Search

Abstract The demand for fish protein continues to increase and currently accounts for 17% of total animal protein consumption by humans. About 90% of marine fish stocks are fished at or above maximum sustainable levels, with aquaculture propagating as one of the fastest growing food sectors to address some of this demand. Cell-cultivated seafood production is an alternative approach to produce nutritionally-complete seafood products to meet the growing demand. This cellular aquaculture approach offers a sustainable, climate resilient and ethical biotechnological approach as an alternative to conventional fishing and fish farming. Additional benefits include reduced antibiotic use and the absence of mercury. Cell-cultivated seafood also provides options for the fortification of fish meat with healthier compositions, such as omega-3 fatty acids and other beneficial nutrients through scaffold, media or cell approaches. This review addresses the biomaterials, production processes, tissue engineering approaches, processing, quality, safety, regulatory, and social aspects of cell-cultivated seafood, encompassing where we are today, as well as the road ahead. The goal is to provide a roadmap for the science and technology required to bring cellular aquaculture forward as a mainstream food source.

Abstract The emerging field of cellular agriculture has accelerated the development of cell-cultivated adipose tissue as an additive to enhance the flavor of alternative meat products. However, there has been limited research to evaluate the sensory profile of in vitro-grown tissues compared to conventionally obtained animal fat. This study aimed to investigate the aromatic characteristics of cell-cultivated fat tissue as a flavor enhancer for meat alternatives. Porcine dedifferentiated fat (PDFAT) cells were clonally isolated and differentiated into adipocytes. This cultured adipose tissue was then analyzed alongside native porcine fat using gas chromatography-mass spectrometry (GC/MS) coupled with descriptive sensory analysis by human consumers. This evaluation enabled quantitative and qualitative assessments of volatile compounds released during cooking for both in vitro and in vivo porcine fats. The volatile profiles generated during the cooking process and fatty aroma characteristics reported by sensory consumers were largely similar between the two fat sources, with some differences in select compounds and aroma attributes. Ultimately, the consumers found comparable overall liking scores reported between the conventional and cultured porcine fats. These findings provide valuable sensory evidence supporting the viability of cell-cultivated adipose tissue as a flavor component of meat alternatives, substituting for conventional animal fat.

Summary: Cultivated meat has the potential to revolutionize food production, but its progress is hindered by fundamental shortcomings of mammalian cells with respect to industrial-scale bioprocesses. Here, we discuss the essential role of cell line engineering in overcoming these limitations, highlighting the balance between the benefits of enhanced cellular traits and the associated regulatory and consumer acceptance challenges. We believe that careful selection of cell engineering strategies, including both genetic and non-genetic modifications, can address this trade-off and is essential to advancing the field.

The increasing global population and demand for meat have led to the need to find sustainable and viable alternatives to traditional production methods. One potential solution is cultivated meat (CM), which involves producing meat in vitro from animal stem cells to generate products with nutritional and sensory properties similar to conventional livestock‐derived meat. This article examines current approaches to CM production and investigates how using insect cells could enhance the process. Cell sources are a critical issue in CM production, alongside advances in culture media, bioreactors for scalability, and scaffold development. Insect cells, compared to commonly used mammalian cells, may offer advantages in overcoming technological challenges that hinder cell culture development and expansion. The objective of this review is to emphasize how insects, as a cell source for CM production, could offer a more sustainable option. A crucial aspect for achieving this goal is a comprehensive understanding of the physiology of muscle and fat cells. In this work, the characteristics of insect and mammalian cells are compared, focusing particularly on muscle and fat cell development, regulatory pathways, hormonal regulation, and tissue composition. Insect cells are a promising source for CM, offering a sustainable and environmentally friendly alternative.

The shortage of tissues and organs for transplantation is an urgent clinical concern. In situ 3D printing is an advanced 3D printing technique aimed at printing the new tissue or organ directly in the patient. The ink for this process is central to the outcomes, and must meet specific requirements such as rapid gelation, shape integrity, stability over time, and adhesion to surrounding healthy tissues. Among natural materials, silk fibroin exhibits fascinating properties that have made it widely studied in tissue engineering and regenerative medicine. However, further improvements in silk fibroin inks are needed to match the requirements for in situ 3D printing. In the present study, silk fibroin-based inks were developed for in situ applications by exploiting covalent crosslinking process consisting of a pre-photo-crosslinking prior to printing and in situ enzymatic crosslinking. Two different silk fibroin molecular weights were characterized and the synergistic effect of the covalent bonds with shear forces enhanced the shift in silk secondary structure toward β-sheets, thus, rapid stabilization. These hydrogels exhibited good mechanical properties, stability over time, and resistance to enzymatic degradation over 14 days, with no significant changes over time in their secondary structure and swelling behavior. Additionally, adhesion to tissues in vitro was demonstrated.

