30 research outputs found
The combined molecular adjuvant CASAC enhances the CD8+ T cell response to a tumor-associated self-antigen in aged, immunosenescent mice
BACKGROUND: Ineffective induction of T cell mediated immunity in older individuals remains a persistent challenge for vaccine development. Thus, there is a need for more efficient and sophisticated adjuvants that will complement novel vaccine strategies for the elderly. To this end, we have investigated a previously optimized, combined molecular adjuvant, CASAC (Combined Adjuvant for Synergistic Activation of Cellular immunity), incorporating two complementary Toll-like receptor agonists, CpG and polyI:C, a class-II epitope, and interferon (IFN)-γ in aged mice. FINDINGS: In aged mice with typical features of immunosenescence, antigen specific CD8+ T cell responses were stimulated after serial vaccinations with CASAC or Complete/Incomplete Freund's Adjuvant (CFA/IFA) and a class I epitope, deriving either from ovalbumin (SIINFEKL, SIL) or the melanoma-associated self-antigen, tyrosinase-related protein-2 (SVYDFFVWL, SVL). Pentamer analysis revealed that aged, CASAC/SIL-vaccinated animals had substantially higher frequencies of H-2K(b)/SIL-specific CD8+ T cells compared to the CFA/IFA-vaccinated groups. Similarly, higher frequencies of H-2K(b)/SVL-pentamer+ and IFN-γ+ CD8+ T cells were detected in the aged, CASAC + SVL-vaccinated mice than in their CFA/IFA-vaccinated counterparts. In both antigen settings, CASAC promoted significantly better functional CD8+ T cell activity. CONCLUSION: These studies demonstrate that functional CD8+ T cells, specific for both foreign and tumour-associated self-antigens, can be effectively induced in aged immunosenescent mice using the novel multi-factorial adjuvant CASAC
Radio emission from Supernova Remnants
The explosion of a supernova releases almost instantaneously about 10^51 ergs
of mechanic energy, changing irreversibly the physical and chemical properties
of large regions in the galaxies. The stellar ejecta, the nebula resulting from
the powerful shock waves, and sometimes a compact stellar remnant, constitute a
supernova remnant (SNR). They can radiate their energy across the whole
electromagnetic spectrum, but the great majority are radio sources. Almost 70
years after the first detection of radio emission coming from a SNR, great
progress has been achieved in the comprehension of their physical
characteristics and evolution. We review the present knowledge of different
aspects of radio remnants, focusing on sources of the Milky Way and the
Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief
overview of theoretical background, analyze morphology and polarization
properties, and review and critical discuss different methods applied to
determine the radio spectrum and distances. The consequences of the interaction
between the SNR shocks and the surrounding medium are examined, including the
question of whether SNRs can trigger the formation of new stars. Cases of
multispectral comparison are presented. A section is devoted to reviewing
recent results of radio SNRs in the Magellanic Clouds, with particular emphasis
on the radio properties of SN 1987A, an ideal laboratory to investigate
dynamical evolution of an SNR in near real time. The review concludes with a
summary of issues on radio SNRs that deserve further study, and analyzing the
prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure
Fine Tuning of Globin Gene Expression by DNA Methylation
Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γ(A) and γ(G) genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse system that allowed us to control γ(A) methylation during development. DNA methylation causes a 20-fold repression of γ(A) both in non-erythroid and adult erythroid cells. In erythroid cells this modification works as a dominant mechanism to repress γ gene expression, probably through changes in histone acetylation that prevent the binding of erythroid transcription factors to the promoter. These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. In addition, our findings provide a mechanism for understanding the high levels of γ-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate γ-globin expression in patients with β-hemoglobinopathies
Spectropolarimetry of stars across the H-R diagram
The growing sample of magnetic stars shows a remarkable diversity in the
properties of their magnetic fields. The overall goal of current studies is to
understand the origin, evolution, and structure of stellar magnetic fields in
stars of different mass at different evolutionary stages. In this chapter we
discuss recent measurements together with the underlying assumptions in the
interpretation of data and the requirements, both observational and
theoretical, for obtaining a realistic overview of the role of magnetic fields
in various types of stars.Comment: 23 pages, 3 figures, chapter 7 of "Astronomical Polarisation from the
Infrared to Gamma Rays", published in Astrophysics and Space Science Library
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Supernova remnants: the X-ray perspective
Supernova remnants are beautiful astronomical objects that are also of high
scientific interest, because they provide insights into supernova explosion
mechanisms, and because they are the likely sources of Galactic cosmic rays.
X-ray observations are an important means to study these objects.And in
particular the advances made in X-ray imaging spectroscopy over the last two
decades has greatly increased our knowledge about supernova remnants. It has
made it possible to map the products of fresh nucleosynthesis, and resulted in
the identification of regions near shock fronts that emit X-ray synchrotron
radiation.
In this text all the relevant aspects of X-ray emission from supernova
remnants are reviewed and put into the context of supernova explosion
properties and the physics and evolution of supernova remnants. The first half
of this review has a more tutorial style and discusses the basics of supernova
remnant physics and thermal and non-thermal X-ray emission. The second half
offers a review of the recent advances.The topics addressed there are core
collapse and thermonuclear supernova remnants, SN 1987A, mature supernova
remnants, mixed-morphology remnants, including a discussion of the recent
finding of overionization in some of them, and finally X-ray synchrotron
radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2
column-layout. 78 pages, 42 figures. This replaced version has some minor
language edits and several references have been correcte
A Nearby Repeating Fast Radio Burst in the Direction of M81
We report on the discovery of FRB 20200120E, a repeating fast radio burst
(FRB) with low dispersion measure (DM), detected by the Canadian Hydrogen
Intensity Mapping Experiment (CHIME)/FRB project. The source DM of 87.82 pc
cm is the lowest recorded from an FRB to date, yet is significantly
higher than the maximum expected from the Milky Way interstellar medium in this
direction (~ 50 pc cm). We have detected three bursts and one candidate
burst from the source over the period 2020 January-November. The baseband
voltage data for the event on 2020 January 20 enabled a sky localization of the
source to within 14 sq. arcmin (90% confidence). The FRB localization
is close to M81, a spiral galaxy at a distance of 3.6 Mpc. The FRB appears on
the outskirts of M81 (projected offset 20 kpc) but well inside its
extended HI and thick disks. We empirically estimate the probability of chance
coincidence with M81 to be . However, we cannot reject a Milky Way
halo origin for the FRB. Within the FRB localization region, we find several
interesting cataloged M81 sources and a radio point source detected in the Very
Large Array Sky Survey (VLASS). We searched for prompt X-ray counterparts in
Swift/BAT and Fermi/GBM data, and for two of the FRB 20200120E bursts, we rule
out coincident SGR 180620-like X-ray bursts. Due to the proximity of FRB
20200120E, future follow-up for prompt multi-wavelength counterparts and
sub-arcsecond localization could be constraining of proposed FRB models
Testes de função pulmonar e mortalidade após o transplante de células-tronco hematopoiéticas Hematopoietic stem cell transplantation: pulmonary function tests and post-transplant mortality
OBJETIVO: Verificar se os resultados dos testes de função pulmonar realizados em pacientes submetidos a transplante de células-tronco hematopoiéticas (TCTH) estão associados com a mortalidade após o procedimento. MÉTODOS: Estudo prospectivo no qual foram incluÃdos pacientes maiores de 15 anos submetidos a TCTH alogênico, entre janeiro de 2007 e março de 2008, no Hospital das ClÃnicas da Universidade Federal de Minas Gerais, em Belo Horizonte (MG), e que realizaram espirometria, medida de volumes pulmonares e medida de DLCO antes do TCTH. Os testes foram repetidos seis meses, um ano e dois anos após TCTH. Para a análise de sobrevida, foram utilizados o método de Kaplan-Meier e testes de log-rank bicaudal. O risco relativo (RR) e IC95% foram calculados por meio do ajuste do modelo de riscos