The paper presents the analysis of ongoing implementation of environmental protection policies into deep seabed mining projects of Clarion-Clipperton Fracture Zone, (CCZ). Short introduction to the ...current environmental regime in the Area under UNCLOS jurisdiction is presented and potential impact of deep seabed mining is discussed. Selected results of efforts to minimize the impact on the marine environment and environmental baseline studies are described.
Este artículo busca problematizar la actual expansión de la educación emocional (EE) en las escuelas, complementando la lectura crítica que señala sus vínculos con la racionalidad neoliberal. Se ...parte de hallazgos de una investigación cualitativa exploratoria sobre el ingreso de la EE en escuelas secundarias del Área Metropolitana de Buenos Aires, Argentina, que ponen de relieve que esta propuesta legitimaría su implementación al apelar a una crítica a la escuela tradicional. Se interroga, por consiguiente, la configuración histórica de los discursos críticos-educativos que dieron lugar a la categoría de la "escuela tradicional", para comprender su reapropiación por parte de la EE. Este análisis también pone en evidencia que la EE, lejos de ser un enfoque novedoso, refuerza patrones conservadores sedimentados en el campo educativo. Se discute, asimismo, la lectura sobre la fagocitación neoliberal del discurso de la crítica educativa, para concluir sobre la necesidad de una "crítica de la crítica".
BACKGROUND
Extracellular nucleic acids circulate in plasma. They are expected to be present in manufactured blood products eligible for transfusion, but little is known about their biological ...activity on human cells. The aim of this study is to investigate whether cell‐free nucleic acids (CFNAs) are present and biologically active in red blood cell units (RBCUs), fresh frozen plasmas, and platelet concentrates.
STUDY DESIGN AND METHODS
CFNAs were extracted from RBCUs, fresh frozen plasma, and platelet concentrates. Their nature and structure were analyzed by regular methods of nucleic acid detection/quantification. A normalized polymerase chain reaction combining amplification of a CFNA marker (Alu 115) and amplification of an internal nonhuman DNA control spiked in all samples (phiX 174) was developed to study CFNA release after RBCU storage. The impact of CFNAs on gene regulation was tested by microarray after coculture with peripheral blood mononuclear cells and macrophages.
RESULTS
Extracellular double‐stranded DNA was present in all blood products, with higher amounts found in cellular suspensions (RBCUs and platelet concentrates). Storage up to 40 days did not influence release from RBCUs, and CFNA amount varied considerably from one unit to another. Microarray experiments showed that exposition of macrophages to CFNA increased the expression of genes involved in the innate immune response including chemokines, chemokine receptors, and receptors of the innate response.
CONCLUSION
CFNAs are present in blood products. Immunoregulatory properties of CFNA are shown in vitro, providing new insights on biologically active components of blood products besides those for intended therapeutic use.
Stateless Socialism Abramowski, Edward
Praktyka Teoretyczna,
2018
27
Journal Article
Recenzirano
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"Stateless socialism‖" is the fourth chapter of Edward Abramowski‘s book Socialism and State. A Contribution to the Critique of Contemporary Socialism. Abramowski, a Polish political philosopher and ...social theorist, was also one of the founders of the cooperative movement in Poland. Written at the turn of 1903 and 1904 and published in 1904 (Polish Society of Publishers, Lviv) under the alias ―M. A. Czajkowski‖, Socialism and State is one of Abramowski‘s most important works, and is devoted to the philosophical justifications of socialist politics, the subversive character of social facts, and the doctrine of stateless socialism, the realisation of which was, according to Abramowski, the cooperative movement. In opposition to both classical Marxism and the social-democratic trend, which found in the state a tool by which the workers‘ movement would free itself from the chains of capitalism, by taking over, democratizing, and at the same time expanding state institutions, Abramowski proposes a vision of a grassroots revolution of specialised associations. Their ideology does not constitute a political doctrine, but is political practice itself, the domain of the common that allows the masses to create an autonomous subjective experience. Thus, the philosopher presents his concept of class struggle, grasped as a creative element of differentiation of forms of socialisation. This understanding also allows him to define class not as a substantial feature of a political subject, but as a kind of condition or action. He perceives the revolution as a transformation of the subject position in relation to the socio-economic conditions that define it, an ethical change that opens new possibilities for community life in the heart of the ancien regime.
Chimeric antigen receptors (CARs) combine T cell activation with antibody-mediated tumor antigen specificity, bypassing the need for T cell receptor (TCR) ligation. A limitation of CAR technology is ...on-target off-tumor toxicity caused by target antigen expression on normal cells. Using GD2 as a model cancer antigen, we hypothesized that this could be minimized by using T cells expressing Vγ9Vδ2 TCR, which recognizes transformed cells in a major histocompatibility complex (MHC)-unrestricted manner, in combination with a co-stimulatory CAR that would function independently of the TCR. An anti-GD2 CAR containing a solitary endodomain derived from the NKG2D adaptor DAP10 was expressed in Vγ9Vδ2+ T cells. Differential ligation of the CAR and/or TCR using antibody-coated beads showed that pro-inflammatory cytokine response depended on activation of both receptors. Moreover, in killing assays, GD2-expressing neuroblastoma cells that engaged the Vγ9Vδ2 TCR were efficiently lysed, whereas cells that expressed GD2 equivalently but did not engage the Vγ9Vδ2 TCR were untouched. Differentiation between X-on tumor and X-off tumor offers potential for safer immunotherapy and broader target selection.
