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Cell Squeeze is a novel technology that relies on temporarily disrupting the cell membrane to deliver cargo directly into the cytosol. This approach is applicable to a broad range of cell types (peripheral blood mononuclear cells, red blood cells, hematopoietic stem cells, etc.) and cargos (peptides, proteins, small molecules, nucleic acids, and gene-editing complexes) while minimally disrupting normal cell function. By enabling direct cytosolic delivery, one can use this technology to dramatically enhance major histocompatibility complex (MHC) class I presentation of antigens (Ags) for CD8+ T-cell activation—a longstanding challenge for the therapeutic cancer vaccine field that has generally relied on cross-presentation of endocytosed Ags. In addition, by coupling improved MHC class I presentation with coexpression of additional stimulatory factors or systemic immune modulators, one can further enhance the potential impact of an antitumor CD8 response. Pursuing a more direct cellular engineering strategy, which is independent of viral transduction, genetic manipulation, and expansion steps, enables

Abstract Emotion recognition shows large inter-individual variability, and is substantially affected by childhood trauma as well as modality, emotion portrayed, and intensity. While research suggests childhood trauma influences emotion recognition, it is unclear whether this effect is consistent when controlling for interrelated individual differences. Further, the universality of the effects has not been explored, most studies have not examined differing modalities or intensities. This study examined childhood trauma’s association with accuracy, when controlling for alexithymia and psychopathy traits, and if this varied across modality, emotion portrayed, and intensity. An adult sample (N = 122) completed childhood trauma, alexithymia, and psychopathy questionnaires and three emotion tasks: faces, voices, audio-visual. When investigating childhood trauma alone, there was a significant association with poorer accuracy when exploring modality, emotion portrayed, and intensity. When controlling for alexithymia and psychopathy, childhood trauma remained significant when exploring emotion portrayed, however, it was no longer significant when exploring modality and intensity. In fact, alexithymia was significant when exploring intensity. The effect sizes overall were small. Our findings suggest the importance of controlling for interrelated individual differences. Future research should explore more sensitive measures of emotion recognition, such as intensity ratings and sensitivity to intensity, to see if these follow accuracy findings.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via immunological modulations. Here, we summarize the molecular, cellular, and clinical implications of IDH mutations in gliomas as well as current diagnostic techniques.

Previous research demonstrated the distribution of distinct microbial communities in the equine hindgut surrounding the pelvic flexure. The current study evaluated gene expression in epithelial tissues surrounding the pelvic flexure to characterize patterns that might correlate with microbial distribution. Gene expression was determined by analyzing RNA sequence data from the pelvic flexure, the left and right ventral colon, and the left and right dorsal colon. An average of 18,330 genes were expressed across the five tissues sampled. Most of the genes showed some level of expression in all five tissues. Tissue-restricted patterns of expression were also observed. Genes with restricted expression in the left ventral and left dorsal colons have communication, signaling, and regulatory functions that correlate with their known physiology. In contrast, genes expressed exclusively in the pelvic flexure have diverse functions. The ontology of genes differentially expressed between the pelvic flexure and the surrounding tissues was associated with immune functions and signaling processes. Despite being non-significant, these enrichment trends were reinforced by the functions of statistically significant expression differences between tissues of the hindgut. These results provide insight into the physiology of the equine hindgut epithelium that might influence the microbiota and its distribution.

Chronic myeloid leukemia (CML) is associated with several breakpoint regions that result in different BCR::ABL1 fusion transcripts. These include the major breakpoint region (M-BCR), minor breakpoint region (m-BCR), and mu breakpoint region (u-BCR) corresponding to p210, p190, and p230 fusion transcripts, respectively. This patient is a 38-year-old female with a new diagnosis of CML in chronic phase. A novel p210 fusion transcript splice variant was detected with qualitative reverse transcription PCR and capillary electrophoresis. Subsequent FISH study was performed, which revealed 86.5% positive for the BCR::ABL1 fusion. Quantitative real-time polymerase chain reaction (PCR) showed a negative result for the p210 fusion transcript. The variant was further characterized by Sanger sequencing. This variant is in-frame and predicted to be functional. This case illustrates the need for a combination of different testing techniques to fully characterize the rare BCR::ABL1 fusion transcripts.

