429 research outputs found
Exploring Arts Integration in Language Arts Instruction for Elementary Education
The purpose of this thesis is to provide insight on how arts integration in English language arts education increases engagement and achievement in students and teachers alike. Throughout my analysis of literature, local field research in two Central Florida public elementary schools, and my creation of a five-day arts-integrated writing unit, I found that arts integration, especially when utilizing Leonard Bernstein’s Artful Learning Method was observed to show a positive impact on students. Arts integration allowed for a child’s natural curiosity and instinct to create to take over, which created authentic learning experiences for the students. The research also demonstrated that arts integration enabled teachers to utilize their creativity, which in turn positively changed their perspectives on their career and teaching experience. Observations and the research literature examined in this thesis showed that arts integration can be a valuable outlet for both students and teachers, yet not always utilized due to high stakes testing, budgetary concerns, and time constraints in the elementary classroom
Genetic characterization, current model systems and prognostic stratification in PAX fusion-negative vs. PAX fusion-positive rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents and accounts for approximately 2% of soft tissue sarcomas in adults. It is subcategorized into distinct subtypes based on histological features and fusion status
C-MYC rearrangements are frequent in aggressive mature B-cell lymphoma with atypical morphology
Diagnosis and classification of aggressive mature B-cell lymphoma with atypical morphology remains a challenge. To identify factors that may contribute to the atypical morphology, we selected eight such cases and evaluated their morphologic, immunophenotypic and cytogenetic features and clinical outcomes. The neoplastic cells showed a diffuse monotonous infiltrating pattern with a spectrum of morphology including: 1) L1 lymphoblastic; 2) centroblastic; 3) immunoblastic; and 4) mixed centroblastic and immunoblastic. The lymphoma cells in most cases were positive for CD10 and/or BCL6, and showed BCL2 expression. 6 of 8 cases showed C-MYC rearrangements, and interestingly, all 6 cases demonstrated a proliferation index of ≤90%. 3 of the 6 cases also demonstrated t(14;18). Clinical follow-up indicated that aggressive mature B-cell lymphoma may benefit from more intensified chemotherapeutic regimens used for BL. Our study suggests that aggressive mature B-cell lymphoma with atypical morphology may be another “grey zone lymphoma” lying in the spectrum between Burkitt lymphoma and diffuse large B-cell lymphoma
DICER1 tumor predisposition syndrome: An evolving story initiated with the pleuropulmonary blastoma
DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation
Loss of chromosome 3q is a prognostic marker in fusion-negative rhabdomyosarcoma
PURPOSE: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures.
METHODS: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for prognostically significant CNV aberrations in
RESULTS: Chr8 gain is a highly prevalent CNV in embryonal RMS and shows slightly improved prognosis. Meanwhile, loss of chr3q was associated with worse outcome in FN-RMS compared with FP-RMS.
CONCLUSION: The pathogenesis of STS including FN-RMS remains poorly understood, emphasizing the need for new therapeutic advances and adequate risk stratification. Our data demonstrate that loss of chr3q is associated with poor OS in FN-RMS, supporting it as an important tool for risk stratification
Ex vivo to in vivo model of malignant peripheral nerve sheath tumors for precision oncology
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas that often develop in patients with neurofibromatosis type 1 (NF1). To address the critical need for novel therapeutics in MPNST, we aimed to establish an ex vivo 3D platform that accurately captured the genomic diversity of MPNST and could be utilized in a medium-throughput manner for drug screening studies to be validated in vivo using patient-derived xenografts (PDX).
METHODS: Genomic analysis was performed on all PDX-tumor pairs. Selected PDX were harvested for assembly into 3D microtissues. Based on prior work in our labs, we evaluated drugs (trabectedin, olaparib, and mirdametinib) ex vivo and in vivo. For 3D microtissue studies, cell viability was the endpoint as assessed by Zeiss Axio Observer. For PDX drug studies, tumor volume was measured twice weekly. Bulk RNA sequencing was performed to identify pathways enriched in cells.