Given the expanding global population and finite resources, it is imperative to explore alternative technologies for food production. These technologies play a crucial role in ensuring the provision of safe, nutritious, and sustainable food options to meet the growing demand. Cellular agriculture plays an important in developing an alternative method for developing food products. While, cellular agriculture is emerging rapidly, food safety aspects and regulatory frameworks stayed behind. Despite developing several regulatory framework papers on cellular agriculture, there is no systematic approach for developing a comprehensive food safety plan (FSP), particularly for cultivated seafood. Thus, the overall goal of this article is to develop a FSP for cultivated seafood. The main differences between the food safety plan for cultivated seafood and the conventional seafood industries were the number of allergens in cultivated seafood products, including soy, wheat, and fish cells, compared to only fish for the conventional seafood industry. In addition, there are several hazards associated with mycoplasma in cultivated seafood, which should be considered. This guidance intends to help regulatory agencies, food safety experts, startup companies, and the cultivated seafood industry by providing a valuable platform to develop regulations, guidance, and food safety plans applicable to most cultivated seafood companies. This article will also help the industry to identify the hazards in their processing line and develop preventive controls, and as a comprehensive food safety plan, it could be easily adapted for other cultivated seafood products. This guidance applied systematic approaches to developing food safety plans using cell culture, pharmaceuticals, fermentation, seafood, meat, and aquaponics safety plans, collaborating with experts with different backgrounds, and working closely with the conventional and cultivated meat and seafood industries.

Abstract Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation and neurodegeneration. However, cell-type-specific contributions and crosstalk between neurons, microglia, and astrocytes in mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional in vitro triculture tissue model of a contusion injury composed of neurons, microglia, and astrocytes and examined the contributions of mitochondrial dysregulation to neuroinflammation and progression of injury-induced neurodegeneration. Pharmacological studies presented here suggest that fragmented mitochondria released by microglia are a key contributor to secondary neuronal damage progression after contusion injury, a pathway that requires astrocyte-microglia crosstalk. Controlling mitochondrial dysfunction thus offers an exciting option for developing therapies for TBI patients.

Cellular agriculture holds the potential to address sustainability, food security, and agricultural resilience. Within the cell-based meat supply chain, one of the key steps is developing sustainable scaffolding. In this study, we evaluated the impact of decellularized banana leaves, various coating materials including soy protein and gelatine, and different cell seeding strategies on cell viability, cell growth, cell alignment, and the response of the materials to thermal processing. Kinetics of the quality degradation of the scaffolds with and without cells were determined through kinetics equations. The efficiency of decellularization was verified through DNA quantification, which decreased from 445 ng/mg in fresh banana leaves to non-detectable levels in the decellularized samples. The alignment of cells on gelatin-coated samples was the highest among the samples, with a dominant orientation of 65.8°, compared to soy-coated and uncoated samples, with dominant orientations of 9.2° and −6.3°, respectively. The kinetics of shrinkage indicated that coating with soy and the presence of cells increased the activation energy due to the higher energy required for protein denaturation. The kinetics of area changes in plain scaffolds without cells followed a first-order pattern, while with seeded cells a second-order pattern was followed. Overall, the results showed that decellularized banana leaves provide sustainable scaffoldings for cellular agriculture applications. In addition, soy coating provided many benefits for decellularized samples by supporting cell adhesion and cell proliferation.

Summary: Cultivated meat (also known as cultured meat) is a promising technology that faces substantial cost barriers, which are currently driven by the price of media components. Particularly, growth factors such as fibroblast growth factor 2 (FGF2) drive the cost of serum-free media for relevant cells, including muscle satellite cells. Here, we engineered immortalized bovine satellite cells (iBSCs) for inducible expression of FGF2 and/or mutant RasG12V to overcome media growth factor requirements through autocrine signaling. Engineered cells were able to proliferate over multiple passages in FGF2-free medium, thereby eliminating the need for this costly component. Additionally, cells maintained their myogenicity, albeit with reduced myotube formation. Ultimately, this offers a proof of principle for lower-cost cultured meat production through cell line engineering. Science for society: Cultivated meat is an emerging technology that aims to produce meat through cell culture rather than conventional animal agriculture. By decoupling meat from animals, cultivated meat is projected to dramatically reduce the environmental impact of meat while simultaneously improving animal welfare and human health. To date, however, cultivated meat production is hindered by high costs, which are driven by the cell culture media. In particular, recombinant growth-promoting factors such as fibroblast growth factor 2 (FGF2) contribute a majority of the cost of these media. Here, we engineer bovine muscle stem cells to endogenously activate the growth-promoting signaling cascades that are typically triggered by exogenous FGF2, thereby eliminating the need for this costly media component. This approach offers a step toward engineering cultivated meat cells for expansion in recombinant protein-free media, an approach that would dramatically lower the cost of production.

