bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Strong Gravitational Lens Is Worth a Thousand Dark Matter Halos: Inference on Small-scale Structure Using Sequential Methods
Authors: Wagner-Carena Sebastian , Lee Jaehoon , Pennington Jeffrey , Aalbers Jelle , Birrer Simon , Wechsler Risa H. 
Published: November 2024

Abstract
Strong gravitational lenses are a singular probe of the Universe’s small-scale structure—they are sensitive to the gravitational effects of low-mass (<1010
M
⊙) halos even without a luminous counterpart. Recent strong-lensing analyses of dark matter structure rely on simulation-based inference (SBI). Modern SBI methods, which leverage neural networks as density estimators, have shown promise in extracting the halo-population signal. However, it is unclear whether the constraints from these models are limited by the methodology or the data. In this study, we introduce an accelerator-optimized simulation pipeline that can generate lens images with realistic subhalo populations in milliseconds. Leveraging this simulator, we identify the main limitation of our fiducial SBI analysis: training set size. We then adopt a sequential neural posterior estimation (SNPE) approach, allowing us to refine the training distribution to align with the observed data. Using only one-fifth as many mock Hubble Space Telescope images, SNPE matches the constraints on the low-mass halo population produced by our best nonsequential model. Our experiments suggest that an over 3 order-of-magnitude increase in training set size and GPU hours would be required to achieve an equivalent result without sequential methods. While the full potential of the existing lens sample remains to be explored, the notable improvement in constraining power enabled by our sequential approach highlights that current constraints are limited primarily by methodology and not the data itself. Moreover, our results emphasize the need to treat training set generation and model optimization as interconnected stages of any cosmological analysis using SBI.
Radial Wave in the Galactic Disk: New Clues to Discriminate Different Perturbations
Authors: Cao Chengye , Li Zhao-Yu , Schönrich Ralph , Antoja Teresa 
Published: November 2024

Abstract
Decoding the key dynamical processes that shape the Galactic disk structure is crucial for reconstructing the Milky Way’s evolution history. The second Gaia data release unveils a novel wave pattern in the L

Z
−〈V

R
〉 space, but its formation mechanism remains elusive due to the intricate nature of involved perturbations and the challenges in disentangling their effects. Utilizing the latest Gaia DR3 data, we find that the L

Z
−〈V

R
〉 wave systematically shifts toward lower L

Z
for dynamically hotter stars with larger J

Z
values. The amplitude of this phase shift between stars of different dynamical hotness (ΔL

Z
) peaks at around 2100 km s−1 kpc. To differentiate the role of different perturbations, we perform three sets of test particle simulations, wherein a satellite galaxy, transient spiral arms, and a bar plus the transient spiral arms act as the sole perturber, respectively. Under the satellite impact, the phase shift amplitude ΔL

Z
decreases toward higher L

Z
, which we interpret through a toy model of radial phase mixing. While neither the transient spiral arms nor the bar generates an azimuthally universal phase shift variation pattern, combining the bar and spirals generates a characteristic ΔL

Z
peak at the 2:1 outer Lindblad resonance (OLR) of the bar, qualitatively resembling the observed feature. Therefore, the L

Z
−〈V

R
〉 wave is more likely of internal origin. Furthermore, linking the ΔL

Z
peak to the 2:1 OLR offers a novel approach to constraining the pattern speed of the Galactic bar, supporting the long/slow bar model.
Electron Influence on the Parallel Proton Firehose Instability in 10-moment, Multifluid Simulations
Authors: Walters Jada , Klein Kristopher G. , Lichko Emily , Juno James , TenBarge Jason M. 
Published: November 2024

Abstract
Instabilities driven by pressure anisotropy play a critical role in modulating the energy transfer in space and astrophysical plasmas. For the first time, we simulate the evolution and saturation of the parallel proton firehose instability using a multifluid model without adding artificial viscosity. These simulations are performed using a 10-moment, multifluid model with local and gradient relaxation heat-flux closures in high-β proton–electron plasmas. When these higher-order moments are included and pressure anisotropy is permitted to develop in all species, we find that the electrons have a significant impact on the saturation of the parallel proton firehose instability, modulating the proton pressure anisotropy as the instability saturates. Even for lower β's more relevant to heliospheric plasmas, we observe a pronounced electron energization in simulations using the gradient relaxation closure. Our results indicate that resolving the electron pressure anisotropy is important to correctly describe the behavior of multispecies plasma systems.
A New Framework for Understanding Systematic Errors in Cluster Lens Modeling. III. Deflection from Large-Scale Structure
Authors: Madhava Aniruddha , Keeton Charles R. 
Published: November 2024

