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

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

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

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Prognostic and predictive biomarkers to cyclin-dependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA (ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy.Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model.201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms.We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted

Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer.

Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary end point, decreased Ki67, occured in 12% of TNBC. In secondary end point analyses, HR deficiency was identified in 69% of TNBC with the mutational-signature-based HRDetect assay. Cancers with HRDetect mutational signatures of HR deficiency had a functional defect in HR, assessed by impaired RAD51 foci formation on end of treatment biopsy. Following rucaparib treatment there was no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identified activity of rucaparib, with end of treatment ctDNA levels suppressed by rucaparib in mutation-signature HR-deficient cancers. In ad hoc analysis, rucaparib induced expression of interferon response genes in HR-deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors

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

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Purpose: Prognostic and predictive biomarkers to cyclindependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA ( ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/ overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted