359 research outputs found
Far-Infrared and Sub-Millimeter Observations and Physical Models of the Reflection Nebula Ced 201
ISO [C II] 158 micron, [O I] 63 micron, and H_2 9 and 17 micron observations
are presented of the reflection nebula Ced 201, which is a photon-dominated
region illuminated by a B9.5 star with a color temperature of 10,000 K (a cool
PDR). In combination with ground based [C I] 609 micron, CO, 13CO, CS and HCO+
data, the carbon budget and physical structure of the reflection nebula are
constrained. The obtained data set is the first one to contain all important
cooling lines of a cool PDR, and allows a comparison to be made with classical
PDRs. To this effect one- and three-dimensional PDR models are presented which
incorporate the physical characteristics of the source, and are aimed at
understanding the dominant heating processes of the cloud. The contribution of
very small grains to the photo-electric heating rate is estimated from these
models and used to constrain the total abundance of PAHs and small grains.
Observations of the pure rotational H_2 lines with ISO, in particular the S(3)
line, indicate the presence of a small amount of very warm, approximately 330
K, molecular gas. This gas cannot be accommodated by the presented models.Comment: 32 pages, 7 figures, in LaTeX. To be published in Ap
Wind clumping and the wind-wind collision zone in the Wolf-Rayet binary gamma Velorum
We present XMM-Newton observations of gamma^2 Velorum (WR 11, WC8+O7.5III, P
= 78.53 d), a nearby Wolf-Ray binary system, at its X-ray high and low states.
At high state, emission from a hot collisional plasma dominates from about 1 to
8 keV. At low state, photons between 1 and 4 keV are absorbed. The hot plasma
is identified with the shock zone between the winds of the primary Wolf-Rayet
star and the secondary O giant. The absorption at low state is interpreted as
photoelectric absorption in the Wolf-Rayet wind. This absorption allows us to
measure the absorbing column density and to derive a mass loss rate 8x10^{-6}
M_sun/yr for the WC8 star. This mass loss rate, in conjunction with a previous
Wolf-Rayet wind model, provides evidence for a clumped WR wind. A clumping
factor of 16 is required. The X-ray spectra below 1 keV (12 Ang) show no
absorption and are essentially similar in both states. There is a rather clear
separation in that emission from a plasma hotter than 5 MK is heavily absorbed
in low state while the cooler plasma is not. This cool plasma must come from a
much more extended region than the hot material. The Neon abundance in the
X-ray emitting material is 2.5 times the solar value. The unexpected detection
of CV (25.3 Ang) and CVI (31.6 Ang) radiative recombination continua at both
phases indicates the presence of a cool (~40,000 K) recombination region
located far out in the binary system.Comment: 16 page
Photoproduction of scalar mesons on protons and nuclei
We study the photoproduction of scalar mesons close to the threshold of
f_0(980) and a_0(980) using a unitary chiral model. Peaks for both resonances
show up in the invariant mass distributions of pairs of pseudoscalar mesons. A
discussion is made on the photoproduction of these resonances in nuclei, which
can shed light on their nature, a subject of continuous debate.Comment: 25 pages, 9 figures, accepted for publication in Phys Rev
Novel chimerized IgA CD20 antibodies : Improving neutrophil activation against CD20-positive malignancies
ABSTRACT Current combination therapies elicit high response rates in B cell malignancies, often using CD20 antibodies as the backbone of therapy. However, many patients eventually relapse or develop progressive disease. Therefore, novel CD20 antibodies combining multiple effector mechanisms were generated. To study whether neutrophil-mediated destruction of B cell malignancies can be added to the arsenal of effector mechanisms, we chimerized a panel of five previously described murine CD20 antibodies to the human IgG1, IgA1 and IgA2 isotype. Of this panel, we assessed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and direct cell death induction capacity and studied the efficacy in two different in vivo mouse models. IgA antibodies outperformed IgG1 antibodies in neutrophil-mediated killing in vitro, both against CD20-expressing cell lines and primary patient material. In these assays, we observed loss of CD19 with both IgA and IgG antibodies. Therefore, we established a novel method to improve the assessment of B-cell depletion by CD20 antibodies by including CD24 as a stable cell marker. Subsequently, we demonstrated that only IgA antibodies were able to reduce B cell numbers in this context. Additionally, IgA antibodies showed efficacy in both an intraperitoneal tumor model with EL4 cells expressing huCD20 and in an adoptive transfer model with huCD20-expressing B cells. Taken together, we show that IgA, like IgG, can induce ADCC and CDC, but additionally triggers neutrophils to kill (malignant) B cells. We conclude that antibodies of the IgA isotype offer an attractive repertoire of effector mechanisms for the treatment of CD20-expressing malignancies.Peer reviewe
Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science
SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry
out the first all-sky spectral survey and provide for every 6.2" pixel a
spectra between 0.75 and 4.18 m [with R41.4] and 4.18 and 5.00
m [with R135]. The SPHEREx team has proposed three specific science
investigations to be carried out with this unique data set: cosmic inflation,
interstellar and circumstellar ices, and the extra-galactic background light.
