69 research outputs found

    Cálculo de trocadores de calor tipo casco e tubos por partes com determinação das curvas de temperatura e perda de carga

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    Este trabalho trata do desenvolvimento de procedimen~os de cálculo de trocadores de calor tipo carcaça e tubos , com troca de calor sensivel . São desenv.ol vi dos dois procedimentos de cálculo. O primeiro considera o trocador de calor. dividido em partes e calcula o fluxo térmico em cada par te empregando a equação Q = UAC LMTD. F). A troca térmica Lotal é a soma das trocas térmicas das partes. O segundo, além de dividir o trocador de calor em partes, acompanha a corrent..e nos tubos e calcula o fluxo térmico para cada passe nos tubos de cada parte empregando a diferença de temperatura localizada , Q = UACTmc-Tmt) , e a troca térmica total é o somatório das trocas ~érmicas nos passes de cada parte. O estudo considera as principais equações e métodos para o cálculo da transferéncia de c alor e perda de carga. Os resultados obtidos através destes procedimentos são comparados com os resultados do cálculo que considera as propriedades nas temperaturas médias (método tradicional de cálculo) e com os resultados obLidos com um programa de grande utilização internacional a nivel comercial desenvolvido por empresa americana .This work presents and tube h «?at numerical procedures exchanger wi th sensi b l e for heat Two k i nds .of p r ocedur e a re presented both di vi di ng the heal exchanger in n parts. The f i r sl analysis performs the heal Lransfer aL each parL using Lhe fundamental equalion: Q = UACLMTD.F). The overall heal Lransfer is the summaLion of Lhe heaL of lhe n parLs . The second one performs Lhe heal Lransfer sLep by slep foll owing Lhe flow i n Lhe Lube. The heaL Lransfer equalion uses lhe local LemperaLure difference: Q = UACTmc - TmL). The overall heaL is also Lhe summalion o f the heaL of the n par ts. Both procedures calcul aLes the pressure drop through Lhe whole heaL exchanger. The resul Ls from boLh procedures are compared wi th oLher method and a good agr eemenL was found

    Educação ambiental, gênero, sexualidade e luta de classes: algumas reflexões sobre política, educação crítica e transformação social

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    A educação ambiental e as questões de gênero e sexualidade contribuem para o processo de emancipação humana e devem ser discutidas na educação escolar, especialmente na escola pública. Visto que o desenvolvimento de um processo que objetiva a construção de uma sociedade igualitária e justa, só pode ocorrer a partir dos embates dentro do modo de produção capitalista, ou seja, a partir de um processo histórico de luta, defende- se que as discussões sobre as questões de gênero e sexualidade bem como a educação ambiental devem orientar-se a partir da filosofia da práxis. Desta forma, a partir de Saviani (2005, 2008, 2011), Lukács (1969, 1978, 1979), Biancon, (2016), este artigo tem como objetivo apresentar a necessidade da participação política para a transformação da sociedade contemporânea e analisar o papel da educação crítica no processo de transformação social considerando a educação ambiental e as discussões de gênero e sexualidade e a luta de classe. Como método de análise adotou-se o materialismo histórico dialético.

    Perspectivas em educação, uma intervenção do programa PIBID UENP Biologia

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    Anais do II Seminário Seminário Estadual PIBID do Paraná: tecendo saberes / organizado por Dulcyene Maria Ribeiro e Catarina Costa Fernandes — Foz do Iguaçu: Unioeste; Unila, 2014O conhecimento da comunidade onde uma determinada escola está inserida se mostra fundamental para o desenvolvimento de estratégias com vista a ampliar o nível de qualidade da educação pública. Desse modo o grupo de pibidianos da Universidade Estadual do Norte do Paraná, vem desenvolvendo um projeto em parceria com escolas de Jacarezinho e em Santo Antônio da Platina, tendo como ponto de partida, o estudo dos planos diretores de tais municípios, visando conhecer a realidade local. A proposta caracteriza-se por um projeto interdisciplinar na área de Educação Ambiental e Educação das relações de gênero e sexualidades. Temas por vezes ausentes da formação inicial de professores ou apresentados de forma superficial na formação continuada desses profissionais. O presente artigo, fruto de um trabalho inicial trará as perspectivas dos dois municípios presentes nos planos diretore

    Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation

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    Acute graft-versus-host disease (aGVHD) results in significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Noninvasive diagnostic and prognostic tests for aGVHD are currently lacking, but would be beneficial in predicting aGVHD and improving the safety of allo-HSCT. Circulating microRNAs exhibit marked stability and may serve as biomarkers in several clinical settings. Here, we evaluated the use of circulating microRNAs as predictive biomarkers of aGVHD in lymphoma patients after allo-HSCT from matched unrelated donors (MUDs). After receiving informed consent, we prospectively collected plasma samples from 24 lymphoma patients before and after unmanipulated MUD allo-HSCT; microRNAs were then isolated. Fourteen patients developed aGVHD symptoms at a median of 48 days (range: 32–90) post-transplantation. Two patients developed intestinal GVHD, eight cutaneous GVHD, and four multiorgan GVHD. The microRNA expression profile was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MicroRNAs 194 and 518f were significantly upregulated in aGVHD samples compared with samples taken from non-aGVHD patients. Remarkably, these upregulated microRNAs could be detected before the onset of aGVHD. Pathway prediction analysis indicated that these microRNAs may regulate critical pathways involved in aGVHD pathogenesis. Considering the noninvasive characteristics of plasma sampling and the feasibility of detecting miRNAs after allo-HSCT using real-time polymerase chain reaction, our results indicate that circulating microRNAs have the potential to enable an earlier aGVHD diagnosis and might assist in individualizing therapeutic strategies after MUD allo-HSCT. Nevertheless, standardization of blood sampling and analysis protocols is mandatory for the introduction of miRNA profiling into routine clinical use

    Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma

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    In multiple myeloma, novel treatments with proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs) have prolonged survival but the disease remains incurable. At relapse, next-generation sequencing has shown occasional mutations of drug targets but has failed to identify unifying features that underlie chemotherapy resistance. We studied 42 patients refractory to both PIs and IMiDs. Whole-exome sequencing was performed in 40 patients, and RNA sequencing (RNA-seq) was performed in 27. We found more mutations than were reported at diagnosis and more subclonal mutations, which implies ongoing evolution of the genome of myeloma cells during treatment. The mutational landscape was different from that described in published studies on samples taken at diagnosis. The TP53 pathway was the most frequently inactivated (in 45% of patients). Conversely, point mutations of genes associated with resistance to IMiDs were rare and were always subclonal. Refractory patients were uniquely characterized by having a mutational signature linked to exposure to alkylating agents, whose role in chemotherapy resistance and disease progression remains to be elucidated. RNA-seq analysis showed that treatment or mutations had no influence on clustering, which was instead influenced by karyotypic events. We describe a cluster with both amp(1q) and del(13) characterized by CCND2 upregulation and also overexpression of MCL1, which represents a novel target for experimental treatments. Overall, high-risk features were found in 65% of patients. However, only amp(1q) predicted survival. Gene mutations of IMiD and PI targets are not a preferred mode of drug resistance in myeloma. Chemotherapy resistance of the bulk tumor population is likely attained through differential, yet converging evolution of subclones that are overall variable from patient to patient and within the same patient

    A novel in-house deep sequencing method for non-invasive disease monitoring in multiple myeloma patients

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    Background: Novel and more effective treatment strategies have sig- nificantly prolonged multiple myeloma (MM) survival and raised inter- est in the depth of response. This implies the need of highly sensitive assays such as the determination of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) and next generation sequencing (NGS) of immunoglobulin (IGH) gene rearrangements. Ongoing studies are examining circulating cell-free tumor DNA (cfDNA) as a sensitive measure of small amounts of residual cells. In the present study, we de- scribe and analytically validate a simplified in-house deep-sequencing method to identify and quantify residual tumor burden in MM patients from plasma samples. Methods: We retrospectively analyzed 25 MM paired tumor (n=25) and plasma samples (n=48) obtained at diagnosis and at specified time points during treatment. Genomic DNA (gDNA) and cfDNA were extracted from selected CD138+ plasma cells (PC) and from plasma (Qiagen). IGH gene rearrangements were amplified, qual- ity assessed (Agilent hsDNA kit) and sequenced on Ion Torrent PGM. Raw reads were filtered and aligned using IMGT germline database andaggregated into clonotypes. Post-processing analyses were performed using VDJtools and customized R scripts. Results: Our sequencing method successfully identified a IGH MM clonotype in 88% of tumor samples (22/25), subsequently detected in plasma of all 22 cases (me- dian 4.7% of total filtered reads). Levels of the IGH clonotype in cfDNA distinguished between groups of patients with different prognosis: pa- tients with levels >4.7% prior to therapy, had significantly shorter PFS than patients with levels10-5 vs 15\ub15 months for frequencies=10-5 vs 37\ub14 months for frequencies<10- 5). Those patients are in CR and characterized by PC frequencies <10- 5 by MFC, and are therefore defined as MRD-negative. Conclusions: Results of this study support the clinical applicability of quantifying tumor levels by our in-house deep-sequencing of IGH gene rearrange- ments in plasma of MM patients

