1,721,190 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variants in Hdac9 Intronic Enhancer as Candidates for Skin Tumor Susceptibility Locus
Full text linkHealth Professions - Laboratory/Cellular: 3rd Place (The Ohio State University Denman Undergraduate Research Forum)Non-melanoma skin cancers (NMSC) are the most common forms of cancer in the world accounting for nearly half of all cancer diagnoses. Rates of NMSC are on the rise with an over 300% increase in diagnosis of these cancers in the last 20 years. While environmental risk factors for skin cancers are well understood, little is known about genetic risk factors for these cancers. Mouse linkage studies have identified several loci housing skin cancer susceptibility genes. Human tumors show evidence of preferential allelic imbalance for polymorphisms in Hdac9, a gene mapping to one of the linkage regions, Skts5. One intron in the Hdac9 gene between exons 8 and 9 contains an enhancer for Twist1, affecting limb development and phenotypes in the skin. Twist1 is a known regulator of skin differentiation and has a documented role in cancer. The hypothesis of this study is that this enhancer locus plays a role in the differential risk for NMSC between the cancer susceptible NIH/Ola and cancer resistant Spretus/EiJ mice. Sequence analyses identified several polymorphisms between these strains in this intron which are predicted by in silico methods to disrupt transcription factor binding. To investigate in vitro effects of these variants, intron fragments from both NIH/Ola and Spret/EiJ murine DNA were cloned into an enhancer reporting PGL3 vector and transfected into both normal keratinocyte C5N and squamous cell carcinoma A5 cells. Luciferase assay and real-time PCR data suggest these variants are responsible for changes in gene expression, specifically in the Twist1 gene. Chromatin Immunoprecipitation studies are being performed to test whether transcription factors, Oct1 and Gata3 that are predicted to differentially bind the NIH/Ola and Spret/EiJ enhancer , are involved in the differential Twist1 expression. This project has the potential implication of discovering the role a specific gene locus, Skts5, plays in NMSC risk.College of Health and Rehabilitation Sciences: Honors Thesis ScholarshipAcademic Major: Biomedical Scienc
Interactions Between PIK3CA and MAP3K1 Pathways in Breast Cancer
Full text linkIntroduction/Background: Breast cancer is one of the leading causes of death in the United States, with one in eight women being diagnosed in their lifetimes. Many tumors are susceptible to treatment targeted towards their specific molecular subtypes. One such biomarker based on molecular subtype is the human epidermal growth factor receptor 2 (HER2). HER2-positive tumors historically have been associated with poorer outcomes, but in recent years targeted therapies have significantly improved prognoses. However, many tumors develop resistance to drugs targeting those molecules. One study of interest found that in patients treated with anti- HER2 agent trastuzumab, individuals harboring PIK3CA mutations experienced markedly reduced progression free survival following treatment compared to wild type patients. PIK3CA also displays interactions with the MAPK signaling pathway. Our laboratory found that nucleotide variants (SNVs) at the MAP3K1 locus associated with PIK3CA mutations in breast tumors. Understanding the link between PIK3CA and MAP3K1 may help to develop more individualized treatments for patients with HER2+ tumors or other PIK3CA mutated tumors.
Methods: Isogenic MCF10A and 12A cell lines with wild-type (WT) and PIK3CA H1047R knock-in (KI) variants were used as in vitro models of breast cancer. MAP3K1 expression was knocked down through transfection, utilizing siRNAs to create cells deficient in MAP3K1. MTT assays were performed to analyze differences in proliferation between cellular conditions. Protein was extracted for western blotting to confirm MAP3K1 knock-down, using GAPDH as a control.
Results: Western blot analysis of transfected cell lines confirmed that siRNAs were successful in knocking down expression of the MAP3K1 protein. MTT analysis showed that knocking down MAP3K1 resulted in increased fold growth in PIK3CA KI cells compared to WT. Data collection and analysis in other cell lines for greater validity is currently still ongoing.