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.

Abstract Cell-cultivated fish offers the potential for a more ethical, sustainable, and safe seafood system. However, fish cell culture is relatively understudied in comparison to mammalian cells. Here, we established and characterized a continuous Atlantic mackerel (Scomber scombrus) skeletal muscle cell line (“Mack” cells). The cells were isolated from muscle biopsies of fresh-caught fish, with separate isolations performed from two distinct fish. Mack1 cells (cells from the first isolation) were cultured for over a year and subcultured over 130 times. The cells proliferated at initial doubling times of 63.9 h (± 19.1 SD). After a spontaneous immortalization crisis from passages 37–43, the cells proliferated at doubling times of 24.3 h (± 4.91 SD). A muscle phenotype was confirmed through characterization of muscle stemness and differentiation via paired-box protein 7 and myosin heavy chain immunostaining, respectively. An adipocyte-like phenotype was also demonstrated for the cells through lipid accumulation, confirmed via Oil Red O staining and quantification of neutral lipids. New qPCR primers (HPRT, PAX3B, MYOD1, MYOG, TNNT3A, and PPARG) were tailored to the mackerel genome and used to characterize mackerel cell genotypes. This work provides the first spontaneously immortalized fish muscle cell line for research, ideally serving as a reference for subsequent investigation.

Silk and silk derivatives have emerged as a possible alternative in surgical device development, offering mechanical strength, biocompatibility, and environmental sustainability. Through a systematic review following PRISMA guidelines, this study evaluated silk fibroin’s application across pre-clinical and clinical settings, focusing on its role as screws and plates for osteofixation. A comprehensive search yielded 245 studies, with 33 subjected to full-text review and 15 ultimately included for qualitative analysis. The findings underscore silk fibroin’s superior properties, including its tunable degradation rates and ability to be functionalized with therapeutic agents. In vivo and in vitro studies demonstrated its efficacy in enhancing bone healing, offering improved outcomes in osteofixation, particularly for craniofacial defects. Silk fibroin’s remarkable attributes in biodegradation and drug release capabilities underscore its potential to enhance patient care. Ultimately, silk fibroin’s integration into surgical practices promises a revolution in patient outcomes and environmental sustainability. Its versatility, coupled with the continuous progress in fabrication techniques, signals a promising horizon for its widespread acceptance in the medical field, potentially establishing a new benchmark in surgical treatment. Further research is expected to solidify the transition of silk products from basic science to patient care, paving the way for widespread use in various surgical applications.

Volumetric additive manufacturing of protein scaffolds has a wide range of possible biomedical applications. Here the authors report on the bioprinting of unmodified silk sericin and silk fibroin inks with shape-memory and tuneable mechanical properties and demonstrate the potential of the inks in different applications.

Toothbrush handles made from synthetic polymers like polypropylene and polyethylene accumulate in the environment at an annual rate of 1 billion devices per year and without significant degradation, resulting in severe burdens particularly in marine environments. Herein, we report a new process to generate these plastic handles using natural, biopolymer-based components using a direct thermoplastic molding approach, that also offers on-demand degradation of the materials. The materials are prepared directly from whole silk cocoons that are thermoplastically transformed into biodegradable plastic parts for consumer needs, here in the form of toothbrush handles; either with silk alone or in combination with other natural sourced materials such as cellulose, chitosan and hydroxyapatite. We demonstrate the on-demand degradation of these bioplastics in different ways, using natural exogenous protease digestion either offered through soil exposure of the silk based plastics or via unique on-demand activation of proteases sequestered in the plastic materials to drive the degradation on-demand (hydration). The approaches described here demonstrate a new approach to bio-plastic formation and degradation from biopolymers that offers widespread options for future consumer materials with a focus on sustainability.