Recently we found compelling evidence for a gravitational-wave background with Hellings and Downs (HD) correlations in our 15 yr data set. These correlations describe gravitational waves as predicted by general relativity, which has two transverse polarization modes. However, more general metric theories of gravity can have additional polarization modes, which produce different interpulsar correlations. In this work, we search the NANOGrav 15 yr data set for evidence of a gravitational-wave background with quadrupolar HD and scalar-transverse (ST) correlations. We find that HD correlations are the best fit to the data and no significant evidence in favor of ST correlations. While Bayes factors show strong evidence for a correlated signal, the data does not strongly prefer either correlation signature, with Bayes factors ∼2 when comparing HD to ST correlations, and ∼1 for HD plus ST correlations to HD correlations alone. However, when modeled alongside HD correlations, the amplitude and spectral index posteriors for ST correlations are uninformative, with the HD process accounting for the vast majority of the total signal. Using the optimal statistic, a frequentist technique that focuses on the pulsar-pair cross-correlations, we find median signal-to-noise ratios of 5.0 for HD and 4.6 for ST correlations when fit for separately, and median signal-to-noise ratios of 3.5 for HD and 3.0 for ST correlations when fit for simultaneously. While the signal-to-noise ratios for each of the correlations are comparable, the estimated amplitude and spectral index for HD are a significantly better fit to the total signal, in agreement with our Bayesian analysis.

Optogenetic or pharmacological modulation of hypocretin neurons impacts mouse impulsivity in a Go/No-Go task, suggesting that these neurons play a key role in integrating salient stimuli and guiding responses to various environmental cues.

Pulsar timing array experiments have recently uncovered evidence for a nanohertz gravitational wave background by precisely timing an ensemble of millisecond pulsars. The next significant milestones for these experiments include characterizing the detected background with greater precision, identifying its source(s), and detecting continuous gravitational waves from individual supermassive black hole binaries. To achieve these objectives, generating accurate and precise times of arrival of pulses from pulsar observations is crucial. Incorrect polarization calibration of the observed pulsar profiles may introduce errors in the measured times of arrival. Further, previous studies have demonstrated that robust polarization calibration of pulsar profiles can reduce noise in the pulsar timing data and improve timing solutions. In this paper, we investigate and compare the impact of different polarization calibration methods on pulsar timing precision using three distinct calibration techniques: the Ideal Feed Assumption (IFA), Measurement Equation Modeling (MEM), and Measurement Equation Template Matching (METM). Three NANOGrav pulsars—PSRs J1643−1224, J1744−1134, and J1909−3744—observed with the 800 MHz and 1.5 GHz receivers at the Green Bank Telescope (GBT) are utilized for our analysis. Our findings reveal that all three calibration methods enhance timing precision compared to scenarios where no polarization calibration is performed. Additionally, among the three calibration methods, the IFA approach generally provides the best results for timing analysis of pulsars observed with the GBT receiver system. We attribute the comparatively poorer performance of the MEM and METM methods to potential instabilities in the reference noise diode coupled to the receiver and temporal variations in the profile of the reference pulsar, respectively.