Conclusions: Based on the results of the MTT assays, initial studies indicate MAP3K1 expression has a negative correlation vs PIK3CA mutation on tumor growth. Cells with lower levels of MAP3K1 protein and PIK3CA mutations showed increased proliferation. Further investigation of these two pathways could help to better understand how they influence each other.No embargoAcademic Major: Biomedical Scienc
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Deciphering the Clinical Significance of BRCA Variants
Full text linkThe identification of genes predisposing individuals for specific diseases has increased the value of genetic testing. Two genes, BRCA1 and BRCA2, have been shown to be significant in hereditary breast and ovarian cancers. Unfortunately, the mutation results of BRCA genetic testing are sometimes unclear. A class of mutations, termed “variants of uncertain significance” (VUS), provides inconclusive and unhelpful results in genetic testing because it is unknown whether these variants are cancer causing mutations or neutral polymorphisms. In our study, we combined independent variables including tumor loss of heterozygosity, co-occurrence with a known deleterious mutation in trans, sequence conservation or splice site analysis, pathological data (estrogen receptor, progesterone receptor, and Her2Neu status; tumor grade; and tumor histology), and personal cancer history (age of onset and cancer type) to try to classify VUS as deleterious or neutral. This selection of data allows one to assess the pathogenicity of VUS without segregation analysis or familial information, which is often unavailable because of family absence or unwillingness to undergo genetic testing. With these independent data sources, we used a modified multifactorial approach for each variant to calculate a final likelihood score. We were able to utilize our method with 98% sensitivity and 76% specificity on 57 tumor samples from 44 known deleterious variants. Additionally, we evaluated 56 tumor samples from 54 unique classified and unclassified variants. Among the 33 unclassified VUS, we quantified 21 as neutral. The classification of VUS as deleterious or neutral will aid patient care, specifically improving future decision making regarding screening, chemoprevention, prophylactic treatment, and familial risk.Mayers Summer Research FellowshipArts and Sciences Undergraduate Research ScholarshipThe Ohio State University Comprehensive Cancer CenterA one-year embargo was granted for this item
Functional analysis of DcpS as a candidate cutaneous squamous cell carcinoma susceptibility gene
Full text linkDCPS is a candidate cutaneous squamous cell carcinoma (SCC) susceptibility gene as determined by allelic imbalance mapping of paired SCC and genomic blood DNA samples. DCPS shows no protein expression in 23% of human SCCs on a tissue microarray, and reduced protein expression in another 30%. This is in contrast to strong staining for DCPS in 100% of normal tissue samples. DCPS, a decapping scavenger enzyme, influences the pool of available cap-binding proteins and, in turn, impacts aspects of mRNA metabolism like pre-mRNA splicing and decay. The hypothesis driving this research is that DCPS acts as a tumor suppressor. To test this hypothesis, functional effects of increasing and decreasing expression of DcpS in a mouse keratinocyte cell line have been studied. First intron splicing and exon skipping is enhanced in DcpS overexpression cell lines, while splicing of the second intron is not affected by DcpS expression. DcpS knockdown cell lines were found to have more stable mRNA compared to a control cell line. DcpS knockdown cell lines exhibit less growth than normal and overexpression cell lines. Cell migration is not affected by DcpS expression. DcpS knockdown cell lines exhibit more apoptosis than normal and overexpression cell lines. Finally, there is a greater percentage of cells in the S and G2-M phases of the cell cycle in DcpS knockdown cell lines compared to mock and overexpression cell lines. From these studies it appears that while DcpS may affect mRNA splicing and stability, decreased levels of DcpS do not result in a cancer phenotype. Rather, decreased levels of DcpS seem to lead to an anti-tumorigenic phenotype. Future directions may include examining the effect of UV radiation on these phenotypes and determining other proteins with which DcpS interacts.Pelotonia Undergraduate Research FellowshipSchool of Allied Medical Professions ScholarshipA one-year embargo was granted for this item
Variants in Hdac9 Intronic Enhancer as Candidates for Skin Tumor Susceptibility 5 (Skts5) Locus
Full text linkNon-melanoma skin cancers (NMSC) are the most common forms of cancer in the world accounting for nearly half of all cancer diagnoses. Rates of NMSC are on the rise with an over 300% increase in diagnosis of these cancers in the last 20 years. While environmental risk factors for skin cancer such as ultraviolet light (UV) exposure are well understood, little is known about inherited genetic risk factors for these cancers. Mouse linkage studies have identified several loci housing skin cancer susceptibility genes (susceptibility to skin cancer or Skts). Human tumors show evidence of preferential allelic imbalance for polymorphisms in Hdac9, a gene mapping to one of the linkage regions, Skts5. An intron in the Hdac9 gene between exons 8 and 9 was shown by others to contain an enhancer for Twist1 which affects early limb development and phenotypes in the skin. Twist1 is a known regulator of skin differentiation and has a documented role in cancer including metastasis and cell growth. The hypothesis of this study is that this enhancer locus plays a role in the differential risk for NMSC between the cancer susceptible NIH/Ola and cancer resistant Spretus/EiJ mice. To test this hypothesis, we first looked for sequence differences between the strains. Sequence analyses led to the identification of several polymorphisms in this intron which are predicted by multiple in silico methods to disrupt known transcription factor binding. To investigate the in vitro effects of these variants, intron fragments from both NIH/Ola and Spret/EiJ murine DNA were cloned into an enhancer pGL3 reporter vector and transfected into both normal keratinocyte C5N and squamous cell carcinoma A5 cells. Luciferase assay and real-time PCR data suggests these variants are responsible for changes in gene expression, specifically in the Twist1 gene. Chromatin immunoprecipitation studies found that two transcription factors, Gata3 and Oct1, preferentially bind to NIH or Spretus DNA respectively at the enhancer locus, suggesting a possible mechanism for enhancer activity. In summary, variants at the Hdac9 intron 8 enhancer appear to affect Twist1 expression and may explain the skin cancer susceptibility locus Skts5.2012 Pelotonia Undergraduate Research Fellowship2013-2014 School of Health and Rehabilitation Sciences Thesis ScholarshipA one-year embargo was granted for this item.Academic Major: Biomedical Scienc
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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