Developing a Digital Voice: Embedding Digital Communication Platforms, Networks, and Technologies in the 21st-Century Classroom

Introductory communication courses are an invaluable resource for improving students’ abilities to speak confidently, passionately, and persuasively, while also inspiring them to become more engaged citizens. However, digital media present new opportunities and challenges for designing courses that are relevant to students’ personal and professional interests and goals. Instructors who incorporate digital communication platforms, networks, and technologies into their classrooms can better prepare students to meet the complex demands of the technologically-mediated 21st century. In this essay, I offer 10 best practices for developing students’ digital media literacies within multiple communication contexts

Epigenetic changes in histone acetylation underpin resistance to the topoisomerase I inhibitor irinotecan.

The topoisomerase I (TOP1) inhibitor irinotecan triggers cell death by trapping TOP1 on DNA, generating cytotoxic protein-linked DNA breaks (PDBs). Despite its wide application in a variety of solid tumors, the mechanisms of cancer cell resistance to irinotecan remains poorly understood. Here, we generated colorectal cancer (CRC) cell models for irinotecan resistance and report that resistance is neither due to downregulation of the main cellular target of irinotecan TOP1 nor upregulation of the key TOP1 PDB repair factor TDP1. Instead, the faster repair of PDBs underlies resistance, which is associated with perturbed histone H4K16 acetylation. Subsequent treatment of irinotecan-resistant, but not parental, CRC cells with histone deacetylase (HDAC) inhibitors can effectively overcome resistance. Immunohistochemical analyses of CRC tissues further corroborate the importance of histone H4K16 acetylation in CRC. Finally, the resistant clones exhibit cross-resistance with oxaliplatin but not with ionising radiation or 5-fluoruracil, suggesting that the latter two could be employed following loss of irinotecan response. These findings identify perturbed chromatin acetylation in irinotecan resistance and establish HDAC inhibitors as potential therapeutic means to overcome resistance

Real-World Examples for Engaging Students in Chemistry

What do consumer electronics, water treatment, and cooking all share? Chemistry! Use real-world examples to engage students in introductory chemistry topics such as the periodic table, bonding, chemical reactions, etc. This session will have an interactive discussion about how chemistry is important in everyday life and provide examples of activities and projects you can use in your classroom. Please share at least one idea about how you use real-world examples in your class

Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

The spectrum and clinical impact of epigenetic modifier mutations in myeloma

Epigenetic dysregulation is known to be an important contributor to myeloma pathogenesis but, unlike in other B cell malignancies, the full spectrum of somatic mutations in epigenetic modifiers has not been previously reported. We sought to address this using results from whole-exome sequencing in the context of a large prospective clinical trial of newly diagnosed patients and targeted sequencing in a cohort of previously treated patients for comparison.Whole-exome sequencing analysis of 463 presenting myeloma cases entered in the UK NCRI Myeloma XI study and targeted sequencing analysis of 156 previously treated cases from the University of Arkansas for Medical Sciences. We correlated the presence of mutations with clinical outcome from diagnosis and compared the mutations found at diagnosis with later stages of disease.In diagnostic myeloma patient samples we identify significant mutations in genes encoding the histone 1 linker protein, previously identified in other B-cell malignancies. Our data suggest an adverse prognostic impact from the presence of lesions in genes encoding DNA methylation modifiers and the histone demethylase KDM6A/UTX. The frequency of mutations in epigenetic modifiers appears to increase following treatment most notably in genes encoding histone methyltransferases and DNA methylation modifiers.Numerous mutations identified raise the possibility of targeted treatment strategies for patients either at diagnosis or relapse supporting the use of sequencing-based diagnostics in myeloma to help guide therapy as more epigenetic targeted agents become available

Avaliação da resistência química de concretos poliméricos em ambientes agressivos

The aim of this study was to evaluate the chemical strength of polymeric concretes. Four different concentrations of two unsaturated polyester resins (isophtalic and orthophtalic) , summing up eight chemical mortar compositions, were analyzed. Samples were submitted to alkaline and saline solutions, which are usually responsible for corrosive processes in industrial environments. Results showed that the studied mortar compositions did not suffer any physical changes on their surface nor significant mass loss. However, flexural strength decreased in samples submitted to aggressive environments. Despite this significant decrease in the flexural strength, the remaining values were much higher than those usually observed in concrete mixtures produced with Portland cement. Moreover, according to the statistical analysis, resin type and concentration, and type of solution significantly influenced the chemical strength of the studied polymeric concretes.Este trabalho apresenta uma avaliação da resistência química de concretos poliméricos. Para o presente estudo foram utilizados dois tipos de resinas poliéster insaturadas, uma isoftálica e outra ortoftálica. Os aglomerantes foram utilizados em quatro diferentes concentrações, totalizando oito composições químicas de concretos. As amostras foram submetidas a soluções alcalinas e salinas freqüentemente responsáveis por processos corrosivos em ambientes industriais. Todas as composições em estudo não sofreram alterações físicas em suas superfícies e nem mesmo perda de massa significativa. Constatou-se diminuição da resistência à tração na flexão das amostras submetidas aos meios agressores, entretanto, mesmo nas amostras cuja resistência sofreu maiores decréscimos, os valores remanescentes são muito maiores do que aqueles observados, usualmente, em concretos produzidas com cimento Portland. Por intermédio de análise estatística, constatou-se que o tipo de resina, o teor de resina e o tipo de solução exercem efeito significativo sobre a resistência química dos concretos poliméricos em estudo

Avaliação das propriedades mecânicas e da flamabilidade de concretos poliméricos produzidos com resina PET e retardante de chamas reciclados

Estes compósitos exibem excelentes propriedades mecânicas, mas devem ser adaptados às propriedades de combustibilidade. O estudo teve como objetivo, produzir concretos poliméricos utilizando alumina residual, como retardante de chamas, originados do beneficiamento industrial metalúrgico. Os compósitos tem como aglomerante a resina poliéster ortoftálica reciclada a partir do PET, como agregados foi adotada a areia de rio e a cinza volante como fíler. Foram utilizados dois tipos de retardantes de chama: um resíduo, a alumina de polimento, e o outro virgem, alumina comercial em quatro diferentes percentagens de 15, 30, 45 e 60% em massa, em relação à resina. As amostras foram submetidas ao ensaio de resistência tração na flexão e de resistência às temperaturas de 125, 225 e 325 °C. Os resultados tiveram tratamento estatístico, a fim de avaliar o nível de significância das variáveis em relação às propriedades estudadas. Os valores de resistência à tração na flexão  atingiram os 30 MPa. A análise estatística mostrou que os fatores, mudanças de temperatura, percentual de adição e da interação entre esses fatores, mostraram grande influência sobre as composições estudadas em relação à resistência às temperaturas elevadas. Em termos gerais, pode dizer-se que, o retardante de chamas residual, alumina de polimento, é uma alternativa eficiente para substituir a alumina tri-hidratada comercial em compósitos poliméricos de resina poliéster