79 research outputs found
Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients
In this study we evaluated the potential of expanded NK cells (eNKs) from two sources combined with the mAbs daratumumab and pembrolizumab to target primary multiple myeloma (MM) cells ex vivo. In order to ascertain the best source of NK cells, we expanded and activated NK cells from peripheral blood (PB) of healthy adult donors and from umbilical cord blood (UCB). The resulting expanded NK (eNK) cells express CD16, necessary for carrying out antibody-dependent cellular cytotoxicity (ADCC). Cytotoxicity assays were performed on bone marrow aspirates of 18 MM patients and 4 patients with monoclonal gammopathy of undetermined significance (MGUS). Expression levels of PD-1 on eNKs and PD-L1 on MM and MGUS cells were also quantified. Results indicate that most eNKs obtained using our expansion protocol express a low percentage of PD-1+ cells. UCB eNKs were highly cytotoxic against MM cells and addition of daratumumab or pembrolizumab did not further increase their cytotoxicity. PB eNKs, while effective against MM cells, were significantly more cytotoxic when combined with daratumumab. In a minority of cases, eNK cells showed a detectable population of PD1+ cells. This correlated with low cytotoxic activity, particularly in UCB eNKs. Addition of pembrolizumab did not restore their activity. Results indicate that UCB eNKs are to be preferentially used against MM in the absence of daratumumab while PB eNKs have significant cytotoxic advantage when combined with this mAb
The second data release from the European Pulsar Timing Array I. The dataset and timing analysis
Pulsar timing arrays offer a probe of the low-frequency gravitational wave
spectrum (1 - 100 nanohertz), which is intimately connected to a number of
markers that can uniquely trace the formation and evolution of the Universe. We
present the dataset and the results of the timing analysis from the second data
release of the European Pulsar Timing Array (EPTA). The dataset contains
high-precision pulsar timing data from 25 millisecond pulsars collected with
the five largest radio telescopes in Europe, as well as the Large European
Array for Pulsars. The dataset forms the foundation for the search for
gravitational waves by the EPTA, presented in associated papers. We describe
the dataset and present the results of the frequentist and Bayesian pulsar
timing analysis for individual millisecond pulsars that have been observed over
the last ~25 years. We discuss the improvements to the individual pulsar
parameter estimates, as well as new measurements of the physical properties of
these pulsars and their companions. This data release extends the dataset from
EPTA Data Release 1 up to the beginning of 2021, with individual pulsar
datasets with timespans ranging from 14 to 25 years. These lead to improved
constraints on annual parallaxes, secular variation of the orbital period, and
Shapiro delay for a number of sources. Based on these results, we derived
astrophysical parameters that include distances, transverse velocities, binary
pulsar masses, and annual orbital parallaxes.Comment: 29 pages, 9 figures, 13 tables, Astronomy & Astrophysics in pres
Practical approaches to analyzing PTA data: Cosmic strings with six pulsars
We search for a stochastic gravitational wave background (SGWB) generated by
a network of cosmic strings using six millisecond pulsars from Data Release 2
(DR2) of the European Pulsar Timing Array (EPTA). We perform a Bayesian
analysis considering two models for the network of cosmic string loops, and
compare it to a simple power-law model which is expected from the population of
supermassive black hole binaries. Our main strong assumption is that the
previously reported common red noise process is a SGWB. We find that the
one-parameter cosmic string model is slightly favored over a power-law model
thanks to its simplicity. If we assume a two-component stochastic signal in the
data (supermassive black hole binary population and the signal from cosmic
strings), we get a upper limit on the string tension of () for the two cosmic string models we consider. In extended
two-parameter string models, we were unable to constrain the number of kinks.