Pulsar timing arrays (PTAs) are designed to detect low-frequency gravitational waves (GWs). GWs induce achromatic signals in PTA data, meaning that the timing delays do not depend on radio frequency. However, pulse arrival times are also affected by radio-frequency-dependent “chromatic” noise from sources such as dispersion measure (DM) and scattering delay variations. Furthermore, the characterization of GW signals may be influenced by the choice of chromatic noise model for each pulsar. To better understand this effect, we assess if and how different chromatic noise models affect the achromatic noise properties in each pulsar. The models we compare include existing DM models used by the North American Nanohertz Observatory for Gravitational waves (NANOGrav) and noise models used for the European PTA Data Release 2 (EPTA DR2). We perform this comparison using a subsample of six pulsars from the NANOGrav 15 yr data set, selecting the same six pulsars as from the EPTA DR2 six-pulsar data set. We find that the choice of chromatic noise model noticeably affects the achromatic noise properties of several pulsars. This is most dramatic for PSR J1713+0747, where the amplitude of its achromatic red noise lowers from ${\mathrm{log}}_{10}{A}_{\mathrm{RN}}=-{14.1}_{-0.1}^{+0.1}$ to $-{14.7}_{-0.5}^{+0.3}$ , and the spectral index broadens from ${\gamma }_{\mathrm{RN}}={2.6}_{-0.4}^{+0.5}$ to ${\gamma }_{\mathrm{RN}}={3.5}_{-0.9}^{+1.2}$ . We also compare each pulsar's noise properties with those inferred from the EPTA DR2, using the same models. From the discrepancies, we identify potential areas where the noise models could be improved. These results highlight the potential for custom chromatic noise models to improve PTA sensitivity to GWs.

PINT is a pure-Python framework for high-precision pulsar timing developed on top of widely used and well-tested Python libraries, supporting both interactive and programmatic data analysis workflows. We present a new frequentist framework within PINT to characterize the single-pulsar noise processes present in pulsar timing data sets. This framework enables parameter estimation for both uncorrelated and correlated noise processes, as well as model comparison between different timing and noise models in a computationally inexpensive way. We demonstrate the efficacy of the new framework by applying it to simulated data sets as well as a real data set of PSR B1855+09. We also describe the new features implemented in PINT since it was first described in the literature.

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 1 σ . 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.

The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between 2021 April 16 and 17 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multifrequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment and the 100 m Green Bank Telescope in a 3 yr period encompassing the shape change event, between 2020 February and 2023 February. As of 2023 February, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying time-of-arrival residuals display a strong nonmonotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν ) nor a change in dispersion measure alone (which would produce a delay proportional to ν ^−2 ). However, it does bear some resemblance to the two previous “chromatic timing events” observed in J1713+0747, as well as to a similar event observed in PSR J1643−1224 in 2015.

The radio galaxy 3C 66B has been hypothesized to host a supermassive black hole binary (SMBHB) at its center based on electromagnetic observations. Its apparent 1.05 yr period and low redshift (∼0.02) make it an interesting testbed to search for low-frequency gravitational waves (GWs) using pulsar timing array (PTA) experiments. This source has been subjected to multiple searches for continuous GWs from a circular SMBHB, resulting in progressively more stringent constraints on its GW amplitude and chirp mass. In this paper, we develop a pipeline for performing Bayesian targeted searches for eccentric SMBHBs in PTA data sets, and test its efficacy by applying it to simulated data sets with varying injected signal strengths. We also search for a realistic eccentric SMBHB source in 3C 66B using the NANOGrav 12.5 yr data set employing PTA signal models containing Earth term-only as well as Earth+pulsar term contributions using this pipeline. Due to limitations in our PTA signal model, we get meaningful results only when the initial eccentricity e _0 < 0.5 and the symmetric mass ratio η > 0.1. We find no evidence for an eccentric SMBHB signal in our data, and therefore place 95% upper limits on the PTA signal amplitude of 88.1 ± 3.7 ns for the Earth term-only and 81.74 ± 0.86 ns for the Earth+pulsar term searches for e _0 < 0.5 and η > 0.1. Similar 95% upper limits on the chirp mass are (1.98 ± 0.05) × 10 ^9 and (1.81 ± 0.01) × 10 ^9 M _☉ . These upper limits, while less stringent than those calculated from a circular binary search in the NANOGrav 12.5 yr data set, are consistent with the SMBHB model of 3C 66B developed from electromagnetic observations.