    A targeted sequencing approach in multiple myeloma reveals a complex landscape of genomic lesions that has implications for prognosis

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    Background: Next-generation sequencing (NGS) studies have shown that mul- tiple myeloma is a heterogeneous disease with a complex subclonal architecture and few recurrently mutated genes. The analysis of smaller regions of interest in the genome (\u201ctargeted studies\u201d) allows interrogation of recurrent genomic events with reduces complexity of downstream analysis at a lower price. Aims: Here, we performed the largest targeted study to date in multiple myelo- ma to analyze gene mutations, deletions and amplifications, chromosomal copy number changes and immunoglobulin heavy chain locus (IGH) translo- cations and correlate results with biological and clinical features. Methods: We used Agilent SureSelect cRNA pull down baits to target: 246 genes implicated in myeloma or cancer in general in a mixed gene discovery/confirmation effort; 2538 single nucleotide polymorphisms to detect amplifications and deletions at the single-gene and chromosome level; the IGH locus to detect translocations. We sequenced unmatched DNA from CD138- purified plasma cells from 418 patients with multiple myeloma at diagnosis, with a median follow-up of 5.3 years. We sequenced at an average depth of 337x using Hiseq2000 machines (Illumina Inc.). We applied algorithms developed in- house to call genomic events, filtering out potential artifacts and germline vari- ants. We then ranker each event on its likelihood of being \u201concogenic\u201d based on clustering, recurrence and cross-reference with the COSMIC database. Results: We identified 2270 gene mutations in 412/418 patients, and of those 688 were oncogenic. 342 patients harbored at least one oncogenic mutation. 215/246 genes showed at lease one likely somatic mutation, but only 106 showed at least one oncogenic mutation. 63% of oncogenic mutations were accounted for by the top 9 driver genes previously identified (KRAS, NRAS, TP53, FAM46C, BRAF, DIS3, TRAF3, SP140, IRF4), implying our gene discov- ery effort did not identify novel mutated genes. We included deletion of tumor suppressors, amplification of oncogenes, chromosomal copy number changes and IGH translocations for a total of 76 variables, so that 413/418 patients showed at least one informative driver genomic event, (median 4/patient). We investigated pairwise associations between events and found significant corre- lations, such as TP53 mutations and del(17p), CYLD mutations and del(16), FAM46C mutations and del(1p), SF3B1 mutations and t(11;14). Hotspots muta- tions of IRF4 lysine p.123 showed an inverse correlation with a hyperdiploid karyotype and del(16) as opposed to other missense mutations scattered along the gene, which has pathogenic implications. Survival was negatively affected by the cumulative burden of lesions in an almost linear fashion, with median survival of 10.97 and 4.07 years in patients with =7 lesions respectively, and this was independent of the nature of the genomic events. Given the het- erogeneity and complex interplay of the variables we fitted a cox-proportional hazard model to predict survival. We found that mutations in TP53, amplifications of MYC, deletions of CYLD, amp(1q), del12p13.31 and del17p13 where the only significant events, all promoting shorter survival. In particular, TP53 muta- tions and deletions, often co-occurring, had an additive effect so that carriers of both showed a dismal survival of 17 months (Figure 1).Summary/Conclusions: Due to the complex genomic landscape in MM, a discovery effort still requires large studies to derive significant associations. We conclude that a targeted sequencing approach may provide prognostic models and give insights into myeloma biology

    Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups

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    In multiple myeloma, next-generation sequencing (NGS) has expanded our knowledge of genomic lesions, and highlighted a dynamic and heterogeneous composition of the tumor. Here we used NGS to characterize the genomic landscape of 418 multiple myeloma cases at diagnosis and correlate this with prognosis and classification. Translocations and copy number abnormalities (CNAs) had a preponderant contribution over gene mutations in defining the genotype and prognosis of each case. Known and novel independent prognostic markers were identified in our cohort of proteasome inhibitor and immunomodulatory drug-treated patients with long follow-up, including events with context-specific prognostic value, such as deletions of the PRDM1 gene. Taking advantage of the comprehensive genomic annotation of each case, we used innovative statistical approaches to identify potential novel myeloma subgroups. We observed clusters of patients stratified based on the overall number of mutations and number/type of CNAs, with distinct effects on survival, suggesting that extended genotype of multiple myeloma at diagnosis may lead to improved disease classification and prognostication
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