O ensino da geografia em Santa Maria / RS

Sem resumo no original

Immunotherapy of human cancers using gene modified T lymphocytes

Adoptive T cell therapies can produce objective clinical responses in patients with hematologic and solid malignancies. Genetic manipulation of T lymphocytes has been proposed as a means of increasing the potency and range of this anti-tumor activity. We now review how coupling expression of transgenic receptors with countermeasures against potent tumor immune evasion strategies is proving highly effective in pre-clinical models and describe how these approaches are being evaluated in human subjects

Engineered CAR T cell therapy for solid tumors

The adoptive transfer of T cells redirected to tumor-associated antigens via transgenic expression of chimeric antigen receptors (CARs) has produced impressive clinical responses in patients with hematologic malignances. However the successful extension of this therapy to solid tumors has proven challenging due to i) the paucity of target antigens that are tumor selective, leading to a heightened risk of “on-target, off-tumor” toxicities and, ii) the suppressive tumor microenvironment, which subverts T cell effector function. Therefore, to overcome these limitations we have programmed T cells with a combination of receptors that recognize a gene expression pattern that is unique to the tumor site and whose endodomains deliver intracellular signals 1, 2 and 3 (antigen, co-stimulation and cytokine) required for optimal T cell activation and protection from suppressive factors present at the tumor site. The current presentation will not only highlight our T cell engineering improvements but also our process optimization, including the incorporation of the G-Rex device, to facilitate the clinical and commercial development of potentially curative therapie

Association of Attachment and Reflective Function with Baseline Symptoms in Child and Adolescent Psychodynamic Psychotherapy

The present study aimed to verify the associations between symptoms reported at baseline, attachment style and reflective function (RF) in children and adolescents. For this, we conducted a cross-sectional and naturalistic study, including 90 children and adolescents aged between 9 and 17 years old (M = 13.04, SD = 2.72). Instruments were a demographic form, the Child Behavior Checklist, the Friends and Family Interview and the Reflective Function Questionnaire for Youths. From our findings, internalizing symptoms were reported in 74.4% of the cases, and externalizing symptoms in 55.6%. Concerning the attachment styles, 46.7% of the cases were classified as insecure-dismissing, 38.9% as insecure-preoccupied, 10% as secure and 4.4% as disorganized. Participants’ scores for RF were low. We found associations between attachment styles and anxiety, depression and withdrawal symptoms. We found significant differences between the insecuredismissing style and the insecure-preoccupied and disorganized styles groups regarding anxiety and depression symptoms. The secure attachment style group showed significant differences in withdrawal symptoms when compared to insecure attachment style groups. Further studies exploring associations between attachment styles, RF and psychopathology in childhood and adolescence, could contribute to the evaluation and planning of psychotherapies processes with this population

Abandono de psicoterapia psicanalítica por adolescentes: uma revisão narrativa

Fenômeno frequente, embora pouco estudado, o abandono da psicoterapia por parte de adolescentes é preocupante, visto que uma expressiva parcela deles possui problemas de saúde mental. Nesse sentido, esta revisão narrativa tem como objetivo compreender por que os jovens abandonam a psicoterapia psicanalítica. Características dos adolescentes têm sido relacionadas ao abandono, como idade e gênero, e variáveis clínicas, como comportamento antissocial e delinquente, embora ainda não haja consenso. Atributos do processo terapêutico, como a qualidade da aliança terapêutica e variáveis do terapeuta, também estão associadas à manutenção ou não da psicoterapia. Concluiu-se que a literatura progrediu no entendimento dos motivos que levam os adolescentes a interromperem os tratamentos psicanalíticos, com ênfase para fatores clínicos e aspectos do processo terapêutico. No entanto, mais estudos são necessários para o avanço na compreensão e prevenção do fenômeno