We present the results of a Bayesian search for gravitational wave (GW) memory in the NANOGrav 12.5 yr data set. We find no convincing evidence for any gravitational wave memory signals in this data set. We find a Bayes factor of 2.8 in favor of a model that includes a memory signal and common spatially uncorrelated red noise (CURN) compared to a model including only a CURN. However, further investigation shows that a disproportionate amount of support for the memory signal comes from three dubious pulsars. Using a more flexible red-noise model in these pulsars reduces the Bayes factor to 1.3. Having found no compelling evidence, we go on to place upper limits on the strain amplitude of GW memory events as a function of sky location and event epoch. These upper limits are computed using a signal model that assumes the existence of a common, spatially uncorrelated red noise in addition to a GW memory signal. The median strain upper limit as a function of sky position is approximately 3.3 × 10 ^−14 . We also find that there are some differences in the upper limits as a function of sky position centered around PSR J0613−0200. This suggests that this pulsar has some excess noise that can be confounded with GW memory. Finally, the upper limits as a function of burst epoch continue to improve at later epochs. This improvement is attributable to the continued growth of the pulsar timing array.

Abstract Current guidelines recommend that Acute Myeloid Leukemia (AML) patients with NPM1 mutations should be monitored for measurable residual disease by quantifying the transcripts and normalizing them to ABL1 transcripts. In this short report, a simple and highly accurate method to quantify the NPM1 mutant transcript normalized to the wild‐type NPM1 transcript is presented. The percent mutant transcript correlates very well to the corresponding mutant allele frequency as determined by DNA‐based methods allowing direct comparison of investigational studies that use RNA‐based or DNA‐based methods for monitoring NPM1 mutations.

The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has reported evidence for the presence of an isotropic nanohertz gravitational-wave background (GWB) in its 15 yr data set. However, if the GWB is produced by a population of inspiraling supermassive black hole binary (SMBHB) systems, then the background is predicted to be anisotropic, depending on the distribution of these systems in the local Universe and the statistical properties of the SMBHB population. In this work, we search for anisotropy in the GWB using multiple methods and bases to describe the distribution of the GWB power on the sky. We do not find significant evidence of anisotropy. By modeling the angular power distribution as a sum over spherical harmonics (where the coefficients are not bound to always generate positive power everywhere), we find that the Bayesian 95% upper limit on the level of dipole anisotropy is ( C _l _=1 / C _l _=0 ) < 27%. This is similar to the upper limit derived under the constraint of positive power everywhere, indicating that the dipole may be close to the data-informed regime. By contrast, the constraints on anisotropy at higher spherical-harmonic multipoles are strongly prior dominated. We also derive conservative estimates on the anisotropy expected from a random distribution of SMBHB systems using astrophysical simulations conditioned on the isotropic GWB inferred in the 15 yr data set and show that this data set has sufficient sensitivity to probe a large fraction of the predicted level of anisotropy. We end by highlighting the opportunities and challenges in searching for anisotropy in pulsar timing array data.

The R132H isocitrate dehydrogenase one (IDH1) mutation is a prognostic biomarker present in a subset of gliomas and is associated with heightened survival when paired with aggressive surgical resection. In this study, we establish proof-of-principle for rapid colorimetric detection of the IDH1-R132H mutation in tumor samples in under 1 hour without the need for a nucleic acid extraction. Colorimetric peptide nucleic acid loop-mediated isothermal amplification (CPNA-LAMP) utilizes 4 conventional LAMP primers, a blocking PNA probe complementary to the wild-type sequence, and a self-annealing loop primer complementary to the single nucleotide variant to only amplify the DNA sequence containing the mutation. This assay was evaluated using IDH1-WT or IDH1-R132H mutant synthetic DNA, wild-type or IDH1-R132H mutant U87MG cell lysates, and tumor lysates from archived patient samples in which the IDH1 status was previously determined using immunohistochemistry (IHC). Reactions were performed using a hot water bath and visually interpreted as positive by a pink-to-yellow color change. Results were subsequently verified using agarose gel electrophoresis. CPNA-LAMP successfully detected the R132H single nucleotide variant, and results from tumor lysates yielded 100% concordance with IHC results, including instances when the single nucleotide variant was limited to a portion of the tumor. Importantly, when testing the tumor lysates, there were no false positive or false negative results.