It is readily apparent, however, that many other questions in astrophysics and
planetary sciences could be addressed with the SPHEREx data. The SPHEREx team
convened a community workshop in February 2016, with the intent of enlisting
the aid of a larger group of scientists in defining these questions. This paper
summarizes the rich and varied menu of investigations that was laid out. It
includes studies of the composition of main belt and Trojan/Greek asteroids;
mapping the zodiacal light with unprecedented spatial and spectral resolution;
identifying and studying very low-metallicity stars; improving stellar
parameters in order to better characterize transiting exoplanets; studying
aliphatic and aromatic carbon-bearing molecules in the interstellar medium;
mapping star formation rates in nearby galaxies; determining the redshift of
clusters of galaxies; identifying high redshift quasars over the full sky; and
providing a NIR spectrum for most eROSITA X-ray sources. All of these
investigations, and others not listed here, can be carried out with the nominal
all-sky spectra to be produced by SPHEREx. In addition, the workshop defined
enhanced data products and user tools which would facilitate some of these
scientific studies. Finally, the workshop noted the high degrees of synergy
between SPHEREx and a number of other current or forthcoming programs,
including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop,
http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure
Inflammation Aggravates Disease Severity in Marfan Syndrome Patients
BACKGROUND: Marfan syndrome (MFS) is a pleiotropic genetic disorder with major features in cardiovascular, ocular and skeletal systems, associated with large clinical variability. Numerous studies reveal an involvement of TGF-beta signaling. However, the contribution of tissue inflammation is not addressed so far. METHODOLOGY/PRINCIPAL FINDINGS: Here we showed that both TGF-beta and inflammation are up-regulated in patients with MFS. We analyzed transcriptome-wide gene expression in 55 MFS patients using Affymetrix Human Exon 1.0 ST Array and levels of TGF-beta and various cytokines in their plasma. Within our MFS population, increased plasma levels of TGF-beta were found especially in MFS patients with aortic root dilatation (124 pg/ml), when compared to MFS patients with normal aorta (10 pg/ml; p = 8x10(-6), 95% CI: 70-159 pg/ml). Interestingly, our microarray data show that increased expression of inflammatory genes was associated with major clinical features within the MFS patients group; namely severity of the aortic root dilatation (HLA-DRB1 and HLA-DRB5 genes; r = 0.56 for both; False Discovery Rate(FDR) = 0%), ocular lens dislocation (RAET1L, CCL19 and HLA-DQB2; Fold Change (FC) = 1.8; 1.4; 1.5, FDR = 0%) and specific skeletal features (HLA-DRB1, HLA-DRB5, GZMK; FC = 8.8, 7.1, 1.3; FDR = 0%). Patients with progressive aortic disease had higher levels of Macrophage Colony Stimulating Factor (M-CSF) in blood. When comparing MFS aortic root vessel wall with non-MFS aortic root, increased numbers of CD4+ T-cells were found in the media (p = 0.02) and increased number of CD8+ T-cells (p = 0.003) in the adventitia of the MFS patients. CONCLUSION/SIGNIFICANCE: In conclusion, our results imply a modifying role of inflammation in MFS. Inflammation might be a novel therapeutic target in these patients
Immediate versus postponed intervention for infected necrotizing pancreatitis
BACKGROUND Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, −1; 95% confidence interval [CI], −12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Low relapse risk in poor risk AML after conditioning with 10-day decitabine, fludarabine and 2 Gray TBI prior to allogeneic hematopoietic cell transplantation.
Patients with poor risk acute myeloid leukemia (AML) have a dismal outcome. We hypothesized that combining decitabine with a standard non-myeloablative (NMA) conditioning regimen prior to allogeneic hematopoietic cell transplantation (allo HCT), might decrease the relapse incidence. We conducted a multicenter prospective phase II study (NCT02252107) with 10-day decitabine (20 mg/m(2)/day) integrated in a standard non-myeloablative conditioning regimen (3 days fludarabine 30 mg/m(2) with 2 Gray total body irradiation (TBI)). Patients with AML ≥ 18 years in 1st (in)complete remission (CR/CRi) with a poor or very poor risk profile, as defined by the HOVON-132 protocol, were eligible. Results: Forty-six patients (median age 60; range 23-74) were included. Median follow up time was 44 months (range 31-65 months). The cumulative 1-year incidence of relapse and NRM were respectively 23% and 11%. Incidence of grade III-IV acute graft-vs-host-disease (GVHD) and severe chronic GVHD were 13% and 20%, respectively. One-year OS was 70%. Application of ELN 2017 risk classification to the study cohort revealed a cumulative one-year relapse rate of respectively 31% and 13% for the adverse and intermediate risk patients. To conclude, the 10-day DEC/FLU/TBI conditioning regimen prior to allo HCT in poor risk AML patients is effective and feasible
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