Abstract
Interpreting and reconstructing distant sources that are gravitationally lensed by galaxy clusters requires accurate and precise lens models. While high-quality data sets have reduced statistical errors in such models, systematic errors remain important. We examine systematic lensing effects caused by density fluctuations due to large-scale structure along the line of sight. We use a multiplane ray-tracing algorithm with the IllustrisTNG 100-3 cosmological simulation of matter distribution and compute the statistical distributions of shear, convergence, and higher-order deflections using two Hubble Frontier Field clusters as examples (A2744 and MACS J0416.1−2403). The cosmic shear distribution is Gaussian in each component, while the cosmic convergence distribution is skewed such that 1 + κ is consistent with a log-normal distribution; the standard deviations for these quantities are at the level of a few to 10%, depending on the redshift of the source. The deflection from higher-order terms beyond convergence and shear has significant scatter: the rms deflection is ∼15″, considerably larger than the image position residuals for current lens models. These results indicate that line-of-sight deflection effects due to large-scale structure can significantly impact lens models and should not be neglected. We present results in forms that can be incorporated into future cluster lens models.
Identifying Jittering Jet-shaped Ejecta in the Cygnus Loop Supernova Remnant
Authors: Shishkin Dmitry , Kaye Roy , Soker Noam 
Published: November 2024

Abstract
Analyzing images of the Cygnus Loop, a core-collapse supernova (CCSN) remnant, in different emission bands, we identify a point-symmetrical morphology composed of three symmetry axes that we attribute to shaping by three pairs of jets. The main jet axis has an elongated S shape, appearing as a faint narrow zone in visible and UV. We term it the S-shaped hose, and the structure of three symmetry lines the point-symmetric wind rose. The two other lines connect a protrusion (an ear or a bulge) with a hole on the opposite side of the center (a nozzle or a cavity), structures that we identify in the X-ray, UV, visible, IR, and/or radio images. There is a well-known blowout at the southern end of the S-shaped hose, and we identify a possible opposite blowout at the northern end of the S-shaped hose. The point-symmetrical morphology of the Cygnus Loop is according to the expectation of the jittering jets explosion mechanism (JJEM) of CCSNe, where several to few tens of pairs of jets with stochastically varying directions explode the star. The three pairs of jets that shaped the wind-rose structure of the Cygnus Loop are the last energetic pairs of this series of jets. Our study further supports the JJEM as the main explosion mechanism of CCSNe.
An Independent Measure of the Kinematic Dipole from SDSS
Authors: Tiwari Prabhakar , Schwarz Dominik J. , Zhao Gong-Bo , Durrer Ruth , Kunz Martin , Padmanabhan Hamsa 
Published: November 2024

Abstract
We utilize the Sloan Digital Sky Survey (SDSS) extended Baryon Oscillation Spectroscopic Survey and Baryon Oscillation Spectroscopic Survey catalogs with precise spectroscopic redshifts to estimate the kinematic redshift dipole caused by the proper motion of the solar system. We find that the velocity extracted from the kinematic dipole is consistent with cosmic microwave background (CMB) inferred values. Although the small sky coverage and limited number density of the SDSS sources constrain us from obtaining precise and robust measurements, we leverage the redshift dipole method to estimate the kinematic dipole. The velocity measurements in this study are insensitive to intrinsic clustering, associated with the source count dipole. The kinematic dipole measured in this work and its consistency with CMB values do not guarantee isotropy at large scales. The anisotropy (excess dipole) measured with the NRAO VLA Sky Survey and the Wide-field Infrared Survey Explorer Catalog could be due to the intrinsic distribution of galaxies. The results in this work focus solely on the kinematic dipole term.
Time Variation of the Solar Tachocline
Authors: Basu Sarbani , Andrade de Aguiar Wesley Antônio Machado , Korzennik Sylvain G. 
Published: November 2024

