414. CAR Spacers Including NGFR Domains Allow Efficient T-Cell Tracking and Mediate Superior Antitumor Effects

In conclusion, we demonstrated that the incorporation of the LNGFR marker gene directly in the CAR sequence allows for a single molecule to work as a therapeutic and as a selection/tracking gene and shows an increased efficacy/safety profile compared to the IgG1-CH2CH3 spacer

Flattening mountains: Micro-fabrication of planar replicas for bullet lateral striae analysis

The application of replica molding has proven to be a valuable tool in the analysis of different forensic evidences in particular for its ability to extract the toolmarks from complex sample surfaces. A well known problem in the analysis of ballistic evidences is the accurate characterization of the lateral striae of real bullets seized on crime scenes after shots, due primarily to impact deformations and to unpredictable issues related to laboratory illumination setup. To overcome these problems a possible way is to confine over a flat surface all the features still preserving their three dimensionality. This can be achieved by a novel application of replica molding performed onto the relevant lateral portion of the bullet surface. A quasi-two-dimensional negative copy of the original tridimensional indented surface has been thus fabricated. It combines the real tridimensional topography of class characteristics (land and groove impressions) and of individual caracteristics (striae) impressed by rifled barrels on projectiles, moreover with the possibility of quantitative characterization of these features in a planar configuration, that will allow one-shot comparison of the "whole striae landscape" without the typical artifacts arising from the bullet shape and the illumination issue. A detailed analysis has been carried on at the morphological level by standard optical and scanning electron microscopy, while the 3D topography has been characterized by white light optical profilometry. A quantitative characterization of toolmarks of bullets derived from ammunitions shot by guns of large diffusion, as the Beretta 98 FS cal. 9×21mm, has been performed and will be presented ranging between the whole landscape and the sub-μm resolution. To investigate the real potentiality of this technique, the experiment has been extended to highly impact-deformed projectiles

Automation in urinalysis: evaluation of three urine test strip analysers

A clinical laboratory evaluation was conducted on the Clinitek Auto 2000, the Super Aution Analyzer and the Urotron RL9 for the determination of glucose, protein, pH, blood, ketone-bodies and bilirubin

Improving honey identification: stable isotope ratios variability of mono and polyfloral honeys from the citrus growing area of Salto/Concordia and from Uruguayan coastal areas

Concordia in Argentina and Salto in Uruguay are two neighbouring regions famous for the production of a precious citrus honey, whose valorisation passes through the ability to guarantee its geographical origin. In this study the influence of the different botanical origins (monofloral and polyfloral) within the same region of origin on the different stable isotope ratios was evaluated. Moreover, the effectiveness of the stable isotope ratio parameters δ13Choney, δ13Cprotein, δ15Nprotein, δ34Sprotein, δ2 Hprotein and δ18Oprotein to discriminate between honeys produced in the internal border regions between Argentina and Uruguay (namely, Concordia and Salto) and honeys sampled in the two different Uruguayan coastal regions (Canelones and Maldonado) was tested on 82 monofloral and polyfloral honey samples. The results show that the different stable isotope ratios, except that of nitrogen, are not significantly influenced by the botanical origin of the samples. The sulphur isotopic ratio of proteins and carbon of honey are the most significant parameters for discriminating the geographical origin of the honeys considered. Applied a Principal Component Analysis, the first two factors overall explain 63.5% of the total variance, while the Discriminant Analysis provided optimal discrimination between the three origins, reaching a minimum of 96.7% correct reclassification

The Social Transmission of Attractiveness Stereotypes: An Investigation of Parental Expectations of Children\u27s Behavior