We report on the results of an image-based search for pulsar candidates toward the Galactic bulge. We used mosaic images from the MeerKAT radio telescope that were taken as part of a 173 deg ^2 survey of the bulge and Galactic center of our Galaxy at L band (856–1712 MHz) in all four Stokes I , Q , U , and V . The image rms noise levels of 12–17 μ Jy ba ^−1 represent a significant increase in sensitivity over past image-based pulsar searches. Our primary search criterion was circular polarization, but we used other criteria, including linear polarization, in-band spectral index, compactness, variability, and multiwavelength counterparts to select pulsar candidates. We first demonstrate the efficacy of this technique by searching for polarized emission from known pulsars and comparing our results with measurements from the literature. Our search resulted in a sample of 75 polarized sources. Bright stars or young stellar objects were associated with 28 of these sources, including a small sample of highly polarized dwarf stars with pulsar-like steep spectra. Comparing the properties of this sample with the known pulsars, we identified 30 compelling candidates for pulsation follow-up, including two sources with both strong circular and linear polarization. The remaining 17 sources are either pulsars or stars, but we cannot rule out an extragalactic origin or image artifacts among the brighter, flat-spectrum objects.

Late-time (∼a year) radio follow-up of optically discovered tidal disruption events (TDEs) is increasingly resulting in detections at radio wavelengths, and there is growing evidence for this late-time radio activity to be common to the broad class of subrelativistic TDEs. Detailed studies of some of these TDEs at radio wavelengths are also challenging the existing models for radio emission. Using all-sky multiepoch data from the Australian Square Kilometre Array Pathfinder (ASKAP), taken as a part of the Rapid ASKAP Continuum Survey (RACS), we searched for radio counterparts to a sample of optically discovered TDEs. We detected late-time emission at RACS frequencies (742–1032 MHz) in five TDEs, reporting the independent discovery of radio emission from TDE AT 2019ahk and extending the time baseline out to almost 3000 days for some events. Overall, we find that at least ${22}_{-11}^{+15} \% $ of the population of optically discovered TDEs has detectable radio emission in the RACS survey, while also noting that the true fraction can be higher given the limited cadence (two epochs separated by ∼3 yr) of the survey. Finally, we project that the ongoing higher-cadence (∼2 months) ASKAP Variable and Slow Transients survey can detect ∼20 TDEs in its operational span (4 yr), given the current rate from optical surveys.

We present a systematic search for tidal disruption events (TDEs) using radio data from the Variables and Slow Transients (VAST) Pilot Survey conducted using the Australian Square Kilometre Array Pathfinder. Historically, TDEs have been identified using observations at X-ray, optical, and ultraviolet wavelengths. After discovery, a few dozen TDEs have been shown to have radio counterparts through follow-up observations. With systematic time-domain radio surveys becoming available, we can now identify new TDEs in the radio regime. A population of radio-discovered TDEs has the potential to provide several key insights including an independent constraint on their volumetric rate. We conducted a search to select variable radio sources with a single prominent radio flare and a position consistent within 2 σ of the nucleus of a known galaxy. While TDEs were the primary target of our search, sources identified in this search may also be consistent with active galactic nuclei exhibiting unusual flux density changes at the timescales probed, uncharacteristically bright supernovae, or a population of gamma-ray bursts. We identify a sample of 12 radio-bright candidate TDEs. The timescales and luminosities range from ∼6 to 230 days and ∼10 ^38 to 10 ^41 erg s ^−1 , respectively, consistent with models of radio emission from TDEs that launch relativistic jets. After calculating the detection efficiency of our search using a Monte Carlo simulation of TDEs, and assuming all 12 sources are jetted TDEs, we derive a volumetric rate for jetted TDEs of ${0.80}_{-0.23}^{+0.31}$ Gpc ^−3 yr ^−1 , consistent with previous empirically estimated rates.

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.

We present a timing solution for the 5.31 ms spider millisecond pulsar (MSP) J1242−4712, discovered with the GMRT. PSR J1242−4712 orbits a companion of minimum mass 0.08 M _⊙ with an orbital period of 7.7 hr and occupies a relatively unexplored region in the orbital period versus companion mass space. We did not detect gamma-ray pulsations for this MSP, and also could not identify the optical counterpart for PSR J1242–4712 in available optical/near-infrared data. The profile of J1242−4712 evolves with frequency, showing a clear single component at lower frequencies and a three-component profile at 650 MHz. PSR J1242−4712 eclipses for a very short duration near superior conjunction (orbital phase ∼ 0.23−0.25) below 360 MHz. Moreover, significant dispersion measure delays and errors in the pulse times of arrivals are observed near inferior conjunction (orbital phase ∼ 0.7), along with an observed eclipse in one epoch at 650 MHz. Observed eclipses and significant orbital period variability suggest that PSR J1242−4712 is possibly not a helium star−white dwarf binary, but has a semi- or nondegenerate companion, indicating that this is a “spider” MSP lying in a region between typical black widows and redbacks. This system may represent a distinct category of spider MSPs, displaying characteristics that bridge the gap between known black widow and redback MSPs.

