bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of the Extended γ-Ray Emission from the New Supernova Remnant G321.3–3.9 with Fermi-LAT
Authors: Guo Xiaolei , Liu Xi 
Published: November 2024

Abstract
With the 15 yr of Pass 8 data recorded by the Fermi Large Area Telescope, we report the detection of an extended gigaelectronvolt emission component with a 68% containment radius of 0.°85, which is spatially associated with the newly identified supernova remnant (SNR) G321.3–3.9. The γ-ray spectrum is best described by a log-parabola model in the energy range of 100 MeV–1 TeV, which shows a significant spectral curvature at ∼1 GeV. Either a leptonic or a hadronic model could explain the multiwavelength data of G321.3–3.9, while the leptonic model predicts a too-low strength of magnetic field. Also considering the flat radio spectrum of G321.3–3.9 and the γ-ray upper limit in the low energy band, the hadronic model is favored. The spatial coincidence between the γ-ray morphology and the diffuse thermal X-ray emission of G321.3–3.9 and the curved gigaelectronvolt γ-ray spectrum make G321.3–3.9 similar to the typical middle-aged SNRs interacting with molecular clouds (MCs). Such characteristics provide further evidence of the potential hadronic origin for its γ-ray emission. However, there is no MC detected around G321.3–3.9, which challenges the hadronic model.
Well-balanced High-order Finite Difference Weighted Essentially Nonoscillatory Schemes for a First-order Z4 Formulation of the Einstein Field Equations
Authors: Balsara Dinshaw , Bhoriya Deepak , Zanotti Olindo , Dumbser Michael 
Published: November 2024

Abstract
We develop a new class of high-order accurate well-balanced finite difference (FD) weighted essentially nonoscillatory (WENO) methods for numerical general relativity (GR), which can be applied to any first-order reduction of the Einstein field equations, even if nonconservative terms are present. We choose the first-order nonconservative Z4 formulation of the Einstein equations, which has a built-in cleaning procedure that accounts for the Einstein constraints and that has already shown its ability in keeping stationary solutions stable over long timescales. By introducing auxiliary variables, the vacuum Einstein equations in first-order form constitute a partial differential equation system of 54 equations that is naturally nonconservative. We show how to design FD-WENO schemes that can handle nonconservative products. Different variants of FD WENO are discussed, with an eye to their suitability for higher-order accurate formulations for numerical GR. We successfully solve a set of fundamental tests of numerical GR with up to ninth-order spatial accuracy. Due to their intrinsic robustness, flexibility, and ease of implementation, FD-WENO schemes can effectively replace traditional central finite differencing in any first-order formulation of the Einstein field equations, without any artificial viscosity. When used in combination with well-balancing, the new numerical schemes preserve stationary equilibrium solutions of the Einstein equations exactly. This is particularly relevant in view of the numerical study of the quasi-normal modes of oscillations of relevant astrophysical sources. In conclusion, general relativistic high-energy astrophysics could benefit from this new class of numerical schemes and the ecosystem of desirable capabilities built around them.
Malentendus spécifiques et malentendus transverses dans la géographie scolaire
Authors: Naudet Cédric 
Published: November 2024

L’article propose d’interroger la géographie scolaire au prisme des malentendus socio-scolaires. L’analyse s’appuie sur des observations participantes dans des dispositifs « devoirs faits » en collège et en lycée. Elle amène à distinguer différents types de malentendus relevant tant de dimensions transverses aux disciplines scolaires (attendus littératiés, disciplination, attendus opaques) que de particularités de la culture disciplinaire (raisonnement disciplinaire, exigences des objets de savoirs, identité à engager dans une activité). La typologie distinguée permet une perspective comparatiste et ouvre un nouveau champ d’interrogation pour la géographie scolaire.
Poignant Experiences and the Nonteleological Teachable Moment
Authors: Östman Leif , Garrison Jim , Van Poeck Katrien 
Published: November 2024

This article focuses on the ‘teachable moment’ that occurs when teachers and students engage in meaningful inquiry regarding problematic situations involving themselves and the subject matter being taught. While the teachable moment is nearly always conceived teleologically, the authors here discuss the educative potential of nonteleological teachable moments which are not driven by predetermined curricular objectives but elicited by poignant experiences. They present empirical examples of three types of teachable moments and discuss these with the help of pragmatist didactic models. This shows a fourfold pedagogical value of nonteleological teachable moments: they trigger a strong intrinsic motivation to learn, they are subjectivating as they appeal to the participants as persons and not merely as students compliantly fulfilling tasks, they can give rise to collective inquiry and learning in which the object of the poignant experience becomes a shared matter of concern, and they are incubators for creativity.
Introduction
Authors: Hélie Claire 
Published: November 2024