Abstract
We have used solar oscillation frequencies and frequency splittings obtained over solar cycles 23 and 24 and the rising phase of solar cycle 25 to investigate whether the tachocline properties (the change in the rotation rate across the tachocline. i.e., the jump, the width, and the position) show any time variation. We confirm that the change in rotation rate across the tachocline changes substantially; however, the change does not show a simple correlation with solar cycle unlike, for instance, changes in mode frequencies. The change during the ascending phase of solar cycle 25 is almost a mirror image of the change during the descending part of solar cycle 24, tempting us to speculate that the tachocline has a much longer period than either the sunspot or the magnetic cycle. We also find that the position of the tachocline, defined as the midpoint of the change in rotation rate, showed significant changes during solar cycle 24. The width of the tachocline, on the other hand, has shown significant changes during solar cycle 23 but not later. The change in the tachocline becomes more visible if we look at the upper and lower extents of the tachocline, defined as (position ± width). We find that for epochs around solar maxima and minima, the extent decreases before increasing again—a few more years of data should clarify this trend. Our results reinforce the need to continue helioseismic monitoring of the Sun to understand solar activity and its evolution.
The emergence of Alopecia Areata is not dependent on perforin-mediated cytolysis
Authors: Lensing Maddison , Connell Samuel , Kahl Payton , Zhu Zhaowen , Ayush Otgonzaya , Goverman Joan , Jabbari Ali 
Published: November 2024

Abstract
Alopecia Areata (AA) is a prevalent autoimmune disease that presents as nonscarring hair loss. AA is associated with the loss of immune tolerance to the hair follicle and marked by a robust immune cell infiltration and production of pro-inflammatory cytokines. In AA, CD8 T cells accumulate around and within the hair follicle and have been identified as pathogenic effectors of disease. The close spatial relationship between cytotoxic CD8 T cells and the hair follicle end-organ target invites further study of the interactions between them. Our transcriptional analysis has revealed CD8 T cells infiltrating AA skin exhibit increased gene expression of perforin and granzymes, which are key mediators of cytolysis. However, the contributions of these cytolytic molecules in AA are currently unknown. Our objective was to investigate the role of perforin in the onset of AA by using C3H/HeJ mice globally deficient in Prf1 (PKO). Interestingly, PKO mice were capable of developing spontaneous AA. Using a skin-graft induction model, we observed that wild type (WT) and PKO recipient mice showed equivalent onset and progression of AA. However, when a CD8-induction model was used, we found CD8 T cells from PKO AA mice were inferior at inducing disease when compared to CD8 T cells from WT AA mice. Overall, our findings suggest that perforin-mediated cytolysis is not required for the autoimmune attack of the hair follicle, and that other effector mechanisms of CD8 T cells are drivers of AA.
Identification of candidate biomarkers for Coronary Artery Disease by Spectral Flow-cytometry
Authors: Kumar Sunil , Oliaeimotlagh Mohammad , Ley Klaus 
Published: November 2024

Abstract
Atherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disease of the vessel wall with a secondary autoimmune component based on a loss of tolerance to self-antigens. Soluble biomarkers for ASCVD include hsCRP and IL-6, but these are not specific for ASCVD. Cell-based immune biomarkers for ASCVD are not established. Here, we identified surface markers in human peripheral blood mononuclear cells (PBMCs) using spectral flow cytometry. The PBMCs came from the Cardiovascular Assessment Virginia (CAVA) cohort with angiographically verified coronary artery disease (CAD) or not. Cell types were identified by established lineage markers. In myeloid cells, 24 surface markers were labeled and analyzed. In nonclassical monocytes (CD14-CD16+), we found that CD38 was significantly higher in cases than controls (p&lt;2.2E-16). This was also true in all 25 male subjects tested, which was driven by a large signal in 15 younger males (age below median 70). To test the impact of statin use, we stratified male subjects by statin use and diabetes. In both subgroups, CAD cases showed significantly higher CD38 expression in NMOs than controls. In 5 female subjects tested, NMO CD38 expression was also significantly higher in cases than controls. This group was too small to test further subsets. We conclude that CD38 in NMOs is significantly higher in most subjects with CAD and represents a good candidate immune cell surface biomarker that needs to be validated in other cohorts.
TLR9 regulates tolerance of developing and mature anti-DNA B cells
Authors: Nickerson Kevin , Marinov Anthony , Wang Yujuan , Cullen Jaime , Brown Aiden , Marburger Brady , Thomas Kayla , Baron Kassandra , Shlomchik Mark 
Published: November 2024

