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Optical Spectroscopy Of X-Ray Sources In The Extended Chandra Deep Field South
We present the first results of our optical spectroscopy program aimed to provide redshifts and identifications for the X-ray sources in the Extended Chandra Deep Field South. A total of 339 sources were targeted using the IMACS spectrograph at the Magellan telescopes and the VIMOS spectrograph at the VLT. We measured redshifts for 186 X-ray sources, including archival data and a literature search. We find that the active galactic nucleus (AGN) host galaxies have on average redder rest-frame optical colors than nonactive galaxies, and that they live mostly in the "green valley." The dependence of the fraction of AGNs that are obscured on both luminosity and redshift is confirmed at high significance and the observed AGN spatial density is compared with the expectations from existing luminosity functions. These AGNs show a significant difference in the mid-IR to X-ray flux ratio for obscured and unobscured AGNs, which can be explained by the effects of dust self-absorption on the former. This difference is larger for lower luminosity sources, which is consistent with the dust opening angle depending on AGN luminosity.National Aeronautics and Space Administration PF8-90055, NAS8-03060NSF AST0407295Spitzer JPL RSA1288440Natural Science and Engineering Research Council of Canada (NSERC)National Academy of SciencesNASA/INTEGRAL NNG05GM79GAstronom
Spitzer Constraints on the Stellar Populations of Lyman-Alpha Emitting Galaxies at z = 3.1
We investigate the stellar populations of a sample of 162 Lyman-alpha
emitting galaxies (LAEs) at z = 3.1 in the Extended Chandra Deep Field South,
using deep Spitzer IRAC data available from the GOODS and SIMPLE surveys to
derive reliable stellar population estimates. We divide the LAEs according to
their rest-frame near-IR luminosities into IRAC-detected and IRAC-undetected
samples. About 70% of the LAEs are undetected in 3.6 micron down to [3.6] =
25.2 AB. Stacking analysis reveals that the average stellar population of the
IRAC-undetected sample has an age of ~ 200 Myr and a mass of ~ 3x10^8 solar
masses, consistent with the expectation that LAEs are mostly young and low-mass
galaxies. On the other hand, the IRAC-detected LAEs are on average
significantly older and more massive, with an average age > 1 Gyr and mass ~
10^10 solar masses. Comparing the IRAC colors and magnitudes of the LAEs to z ~
3 Lyman break galaxies (LBGs) shows that the IRAC-detected LAEs lie at the
faint blue end of the LBG color-magnitude distribution, suggesting that
IRAC-detected LAEs may be the low mass extension of the LBG population. We also
present tentative evidence for a small fraction (~ 5%) of obscured AGN within
the LAE sample. Our results suggest that LAEs posses a wide range of ages and
masses. Additionally, the presence of evolved stellar populations inside LAEs
suggests that the Lyman-alpha luminous phase of galaxies may either be a
long-lasting or recurring phenomenon.Comment: Accepted for publication in ApJ; 5 pages, 4 figure
Mid-infrared Properties and Color Selection for X-ray Detected AGN in the MUSYC ECDF-S field
We present the mid-infrared colors of X-ray-detected AGN and explore
mid-infrared selection criteria. Using a statistical matching technique, the
likelihood ratio, over 900 IRAC counterparts were identified with a new MUSYC
X-ray source catalog that includes ~1000 published X-ray sources in the Chandra
Deep Field-South and Extended Chandra Deep Field-South. Most X-ray-selected AGN
have IRAC spectral shapes consistent with power-law slopes, f_{nu} ~
nu^{alpha}, and display a wide range of colors, -2 < alpha < 2. Although X-ray
sources typically fit to redder (more negative alpha) power-laws than non-X-ray
detected galaxies, more than 50% do have flat or blue (galaxy-like) spectral
shapes in the observed 3-8 micron band. Only a quarter of the X-ray selected
AGN detected at 24 micron are well fit by featureless red power laws in the
observed 3.6-24 micron, likely the subset of our sample whose infrared spectra
are dominated by emission from the central AGN region. Most IRAC
color-selection criteria fail to identify the majority of X-ray-selected AGN,
finding only the more luminous AGN, the majority of which have broad emission
lines. In deep surveys, these color-selection criteria select 10-20% of the
entire galaxy population and miss many moderate luminosity AGN.Comment: 29 pages, including 7 figures. Accepted for publication in the
Astrophysical Journa
Star formation in the CDFS: observations confront simulations
We investigate the star formation history of the universe using FIREWORKS, a
multiwavelength survey of the CDFS. We study the evolution of the specific star
formation rate (sSFR) with redshift in different mass bins from z = 0 to z ~ 3.