We test two approximate and fast Bayesian data analysis methods against the
most rigorous analysis and find consistent results. These two fast and
efficient methods are applicable to all SGWBs, independent of their source, and
will be crucial for analysis of extended data sets.Comment: 13 pages, 5 figure
Practical approaches to analyzing PTA data: Cosmic strings with six pulsars
We search for a stochastic gravitational wave background (SGWB) generated by a network of cosmic strings using six millisecond pulsars from Data Release 2 (DR2) of the European Pulsar Timing Array (EPTA). We perform a Bayesian analysis considering two models for the network of cosmic string loops, and compare it to a simple power-law model which is expected from the population of supermassive black hole binaries. Our main strong assumption is that the previously reported common red noise process is a SGWB. We find that the one-parameter cosmic string model is slightly favored over a power-law model thanks to its simplicity. If we assume a two-component stochastic signal in the data (supermassive black hole binary population and the signal from cosmic strings), we get a 95% upper limit on the string tension of log10(Gμ)<-9.9 (-10.5) for the two cosmic string models we consider. In extended two-parameter string models, we were unable to constrain the number of kinks. We test two approximate and fast Bayesian data analysis methods against the most rigorous analysis and find consistent results. These two fast and efficient methods are applicable to all SGWBs, independent of their source, and will be crucial for analysis of extended datasets
The second data release from the European Pulsar Timing Array IV. Search for continuous gravitational wave signals
We present the results of a search for continuous gravitational wave signals
(CGWs) in the second data release (DR2) of the European Pulsar Timing Array
(EPTA) collaboration. The most significant candidate event from this search has
a gravitational wave frequency of 4-5 nHz. Such a signal could be generated by
a supermassive black hole binary (SMBHB) in the local Universe. We present the
results of a follow-up analysis of this candidate using both Bayesian and
frequentist methods. The Bayesian analysis gives a Bayes factor of 4 in favor
of the presence of the CGW over a common uncorrelated noise process, while the
frequentist analysis estimates the p-value of the candidate to be 1%, also
assuming the presence of common uncorrelated red noise. However, comparing a
model that includes both a CGW and a gravitational wave background (GWB) to a
GWB only, the Bayes factor in favour of the CGW model is only 0.7. Therefore,
we cannot conclusively determine the origin of the observed feature, but we
cannot rule it out as a CGW source. We present results of simulations that
demonstrate that data containing a weak gravitational wave background can be
misinterpreted as data including a CGW and vice versa, providing two plausible
explanations of the EPTA DR2 data. Further investigations combining data from
all PTA collaborations will be needed to reveal the true origin of this
feature.Comment: 12 figures, 15 pages, to be submitte
The second data release from the European Pulsar Timing Array III. Search for gravitational wave signals
We present the results of the search for an isotropic stochastic gravitational wave background (GWB) at nanohertz frequencies using the second data release of the European Pulsar Timing Array (EPTA) for 25 millisecond pulsars and a combination with the first data release of the Indian Pulsar Timing Array (InPTA). A robust GWB detection is conditioned upon resolving the Hellings-Downs angular pattern in the pairwise cross-correlation of the pulsar timing residuals. Additionally, the GWB is expected to yield the same (common) spectrum of temporal correlations across pulsars, which is used as a null hypothesis in the GWB search. Such a common-spectrum process has already been observed in pulsar timing data. We analysed (i) the full 24.7-year EPTA data set, (ii) its 10.3-year subset based on modern observing systems, (iii) the combination of the full data set with the first data release of the InPTA for ten commonly timed millisecond pulsars, and (iv) the combination of the 10.3-year subset with the InPTA data. These combinations allowed us to probe the contributions of instrumental noise and interstellar propagation effects. With the full data set, we find marginal evidence for a GWB, with a Bayes factor of four and a false alarm probability of 4%. With the 10.3-year subset, we report evidence for a GWB, with a Bayes factor of 60 and a false alarm probability of about 0.1% (≳3σ significance). The addition of the InPTA data yields results that are broadly consistent with the EPTA-only data sets, with the benefit of better noise modelling. Analyses were performed with different data processing pipelines to test the consistency of the results from independent software packages. The latest EPTA data from new generation observing systems show non-negligible evidence for the GWB. At the same time, the inferred spectrum is rather uncertain and in mild tension with the common signal measured in the full data set. However, if the spectral index is fixed at 13/3, the two data sets give a similar amplitude of (2.5 ± 0.7) × 10−15 at a reference frequency of 1 yr−1. Further investigation of these issues is required for reliable astrophysical interpretations of this signal. By continuing our detection efforts as part of the International Pulsar Timing Array (IPTA), we expect to be able to improve the measurement of spatial correlations and better characterise this signal in the coming years
The second data release from the European Pulsar Timing Array: IV. Implications for massive black holes, dark matter, and the early Universe