Ce numéro d’Études britanniques contemporaines est issu du colloque annuel de la SEAC organisé par le CECILLE et l’Université de Lille à l’automne 2023. Le colloque se proposait d’interroger les points cardinaux non plus seulement comme coordonnées géographiques, mais aussi comme catégories de pensée. Ce numéro d’Études Britanniques Contemporaines réunit huit articles sur la régionalité dans la littérature britannique contemporaine. Cette introduction propose quelques pistes d’exploration des points cardinaux, principes régulateurs de notre position dans le monde que la littérature s’amuse à déstabiliser.
The ‘Temptation of Indifference’ and the Search for an Elemental South in A.S. Byatt’s ‘Crocodile Tears’ (Elementals)
Authors: Tollance Pascale 
Published: November 2024

Heading south to seek oblivion or erasure may be considered as something of a topos. What the aptly named Patricia Nimmo in Byatt’s ‘Crocodile Tears’ chooses to call ‘indifference’ is a mild word for the character’s mystifying reaction to the death of her husband, struck by a violent heart attack in an art gallery: catching a glimpse of the body, Patricia runs off, leaving it for others to deal with. Her escape involves several brushes with death from which she is saved, as it happens, by a Northerner encountered in the city of Nîmes. The overall trajectory of the story seems almost too simple: the headlong flight south comes to an end when the first step is taken towards a process of mourning which is not only marked by a return to the North but by the restoration of polarities threatened by ‘the temptation of indifference’. Such simplicity is nevertheless challenged from the beginning by the tension at work between the dream of an ‘elemental’ South, associated with the possibility of driving story and history out of the landscape, and a haunting textual south which creeps back at every turn. As storylines multiply and get woven into Patricia’s own story, the 75-page long text turns into a dense visual and textual network and Byatt’s South into a place in the making that transforms itself at every step at the same time as it transforms the character. ‘Indifference’ itself becomes ambivalent as it turns into an exploratory mode. The numbing of emotions offers a vantage point to conduct an experiment in seeing which welcomes whatever presents itself to the eye. The journey which starts in a London gallery and moves to the deep yellow South of Van Gogh recounts an imaginary flight which is not just an illusory flight. It takes the form of an intense material encounter which produces a series of striking pictures, an intricate landscape that remains after the journey has ended.
Circulating oxidized mitochondrial DNA drives autoimmunity
Authors: Xian Hongxu 
Published: November 2024

Abstract
The innate immune system instructs adaptive immune activation to maintain host homeostasis, dysregulations of which underly many immune pathologies. Despite the multifold interactions, it is unclear whether innate immune responses are sufficient to enable adaptive activation and provoke disease. Breakdown of self-tolerance in T and B cells results in autoimmunity, yet innate immune control of self-reactivity is poorly understood. Mitochondrial DNA (mtDNA) recently has emerged in autoimmune disorders. However, it is unclear how mitochondrial stress associated with inflammation skews downstream aberrant adaptive responses. Here we show circulating cell-free (ccf-) oxidized (Ox-) mtDNA, induced during NLRP3 inflammasome activation, drives antibody mediated systematic autoimmunity. Abundant ccf-Ox-mtDNA in mice triggered by persistent peritonitis leads to SLE-like pathologies, development of which specifically relies on the oxidation of mtDNA. Although non-oxidized and Ox-mtDNA are both interferogenic to induce IFN-I signaling in pDCs, only Ox-mtDNA induces caspase-1 activation and IL-21 and IL-1β production, required for Tfh responses to support antibody production, leading to GC reactions and pathogenic antibodies deposition on kidney. This study establishes Ox-mtDNA ascribed by diverse chronic inflammatory diseases as a key to engage self-tolerance breach, highlights the innate immune origins of autoimmunity, and provides therapeutic targets for autoimmune disorders.
Autoimmune regulator deficiency causes sterile epididymitis and infertility characterized by infiltration of iron-laden macrophages
Authors: Ahn Soo Hyun , Grzesiak Geoffrey , Halgren Katrina , MacRenaris Keith , Sue Aaron , O'Halloran Tom , Petroff Margaret , Crawford Andrew 
Published: November 2024