We find that the sSFR increases with redshift for all masses. The logarithmic
increase of the sSFR with redshift is nearly independent of mass, but this
cannot yet be verified at the lowest-mass bins at z > 0.8, due to
incompleteness. We convert the sSFRs to a dimensionless growth rate to
facilitate a comparison with a semi-analytic galaxy formation model that was
implemented on the Millennium Simulation. The model predicts that the growth
rates and sSFRs increase similarly with redshift for all masses, consistent
with the observations. However, we find that for all masses, the inferred
observed growth rates increase more rapidly with redshift than the model
predictions. We discuss several possible causes for this discrepancy, ranging
from field-to-field variance, conversions to SFR, and shape of the IMF. We find
that none of these can solve the discrepancy completely. We conclude that the
models need to be adapted to produce the steep increase in growth rate between
redshift z=0 and z=1.Comment: 7 pages, 5 figure
The Multiwavelength Survey by Yale-Chile (MUSYC): Deep Medium-Band optical imaging and high quality 32-band photometric redshifts in the ECDF-S
We present deep optical 18-medium-band photometry from the Subaru telescope
over the ~30' x 30' Extended Chandra Deep Field-South (ECDF-S), as part of the
Multiwavelength Survey by Yale-Chile (MUSYC). This field has a wealth of
ground- and space-based ancillary data, and contains the GOODS-South field and
the Hubble Ultra Deep Field. We combine the Subaru imaging with existing
UBVRIzJHK and Spitzer IRAC images to create a uniform catalog. Detecting
sources in the MUSYC BVR image we find ~40,000 galaxies with R_AB<25.3, the
median 5 sigma limit of the 18 medium bands. Photometric redshifts are
determined using the EAZY code and compared to ~2000 spectroscopic redshifts in
this field. The medium band filters provide very accurate redshifts for the
(bright) subset of galaxies with spectroscopic redshifts, particularly at 0.1 <
z 3.5. For 0.1 < z < 1.2, we find a 1 sigma scatter in \Delta
z/(1+z) of 0.007, similar to results obtained with a similar filter set in the
COSMOS field. As a demonstration of the data quality, we show that the red
sequence and blue cloud can be cleanly identified in rest-frame color-magnitude
diagrams at 0.1 < z < 1.2. We find that ~20% of the red-sequence-galaxies show
evidence of dust-emission at longer rest-frame wavelengths. The reduced images,
photometric catalog, and photometric redshifts are provided through the public
MUSYC website.Comment: 19 pages, 14 image
The evolution of the specific star formation rate of massive galaxies to z ~ 1.8 in the E-CDFS
We study the evolution of the star formation rate (SFR) of mid-infrared (IR)
selected galaxies in the extended Chandra Deep Field South (E-CDFS). We use a
combination of U-K GaBoDS and MUSYC data, deep IRAC observations from SIMPLE,
and deep MIPS data from FIDEL. This unique multi-wavelength data set allows us
to investigate the SFR history of massive galaxies out to redshift z ~ 1.8. We
determine star formation rates using both the rest-frame ultraviolet luminosity
from young, hot stars and the total IR luminosity of obscured star formation
obtained from the MIPS 24 um flux. We find that at all redshifts the galaxies
with higher masses have substantially lower specific star formation rates than
lower mass galaxies. The average specific star formation rates increase with
redshift, and the rate of incline is similar for all galaxies (roughly
(1+z)^{n}, n = 5.0 +/- 0.4). It does not seem to be a strong function of galaxy
mass. Using a subsample of galaxies with masses M_*> 10^11 M_sun, we measured
the fraction of galaxies whose star formation is quenched. We consider a galaxy
to be in quiescent mode when its specific star formation rate does not exceed
1/(3 x t_H), where t_H is the Hubble time. The fraction of quiescent galaxies
defined as such decreases with redshift out to z ~ 1.8. We find that, at that
redshift, 19 +/-9 % of the M_* > 10^11 M_sun sources would be considered
quiescent according to our criterion.Comment: 7 pages, 6 figures, accepted for publication in Ap
A Public, K-Selected, Optical-to-Near-Infrared Catalog of the Extended Chandra Deep Field South (ECDFS) from the MUltiwavelength Survey by Yale-Chile (MUSYC)
We present a new K-selected, optical-to-near-infrared photometric catalog of
the Extended Chandra Deep Field South (ECDFS), making it publicly available to
the astronomical community. The dataset is founded on publicly available
imaging, supplemented by original zJK imaging data obtained as part of the
MUltiwavelength Survey by Yale-Chile (MUSYC). The final photometric catalog
consists of photometry derived from nine band U-K imaging covering the full
0.5x0.5 sq. deg. of the ECDFS, plus H band data for approximately 80% of the
field. The 5sigma flux limit for point-sources is K = 22.0 (AB). This is also
the nominal completeness and reliability limit of the catalog: the empirical
completeness for 21.75 < K < 22.00 is 85+%. We have verified the quality of the
catalog through both internal consistency checks, and comparisons to other
existing and publicly available catalogs. As well as the photometric catalog,
we also present catalogs of photometric redshifts and restframe photometry
derived from the ten band photometry. We have collected robust spectroscopic
redshift determinations from published sources for 1966 galaxies in the
catalog. Based on these sources, we have achieved a (1sigma) photometric
redshift accuracy of Dz/(1+z) = 0.036, with an outlier fraction of 7.8%. Most
of these outliers are X-ray sources. Finally, we describe and release a utility
for interpolating restframe photometry from observed SEDs, dubbed InterRest.