proporcionais de Cox. O modelo de regressão de Cox foi utilizado na análise multivariada. RESULTADOS: Dos 54 pacientes incluÃdos, 40 (74,1%) apresentaram resultados normais de função pulmonar antes do TCTH. Ocorreram 23 óbitos (42,6%) em dois anos após o TCTH, sendo que 19 aconteceram antes de 100 dias. Dos 23 óbitos, 11 (47,8%) foram por septicemia e 10 (43,4%) por insuficiência respiratória aguda associada à septicemia. As únicas variáveis que mostraram associação significativa com mortalidade após TCTH foram alteração na espirometria antes do TCTH (RR = 3,2; p = 0,016) e doador não aparentado (RR = 9,0; p < 0,001). CONCLUSÕES:A realização da espirometria antes do TCTH fornece valores basais para comparações futuras. Alterações nesses resultados indicam um maior risco de mortalidade após o TCTH, embora esses não contraindicam o procedimento.<br>OBJECTIVE:To determine whether the results of pulmonary function tests carried out in patients subsequently submitted to hematopoietic stem cell transplantation (HSCT) are associated with post-HSCT mortality. METHODS: This was a prospective study involving patients older than 15 years of age who were submitted to allogenic HSCT between January of 2007 and March of 2008 at the Hospital das ClÃnicas da Universidade Federal de Minas Gerais, located in the city of Belo Horizonte, Brazil. Prior to HSCT, all of the patients underwent spirometry, determination of lung volumes, and determination of DLCO. Those same tests were repeated six months, one year, and two years after HSCT. Kaplan-Meier curves and two-tailed log-rank tests were used for survival analysis. The relative risk (RR) and 95% CI were calculated using the Cox proportional hazards model. The Cox regression model was used in the multivariate analysis. RESULTS:The pre-HSCT pulmonary function results were normal in 40 (74.1%) of the 54 patients evaluated, 19 (35.2%) of whom died within the first 100 days after HSCT. By the end of the two-year follow-up period, 23 patients (42.6%) had died, the most common causes of death being septicemia, observed in 11 (47.8%), and septicemia-related respiratory insufficiency, observed in 10 (43.4%). The only variables significantly associated with post-HSCT mortality were alterations in spirometry results prior to HSCT (RR = 3.2; p = 0.016) and unrelated donor (RR = 9.0; p < 0.001). CONCLUSIONS: Performing spirometry prior to HSCT provides baseline values for future comparisons. Although alterations in spirometry results reveal a higher risk of post-HSCT mortality, such alterations do not contraindicate the procedure
No Evidence for Galactic Latitude Dependence of the Fast Radio Burst Sky Distribution
Abstract
We investigate whether the sky rate of fast radio bursts (FRBs) depends on Galactic latitude using the first catalog of FRBs detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst (CHIME/FRB) Project. We first select CHIME/FRB events above a specified sensitivity threshold in consideration of the radiometer equation, and then we compare these detections with the expected cumulative time-weighted exposure using Anderson–Darling and Kolmogorov–Smirnov tests. These tests are consistent with the null hypothesis that FRBs are distributed without Galactic latitude dependence (p-values distributed from 0.05 to 0.99, depending on completeness threshold). Additionally, we compare rates in intermediate latitudes (∣b∣ < 15°) with high latitudes using a Bayesian framework, treating the question as a biased coin-flipping experiment–again for a range of completeness thresholds. In these tests the isotropic model is significantly favored (Bayes factors ranging from 3.3 to 14.2). Our results are consistent with FRBs originating from an isotropic population of extragalactic sources.</jats:p