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.

We present an intensive multiwavelength monitoring campaign of the quasar PG 1302−102 with Swift and the Las Cumbres Observatory network telescopes. At z ∼ 0.3, it tests the limits of the reverberation mapping (RM) technique in probing the accretion disk around a supermassive black hole (SMBH) and extends the parameter space to high masses and high accretion rates. This is also the first time the RM technique has been applied to test disk structures predicted in the SMBH binary model that has been suggested for this source. PG 1302−102 was observed at a ∼daily cadence for ∼9 months in 14 bands spanning from X-ray to UV and optical wavelengths, and it shows moderate to significant levels of variability correlated between wavelengths. We measure the interband time lags, which are consistent with a τ ∝ λ ^4/3 relation as expected from standard disk reprocessing, albeit with large uncertainties. The disk size implied by the lag spectrum is consistent with the expected disk size for its black hole mass within uncertainties. While the source resembles other reverberation-mapped active galactic nuclei in many respects, and we do not find evidence supporting the prevalent hypothesis that it hosts an SMBH binary, we demonstrate the feasibility of studying SMBH binaries from this novel angle and suggest possibilities for the LSST Deep Drilling Fields.

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.

One of the open questions following the discovery of GW170817 is whether neutron star (NS) mergers are the only astrophysical sites capable of producing r -process elements. Simulations have shown that 0.01–0.1 M _⊙ of r -process material could be generated in the outflows originating from the accretion disk surrounding the rapidly rotating black hole that forms as a remnant to both NS mergers and collapsing massive stars associated with long-duration gamma-ray bursts (collapsars). The hallmark signature of r -process nucleosynthesis in the binary NS merger GW170817 was its long-lasting near-infrared (NIR) emission, thus motivating a systematic photometric study of the light curves of broad-lined stripped-envelope (Ic-BL) supernovae (SNe) associated with collapsars. We present the first systematic study of 25 SNe Ic-BL—including 18 observed with the Zwicky Transient Facility and 7 from the literature—in the optical/NIR bands to determine what quantity of r -process material, if any, is synthesized in these explosions. Using semi-analytic models designed to account for r -process production in SNe Ic-BL, we perform light curve fitting to derive constraints on the r -process mass for these SNe. We also perform independent light curve fits to models without the r -process. We find that the r -process-free models are a better fit to the light curves of the objects in our sample. Thus, we find no compelling evidence of r -process enrichment in any of our objects. Further high-cadence infrared photometric studies and nebular spectroscopic analysis would be sensitive to smaller quantities of r -process ejecta mass or indicate whether all collapsars are completely devoid of r -process nucleosynthesis.

We report the discovery of a young, highly scattered pulsar in a search for highly circularly polarized radio sources as part of the Australian Square Kilometre Array Pathfinder Variables and Slow Transients survey. In follow-up observations with the Parkes radio telescope, Murriyang, we identified PSR J1032−5804 and measured a period of 78.7 ms, a dispersion measure of 819 ± 4 pc cm ^−3 , a rotation measure of −2000 ± 1 rad m ^−2 , and a characteristic age of 34.6 kyr. We found a pulse scattering timescale at 3 GHz of ∼22 ms, implying a timescale at 1 GHz of ∼3845 ms, which is the third most scattered pulsar known and explains its nondetection in previous pulsar surveys. We discuss the identification of a possible pulsar wind nebula and supernova remnant in the pulsar’s local environment by analyzing the pulsar spectral energy distribution and the surrounding extended emission from multiwavelength images. Our result highlights the possibility of identifying extremely scattered pulsars from radio continuum images. Ongoing and future large-scale radio continuum surveys will offer us an unprecedented opportunity to find more extreme pulsars (e.g., highly scattered, highly intermittent, and highly accelerated), which will enhance our understanding of the characteristics of pulsars and the interstellar medium.

A substitution of FBS in culturing of bovine satellite cells for the purpose of culturing meat is presented, addressing both basal media and growth factors in relation to proliferating and differentiating cells.