The NANOGrav 15 yr data set shows evidence for the presence of a low-frequency gravitational-wave background (GWB). While many physical processes can source such low-frequency gravitational waves, here we analyze the signal as coming from a population of supermassive black hole (SMBH) binaries distributed throughout the Universe. We show that astrophysically motivated models of SMBH binary populations are able to reproduce both the amplitude and shape of the observed low-frequency gravitational-wave spectrum. While multiple model variations are able to reproduce the GWB spectrum at our current measurement precision, our results highlight the importance of accurately modeling binary evolution for producing realistic GWB spectra. Additionally, while reasonable parameters are able to reproduce the 15 yr observations, the implied GWB amplitude necessitates either a large number of parameters to be at the edges of expected values or a small number of parameters to be notably different from standard expectations. While we are not yet able to definitively establish the origin of the inferred GWB signal, the consistency of the signal with astrophysical expectations offers a tantalizing prospect for confirming that SMBH binaries are able to form, reach subparsec separations, and eventually coalesce. As the significance grows over time, higher-order features of the GWB spectrum will definitively determine the nature of the GWB and allow for novel constraints on SMBH populations.

Evidence for a low-frequency stochastic gravitational-wave background has recently been reported based on analyses of pulsar timing array data. The most likely source of such a background is a population of supermassive black hole binaries, the loudest of which may be individually detected in these data sets. Here we present the search for individual supermassive black hole binaries in the NANOGrav 15 yr data set. We introduce several new techniques, which enhance the efficiency and modeling accuracy of the analysis. The search uncovered weak evidence for two candidate signals, one with a gravitational-wave frequency of ∼4 nHz, and another at ∼170 nHz. The significance of the low-frequency candidate was greatly diminished when Hellings–Downs correlations were included in the background model. The high-frequency candidate was discounted due to the lack of a plausible host galaxy, the unlikely astrophysical prior odds of finding such a source, and since most of its support comes from a single pulsar with a commensurate binary period. Finding no compelling evidence for signals from individual binary systems, we place upper limits on the strain amplitude of gravitational waves emitted by such systems. At our most sensitive frequency of 6 nHz, we place a sky-averaged 95% upper limit of 8 × 10 ^−15 on the strain amplitude. We also calculate an exclusion volume and a corresponding effective radius, within which we can rule out the presence of black hole binaries emitting at a given frequency.

Pulsar timing array collaborations, such as the North American Nanohertz Observatory for Gravitational Waves (NANOGrav), are seeking to detect nanohertz gravitational waves emitted by supermassive black hole binaries formed in the aftermath of galaxy mergers. We have searched for continuous waves from individual circular supermassive black hole binaries using NANOGrav’s recent 12.5 yr data set. We created new methods to accurately model the uncertainties on pulsar distances in our analysis, and we implemented new techniques to account for a common red-noise process in pulsar timing array data sets while searching for deterministic gravitational wave signals, including continuous waves. As we found no evidence for continuous waves in our data, we placed 95% upper limits on the strain amplitude of continuous waves emitted by these sources. At our most sensitive frequency of 7.65 nHz, we placed a sky-averaged limit of h _0 < (6.82 ± 0.35) × 10 ^−15 , and h _0 < (2.66 ± 0.15) × 10 ^−15 in our most sensitive sky location. Finally, we placed a multimessenger limit of ${ \mathcal M }\lt (1.41\pm 0.02)\times {10}^{9}\,{M}_{\odot }$ on the chirp mass of the supermassive black hole binary candidate 3C 66B.

We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves. The correlations follow the Hellings–Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of 10 ^14 , and this same model is favored over an uncorrelated common power-law spectrum model with Bayes factors of 200–1000, depending on spectral modeling choices. We have built a statistical background distribution for the latter Bayes factors using a method that removes interpulsar correlations from our data set, finding p = 10 ^−3 (≈3 σ ) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of interpulsar correlations yields p = 5 × 10 ^−5 to 1.9 × 10 ^−4 (≈3.5 σ –4 σ ). Assuming a fiducial f ^−2/3 characteristic strain spectrum, as appropriate for an ensemble of binary supermassive black hole inspirals, the strain amplitude is ${2.4}_{-0.6}^{+0.7}\times {10}^{-15}$ (median + 90% credible interval) at a reference frequency of 1 yr ^−1 . The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings–Downs correlations points to the gravitational-wave origin of this signal.

