SOBRE O MARXISMO E O LENINISMO. : DEBATE COM CHARLES BETTELHEIM E ROBERT LINHART*

Em Communisme, há cerca de um ano, demos início a um trabalho de reflexão sobre uma série de problemas ligados entre si: a relação dos revolucionários de diferentes países com os países socialistas, as origens do revisionismo, a questão Stálin... Todos esses problemas são colocados em função das tarefas, em particular da luta teórica no período atual, tendo em vista os ataques dos quais o marxismo e o leninismo são objeto por todos os lados. Ao que parece, o livro de Bettelheim (Les luttes de classes en URSS,[i] cujo volume 2 acaba de ser publicado) e o livro de Linhart (Lénine, les paysans, Taylor)[ii] colocam, cada um à sua maneira, a questão do tipo de defesa do marxismo que se deve promover. Para nós, este é um debate político importante. Bettelheim aborda o problema do desenvolvimento do marxismo, da origem desse desenvolvimento, da relação entre o marxismo e as ideologias alheias ao marxismo, presentes no “marxismo historicamente constituído”. Por outro lado, Linhart fala da necessidade de uma “defesa crítica” do leninismo contra os numerosos ataques que ele sofre, ou seja, uma defesa que leve em conta o leninismo como “movimento de contradições”.   [i] [Nota do tradutor]: O livro Les luttes de classes en URSS foi publicado na França pelas editoras Seuil e Maspero em três volumes, sendo o último dividido em dois tomos: volume 1. Première période 1917-1923 (em 1974); volume 2. Deuxième période 1923-1930 (em 1977); volume 3. (tomo 1) Troisième période 1930-1941: les dominés (em 1982); e volume 3. (tomo 2) Troisième période 1930-1941: les dominants (em 1983). Em língua portuguesa, encontramos duas traduções desta obra: uma delas intitulada A luta de classes na União Soviética, que foi publicada pela editora Paz e Terra e abrange apenas os dois primeiros volumes que foram lançados em 1979 e 1983; a outra edição foi publicada na íntegra em Portugal entre 1976 e 1986 por Publicações Europa-América com o título mais fiel ao original: As lutas de classes na URSS. [ii] [Nota do tradutor]: O livro Lenin, les paysans, Taylor foi publicado na França pela editora Seuil em 1976. No Brasil, a tradução deste livro intitulada Lenin, os camponeses, Taylor foi lançada pela Editora Marco Zero em 1983

High Bi content GaSbBi alloys

The epitaxial growth, structural, and optical properties of GaSb 1– x Bi x alloys have been investigated. The Bi incorporation into GaSb is varied in the range 0 < x ≤ 9.6% by varying the growth rate (0.31–1.33 μm h−1) at two growth temperatures (250 and 275 °C). The Bi content is inversely proportional to the growth rate, but with higher Bi contents achieved at 250 than at 275 °C. A maximum Bi content of x = 9.6% is achieved with the Bi greater than 99% substitutional. Extrapolating the linear variation of lattice parameter with Bi content in the GaSbBi films enabled a zinc blende GaBi lattice parameter to be estimated of 6.272 Å. The band gap at 300 K of the GaSbBi epitaxial layers decreases linearly with increasing Bi content down to 410 ± 40 meV (3 μm) for x = 9.6%, corresponding to a reduction of ∼35 meV/%Bi. Photoluminescence indicates a band gap of 490 ± 5 meV at 15 K for x = 9.6%

Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

Background: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. Methods and Findings: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/ 8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. Conclusions: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma

A highly efficient and effective motif discovery method for ChIP-seq/ChIP-chip data using positional information

Identification of DNA motifs from ChIP-seq/ChIP-chip [chromatin immunoprecipitation (ChIP)] data is a powerful method for understanding the transcriptional regulatory network. However, most established methods are designed for small sample sizes and are inefficient for ChIP data. Here we propose a new k-mer occurrence model to reflect the fact that functional DNA k-mers often cluster around ChIP peak summits. With this model, we introduced a new measure to discover functional k-mers. Using simulation, we demonstrated that our method is more robust against noises in ChIP data than available methods. A novel word clustering method is also implemented to group similar k-mers into position weight matrices (PWMs). Our method was applied to a diverse set of ChIP experiments to demonstrate its high sensitivity and specificity. Importantly, our method is much faster than several other methods for large sample sizes. Thus, we have developed an efficient and effective motif discovery method for ChIP experiments

