Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia

Background Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell 'fitness' is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patientderived T cells; in this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/ HLA-independent Vδ1+ γδ T cells, represent a promising allogeneic platform. Methods Here we generated and preclinically validated, for the first time, 4-1BB-based CAR-DOTs directed against the interleukin-3α chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. Results CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo, even on tumor rechallenge. Conclusions Our results provide the proof-of-concept for a DOT-based next-generation allogeneic CAR-T therapy for AML

Utilizaçao de Múltiplos Cateteres com Microeletrodos para Mapeamento e Ablaçao Epicárdica Percutânea de Taquicardia Ventricular Sustentada de Etiologia Chagásica

Relata-se um caso de mapeamento e ablaçao epicárdica percutânea de taquicardia ventricular sustentada de etiologia chagásica em que foi utilizada angiografia ventricular direita para orientar a punçao pericárdica. Com o posicionamento de 2 microcateteres octapolares, obteve-se a localizaçao detalhada e a extensao da zona de conduçao lenta da taquicardia clínica. Constatou-se nessa regiao encarrilhamento com fusao oculta e ciclo de retorno igual ao ciclo de frequência da taquicardia. A aplicaçao local de radiofrequência interrompeu a taquicardia em 4 segundos, nao sendo possível sua reinduçao. Conclui-se que a punçao pericárdica pode ser orientada pela angiografia do ventrículo direito e que a utilizaçao de múltiplos cateteres com microeletrodos pode fornecer dados adicionais no mapeamento e na ablaçao epicárdica da taquicardia ventricular de etiologia chagásica

Utilizaçao de Múltiplos Cateteres com Microeletrodos para Mapeamento e Ablaçao Epicárdica Percutânea de Taquicardia Ventricular Sustentada de Etiologia Chagásica

Relata-se um caso de mapeamento e ablaçao epicárdica percutânea de taquicardia ventricular sustentada de etiologia chagásica em que foi utilizada angiografia ventricular direita para orientar a punçao pericárdica. Com o posicionamento de 2 microcateteres octapolares, obteve-se a localizaçao detalhada e a extensao da zona de conduçao lenta da taquicardia clínica. Constatou-se nessa regiao encarrilhamento com fusao oculta e ciclo de retorno igual ao ciclo de frequência da taquicardia. A aplicaçao local de radiofrequência interrompeu a taquicardia em 4 segundos, nao sendo possível sua reinduçao. Conclui-se que a punçao pericárdica pode ser orientada pela angiografia do ventrículo direito e que a utilizaçao de múltiplos cateteres com microeletrodos pode fornecer dados adicionais no mapeamento e na ablaçao epicárdica da taquicardia ventricular de etiologia chagásica

Ablaçao de Via Acessória Lateral Esquerda Oculta Durante o Encarrilhamento de Taquicardia Atrioventricular Ortodrômica: Um Modo de Manter a Estabilidade do Cateter de Ablaçao Durante Aplicaçao de Radiofreqüência

A ablaçao por radiofreqüência de via acessória lateral esquerda é freqüentemente realizada durante a taquicardia ortodrômica. O término da taquicardia durante a aplicaçao de radiofreqüência pode causar instabilidade do cateter de ablaçao. A aplicaçao da radiofreqüência durante o encarrilhamento da taquicardia mantém a freqüência ventricular constante, conferindo maior estabilidade ao cateter e maior eficácia ao procedimento

Ablaçao de Via Acessória Lateral Esquerda Oculta Durante o Encarrilhamento de Taquicardia Atrioventricular Ortodrômica: Um Modo de Manter a Estabilidade do Cateter de Ablaçao Durante Aplicaçao de Radiofreqüência

A ablaçao por radiofreqüência de via acessória lateral esquerda é freqüentemente realizada durante a taquicardia ortodrômica. O término da taquicardia durante a aplicaçao de radiofreqüência pode causar instabilidade do cateter de ablaçao. A aplicaçao da radiofreqüência durante o encarrilhamento da taquicardia mantém a freqüência ventricular constante, conferindo maior estabilidade ao cateter e maior eficácia ao procedimento