Abstract
Men with Autoimmune Polyglandular Syndrome Type 1 (APS-1), a disease caused by a mutation in the gene encoding Autoimmune regulator (Aire), can suffer infertility, but the mechanism is not known. Using transgenic animals and a novel mass spectrometry to detect trace elements (LA-ICP-TOF-MS), we set out to determine the role of immune cells in male infertility using a mouse model of APS-1. We generated a transgenic mouse line with targeted mutations in Aire (AireKO) alone, or in both Aire and Rag1 (AireKORag1KO) using CRISPR/Cas9 on the Balb/c background. The resulting AireKO males were almost completely infertile compared to WT and AireKORag1KO males. All AireKO males (n=10) had epididymitis characterized by fibrosis and infiltration of T and B cells and macrophages as early as 8 weeks of age. LA-ICP-TOF-MS showed increased iron concentration in the interstitium that co-registered with F4/80+ macrophages using structural similarity index matrix. Immune cell infiltration, fibrosis, or iron-laden macrophages were absent in AIREKORAG1KO mice. Our results reveal the importance of Aire-mediated immune tolerance in preservation of fertility and suggest that in the absence of Aire, autoreactive T and B lymphocytes target the epididymis and promote inflammation that ultimately results in fibrosis. Further studies will reveal the specific role of lymphocytes in causing these changes, and the significance of iron deposition in fibrosis development.
Repurposing varicella zoster virus and human papillomavirus vaccines for local immunotherapy against solid tumors
Authors: Cuburu Nicolas , Sethi Shiv , Bradley Claire , Bialkowski Lukas , Yuk Pang , Thompson Cynthia , Schiller John 
Published: November 2024

Abstract
Local immunotherapy against solid tumors is considered a viable approach to stimulate the tumor microenvironment (TME) and anti-tumor immunity. We assessed in situ vaccination with licensed subunit vaccines to leverage preexisting anti-vaccine immunity in a tumor model expressing HPV16 viral oncogenes E6 and E7. We chose Shingrix, a VZV vaccine containing the glycoprotein E (gE), and Gardasil-9, an HPV vaccine containing the L1 virus-like particles (VLP) to preferentially induce CD4 and CD8 T cell responses, respectively. Intratumoral (IT) injection of Shingrix in prevaccinated mice often led to complete regression and elicited CD8 T cell responses against E7. IT injection of an MHC-II-restricted gE peptide with polyI:C also led to durable remission, suggesting a role for gE-specific CD4 T cells. In contrast, IT injection of Gardasil-9 did not delay tumor growth, but IT injection of an MHC-I-restricted L1 peptide with Shingrix led to complete remissions hence overcoming preexisting antibodies against native HPV VLP. TME analysis showed that IT injection of Shingrix with Gardasil-derived peptide induced IFN-g, TNF-a and CXCL9 and reshaped the myeloid cell infiltrate. Finally, IT injection of Shingrix and the E7 viral neoantigen peptide led to the eradication of all primary injected and abscopal tumors. Our results indicate that Shingrix is a versatile component for in-situ vaccination which can be combined with peptides derived from licensed vaccines or tumor antigens.
A previously under-recognized role of CXCL12 in endogenous thymic regeneration
Authors: Lagou Maria , Griffen Anthony , Carpenter Randall , Argyris Dimitris , Anastasiadou Dimitra , Chondronikola Anastasia Aristoteleia , Hardas Alexandros , Vallejo Garcia Raquel , Karagiannis Nikos , Mosarvarpour Sara , Licausi Francesca , Briceno Andrea , Guzik Hillary , DesMarais Vera , Cui Min-Hui , Branch Craig , Poutahidis Theofilos 
Published: November 2024

Abstract
The thymus is a primary lymphoid organ for T cell development. Sensitive to stress, it undergoes acute involution in response to cytotoxic stimuli, e.g., cytoablative chemotherapy. Thus, establishing regeneration strategies to restore thymic function is vital for pediatric cancer and transplantation patients receiving such treatments. However, lack of insight for detailed mechanisms of thymic repair has impeded progress towards supporting thymic function in these patients. We developed a mouse model of cyclophosphamide-induced thymic involution, with detailed regeneration kinetics at cell population (flow cytometry) and microanatomical (digital pathology) levels. We found consistent defects of early thymocyte progenitor (ETP) seeding and trafficking during endogenous thymic repair. Single cell ATACseq analysis revealed perturbations in chromatin accessibility of the thymocyte-homing chemokine CXCL12 in various stromal cell subsets, including early developmental stages of cortical thymic epithelial cells (cTEClo) and endothelial cells, suggesting structural adaptations to accommodate ETP trafficking during thymic repair. We currently employ CXCL12 conditional ablation in cTEClo and pharmacological suppression using specific CXCR4 antagonists, to highlight the unreported role of CXCL12/CXCR4 axis in endogenous thymic repair. Together, our efforts shed novel mechanistic insights on the structural and functional adaptations of thymic stromal cells after cytotoxic chemotherapy.
Differential effects of adjuvants on germinal center formation in Influenza vaccination and infection.
Authors: Prellberg Matthew , Noureddine Moataz , Chang Lauren , De Geest Bruno , Schotsaert Michael 
Published: November 2024