The European Pulsar Timing Array (EPTA) and Indian Pulsar Timing Array (InPTA) collaborations have measured a low-frequency common signal in the combination of their second and first data releases, respectively, with the correlation properties of a gravitational wave background (GWB). Such a signal may have its origin in a number of physical processes including a cosmic population of inspiralling supermassive black hole binaries (SMBHBs); inflation, phase transitions, cosmic strings, and tensor mode generation by the non-linear evolution of scalar perturbations in the early Universe; and oscillations of the Galactic potential in the presence of ultra-light dark matter (ULDM). At the current stage of emerging evidence, it is impossible to discriminate among the different origins. Therefore, for this paper, we consider each process separately, and investigated the implications of the signal under the hypothesis that it is generated by that specific process. We find that the signal is consistent with a cosmic population of inspiralling SMBHBs, and its relatively high amplitude can be used to place constraints on binary merger timescales and the SMBH-host galaxy scaling relations. If this origin is confirmed, this would be the first direct evidence that SMBHBs merge in nature, adding an important observational piece to the puzzle of structure formation and galaxy evolution. As for early Universe processes, the measurement would place tight constraints on the cosmic string tension and on the level of turbulence developed by first-order phase transitions. Other processes would require non-standard scenarios, such as a blue-tilted inflationary spectrum or an excess in the primordial spectrum of scalar perturbations at large wavenumbers. Finally, a ULDM origin of the detected signal is disfavoured, which leads to direct constraints on the abundance of ULDM in our Galaxy
The second data release from the European Pulsar Timing Array: II. Customised pulsar noise models for spatially correlated gravitational waves
Aims. The nanohertz gravitational wave background (GWB) is expected to be an aggregate signal of an ensemble of gravitational waves emitted predominantly by a large population of coalescing supermassive black hole binaries in the centres of merging galaxies. Pulsar timing arrays (PTAs), which are ensembles of extremely stable pulsars at approximately kiloparsec distances precisely monitored for decades, are the most precise experiments capable of detecting this background. However, the subtle imprints that the GWB induces on pulsar timing data are obscured by many sources of noise that occur on various timescales. These must be carefully modelled and mitigated to increase the sensitivity to the background signal.Methods. In this paper, we present a novel technique to estimate the optimal number of frequency coefficients for modelling achromatic and chromatic noise, while selecting the preferred set of noise models to use for each pulsar. We also incorporated a new model to fit for scattering variations in the Bayesian pulsar timing package temponest. These customised noise models enable a more robust characterisation of single-pulsar noise. We developed a software package based on tempo2 to create realistic simulations of European Pulsar Timing Array (EPTA) datasets that allowed us to test the efficacy of our noise modelling algorithms.Results. Using these techniques, we present an in-depth analysis of the noise properties of 25 millisecond pulsars (MSPs) that form the second data release (DR2) of the EPTA and investigate the effect of incorporating low-frequency data from the Indian Pulsar Timing Array collaboration for a common sample of ten MSPs. We used two packages, enterprise and temponest, to estimate our noise models and compare them with those reported using EPTA DR1. We find that, while in some pulsars we can successfully disentangle chromatic from achromatic noise owing to the wider frequency coverage in DR2, in others the noise models evolve in a much more complicated way. We also find evidence of long-term scattering variations in PSR J1600-3053. Through our simulations, we identify intrinsic biases in our current noise analysis techniques and discuss their effect on GWB searches. The analysis and results discussed in this article directly help to improve the sensitivity to the GWB signal and they are already being used as part of global PTA efforts
Comparing Recent Pulsar Timing Array Results on the Nanohertz Stochastic Gravitational-wave Background
The Australian, Chinese, European, Indian, and North American pulsar timing array (PTA) collaborations recently reported, at varying levels, evidence for the presence of a nanohertz gravitational-wave background (GWB). Given that each PTA made different choices in modeling their data, we perform a comparison of the GWB and individual pulsar noise parameters across the results reported from the PTAs that constitute the International Pulsar Timing Array (IPTA). We show that despite making different modeling choices, there is no significant difference in the GWB parameters that are measured by the different PTAs, agreeing within 1σ. The pulsar noise parameters are also consistent between different PTAs for the majority of the pulsars included in these analyses. We bridge the differences in modeling choices by adopting a standardized noise model for all pulsars and PTAs, finding that under this model there is a reduction in the tension in the pulsar noise parameters. As part of this reanalysis, we "extended" each PTA's data set by adding extra pulsars that were not timed by that PTA. Under these extensions, we find better constraints on the GWB amplitude and a higher signal-to-noise ratio for the Hellings–Downs correlations. These extensions serve as a prelude to the benefits offered by a full combination of data across all pulsars in the IPTA, i.e., the IPTA's Data Release 3, which will involve not just adding in additional pulsars but also including data from all three PTAs where any given pulsar is timed by more than a single PTA
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