On-target off-tumor toxicity remains one of the key limitations in cancer immunotherapy. Fisher et al. report that co-stimulatory-only chimeric antigen receptors lacking CD3ζ enhance antigen-specific anti-tumor cytotoxicity of Vγ9Vδ2+ γδT cells without toxicity against cells that do not engage the γδTCR.
Sickle cell disease and β-thalassemia affect the production of the adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in adult life (i.e., ...the hereditary persistence of fetal hemoglobin). Mutations clustering ~200 nucleotides upstream of the HBG transcriptional start sites either reduce binding of the LRF repressor or recruit the KLF1 activator. Here, we use base editing to generate a variety of mutations in the -200 region of the HBG promoters, including potent combinations of four to eight γ-globin-inducing mutations. Editing of patient hematopoietic stem/progenitor cells is safe, leads to fetal hemoglobin reactivation and rescues the pathological phenotype. Creation of a KLF1 activator binding site is the most potent strategy - even in long-term repopulating hematopoietic stem/progenitor cells. Compared with a Cas9-nuclease approach, base editing avoids the generation of insertions, deletions and large genomic rearrangements and results in higher γ-globin levels. Our results demonstrate that base editing of HBG promoters is a safe, universal strategy for treating β-hemoglobinopathies.
Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer's disease (AD). More advanced stages are accompanied by microhemorrhages and vasculitis. Peripheral blood-borne macrophages are ...intimately linked to cerebrovascular pathology coincident with AD. Magnetic resonance imaging (MRI) was used to noninvasively study microvascular lesions in amyloid precursor protein transgenic mouse AD models. Foci of signal attenuation were detected in cortical and thalamic brain regions of aged APP23 mice. Their strength and number was considerably enhanced by intravenous administration of iron oxide nanoparticles, which are taken up by macrophages through absorptive endocytosis, 24 h before image acquisition. The number of cortical sites displaying signal attenuation increased with age. Histology at these sites demonstrated the presence of iron-containing macrophages in the vicinity of CAA-affected blood vessels. A fraction of the sites additionally showed thickened vessel walls and vasculitis. Consistent with the visualization of CAA-associated lesions, MRI detected a much smaller number of attenuated signal sites in APP23xPS45 mice, for which a strong presenilin mutation caused a shift toward amyloid β
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, thus reducing vascular amyloid. Similar results were obtained with APP24 and APP51 mice, which develop significantly less CAA and microvascular pathology than APP23. In a longitudinal study, we noninvasively demonstrated the reinforced formation of microvascular pathology during passive amyloid β immunotherapy of APP23 mice. Histology confirmed that foci of signal attenuation reflected an increase in CAA-related lesions. Our data demonstrate that MRI has the sensitivity to noninvasively monitor the development of vascular pathology and its possible enhancement by amyloid β immunotherapy in transgenic mice modeling AD.
Protection of marine environment and reduction of GHG emissions are currently imperative criterion for ship design. For ships in service, including fishing vessels powered by internal combustion ...engines, options of retrofitting are sought to reduce their hydrodynamic resistance and fuel consumption. One such possibility is the addition of a simple-shape bulbous bow, which can be installed at low cost to upgrade a fishing vessel. We present an analysis of the effect that the bulbous bow has on fishing vessel resistance across the whole range of speeds at which the entire work cycle of the vessel is carried out. The resistance was calculated using a calculation of fluid dynamics (CFD) method for the actual size of the vessel. We show that it is possible to develop such a bulbous bow for which the resistance of fishing vessel with a bulbous bow is going to be lower than that of an unmodified shape. For the modified shape of the fishing vessel, fuel consumption, amount and composition of exhaust gases were calculated and the obtained results were compared with the parameters of the vessel without modification. The tests carried out and the obtained calculation results indicate that a significant reduction of fuel consumption and GHG emissions may be obtained for the existing old fishing vessels at low anticipated modernization costs.
This paper presents the economic structure, assumptions, and relations of deep-sea mining project assessment and the results of its evaluation, based on exploration activities and research in the ...field of geology, mining technology, processing technology, and environmental and legislative studies. The Interoceanmetal Joint Organization (IOM) and cooperating organizations conducted a study incorporating those elements of the project that are recognized as most important for commercial viability. On the basis of formulated financial flow of operating and capital expenses of one processing technology the possible market unit price of polymetallic nodules was estimated and the result is presented in this paper. The rapidly changing economic situation, affected inter alia by the COVID-19 pandemic, is reflected in the study and updated results are based on recent changes in metal prices. Although assumptions related to mining costs need to be confirmed during pilot mining tests, promising results have been shown in the case of the use of high-pressure acid leaching processing technology (HPAL) as well as in the case of raw ore sales. A pre-feasibility study of the project will focus on the two most promising variants of the model.
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