Abstract
B cells, and the antibodies they produce, represent one of the most durable, potent, and specific forms of immunological memory for protection against viral infections. Central to this sustained immune protection are germinal centers (GCs), which produce high-affinity antibody secreting plasma cells and memory B cells. Understanding how GC reactions differ from natural infection and vaccine-induced immunity remains a central question of vital importance to inform the next-generation of vaccine design. Here, we investigated GC induction in a mouse model of influenza infection as well as after vaccination with quadrivalent inactivated influenza vaccine (QIV), with or without adjuvants. We observed that in natural infection, GC frequencies are increased in draining lymph nodes, spleen, and lung tissue in a dose-dependent manner. With vaccination, GC formation peaked at 7 days post vaccination (DPV) in the draining lymph and 14 DPV in spleen, except for IMDQ-PC (TLR7/8 agonist), which showed faster GC kinetics. Additionally, adjuvanted QIV vaccines showed enhanced GC B cell induction with greater durability, up to 21 DPV compared to QIV alone in both the draining lymph and spleen, as well as increased total IgG serum titers. Adjuvants represent potent enhancers of humoral immunity with the potential to increase the quality of vaccines. We are currently investigating how adjuvants will affect the memory compartment of humoral immunity and how this compares to natural infection.
No change in HIV cellular burden and lower ADCC despite increased immune activation after combined immunotherapy with peg-IFN-α2b and two broadly neutralizing antibodies in suppressed HIV+ subjects
Authors: Papasavvas Emmanouil , Morris Jessicamarie , Ross Brian , Fair Matthew , Giron Leila , Azzoni Livio , Abdel-Mohsen Mohamed , Mounzer Karam , Kostman Jay , Tebas Pablo , Montaner Luis 
Published: November 2024

Abstract
Background: Pegylated interferon α2b (peg-IFN-α2b) and the broadly neutralizing antibodies (bNabs) 3BNC117 and 10-1074 were individually shown to increase HIV suppression during antiretroviral therapy (ART) interruption (ATI). We evaluated the anti-HIV and immune effect of combined immunotherapy with peg-IFN-α2b+bNAbs in persons with HIV infection (PWH).
Methods: Peripheral blood mononuclear cells and plasma from 14 ART-suppressed PWH were assessed at baseline (ART), ART+4 weeks of peg-IFN-α2b, and ATI+26 weeks of peg-IFN-α2b+bNAbs immunotherapy for: 1) intact HIV DNA, 2) NK constitutive, and in vitro gp120 or IFN-α-induced antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cytotoxicity, and 3) immune activation.
Results: Immunotherapy did not alter cell-associated intact HIV DNA levels nor IFN-α-induced NK direct cytotoxicity. Yet, it decreased gp120-induced ADDC, and the percentage (%) of CD56lo/+CD16+ on CD56+ while increasing the % of CD56hi and CD56lo/+CD16- on CD56+ suggesting that decreased expression of CD16 (Fc receptor) on NK could result to lower ADCC. Immunotherapy also decreased CD57 expression on CD56lo/+CD16+, while increased Tetherin, CD38, HLA-DR, NKp46, and CD169 on immune cells, and pro-inflammatory bisected GlcNAc glycans on bulk IgG.
Conclusion: Decreased ADCC and circulating CD16+ NK cell subsets despite increased immune activation may explain the lack of change in HIV cell burden after Peg-IFN-α2b+bNAbs administration in PWH.
Longitudinal analysis of immunological response to vaccination
Authors: Chenchik Alex , Kobzik Lester , Liu Tianbing , Hu Dongfang , Makhanov Mikhail , Paraiso Kitt , Ghias Khadija , Diehl Paul 
Published: November 2024