Abstract The oral cavity contains distinct microenvironments that serve as oral barriers, such as the non‐shedding surface of the teeth (e.g., enamel), the epithelial mucosa and gingival tissue (attached gingiva) where microbial communities coexist. The interactions and balances between these communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium can lead to chronic inflammation and permanent tissue damage in the case of chronic periodontitis. There are currently no experimental tissue models able to mimic the structural, physical, and metabolic conditions present in the human oral gingival tissue to support the long‐term investigation of host–pathogens imbalances. Herein, the authors report an in vitro 3D anatomical gingival tissue model, fabricated from silk biopolymer by casting a replica mold of an adult human mandibular gingiva to recreate a tooth‐gum unit. The model is based on human primary cultures that recapitulate physiological tissue organization, as well as a native oxygen gradient within the gingival pocket to support human subgingival plaque microbiome with a physiologically relevant level of microbial diversity up to 24 h. The modulation of inflammatory markers in the presence of oral microbiome indicates the humanized functional response of this model and establishes a new set of tools to investigate host–pathogen imbalances in gingivitis and periodontal diseases.

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 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.

We present the detection of rotationally modulated, circularly polarized radio emission from the T8 brown dwarf WISE J062309.94−045624.6 between 0.9 and 2.0 GHz. We detected this high-proper-motion ultracool dwarf with the Australian SKA Pathfinder in 1.36 GHz imaging data from the Rapid ASKAP Continuum Survey. We observed WISE J062309.94−045624.6 to have a time and frequency averaged Stokes I flux density of 4.17 ± 0.41 mJy beam ^−1 , with an absolute circular polarization fraction of 66.3% ± 9.0%, and calculated a specific radio luminosity of L _ν ∼ 10 ^14.8 erg s ^−1 Hz ^−1 . In follow-up observations with the Australian Telescope Compact Array and MeerKAT we identified a multipeaked pulse structure, used dynamic spectra to place a lower limit of B > 0.71 kG on the dwarf’s magnetic field, and measured a P = 1.912 ± 0.005 hr periodicity, which we concluded to be due to rotational modulation. The luminosity and period we measured are comparable to those of other ultracool dwarfs observed at radio wavelengths. This implies that future megahertz to gigahertz surveys, with increased cadence and improved sensitivity, are likely to detect similar or later-type dwarfs. Our detection of WISE J062309.94−045624.6 makes this dwarf the coolest and latest-type star observed to produce radio emission.

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.

Comprehensive characterization of biomedical imaging systems require phantoms that are easy to fabricate and can mimic human tissue. Additionally, with the arrival of engineered tissues, it is key to develop phantoms that can mimic bioengineered samples. In ultrasound and photoacoustic imaging, water-soluble phantom materials such as gelatin undergo rapid degradation while polymer-based materials such as polyvinyl alcohol are not conducive for generating bioengineered tissues that can incorporate cells. Here we propose silk protein-based hydrogels as an ultrasound and photoacoustic phantom material that has potential to provide a 3D environment for long-term sustainable cell growth. Common acoustic, optical, and biomechanical properties such as ultrasound attenuation, reduced scattering coefficient, and Young's modulus were measured. The results indicate that silk acoustically mimics many tissue types while exhibiting similar reduced optical scattering in the wavelength range of 400–1200 nm. Furthermore, silk-based materials can be stored long-term with no change in acoustic and optical properties, and hence can be utilized to assess the performance of ultrasound and photoacoustic systems.

Lipid nanoparticles are promising carriers for oral drug delivery. For bioactive cargos with intracellular targets, e.g. gene-editing proteins, it is essential for the cargo and carrier to remain complexed after crossing the epithelial layer of intestine in order for the delivery system to transport the cargos inside targeted cells. However, limited studies have been conducted to verify the integrity of cargo/carrier nanocomplexes and their capability in facilitating cargo delivery intracellularly after the nanocomplex crossing the epithelial barrier. Herein, we used a traditional 2D transwell system and a recently developed 3D tissue engineered intestine model and demonstrated the synthetic lipid nanoparticle (carrier) and protein (cargo) nanocomplexes are able to cross the epithelial layer and deliver the protein cargo inside the underneath cells. We found that the EC16-63 LNP efficiently encapsulated the GFP-Cre recombinase, penetrated the intestinal monolayer cells in both the 2D cell culture and 3D tissue models through temporarily interrupting the tight junctions between epithelial layer. After transporting across the intestinal epithelia, the EC16-63 and GFP-Cre recombinase nanocomplexes can enter the underneath cells to induce gene recombination. These results suggest that the in vitro 3D intestinal tissue model is useful for identifying effective lipid nanoparticles for potential oral drug delivery.