We present observations and timing analyses of 68 millisecond pulsars (MSPs) comprising the 15 yr data set of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav). NANOGrav is a pulsar timing array (PTA) experiment that is sensitive to low-frequency gravitational waves (GWs). This is NANOGrav’s fifth public data release, including both “narrowband” and “wideband” time-of-arrival (TOA) measurements and corresponding pulsar timing models. We have added 21 MSPs and extended our timing baselines by 3 yr, now spanning nearly 16 yr for some of our sources. The data were collected using the Arecibo Observatory, the Green Bank Telescope, and the Very Large Array between frequencies of 327 MHz and 3 GHz, with most sources observed approximately monthly. A number of notable methodological and procedural changes were made compared to our previous data sets. These improve the overall quality of the TOA data set and are part of the transition to new pulsar timing and PTA analysis software packages. For the first time, our data products are accompanied by a full suite of software to reproduce data reduction, analysis, and results. Our timing models include a variety of newly detected astrometric and binary pulsar parameters, including several significant improvements to pulsar mass constraints. We find that the time series of 23 pulsars contain detectable levels of red noise, 10 of which are new measurements. In this data set, we find evidence for a stochastic GW background.

Pulsar timing arrays (PTAs) are galactic-scale gravitational wave (GW) detectors. Each individual arm, composed of a millisecond pulsar, a radio telescope, and a kiloparsecs-long path, differs in its properties but, in aggregate, can be used to extract low-frequency GW signals. We present a noise and sensitivity analysis to accompany the NANOGrav 15 yr data release and associated papers, along with an in-depth introduction to PTA noise models. As a first step in our analysis, we characterize each individual pulsar data set with three types of white-noise parameters and two red-noise parameters. These parameters, along with the timing model and, particularly, a piecewise-constant model for the time-variable dispersion measure, determine the sensitivity curve over the low-frequency GW band we are searching. We tabulate information for all of the pulsars in this data release and present some representative sensitivity curves. We then combine the individual pulsar sensitivities using a signal-to-noise ratio statistic to calculate the global sensitivity of the PTA to a stochastic background of GWs, obtaining a minimum noise characteristic strain of 7 × 10 ^−15 at 5 nHz. A power-law-integrated analysis shows rough agreement with the amplitudes recovered in NANOGrav’s 15 yr GW background analysis. While our phenomenological noise model does not model all known physical effects explicitly, it provides an accurate characterization of the noise in the data while preserving sensitivity to multiple classes of GW signals.

The 15 yr pulsar timing data set collected by the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) shows positive evidence for the presence of a low-frequency gravitational-wave (GW) background. In this paper, we investigate potential cosmological interpretations of this signal, specifically cosmic inflation, scalar-induced GWs, first-order phase transitions, cosmic strings, and domain walls. We find that, with the exception of stable cosmic strings of field theory origin, all these models can reproduce the observed signal. When compared to the standard interpretation in terms of inspiraling supermassive black hole binaries (SMBHBs), many cosmological models seem to provide a better fit resulting in Bayes factors in the range from 10 to 100. However, these results strongly depend on modeling assumptions about the cosmic SMBHB population and, at this stage, should not be regarded as evidence for new physics. Furthermore, we identify excluded parameter regions where the predicted GW signal from cosmological sources significantly exceeds the NANOGrav signal. These parameter constraints are independent of the origin of the NANOGrav signal and illustrate how pulsar timing data provide a new way to constrain the parameter space of these models. Finally, we search for deterministic signals produced by models of ultralight dark matter (ULDM) and dark matter substructures in the Milky Way. We find no evidence for either of these signals and thus report updated constraints on these models. In the case of ULDM, these constraints outperform torsion balance and atomic clock constraints for ULDM coupled to electrons, muons, or gluons.