Particularly in concert with the wealth of already publicly available data in
the ECDFS, this new MUSYC catalog provides an excellent resource for studying
the changing properties of the massive galaxy population at z < 2. (Abridged)Comment: Re-submitted to ApJSS after a first referee report. 27 pages, 17
figures. MUSYC data is freely available from http://astro.yale.edu/MUSYC .
Links to phot-z and restframe photometry catalogs, as well as to InterRest
access and documentation, including a full walkthrough, can be found at
http://www.strw.leidenuniv.nl/~ent
Effectiveness of FeNO-guided treatment in adult asthma patients: A systematic review and meta-analysis
Objective: Asthma control is generally monitored by assessing symptoms and lung function. However, optimal treatment is also dependent on the type and extent of airway inflammation. Fraction of exhaled Nitric Oxide (FeNO) is a noninvasive biomarker of type 2 airway inflammation, but its effectiveness in guiding asthma treatment remains disputed. We performed a systematic review and meta-analysis to obtain summary estimates of the effectiveness of FeNO-guided asthma treatment. Design: We updated a Cochrane systematic review from 2016. Cochrane Risk of Bias tool was used to assess risk of bias. Inverse-variance random-effects meta-analysis was performed. Certainty of evidence was assessed using GRADE. Subgroup analyses were performed based on asthma severity, asthma control, allergy/atopy, pregnancy and obesity. Data Sources: The Cochrane Airways Group Trials Register was searched on 9 May 2023. Eligibility Criteria: We included randomized controlled trials (RCTs) comparing the effectiveness of a FeNO-guided treatment versus usual (symptom-guided) treatment in adult asthma patients. Results: We included 12 RCTs (2,116 patients), all showing high or unclear risk of bias in at least one domain. Five RCTs reported support from a FeNO manufacturer. FeNO-guided treatment probably reduces the number of patients having â„1 exacerbation (OR = 0.61; 95%CI 0.44 to 0.83; six RCTs; GRADE moderate certainty) and exacerbation rate (RR = 0.67; 95%CI 0.54 to 0.82; six RCTs; moderate certainty), and may slightly improve Asthma Control Questionnaire score (MD = â0.10; 95%CI â0.18 to â0.02, six RCTs; low certainty), however, this change is unlikely to be clinically important. An effect on severe exacerbations, quality of life, FEV1, treatment dosage and FeNO values could not be demonstrated. There were no indications that effectiveness is different in subgroups of patients, although evidence for subgroup analysis was limited. Conclusions: FeNO-guided asthma treatment probably results in fewer exacerbations but may not have clinically important effects on other asthma outcomes
IgA antibody immunotherapy targeting GD2 is effective in preclinical neuroblastoma models
BACKGROUND: Immunotherapy targeting GD2 is very effective against high-risk neuroblastoma, though administration of anti-GD2 antibodies induces severe and dose-limiting neuropathic pain by binding GD2-expressing sensory neurons. Previously, the IgG1 ch14.18 (dinutuximab) antibody was reformatted into the IgA1 isotype, which abolishes neuropathic pain and induces efficient neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) via activation of the Fc alpha receptor (FcαRI/CD89). METHODS: To generate an antibody suitable for clinical application, we engineered an IgA molecule (named IgA3.0 ch14.18) with increased stability, mutated glycosylation sites and substituted free (reactive) cysteines. The following mutations were introduced: N45.2G and P124R (CH1 domain), C92S, N120T, I121L and T122S (CH2 domain) and a deletion of the tail piece P131-Y148 (CH3 domain). IgA3.0 ch14.18 was evaluated in binding assays and in ADCC and antibody-dependent cellular phagocytosis (ADCP) assays with human, neuroblastoma patient and non-human primate effector cells. We performed mass spectrometry analysis of N-glycans and evaluated the impact of altered glycosylation in IgA3.0 ch14.18 on antibody half-life by performing pharmacokinetic (PK) studies in mice injected intravenously