Abstract
Autoreactive B cells can be tolerized by deletion, receptor editing, and anergy. Nuclear antigen-specific B cells (such as anti-DNA) may be subject to unique regulation, as their autoantigens can also signal via Toll-like receptors 7 or 9. Indeed, we previously showed that anti-DNA B cells lacking TLR9 were not deleted, but instead became long-lived, yet anergic, follicular B cells. Here we report that the regulatory effect of TLR9 on anti-DNA development is not due to the Faslpr mutation. However, genetic background plays a role, as on the C57BL/6 background, TLR9 expression causes anti-DNA B cells to become developmentally arrested at the Fraction E to F transition in the spleen; whereas, in the autoimmune-prone MRL genetic background (regardless of Fas), such B cells progress to Fraction F. Further, we show via competitive mixed bone-marrow chimeras that TLR9 in the B cells themselves is necessary for these effects of TLR9, rather than indirectly by controlling anti-DNA Ab production, which can in turn affect self-DNA recognition. Mechanistically, RNAseq of B6 follicular anti-DNA B cells revealed that such B cells deficient in TLR9 are transcriptionally similar to edited—non-autoreactive—B cells and distinct from TLR9-intact anti-DNA cells. Hence, for anti-DNA B cells, TLR9 along with the BCR plays an important role in governing developmental progression, with TLR9 signals leading to a shorter half-life and developmental arrest.
Investigations into the Myhc 334-352-specific TCR transgenic mice reveal a role for cytotoxic CD4 T cells in the development of cardiac autoimmunity.
Authors: Sur Meghna , Rasquinha Mahima , Mone Kiruthiga , Lasrado Ninaad , Massilamany Chandirasegaran , Sobel Raymond , Reddy Jay 
Published: November 2024

Abstract
Myocarditis is a major cause of heart failure in children and young adults that can lead to dilated cardiomyopathy. Lymphocytic myocarditis may result from autoreactive CD4 and CD8 T cells but defining their antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57Bl/6 mice specific to cardiac myosin heavy chain (Myhc)-α 334-352 and found that Myhc-specific TCRs were expressed in both CD4 and CD8 T cells. By backcrossing onto A/J mice for four generations, we noted that Tg T cells from naïve mice respond to Myhc-α 334-352 as evaluated by proliferation assay and carboxyfluorescein succinimidyl ester staining. The T cell responses included significant production of pro-inflammatory cytokines including interferon (IFN)-γ, interleukin-17, granulocyte macrophage-colony stimulating factor, and tumor necrosis factor-α. While the naïve Tg mice had isolated myocardial lesions, immunization with Myhc-α 334-352 led to mild myocarditis, suggesting fully backcrossed mice may show more severe disease. Further studies led us to note that the CD4 T cells displayed the phenotype of cytotoxic T cells (CTLs) akin to those of conventional CD8+ CTLs as determined by the expression of CD107a, IFN-γ and granzyme B. Taken together, the transgenic system described here may be helpful to distinguish the roles of cytotoxic cardiac antigen-specific CD4 T cells vs. those of CD8 T cells in the pathogenesis of myocarditis.
Chronic lung inflammation disrupts the quiescent state of hematopoietic stem cells in a cystic fibrosis mouse model
Authors: Braga Cassia , Mancuso Rubia , Thompson Evrett , Oez Hasan , Gudneppanavar Ravindra , Zhang Ping-Xia , Huang Pamela , Murray Thomas , Egan Marie , Krause Diane , Bruscia Emanuela 
Published: November 2024