Abstract
This study explores the dynamic nature of the immune responses to vaccination with Td (Tetanus-diphtheria), PPSV23 (pneumococcal), and Shingrix (herpes zoster) vaccines. We performed detailed transcriptomic analysis, including genome-wide expression profiling, adaptive immune receptor (AIR) profiling, and single-cell transcriptome analysis of sorted T & B cells. We collected whole blood samples from a single donor at multiple time points before and after vaccination. RNA and DNA were extracted, and the DriverMap™ genome-wide targeted expression profiling (EXP) assay and AIR profiling were run for both T & B cell receptors from RNA and DNA. NGS results were analyzed using the MiXCR pipeline (AIR panel) and Salmon analysis (EXP panel). Whole transcriptome pathway enrichment analysis showed innate immune response with significant activation of interferon and cytokine signaling on Day 2 after immunization, followed by activation of adaptive immunity on Days 7-10, and return to baseline levels by Days 15-22. Response to vaccinations involved both TCR and BCR signaling with significant activation of immunoglobulin clonotypes specific for vaccine antigens. We characterized specific cell types responsible for adaptive immune responses through T/B cell sorting experiments and 10x analysis. This study highlights the importance of integrated transcriptome, immune repertoire, and single-cell profiling analysis to understand the complex interplay of innate and adaptive immune mechanisms.
Yersinia pestis NLP subunit vaccine platform: Protective efficacy and immunological profile
Authors: Davies Michael , Dankmeyer Jennifer , Rill Nathaniel , Klimko Christopher , Shoe Jennifer , Hunter Melissa , Talyansky Yuli , Qiu Ju , Rasley Amy , Fischer Nicholas , Cote Christopher , Biryukov Sergei 
Published: November 2024

Abstract
Yersinia pestis (Yp) is the etiological agent of plague, a disease that remains a concern as demonstrated by recent outbreaks in Madagascar. Infection with Yp results in a rapidly progressing illness that can only be treated with antibiotics. Live attenuated or whole-cell inactivated vaccines confer short-lived protection against bubonic but not pneumonic plague. Subunit vaccine formulations may circumvent some of these shortfalls. Here we compare the immunogenicity generated by the most advanced subunit vaccine (rF1V) against a nanolipoprotein particle (NLP)-based vaccine. BALB/c mice were immunized twice, four weeks apart. Four weeks later, splenocytes and sera were collected for immune profiling and mice were aerosol challenged with Yp CO92. Both formulations induced a strong IgG response against F1 and V proteins, along with a robust memory B cell response and cell-mediated response with Th1- and Th2-related cytokines. NLP-based vaccine induced a stronger cytokine response against F1, V, and F1V proteins relative to the rF1V vaccine. As with rF1V, the inclusion of Alhydrogel in NLP vaccine formulations was critical for enhanced immunogenicity and protective efficacy. Addition of Francisella tularensis antigens to the Yp NLP vaccine platform did not impair vaccine efficacy, based on protection and antibody response. The modularity and lipid bilayer structure of NLPs allows for incorporation of many protective antigens with variable ratios against multiple pathogens.
A non-canonical mechanism of antiviral activity of Oligoadenylate Synthetase 1
Authors: Harioudh Munesh , Perez Joseph , Chong Zhenlu , Nair Sharmila , So Lomon , McCormick Kevin , Ghosh Arundhati , Shao Lulu , Srivastava Rashmi , Soveg Frank , Ebert Thomas , Atianand Maninjay , Hornung Veit , Savan Ram , Diamond Michael , Sarkar Saumendra 
Published: November 2024

Abstract
The translational arrest of protein synthesis is often a cellular response to the virus infection. However, some antiviral proteins continue to be translated through unknown mechanisms during this translational shutdown. Here, we report a mechanism by which antiviral effectors are upregulated during this translational shutdown. We found that interferon (IFN) stimulated gene, Oligoadenylate Synthetase 1 (OAS1), binds AU-rich elements (ARE) of specific mRNA, including IFNβ, prolonging the half-life and continued expression. This increased IFN expression protects from WNV infection in vitro and in vivo via downstream IFNAR signaling. This mechanism is common between human OAS1 and mouse Oas1b, independent of OAS enzyme activity and RNase L. However, human OAS1 inhibits SARS-CoV-2 replication through its canonical enzyme activity via RNase L, thus establishing two different mechanisms of OAS1 antiviral activity. These results establish OAS1 as an ARE-binding protein with a broader non-canonical function that protects IFN expression from translational shutdown.