Eighty-six children from the Utah State University Child Development Laboratories and Hillcrest Elementary School and their parents participated in the study. The study focused on the use of attractiveness stereotyping used by children across four age groups. The study also analyzed the social transmission of attractiveness stereotypes from parents to their children. The study included two parts: 1) a play-preference measure, and 2) a social attribution measure. The stimuli were sketches of twelve children, six toys and six girls. The sketches of children included attractive, unattractive, mesomorphic, endomorphic, handicapped and nonhandicapped children. In the study we found that parents and children use attractiveness stereotypes. Further, parents and children utilized a beauty-is-good assumption when evaluating the children\u27s personalities and social tendencies from the sketches. Finally, we found that parents in this study expected their children to use a similar physical attractiveness hypothesis in their Social judgement

Nuclear Factor \u3baB-Dependent Neurite Remodeling Is Mediated by Notch Pathway

In this study, we evaluated whether a cross talk between nuclear factor \u3baB (NF-\u3baB) and Notch may take place and contribute to regulate cell morphology and/or neuronal network in primary cortical neurons. We found that lack of p50, either induced acutely by inhibiting p50 nuclear translocation or genetically in p50(-/-) mice, results in cortical neurons characterized by reduced neurite branching, loss of varicosities, and Notch1 signaling hyperactivation. The neuronal morphological effects found in p50(-/-) cortical cells were reversed after treatment with the \u3b3-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-1-alanyl 1]-S-phenylglycine t-butyl ester) or Notch RNA interference. Together, these data suggested that morphological abnormalities in p50(-/-) cortical neurons were dependent on Notch pathway hyperactivation, with Notch ligand Jagged1 being a major player in mediating such effect. In this line, we demonstrated that the p50 subunit acts as transcriptional repressor of Jagged1. We also found altered distribution of Notch1 and Jagged1 immunoreactivity in the cortex of p50(-/-) mice compared with wild-type littermates at postnatal day 1. These data suggest the relevance of future studies on the role of Notch/NF-\u3baB cross talk in regulating cortex structural plasticity in physiological and pathological conditions

Mulheres brasileiras e a pandemia do covid-19: reflexões dos desdobramentos para com o trabalho docente

This paper proposes reflections on the teaching labor activity of Brazilian women working in Basic Education, enabling understandings, based on the bibliographic methodology, about gender relations and their intersections, given the contemporary pandemic situation of covid-19, being the objective: reflections on the negative consequences to the teaching work of Brazilian women during the covid-19 pandemic. The results build on the understanding of the presence of whiteness as a privilege to be in teaching since the feminization of teaching in the late nineteenth century, unfolding in the analyzes carried out and dialogued with gender relations, emphasizing greater culturally devaluing overlaps of female teachers which are not white. It is concluded that Brazilian schools must rethink the existing subcultures in the school space and in society, promoting visibility and social changes for culturally constructed oppression.  Este artículo propone reflexiones sobre la actividad laboral docente de las mujeres brasileñas que trabajan en Educación Básica, posibilitando entendimientos, a partir de la metodología bibliográfica, sobre las relaciones de género y sus intersecciones, dada la situación pandémica contemporánea del covid-19, siendo el objetivo: reflexiones sobre la Consecuencias negativas para la labor docente de las mujeres brasileñas durante la pandemia del covid-19. Los resultados parten de la comprensión de la presencia de la blancura como un privilegio de estar en la docencia desde la feminización de la docencia a fines del siglo XIX, desplegándose en los análisis realizados y dialogados con las relaciones de género, enfatizando mayores superposiciones culturalmente desvalorizantes de maestras que no son blancos. Se concluye que las escuelas brasileñas deben repensar las subculturas existentes en el espacio escolar y en la sociedad, promoviendo la visibilidad y los cambios sociales para la opresión construida culturalmente.   PALABRAS CLAVE: Educación. Historia de la educación. Nueva Historia Cultural. Maestras. Género.O presente trabalho propõe reflexões para com a atividade laboral docente de mulheres brasileiras atuantes na Educação Básica, possibilitando compreensões, a partir da metodologia de cunho bibliográfico, sobre as relações dos gêneros e suas intersecções, dada a situação contemporânea pandêmica do covid-19, sendo o objetivo: reflexões sobre os desdobramentos negativos ao trabalho docente de mulheres brasileiras durante a pandemia do covid-19. Os resultados se constroem na compreensão da presença da branquitude como um privilégio para estar na docência desde a feminização do magistério no final do século XIX, desdobrando-se nas análises realizadas e dialogadas com as relações de gêneros, enfatizando maiores sobreposições desvalorizantes culturalmente de mulheres professoras que não são brancas. Conclui-se que as escolas brasileiras devem repensar as subculturas existentes no espaço da escola e na sociedade, promovendo visibilidade e mudanças sociais para opressões culturalmente construídas.

