Literatura e resistência: a força da quebrada diante dos silenciamentos do campo literário

Based on the survey conducted by Regina Dalcastagnè about the profile of the Brazilian writer, intend to problematize the silencing and criteria of eligibility of the literary field, which culminate in a literary production mostly white, heterosexual, and male. This prevalence results in an adjectivation of literature that does not fit this pattern – female, black, indigenous, LGBT, marginal and peripheral literature –, insofar as canonicais literature is assumed to be universal. Dialoguing with the problematizations raised by Dalcastagnè, in the second moment, the article will work with the resistance movements of marginal literature, which opens its doors despite the publishing circuit of the big publishing houses. Will be analyzed two saraus of emblematic importance in this process of decentralization, Cooperifa in São Paulo and Coletivoz in Belo Horizonte, which circulate the strength of marginal literature in their writings.A partir do levantamento realizado por Regina Dalcastagnè sobre o perfil do escritor brasileiro, pretende-se problematizar os silenciamentos e critérios de elegibilidade do campo literário, que culminam numa produção literária majoritariamente branca, heterossexual e masculina. Esta prevalência resulta numa adjetivação de literaturas que não se enquadram nesse padrão -literatura feminina, negra, indígena, LGBT, marginal e periférica-, na medida em que se pressupõe como universal a literatura canônica. Dialogando com as problematizações levantadas por Dalcastagnè, no segundo momento, o artigo trabalhará com os movimentos de resistência da literatura marginal, que abre vão a despeito do circuito de publicação das grandes editoras. Serão analisados brevemente dois saraus de importância emblemática nesse processo de descentralização, a Cooperifa em São Paulo e o Coletivoz em Belo Horizonte, que fazem circular a força da literatura marginal em suas escrevivências.

Proposal for improved nuclear fuel utilisation and economic performance by utilising thorium

A systematic and strategic nuclear power reactor deployment roadmap has been developed for South Africa within the national strategic plan, utilizing thorium-based fuel. The roadmap was developed through analysis of economical, strategic and historical aspects. The accumulated advantages of thorium-based fuels are summarized, which could form the initiative to implement thorium-based nuclear fuels in South Africa. A timeline (which forms the basis of the roadmap) was constructed and consists of three different phases. Phase 1 starts in 2015 and extends to 2030. Phase 2 starts in 2031 and ends in 2044 whilst Phase 3 is from 2045 to 2060. Each phase is discussed with regard to construction, implementation and research activities. This roadmap starts at current pressurized water reactors (PWRs) and advances to future reactor technologies, using an evolutionary approach. In addition to the results reported in this paper, the economic advantages to introducing thorium as a fertile component in PWR fuels as compared to once-through conventional uranium-only cycles is explored (Du Toit & Cilliers, 2014). The economic evaluation compares uranium fuel to thorium-uranium fuel in terms of the fuel cycle costs, reactor downtime costs due to refuelling and income derived from electricity sales

Proposal for improved nuclear fuel utilisation and economic performance by utilising thorium

A systematic and strategic nuclear power reactor deployment roadmap has been developed for South Africa within the national strategic plan, utilizing thorium-based fuel. The roadmap was developed through analysis of economical, strategic and historical aspects. The accumulated advantages of thorium-based fuels are summarized, which could form the initiative to implement thorium-based nuclear fuels in South Africa. A timeline (which forms the basis of the roadmap) was constructed and consists of three different phases. Phase 1 starts in 2015 and extends to 2030. Phase 2 starts in 2031 and ends in 2044 whilst Phase 3 is from 2045 to 2060. Each phase is discussed with regard to construction, implementation and research activities. This roadmap starts at current pressurized water reactors (PWRs) and advances to future reactor technologies, using an evolutionary approach. In addition to the results reported in this paper, the economic advantages to introducing thorium as a fertile component in PWR fuels as compared to once-through conventional uranium-only cycles is explored (Du Toit & Cilliers, 2014). The economic evaluation compares uranium fuel to thorium-uranium fuel in terms of the fuel cycle costs, reactor downtime costs due to refuelling and income derived from electricity sales

A Continuous, Fluorescence-based Assay of µ-Opioid Receptor Activation in AtT-20 Cells