Analyses of pulsar timing data have provided evidence for a stochastic gravitational wave background in the nanohertz frequency band. The most plausible source of this background is the superposition of signals from millions of supermassive black hole binaries. The standard statistical techniques used to search for this background and assess its significance make several simplifying assumptions, namely (i) Gaussianity, (ii) isotropy, and most often, (iii) a power-law spectrum. However, a stochastic background from a finite collection of binaries does not exactly satisfy any of these assumptions. To understand the effect of these assumptions, we test standard analysis techniques on a large collection of realistic simulated data sets. The data-set length, observing schedule, and noise levels were chosen to emulate the NANOGrav 15 yr data set. Simulated signals from millions of binaries drawn from models based on the Illustris cosmological hydrodynamical simulation were added to the data. We find that the standard statistical methods perform remarkably well on these simulated data sets, even though their fundamental assumptions are not strictly met. They are able to achieve a confident detection of the background. However, even for a fixed set of astrophysical parameters, different realizations of the universe result in a large variance in the significance and recovered parameters of the background. We also find that the presence of loud individual binaries can bias the spectral recovery of the background if we do not account for them.

In 1960, Portugal celebrated the five-hundredth anniversary of the death of Prince Henry, a heroic figure acclaimed for his role in the early maritime dis- coveries. The celebrations lasted several months and were sponsored by the Portuguese state. They included a wide variety of diplomatic, academic and cultural initiatives. These festivities were used as an opportunity to unite the Portuguese populous in the face of various potential threats to the Estado Novo which surfaced during this time. Although they were dismissed by the British foreign office, the Royal Navy and Royal Air Force took the opportunity to participate in a heavily publicized naval review as their ‘oldest ally.’ A variety of Anglo-Portuguese exchanges occurred in the academic world through a series of state-sponsored history anthologies, an international con- ference and reciprocal exhibitions on the topic of the Portuguese discoveries. This paper looks at some key individuals that facilitated these exchanges in Britain using the correspondence that they left behind. It shows internatio- nal outreach in the Estado Novo’s official program of celebrations and the pragmatic management of the Anglo-Portuguese alliance.

Women’s Rights International works with rural women and girls who are living in countries at war or with ongoing political violence. In 2005, The Asia Foundation invited Women’s Rights International to Sri Lanka to evaluate the feasibility of a random-sample survey of women to document the impact of the decades-long conflict. The significant imbalance in the risks-to-benefits ratio compelled us to recommend that random-sample surveys that included questions about sexual violence be avoided at that time, especially in the displaced persons areas. Instead, we recommended that three strategies be given priority in situations in which the risks for women are too great to justify a random-sample survey. First, maximize the use of existing information. Second, collect survey data only in partnership with a strong community organization that will use the data for direct tangible benefits. Third, share knowledge that will help build the capacity of local organizations to design surveys that address their priorities, and collect and use their own data following ethical guidelines that maximize the protection of individuals and the wider community. We implemented these recommendations in a partnership with a local organization with a strong history of advocating for women’s rights.

The influence of partisan identification infiltrates all aspects of a democracy. This study employs an innovative design to explore the presidential debate-viewing experience among young citizens. Data were collected from across the United States for all three 2016 presidential debates between Hillary Clinton and Donald Trump using pretest/posttest surveys and debate viewers’ Twitter posts. Examining Twitter expression as a form of political elaboration, the study employs a social identity theoretical perspective to better understand the process through which viewers form political attitudes. Applying the theory of identity-motivated elaboration (TIME) to presidential debates, the current research illuminates how partisan social identification changes the way viewers think about political issues and, resultantly, evaluate candidates and form political opinions. A strong partisan social identification results in greater identity-consistent elaboration and Twitter expression throughout one’s presidential debate viewing, which results in more biased candidate image evaluations and, subsequently, stronger preference for the in-party candidate.

The primary cilium has recently become the focus of intensive investigations into understanding the physical structure and processes of eukaryotic cells. This paper describes two tilt-series image datasets, acquired by transmission electron microscopy, of in situ chick-embryo sternal-cartilage primary cilia. These data have been released under an open-access licence, and are well suited to tomographic reconstruction and modelling of the cilium.