RESULTS: We developed 13 NF1-associated MPNST-PDX and identified mutations or structural abnormalities in NF1 (100%), SUZ12 (85%), EED (15%), TP53 (15%), CDKN2A (85%), and chromosome 8 gain (77%). We successfully assembled PDX into 3D microtissues, categorized as robust (\u3e90% viability at 48 h), good (\u3e50%), or unusable (\u3c50%). We evaluated drug response to robust or good microtissues, namely MN-2, JH-2-002, JH-2-079-c, and WU-225. Drug response ex vivo predicted drug response in vivo, and enhanced drug effects were observed in select models.
CONCLUSIONS: These data support the successful establishment of a novel 3D platform for drug discovery and MPNST biology exploration in a system representative of the human condition
Unmasking intra-tumoral heterogeneity and clonal evolution in NF1-MPNST
Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%-13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones present within the tumor. In the current study, samples were taken from three distinct areas within a single tumor from a patient with an NF1-MPNST. Whole exome sequencing, RNA sequencing, and copy number analysis were performed on each sample. A blood sample was obtained as a germline DNA control. Distinct mutational signatures were identified in different areas of the tumor as well as significant differences in gene expression among the spatially distinct areas, leading to an understanding of the clonal evolution within this patient. These data suggest that multi-regional sampling may be important for driver gene identification and biomarker development in the future
Asteroseismology of the Kepler V777 Her variable white dwarf with fully evolutionary models
DBV stars are pulsating white dwarfs with atmospheres rich in He.
Asteroseismology of DBV stars can provide valuable clues about the origin,
structure and evolution of hydrogen-deficient white dwarfs, and may allow to
study neutrino and axion physics. Recently, a new DBV star, KIC 8626021, has
been discovered in the field of the \emph{Kepler} spacecraft. It is expected
that further monitoring of this star in the next years will enable astronomers
to determine its detailed asteroseismic profile. We perform an
asteroseismological analysis of KIC 8626021 on the basis of fully evolutionary
DB white-dwarf models. We employ a complete set of evolutionary DB white-dwarf
structures covering a wide range of effective temperatures and stellar masses.
They have been obtained on the basis of a complete treatment of the
evolutionary history of progenitors stars. We compute g-mode adiabatic
pulsation periods for this set of models and compare them with the pulsation
properties exhibited by KIC 8626021. On the basis of the mean period spacing of
the star, we found that the stellar mass should be substantially larger than
spectroscopy indicates. From period-to-period fits we found an
asteroseismological model characterized by an effective temperature much higher
than the spectroscopic estimate. In agreement with a recent asteroseismological
analysis of this star by other authors, we conclude that KIC 8626021 is located
near the blue edge of the DBV instability strip, contrarily to spectroscopic
predictions. We also conclude that the mass of KIC 8626021 should be
substantially larger than thought.Comment: 7 pages, 5 figures, 3 tables. To be published in Astronomy and
Astrophysic
Modelo de recuperación de información jurídica basado en ontologías y distancias semánticas
En el ámbito jurídico, el proceso de búsqueda y clasificación de documentos legales, incide en gran manera en el desempeño profesional de los especialistas en Derecho. En este trabajo se propone un modelo de recuperación y clasificación de documentos jurídicos, utilizando ontologías y distancias semánticas, a fin de mejorar la relevancia de los documentos obtenidos en este dominio. Con este objetivo, la validación se llevó a cabo en dos escenarios, y el modelo fue evaluado en base a las métricas de precisión, exhaustividad y F-Score. Los resultados examinados señalan que el modelo propuesto tuvo un mejor desempeño que la búsqueda de ocurrencias literales, obteniendo un valor de F- Score promedio de 95%.Sociedad Argentina de Informática e Investigación Operativ
Modelo de recuperación de información jurídica basado en ontologías y distancias semánticas
En el ámbito jurídico, el proceso de búsqueda y clasificación de documentos legales, incide en gran manera en el desempeño profesional de los especialistas en Derecho. En este trabajo se propone un modelo de recuperación y clasificación de documentos jurídicos, utilizando ontologías y distancias semánticas, a fin de mejorar la relevancia de los documentos obtenidos en este dominio. Con este objetivo, la validación se llevó a cabo en dos escenarios, y el modelo fue evaluado en base a las métricas de precisión, exhaustividad y F-Score. Los resultados examinados señalan que el modelo propuesto tuvo un mejor desempeño que la búsqueda de ocurrencias literales, obteniendo un valor de F- Score promedio de 95%.Sociedad Argentina de Informática e Investigación Operativ
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