Opioids are widely prescribed analgesics, but their use is limited due to development of tolerance and addiction, as well as high variability in individual response. The development of improved opioid analgesics requires high-throughput functional assays to assess large numbers of potential opioid ligands. In this study, we assessed the ability of a proprietary "no-wash" fluorescent membrane potential dye to act as a reporter of µ-opioid receptor (MOR) activation and desensitization via activation of G-protein-coupled inwardly rectifying potassium channels. AtT-20 cells stably expressing mouse MOR were assayed in 96-well plates using the Molecular Devices FLIPR membrane potential dye. Dye emission intensity decreased upon membrane hyperpolarization. Fluorescence decreased in a concentration-dependent manner upon application of a range of opioid ligands to the cells, with high-efficacy agonists producing a decrease of 35% to 40% in total fluorescence. The maximum effect of morphine faded in the continued presence of agonist, reflecting receptor desensitization. The effects of opioids were prevented by prior treatment with pertussis toxin and blocked by naloxone. We have demonstrated this assay to be an effective method for assessing ligand signaling at MOR, which may potentially be scaled up as an additional high-throughput screening technique for characterizing novel opioid ligands.NHMRC Grant Numbers: 1011979 & 104596

Perturbative QCD analyses of the nonleptonic BB meson decays

Based on Brodsky-Lepage approach, the nonleptonic $B$ meson decay branching ratio is derived in terms of three parameters and is geometrically analysed as the 3-surface embedded in the 4-dimensional (abstract) Euclidean space generated by the three parameters and $BR$. Investigating its 2-dimensional sections, we find ranges for these parameters imposed by a comparison with experimental data.Comment: 13 pages, LaTeX format, figures not include

Discussing Challenges in Diagnosis of Tuberculous Meningitis and Neurosarcoidosis.

Isolated chronic granulomatous meningitis remains a diagnostic challenge for the physician. Symptoms are often nonspecific and ancillary tests have low-sensitivity rates, which may delay targeted treatment and lead to increased morbidity and mortality. Here, we discuss the challenges in diagnosing and treating patients with chronic meningitis by reporting two cases of previously healthy patients who presented with granulomatous meningitis on brain biopsy

A comprehensive microarray-based DNA methylation study of 367 hematological neoplasms

Background: Alterations in the DNA methylation pattern are a hallmark of leukemias and lymphomas. However, most epigenetic studies in hematologic neoplasms (HNs) have focused either on the analysis of few candidate genes or many genes and few HN entities, and comprehensive studies are required. Methodology/Principal Findings: Here, we report for the first time a microarray-based DNA methylation study of 767 genes in 367 HNs diagnosed with 16 of the most representative B-cell (n = 203), T-cell (n = 30), and myeloid (n = 134) neoplasias, as well as 37 samples from different cell types of the hematopoietic system. Using appropriate controls of B-, T-, or myeloid cellular origin, we identified a total of 220 genes hypermethylated in at least one HN entity. In general, promoter hypermethylation was more frequent in lymphoid malignancies than in myeloid malignancies, being germinal center mature B-cell lymphomas as well as B and T precursor lymphoid neoplasias those entities with highest frequency of gene-associated DNA hypermethylation. We also observed a significant correlation between the number of hypermethylated and hypomethylated genes in several mature B-cell neoplasias, but not in precursor B- and T-cell leukemias. Most of the genes becoming hypermethylated contained promoters with high CpG content, and a significant fraction of them are targets of the polycomb repressor complex. Interestingly, T-cell prolymphocytic leukemias show low levels of DNA hypermethylation and a comparatively large number of hypomethylated genes, many of them showing an increased gene expression. Conclusions/Significance: We have characterized the DNA methylation profile of a wide range of different HNs entities. As well as identifying genes showing aberrant DNA methylation in certain HN subtypes, we also detected six genes—DBC1, DIO3, FZD9, HS3ST2, MOS, and MYOD1—that were significantly hypermethylated in B-cell, T-cell, and myeloid malignancies. These might therefore play an important role in the development of different HNs

Interrogating Bromodomain Inhibitor Resistance in KMT2A-Rearranged Leukemia Through Combinatorial CRISPR Screens

Bromo- and extra-terminal domain inhibitors (BETi) have exhibited therapeutic activities in many cancers. However, the mechanisms controlling BETi response and resistance are not well understood. We conducted genome-wide loss-of-function CRISPR screens using BETi-treated KMT2A-rearranged (KMT2A-r) cell lines. We revealed that Speckle-type POZ protein (SPOP) gene (Speckle Type BTB/POZ Protein) deficiency caused significant BETi resistance, which was further validated in cell lines and xenograft models. Proteomics analysis and a kinase-vulnerability CRISPR screen indicated that cells treated with BETi are sensitive to GSK3 perturbation. Pharmaceutical inhibition of GSK3 reversed the BETi-resistance phenotype. Based on this observation, a combination therapy regimen inhibiting both BET and GSK3 was developed to impede KMT2A-r leukemia progression in patient-derived xenografts in vivo. Our results revealed molecular mechanisms underlying BETi resistance and a promising combination treatment regimen of ABBV-744 and CHIR-98014 by utilizing unique ex vivo and in vivo KMT2A-r PDX models