512 the cytokine release syndrome crucially contributes to the anti leukemic effects of cd44v6 car t cells

Background: Despite the remarkable clinical results of CD19 CAR-T cells in B-cell leukemias, their long-term efficacy is limited by the emergence of CD19-loss escape variants. Moreover, whether the cytokine release syndrome (CRS) is necessary for durable remissions is a matter of debate. Currently available xenograft models in NSG mice are not suited for studying the antitumor effects of CAR-T cells beyond 3-4 weeks, because of xenograft-versus-host disease (X-GVHD). Moreover, since NSG mice lack functional myeloid cells, the CRS does not develop. Aim: To verify whether the CRS contributes to the antileukemic effects of CAR in an innovative xenotolerant mouse model.Results: NSG mice triple transgenic for human IL-3, GM-CSF and SCF (NSG-3GS) were sub-lethally irradiated and injected intra-liver with human HSCs soon after birth, enabling an accelerated and better balanced lympho-hematopoietic reconstitution compared with NSG mice. Reconstituting human T cells were single CD4+/CD8+ T cells, representing all memory sub-populations. After ex vivo isolation and activation with CD3/CD28-beads and IL-7/IL-15, NSG-3GS T cells were transduced with a CD44v6 CAR, retaining an early-differentiated (stem-cell/central-memory) phenotype and full antitumor functionality against acute myeloid leukemia (AML). NSG-3GS-derived CD44v6 CAR T cells were subsequently infused in tumor-bearing secondary recipients previously humanized with autologous HSCs. CAR-T cells persisted in vivo for at least 6 months and mediated durable leukemia remissions (P<0.001 vs controls) in the absence of X-GVHD. Tumor clearance associated with an acute malaise syndrome, characterized by high fevers and a surge in human IL-6 levels, which was lethal in 30% of the mice. Differently from CD19 CAR-T cells, the CRS by CD44v6 CAR-T cells was significantly anticipated (3 vs 8 days), coinciding with human CD44v6+ monocyte depletion. In humanized mice, previous myeloid-cell depletion by clodronate administration completely prevented this syndrome, but associated with late leukemia relapses. Conversely, mice developing the CRS entered a state of durable and profound remission, as demonstrated by prolonged observation times and secondary transplantation. Conclusions: By using an innovative xenotolerant mouse model, we have demonstrated that the CRS is needed for sustained antileukemic effects by CD44v6 CAR-T cells

Restoration by ketamine of stress-induced maladaptive changes in synaptic function and brain architecture

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Editorial

Inúmeros projetos pedagógicos destacam que a Educação não pode ser concebida como mera aquisição de habilidades intelectuais ou profissionais, indiferente à formação dos valores, comportamentos e emoções. O século XX – em particular o Escolanovismo – deu impulso à proposta de Educação Integral, um modelo educativo que não dissocia desenvolvimento cognitivo do afetivo, conforme o entendimento de Sérgio Paixão, autor do primeiro artigo deste número especial da Educação em Revista. Atualmente a inclusão tornou-se uma das mais importantes bandeiras dos (as) educadores (as) e, atentas a estas questões, reunimos neste fascículo doze artigos perpassados pela temática EDUCAÇÃO INTEGRAL E INCLUSÃO