Wide and deep near-UV (360nm) galaxy counts and the extragalactic background light with the Large Binocular Camera

Deep multicolour surveys are the main tool to explore the formation and evolution of the faint galaxies which are beyond the spectroscopic limit with the present technology. The photometric properties of these faint galaxies are usually compared with current renditions of semianalytical models to provide constraints on the fundamental physical processes involved in galaxy formation and evolution, namely the mass assembly and the star formation. Galaxy counts over large sky areas in the near-UV band are important because they are difficult to obtain given the low efficiency of near-UV instrumentation, even at 8m class telescopes. A large instrumental field of view helps in minimizing the biases due to the cosmic variance. We have obtained deep images in the 360nm U band provided by the blue channel of the Large Binocular Camera at the prime focus of the Large Binocular Telescope. We have derived over an area of ~0.4 sq. deg. the galaxy number counts down to U=27 in the Vega system (corresponding to U=27.86 in the AB system) at a completeness level of 30% reaching the faintest current limit for this wavelength and sky area. The shape of the galaxy counts in the U band can be described by a double power-law, the bright side being consistent with the shape of shallower surveys of comparable or greater areas. The slope bends over significantly at U>23.5 ensuring the convergence of the contribution by star forming galaxies to the EBL in the near-UV band to a value which is more than 70% of the most recent upper limits derived for this band. We have jointly compared our near-UV and K band counts collected from the literature with few selected hierarchical CDM models emphasizing critical issues in the physical description of the galaxy formation and evolution.Comment: Accepted for publication in A&A. Uses aa.cls, 9 pages, 4 figures. Citations update

A change in the optical polarization associated with a gamma-ray flare in the blazar 3C 279

It is widely accepted that strong and variable radiation detected over all accessible energy bands in a number of active galaxies arises from a relativistic, Doppler-boosted jet pointing close to our line of sight. The size of the emitting zone and the location of this region relative to the central supermassive black hole are, however, poorly known, with estimates ranging from light-hours to a light-year or more. Here we report the coincidence of a gamma-ray flare with a dramatic change of optical polarization angle. This provides evidence for co-spatiality of optical and gamma-ray emission regions and indicates a highly ordered jet magnetic field. The results also require a non-axisymmetric structure of the emission zone, implying a curved trajectory for the emitting material within the jet, with the dissipation region located at a considerable distance from the black hole, at about 10^5 gravitational radii.Comment: Published in Nature issued on 18 February 2010. Corresponding authors: Masaaki Hayashida and Greg Madejsk

Hydrophilic antioxidant compounds in orange juice from different fruit cultivars: Composition and antioxidant activity evaluated by chemical and cellular based (Saccharomyces cerevisiae) assays

Antioxidant capacity was evaluated by a cellular model (Saccharomyces cerevisiae) and chemical methods (FRAP, TEAC and total phenols by Folin-Ciocalteu assay) in the hydrophilic fraction (phenolic compounds and ascorbic acid) of orange juices (OJs) from six varieties (Midknight, Delta Seedless, Rohde Red, Seedless, Early and clone Sambiasi), harvested in two seasons. The contents of phenolic compounds and ascorbic acid analyzed, respectively, by UPLC and HPLC were 370.04 76.97 mg/L and 52.05 6.69 mg/100 mL. Variety and season significantly influenced (p < 0.05) composition and antioxidant capacity. TEAC and FRAP values correlated well with individual hydrophilic compounds (R2 > 0.991) but no correlation with cellular assay was observed. An increase in survival rates between 23% and 38% was obtained, excepting for two varieties that showed no activity (Rohde Red and Seedless). Narirutin, naringin-d, ferulic acid-d2, didymin, neoeriocitrin and sinapic acid hexose and caffeic acid-d1 were the phenolic compounds which contributed to survival rates (R2 = 0.979, p < 0.01