with 5âmg/kg antibody solution. A dose escalation study was performed to determine in vivo efficacy of IgA3.0 ch14.18 in an intraperitoneal mouse model using 9464D-GD2 neuroblastoma cells as well as in a subcutaneous human xenograft model using IMR32 neuroblastoma cells. Binding assays and PK studies were compared with one-way analysis of variance (ANOVA), ADCC and ADCP assays and in vivo tumor outgrowth with two-way ANOVA followed by Tukey's post-hoc test. RESULTS: ADCC and ADCP assays showed that particularly neutrophils and macrophages from healthy donors, non-human primates and patients with neuroblastoma are able to kill neuroblastoma tumor cells efficiently with IgA3.0 ch14.18. IgA3.0 ch14.18 contains a more favorable glycosylation pattern, corresponding to an increased antibody half-life in mice compared with IgA1 and IgA2. Furthermore, IgA3.0 ch14.18 penetrates neuroblastoma tumors in vivo and halts tumor outgrowth in both 9464D-GD2 and IMR32 long-term tumor models. CONCLUSIONS: IgA3.0 ch14.18 is a promising new therapy for neuroblastoma, showing (1) increased half-life compared to natural IgA antibodies, (2) increased protein stability enabling effortless production and purification, (3) potent CD89-mediated tumor killing in vitro by healthy subjects and patients with neuroblastoma and (4) antitumor efficacy in long-term mouse neuroblastoma models
IgA antibody immunotherapy targeting GD2 is effective in preclinical neuroblastoma models
BACKGROUND: Immunotherapy targeting GD2 is very effective against high-risk neuroblastoma, though administration of anti-GD2 antibodies induces severe and dose-limiting neuropathic pain by binding GD2-expressing sensory neurons. Previously, the IgG1 ch14.18 (dinutuximab) antibody was reformatted into the IgA1 isotype, which abolishes neuropathic pain and induces efficient neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) via activation of the Fc alpha receptor (FcαRI/CD89). METHODS: To generate an antibody suitable for clinical application, we engineered an IgA molecule (named IgA3.0 ch14.18) with increased stability, mutated glycosylation sites and substituted free (reactive) cysteines. The following mutations were introduced: N45.2G and P124R (CH1 domain), C92S, N120T, I121L and T122S (CH2 domain) and a deletion of the tail piece P131-Y148 (CH3 domain). IgA3.0 ch14.18 was evaluated in binding assays and in ADCC and antibody-dependent cellular phagocytosis (ADCP) assays with human, neuroblastoma patient and non-human primate effector cells. We performed mass spectrometry analysis of N-glycans and evaluated the impact of altered glycosylation in IgA3.0 ch14.18 on antibody half-life by performing pharmacokinetic (PK) studies in mice injected intravenously with 5âmg/kg antibody solution. A dose escalation study was performed to determine in vivo efficacy of IgA3.0 ch14.18 in an intraperitoneal mouse model using 9464D-GD2 neuroblastoma cells as well as in a subcutaneous human xenograft model using IMR32 neuroblastoma cells. Binding assays and PK studies were compared with one-way analysis of variance (ANOVA), ADCC and ADCP assays and in vivo tumor outgrowth with two-way ANOVA followed by Tukey's post-hoc test. RESULTS: ADCC and ADCP assays showed that particularly neutrophils and macrophages from healthy donors, non-human primates and patients with neuroblastoma are able to kill neuroblastoma tumor cells efficiently with IgA3.0 ch14.18. IgA3.0 ch14.18 contains a more favorable glycosylation pattern, corresponding to an increased antibody half-life in mice compared with IgA1 and IgA2. Furthermore, IgA3.0 ch14.18 penetrates neuroblastoma tumors in vivo and halts tumor outgrowth in both 9464D-GD2 and IMR32 long-term tumor models. CONCLUSIONS: IgA3.0 ch14.18 is a promising new therapy for neuroblastoma, showing (1) increased half-life compared to natural IgA antibodies, (2) increased protein stability enabling effortless production and purification, (3) potent CD89-mediated tumor killing in vitro by healthy subjects and patients with neuroblastoma and (4) antitumor efficacy in long-term mouse neuroblastoma models