Abstract
Persistent neutrophilic lung inflammation is a hallmark of Cystic fibrosis (CF) lung disease. Since inflammation affects hematopoietic stem cell (HSCs) proliferation and differentiation toward the myeloid lineage, here we tested the hypothesis that chronic lung inflammation in CF causes expansion of HSCs with a pathological skewing toward myelopoiesis. WT and CF-KO mice were nebulized with LPS for 5 weeks. At 24 hours (T1) or 6 weeks (T2) after the last LPS nebulization mice were euthanized. At T0, T1, and T2 the bone marrow (BM) was collected. Lineage-negative BM cells were obtained and the percent (%) of HSC, multipotent progenitors committed to myelopoiesis (MPP2, MPP3), and lymphopoiesis (MPP4) were assessed. RNA and ATAC sequencing analyses were performed in HSC. At T1, HSC and myeloid-biased multipotent progenitors (MPP2, MPP3) % were higher in CF than in WT. At T2, the % of HSC remained elevated in CF. At T2 CF HSCs retain several increased chromatin-accessible regions and differentially expressed genes (DEGs), while WT HSCs return to their baseline. Biological analysis of DEGs and open chromatin regions in CF HSC at T2 showed pathways associated with proliferation and skew toward myelopoiesis as well as a pro-inflammatory signature. Altogether, our data show that chronic lung inflammation has a long-lasting impact on CF HSCs. Future studies aim to assess the impact of HSC dysregulation on the progression of CF lung diseases and the response to airway infections.
Modulation of neuroinflammation by interleukin-10 in mouse microglial cells
Authors: Nelson Kathryn , Schrantz Nichole , Rivard Jim , Sagarsky Callie , Grant Rainer , Carlson-Habegger Makenna , Larson Megan 
Published: November 2024

Abstract
Microglia are resident macrophages of the central nervous system that are important for maintaining brain homeostasis. Persistent activation of microglia is associated with neuroinflammation in neurodegenerative disorders. Interest in immortalized microglia cell lines as cell culture models to study their biology and role in neuroinflammation has increased in the past decade, with mouse microglial BV-2 cells emerging as an in vitro model for neuronal inflammation similar to primary mouse microglial cells. We report here IL-10 pretreatment of BV-2 cells compared to primary microglia from CD-1 mice. A 45-plex Luminex immunoassay was used to measure IL-10 pretreatment attenuation of TNF-a, IL-6, CCL5/RANTES, and G-CSF secretion from cells treated with IFN-g and LPS. In addition, we demonstrate the effects of small molecule inhibitors MLN4924, tofacitinib (CP 690550), and Cardamonin on IL-10 pretreatment. MLN4924 inhibits the NFkB pathway and decreased secretion of multiple cytokines and chemokines, including TNF-a, IL-6, CCL2/MCP-1, CCL5, CCL3/MIP-1a, and CCL4/MIP-1b. Tofacitinib inhibits the Jak1/Tyk2-STAT3 pathway, decreasing STAT-3 TYR705 phosphorylation, but had little effect on IL-10 cytokine suppression. Interestingly, IL-10 pretreatment increased secretion of IL-1ra, an M2b microglia phenotype marker, and chemokines CCL2 and CCL3. Multiplex immunoassays are a valuable tool for investigating the mechanisms of neuroinflammation in primary and immortalized cell lines.
ATR senses extracellular matrix stiffness and enhances the malignancy of breast cancer by inhibiting the recruitment of CD103+ dendritic cells
Authors: Tu Xinyi , Lou Zhenkun , Mutter Robert 
Published: November 2024

Abstract
The stiffening of the extracellular matrix (ECM), a phenomenon that often promotes metastasis and immunosuppression in many cancers, is a process that is not yet fully understood. Our study reveals that ATR, a molecule primarily recognized for its role in maintaining the genome, plays a crucial role in ECM stiffness-induced immune evasion and metastasis in triple negative breast cancer (TNBC) through DNA repair independent manner. In response to ECM stiffness, ATR activates SUN2, a component of LINC complex. This activation enhances the interaction of SUN2 with outer nuclear membrane proteins KASH1 and KASH2. The interaction between SUN2 and KASH1/2 facilitates the nuclear localization of β-catenin, which in turn promotes epithelial mesenchymal transition (EMT) and reduces the expression of E-cadherin. E-cadherin is essential for attracting CD103+ immune cells that perform anti-tumor immunity. Interestingly, inhibiting ATR reduces EMT in tumor cells, leading to an increase in CD103+ dendritic cell infiltration while decreasing neutrophil and polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) infiltration. Further, we found that ATR levels are inversely correlated with immunotherapy response rates and ATR inhibition sensitizes tumors to immunotherapy. In conclusion, the role of ATR in remodeling the immune environment could be crucial for optimizing the clinical use of ATR inhibitors to overcome immunotherapy resistance.