Abstract Traumatic brain injury (TBI) is a leading cause of death and disability with no specific effective therapy, in part because disease driving mechanisms remain to be elucidated. Receptor interacting protein kinases (RIPKs) are serine/threonine kinases that assemble multi-molecular complexes that induce apoptosis, necroptosis, inflammasome and nuclear factor kappa B activation. Prior studies using pharmacological inhibitors implicated necroptosis in the pathogenesis of TBI and stroke, but these studies cannot be used to conclusively demonstrate a role for necroptosis because of the possibility of off target effects. Using a model of cerebral contusion and RIPK3 and mixed lineage kinase like knockout (MLKL −/−) mice, we found evidence for activation of RIPK3 and MLKL and assembly of a RIPK1-RIPK3-MLKL necrosome complex in pericontusional brain tissue. Phosphorylated forms of RIPK3 and MLKL were detected in endothelium, CD11b + immune cells, and neurons, and RIPK3 was upregulated and activated in three-dimensional human endothelial cell cultures subjected to CCI. RIPK3 −/− and MLKL −/− mice had reduced blood-brain barrier damage at 24 h (p

Osteogenesis-angiogenesis coupling processes play a crucial role in bone regeneration. Here, electric field induced aligned nanofiber layers with tunable thickness were coated on the surface of pore walls inside the deferoxamine (DFO)-laden silk fibroin (SF) and hydroxyapatite (HA) composite scaffolds to regulate the release of DFO to control vascularization dynamically. Longer electric field treatments resulted in gradually thickening layers to reduce the release rate of DFO where the released amount of DFO decreased gradually from 84% to 63% after 28 days. Besides the osteogenic capacity of HA, the changeable release of DFO brought different angiogenic behaviors in bone regeneration process, which provided a desirable niche with osteogenic and angiogenic cues. Anisotropic cues were introduced to facilitate cell migration inside the scaffolds. Changeable cytokine secretion from endothelial cells cultured in the different scaffolds revealed the regulation of cell responses related to vascularization in vitro. Peak expression of angiogenic factors appeared at days 7, 21 and 35 for endothelial cells cultured in the scaffolds with different silk nanofier layers, suggesting the dynamical regulation of angiogenesis. Although all of the scaffolds had the same silk and HA composition, in vitro cell studies indicated different osteogenic capacities for the scaffolds, suggesting that the regulation of DFO release also influenced osteogenesis outcomes in vitro. In vivo, the best bone regeneration occurred in defects treated with the composite scaffolds that exhibited the best osteogenic capacity in vitro. Using a rat bone defect model, healing was achieved within 12 weeks, superior to those treated with previous SF-HA composite matrices. Controlling angiogenic properties of bone biomaterials dynamically is an effective strategy to improve bone regeneration capacity.

The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton’s tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages and plays a crucial role in the tumor microenvironment. However, clinical trials with the drug have resulted in conflicting outcomes against solid tumors. In this study, folic acid-conjugated silk nanoparticles were used for the targeted delivery of IB to the cancer cell lines HeLa, BT-474, and SKBR3 by exploiting the overexpression of folate receptors on their surfaces. The results were compared with those of control healthy cells (EA.hy926). Cellular uptake studies confirmed total internalization of the nanoparticles functionalized by this procedure in the cancer cells after 24 h, compared to nanoparticles not functionalized with folic acid, suggesting that cellular uptake was mediated by folate receptors overexpressed in the cancer cells. The results indicate that the developed nanocarrier can be used for drug targeting applications by enhancing IB uptake in cancer cells with folate receptor overexpression.

As a natural high-performance material with a unique hierarchical structure, silk is endowed with superior mechanical properties. However, the current approaches towards producing regenerated silk fibroin (SF) for the preparation of biomedical devices fail to fully exploit the mechanical potential of native silk materials. In this study, using a top-down approach, we exfoliated natural silk fibers into silk nanofibrils (SNFs), through the disintegration of interfibrillar binding forces. The as-prepared SNFs were employed to reinforce the regenerated SF solution to fabricate orthopedic screws with outstanding mechanical properties (compression modulus > 1.1 GPa in a hydrated state). Remarkably, these screws exhibited tunable biodegradation and high cytocompatibility. After 28 days of degradation in protease XIV solution, the weight loss of the screw was ~20% of the original weight. The screws offered a favorable microenvironment to human bone marrow mesenchymal stem cell growth and spread as determined by live/dead staining, F-action staining, and Alamar blue staining. The synergy between native structural components (SNFs) and regenerated SF solutions to form bionanocomposites provides a promising design strategy for the fabrication of biomedical devices with improved performance.

Large-scale meat production can have negative impacts on public health, the environment and animal welfare. In this Review, the authors consider plant-based and cell-based approaches to meat production and the challenges they face.