Erwartungsbildung über den Wahlausgang und ihr Einfluss auf die Wahlentscheidung

Erwartungen über den Wahlausgang haben einen festen Platz sowohl in Rational-Choice-Theorien des Wählerverhaltens als auch in stärker sozialpsychologisch orientierten Ansätzen. Die Bildung von Erwartungen und ihr Einfluss auf die Wahlentscheidung ist dabei jedoch ein noch relativ unerforschtes Gebiet. In diesem Beitrag werden anhand von Wahlstudien für Belgien, Österreich und Deutschland verschiedene Fragen der Erwartungsbildung und ihrer Auswirkungen untersucht. Zunächst wird die Qualität der Gesamterwartungen analysiert und verschiedene Faktoren identifiziert, die einen systematischen Einfluss auf die Erwartungsbildung haben. Im zweiten Schritt wenden wir uns den Einzelerwartungen über verschiedene Parteien und Koalitionen zu und finden eine moderate Verzerrung zugunsten der präferierten Parteien und Koalitionen. Dabei kann gezeigt werden, dass der Effekt des Wunschdenkens mit dem politischen Wissen und dem Bildungsgrad abnimmt. Schließlich werden in einem letzten Schritt zwei unterschiedliche Logiken für die Auswirkungen von Erwartungen getestet, das rationale Kalkül des koalitionsstrategischen Wählens zur Vermeidung der Stimmenvergeudung sowie der sozialpsychologisch begründete Bandwagon-Effekt. Das Ausmaß an politischem Wissen scheint dabei eine zentrale vermittelnde Variable zwischen den beiden Logiken zu sein

Sn 5 s 2 lone pairs and the electronic structure of tin sulphides: A photoreflectance, high-energy photoemission, and theoretical investigation

The effects of Sn 5 s lone pairs in the different phases of Sn sulphides are investigated with photoreflectance, hard x-ray photoemission spectroscopy (HAXPES), and density functional theory. Due to the photon energy-dependence of the photoionization cross sections, at high photon energy, the Sn 5 s orbital photoemission has increased intensity relative to that from other orbitals. This enables the Sn 5 s state contribution at the top of the valence band in the different Sn-sulphides, SnS, Sn 2 S 3 , and SnS 2 , to be clearly identified. SnS and Sn 2 S 3 contain Sn(II) cations and the corresponding Sn 5 s lone pairs are at the valence band maximum (VBM), leading to ∼ 1.0 –1.3 eV band gaps and relatively high VBM on an absolute energy scale. In contrast, SnS 2 only contains Sn(IV) cations, no filled lone pairs, and therefore has a ∼ 2.3 eV room-temperature band gap and much lower VBM compared with SnS and Sn 2 S 3 . The direct band gaps of these materials at 20 K are found using photoreflectance to be 1.36, 1.08, and 2.47 eV for SnS, Sn 2 S 3 , and SnS 2 , respectively, which further highlights the effect of having the lone-pair states at the VBM. As well as elucidating the role of the Sn 5 s lone pairs in determining the band gaps and band alignments of the family of Sn-sulphide compounds, this also highlights how HAXPES is an ideal method for probing the lone-pair contribution to the density of states of the emerging class of materials with n s 2 configuration

Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Background: We evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity

Epidermal Growth Factor Receptor Activation in Glioblastoma through Novel Missense Mutations in the Extracellular Domain

BACKGROUND: Protein tyrosine kinases are important regulators of cellular homeostasis with tightly controlled catalytic activity. Mutations in kinase-encoding genes can relieve the autoinhibitory constraints on kinase activity, can promote malignant transformation, and appear to be a major determinant of response to kinase inhibitor therapy. Missense mutations in the EGFR kinase domain, for example, have recently been identified in patients who showed clinical responses to EGFR kinase inhibitor therapy. METHODS AND FINDINGS: Encouraged by the promising clinical activity of epidermal growth factor receptor (EGFR) kinase inhibitors in treating glioblastoma in humans, we have sequenced the complete EGFR coding sequence in glioma tumor samples and cell lines. We identified novel missense mutations in the extracellular domain of EGFR in 13.6% (18/132) of glioblastomas and 12.5% (1/8) of glioblastoma cell lines. These EGFR mutations were associated with increased EGFR gene dosage and conferred anchorage-independent growth and tumorigenicity to NIH-3T3 cells. Cells transformed by expression of these EGFR mutants were sensitive to small-molecule EGFR kinase inhibitors. CONCLUSIONS: Our results suggest extracellular missense mutations as a novel mechanism for oncogenic EGFR activation and may help identify patients who can benefit from EGFR kinase inhibitors for treatment of glioblastoma

Genomic insights into cancer-associated aberrant CpG island hypermethylation

Carcinogenesis is thought to occur through a combination of mutational and epimutational events that disrupt key pathways regulating cellular growth and division. The DNA methylomes of cancer cells can exhibit two striking differences from normal cells; a global reduction of DNA methylation levels and the aberrant hypermethylation of some sequences, particularly CpG islands (CGIs). This aberrant hypermethylation is often invoked as a mechanism causing the transcriptional inactivation of tumour suppressor genes that directly drives the carcinogenic process. Here, we review our current understanding of this phenomenon, focusing on how global analysis of cancer methylomes indicates that most affected CGI genes are already silenced prior to aberrant hypermethylation during cancer development. We also discuss how genome-scale analyses of both normal and cancer cells have refined our understanding of the elusive mechanism(s) that may underpin aberrant CGI hypermethylation