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety

T lymphocytes expressing a chimeric antigen receptor (CAR) targeting the CD19 antigen (CAR.19) may be of value for the therapy of B-cell malignancies. Because the in vivo survival, expansion and anti-lymphoma activity of CAR.19 T + cells remain suboptimal even when the CAR contains a CD28 costimulatory endodomain, we generated a novel construct that also incorporates the interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR.19/IL-15). We found that compared with CAR.19 T + cells, iC9/CAR.19/IL-15 T cells had: (1) greater numeric expansion upon antigen stimulation (10-fold greater expansion in vitro, and 3-to 15-fold greater expansion in vivo) and reduced cell death rate (Annexin-V/7-AAD cells 106% for iC9/CAR.19/IL-15 T + cells and 3219% for CAR.19 T + cells); (2) reduced expression of the programmed death 1 (PD-1) receptor upon antigen stimulation (PD-1 cells 15% for iC9/CAR.19/IL-15 T + cells versus 40% for CAR.19 T + cells); and (3) improved antitumor effects in vivo (from 4.7-to 5.4-fold reduced tumor growth). In addition, iC9/CAR.19/IL-15 T + cells were efficiently eliminated upon pharmacologic activation of the suicide gene. In summary, this strategy safely increases the anti-lymphoma/leukemia effects of CAR.19-redirected T lymphocytes and may be a useful approach for treatment of patients with B-cell malignancies

A tunable carbon nanotube electromechanical oscillator

Nanoelectromechanical systems (NEMs) hold promise for a number of scientific and technological applications. In particular, NEMs oscillators have been proposed for use in ultrasensitive mass detection, radio-frequency signal processing, and as a model system for exploring quantum phenomena in macroscopic systems. Perhaps the ultimate material for these applications is a carbon nanotube. They are the stiffest material known, have low density, ultrasmall cross-sections and can be defect-free. Equally important, a nanotube can act as a transistor and thus may be able to sense its own motion. In spite of this great promise, a room-temperature, self-detecting nanotube oscillator has not been realized, although some progress has been made. Here we report the electrical actuation and detection of the guitar-string-like oscillation modes of doubly clamped nanotube oscillators. We show that the resonance frequency can be widely tuned and that the devices can be used to transduce very small forces.Comment: 9 pages, 3 figure

Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal

Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Here, we assessed the potential of immunoglobulin-like domains 1 and 2 (Ig1&2), a decoy protein that activates the receptor tyrosine phosphatase sigma (PTPRS) on FLS, for RA therapy. We report that PTPRS expression is enriched in synovial lining RA FLS and that Ig1&2 reduces migration of RA but not osteoarthritis FLS. Administration of an Fc-fusion Ig1&2 attenuated arthritis in mice without affecting innate or adaptive immunity. Furthermore, PTPRS was down-regulated in FLS by tumor necrosis factor (TNF) via a phosphatidylinositol 3-kinase–mediated pathway, and TNF inhibition enhanced PTPRS expression in arthritic joints. Combination of ineffective doses of TNF inhibitor and Fc-Ig1&2 reversed arthritis in mice, providing an example of synergy between FLS-targeted and immunosuppressive DMARD therapies.publishedVersio

DJ‐1 depletion prevents immunoaging in T‐cell compartments.

Decline in immune function during aging increases susceptibility to different aging‐related diseases. However, the underlying molecular mechanisms, especially the genetic factors contributing to imbalance of naïve/memory T‐cell subpopulations, still remain largely elusive. Here, we show that loss of DJ‐1 encoded by PARK7/DJ‐1, causing early‐onset familial Parkinson’s disease (PD), unexpectedly diminished signs of immunoaging in T‐cell compartments of both human and mice. Compared with two gender‐matched unaffected siblings of similar ages, the index PD patient with DJ‐1 deficiency showed a decline in many critical immunoaging features, including almost doubled non‐senescent T cells. The observation was further consolidated by the results in 45‐week‐old DJ‐1 knockout mice. Our data demonstrated that DJ‐1 regulates several immunoaging features via hematopoietic‐intrinsic and naïve‐CD8‐intrinsic mechanisms. Mechanistically, DJ‐1 depletion reduced oxidative phosphorylation (OXPHOS) and impaired TCR sensitivity in naïve CD8 T cells at a young age, accumulatively leading to a reduced aging process in T‐cell compartments in older mice. Our finding suggests an unrecognized critical role of DJ‐1 in regulating immunoaging, discovering a potent target to interfere with immunoaging‐ and aging‐associated diseases

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13