Objective: Increasing the mass and/or activity of brown adipose tissue (BAT) is one promising avenue for treating obesity and related metabolic conditions, given that BAT has a high potential for energy expenditure and is capable of improving glucose and lipid homeostasis. BAT occurs either in discrete “classical” depots, or interspersed in white adipose tissue (WAT), termed “inducible/recruitable” BAT, or ‘beige/brite’ adipocytes. We and others have demonstrated that bone morphogenetic protein 7 (BMP7) induces brown adipogenesis in committed and uncommitted progenitor cells, resulting in increased energy expenditure and reduced weight gain in mice. BMP7 is therefore a reliable growth factor to induce browning of WAT.Methods: In this study, we sought to deliver BMP7 specifically to subcutaneous (sc)WAT in order to induce tissue-resident progenitor cells to differentiate into energy-expending recruitable brown adipocytes, without off-target effects like bone formation, which can occur when BMPs are in the presence of bone progenitor cells (outside of WAT). BMP7 delivery directly to WAT may also promote tissue innervation, or directly activate mitochondrial activity in brown adipocytes, as we have demonstrated previously. We utilized silk protein in the form of an injectable hydrogel carrying BMP7. Silk scaffolds are useful for in vivo delivery of substances due to favorable material properties, including controlled release of therapeutic proteins in an active form, biocompatibility with minimal immunogenic response, and prior FDA approval for some medical materials. For this study, the silk was engineered to meet desirable release kinetics for BMP7 in order to mimic our prior in vitro brown adipocyte differentiation studies. Fluorescently-labeled silk hydrogel loaded with BMP7 was directly injected into WAT through the skin and monitored by non-invasive in vivo whole body imaging, including in UCP1-luciferase reporter mice, thereby enabling an approach that is translatable to humans.Results: Injection of the BMP7-loaded silk hydrogels into the subcutaneous WAT of mice resulted in “browning”, including the development of multilocular, uncoupling protein 1 (UCP1)-positive brown adipocytes, and an increase in whole-body energy expenditure and skin temperature. In diet-induced obese mice, BMP7-loaded silk delivery to subcutaneous WAT resulted in less weight gain, reduced circulating glucose and lower respiratory exchange ratio (RER).Conclusions: In summary, BMP7 delivery via silk scaffolds directly into scWAT is a novel translational approach to increase browning and energy expenditure, and represents a potential therapeutic avenue for delivering substances directly to adipose depots in pursuit of metabolic treatments.

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.

We present the detection of 661 known pulsars observed with the Australian SKA Pathfinder (ASKAP) telescope at 888 MHz as part of the Rapid ASKAP Continuum Survey (RACS). Detections were made through astrometric coincidence and we estimate the false alarm rate of our sample to be ∼0.5%. Using archival data at 400 and 1400 MHz, we estimate the power-law spectral indices for the pulsars in our sample and find that the mean spectral index is −1.78 ± 0.6. However, we also find that a single power law is inadequate for modeling all the observed spectra. With the addition of flux densities between 150 MHz and 3 GHz from various imaging surveys, we find that up to 40% of our sample show deviations from a simple power-law model. Using Stokes V measurements from the RACS data, we measured the circular polarization fraction for 9% of our sample and find that the mean polarization fraction is ∼10% (consistent between detections and upper limits). Using the dispersion-measure-derived distance, we estimate the pseudo-luminosity of the pulsars and do not find any strong evidence for a correlation with the pulsars’ intrinsic properties.

Although neutron star–black hole binaries have been identified through mergers detected in gravitational waves, a pulsar–black hole binary has yet to be detected. While short-period binaries are detectable due to a clear signal in the pulsar’s timing residuals, effects from a long-period binary could be masked by other timing effects, allowing them to go undetected. In particular, a long-period binary measured over a small subset of its orbital period could manifest via time derivatives of the spin frequency incompatible with isolated pulsar properties. We assess the possibility of pulsars having unknown companions in long-period binaries and put constraints on the range of binary properties that may remain undetected in current data, but that may be detectable with further observations. We find that for 35% of canonical pulsars with published higher-order derivatives, the precision of measurements is not enough to confidently reject binarity (period ≳2 kyr), and that a black hole binary companion could not be ruled out for a sample of pulsars without published constraints if the period is >1 kyr. While we find no convincing cases in the literature, we put more stringent limits on orbital period and longitude of periastron for the few pulsars with published higher-order frequency derivatives ( n ≥ 3). We discuss the detectability of candidates and find that a sample pulsar in a 100 yr orbit could be detectable within 5–10 yr.