grey water’s connective character. My visual essay invites the reader to consider several issues for which I have used the metaphor of grey water. Grey water, just like liminal space or connectives space, holds together and separates at the same time. In a constant state of transition, it dissolves borders, mutates through time and spaces, enfolding shapes and ideas, and unfolding them back into the flow. It gestures toward wholeness and connectivity. Acceptance and sensitivity to ever changing differences and similarities emerging through the murky character of grey water can help us create a new frame of mind in which there is a common consciousness.
Open Access Week 2020
Creators: name: University Of Texas At Austin
Publisher: name: The University of Texas at Austin
Year: 2020
Subjects: open access
OA Week
Open Access Week
OA
scholarly communication

description: OA Week is an international event designed to increase awareness of open access issues. For OA Week 2020, UT Libraries participated solely online. We had multiple blog posts and we updated our Sticker Shock informational poster which was created using Piktochart.
Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children's Oncology Group study
Creators: name: Gao, Y.
name: Hirsch, B.
name: Satwani, P.
name: Wall, D.
name: Patel, N.
name: Pei, Q.
name: Cooper, T.
name: Dvorak, C.C.
name: Stieglitz, E.
name: Mehta, P.A.
name: Loh, M.L.
name: Raimondi, S.
name: Skeens, M.
name: Grupp, S.A.
name: Parker, J.S.
name: Mazor, T.
name: Olshen, A.B.
name: Kahwash, S.
name: Cairo, M.S.
name: Dang, H.
Publisher: name: John Wiley and Sons Inc.
Year: 2018

description: Background: Most patients with juvenile myelomonocytic leukemia (JMML) are curable only with allogeneic hematopoietic cell transplantation (HCT). However, the current standard conditioning regimen, busulfan-cyclophosphamide-melphalan (Bu-Cy-Mel), may be associated with higher risks of morbidity and mortality. ASCT1221 was designed to test whether the potentially less-toxic myeloablative conditioning regimen containing busulfan-fludarabine (Bu-Flu) would be associated with equivalent outcomes. Procedure: Twenty-seven patients were enrolled on ASCT1221 from 2013 to 2015. Pre- and post-HCT (starting Day +30) mutant allele burden was measured in all and pre-HCT therapy was administered according to physician discretion. Results: Fifteen patients were randomized (six to Bu-Cy-Mel and nine to Bu-Flu) after meeting diagnostic criteria for JMML. Pre-HCT low-dose chemotherapy did not appear to reduce pre-HCT disease burden. Two patients, however, received aggressive chemotherapy pre-HCT and achieved low disease-burden state; both are long-term survivors. All four patients with detectable mutant allele burden at Day +30 post-HCT eventually progressed compared to two of nine patients with unmeasurable allele burden (P = 0.04). The 18-month event-free survival of the entire cohort was 47% (95% CI, 21–69%), and was 83% (95% CI, 27–97%) and 22% (95% CI, 03–51%) for Bu-Cy-Mel and Bu-Flu, respectively (P = 0.04). ASCT1221 was terminated early due to concerns that the Bu-Flu arm had inferior outcomes. Conclusions: The regimen of Bu-Flu is inadequate to provide disease control in patients with JMML who present to HCT with large burdens of disease. Advances in molecular testing may allow better characterization of biologic risk, pre-HCT responses to chemotherapy, and post-HCT management.