bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible Gravitational Microlensing Events in the Optical Lightcurve of Active Galaxy S5 0716+714
Authors: Król D. Ł. , Stawarz Ł. , Krzesinski J. , Cheung C. C.
Published: February 2023

A well-known active galaxy of the blazar type, S5 0716+714, is characterized by a particularly high-variability duty cycle on short timescales at optical frequencies. As such, the source was subjected to numerous monitoring programs, including both ground-based as well as spaceborne telescopes. On closer inspection of the most recent accumulation of the data provided by the Transiting Exoplanet Survey Satellite, we have noticed several conspicuous events with “volcano-like” symmetric shape, all lasting for several hours, which closely resemble the achromatic events detected with the previous Whole Earth Blazar Telescope campaigns targeting the source. We propose that those peculiar features could be due to the gravitational microlensing of the innermost segments of the precessing jet in the system by a binary lens. We study the magnification pattern of the lens with the inverse-ray shooting method and the source trajectory parameters with the Python package MuLensModel. In this way, we were able to fit successfully all the selected events with a single lens, adjusting slightly only the source trajectory parameters for each lensing event. Based on the fit results, we postulate the presence of a massive binary lens containing an intermediate-mass black hole, possibly even a supermassive one, and a much less massive companion (by a factor of ≲0.01) located within the host galaxy of the blazar, most likely the central kiloparsec region. We discuss the major physical implications of the proposed scenario regarding the quest for the intermediate-mass and dual supermassive black holes in active galaxies.
Large-scale Spatial Cross-calibration of Hinode/SOT-SP and SDO/HMI
Authors: Fouhey David F. , Higgins Richard E. L. , Antiochos Spiro K. , Barnes Graham , DeRosa Marc L. , Hoeksema J. Todd , Leka K. D. , Liu Yang , Schuck Peter W. , Gombosi Tamas I.
Published: February 2023

We investigate the cross-calibration of the Hinode/Solar Optical Telescope-Spectro-Polarimeter (SOT-SP) and Solar Dynamics Observatory/Helioseismic and Magnetic Imager (SDO/HMI) instrument metadata, specifically the correspondence of the scaling and pointing information. Accurate calibration of these data sets gives the correspondence needed by interinstrument studies and learning-based magnetogram systems, and is required for physically meaningful photospheric magnetic field vectors. We approach the problem by robustly fitting geometric models on correspondences between images from each instrument’s pipeline. This technique is common in computer vision, but several critical details are required when using scanning-slit spectrograph data like Hinode/SOT-SP. We apply this technique to data spanning a decade of the Hinode mission. Our results suggest corrections to the published Level 2 Hinode/SOT-SP data. First, an analysis on approximately 2700 scans suggests that the reported pixel size in Hinode/SOT-SP Level 2 data is incorrect by around 1%. Second, analysis of over 12,000 scans shows that the pointing information is often incorrect by dozens of arcseconds with a strong bias. Regression of these corrections indicates that thermal effects have caused secular and cyclic drift in Hinode/SOT-SP pointing data over its mission. We offer two solutions. First, direct coalignment with SDO/HMI data via our procedure can improve alignments for many Hinode/SOT-SP scans. Second, since the pointing errors are predictable, simple post-hoc corrections can substantially improve the pointing. We conclude by illustrating the impact of this updated calibration on derived physical data products needed for research and interpretation. Among other things, our results suggest that the pointing errors induce a hemispheric bias in estimates of radial current density.
Clinical Evaluation of Different Minimal Invasive Treatment Modalities of Mild to Moderate Dental Fluorosis Using an Intra-oral Spectrophotometer
Authors: Youssef M. N. , Abo Elezz A. F. , Elddamony E. A. , Ghoniem A. F.
Published: February 2023

BACKGROUND: Various treatment modalities are available to improve esthetics of fluorosed teeth based on its severity.
AIM: The aim of the study was to evaluate the clinical performance of different minimal invasive treatment protocols on mild to moderate fluorosed teeth.
METHODS AND MATERIALS: Before the interventions, tooth color coordinates L, a and b were recorded for 160 fluorosed teeth by Vita Easyshade V. Participants were randomly allocated in eight treatment protocols with 20 teeth (n = 20) included in each protocol. Protocol one (P1) Opalescence boost PF 40%. Protocol two (P2) Opalustre. Protocol three (P3) MI-Paste Plus. In protocol four (P4) teeth were treated with Opalustre followed by Opalescence boost PF 40%. In protocol five (P5) Opalescence boost PF 40% was applied followed by MI-Paste Plus, while in protocol six (P6) Opalustre was applied followed by MI-Paste Plus whereas protocol seven (P7) teeth were treated with Opalustre, followed by Opalescence boost PF 40% and finally MI-Paste Plus. Protocol eight (P8) control. All teeth were evaluated immediately for color change (ΔE) after treatment (T1), after 14 days (T2), after 3 months (T3) and after 6 months (T4). Color change (ΔE) was calculated from ΔL, Δa, and Δb recorded at each evaluation time point.
STATISTICAL ANALYSIS: Two-way ANOVA was applied to test the interaction between different variables. ANOVA repeated measures were followed by Duncan multiple range tests (DMRTs) to compare between groups.
RESULTS: In accordance to time, all treatment protocols showed significant color change can be recognized by unexperienced eye (ΔE ≥ 3.7). Immediately after application (T1), the highest color change (ΔE) was recorded in P7. While at 14 days and 3 months follow ups, color change in P4 exceeded P7. After 6 months the highest ΔE was recorded in both P4 and P7 with no significant difference between them. Meanwhile, in Accordance to treatment Protocol, The highest color change was recorded at 3 months (T3) in all treatment protocols. These records were preserved at 6 months follow-up (T4) for all treatment protocols except P1 and P3.
CONCLUSION: Combined treatment protocols of Opalustre and Opalescence boost PF 40% have the highest effect on ΔE regardless of using MI-Paste Plus. MI-Paste Plus provides stability of ΔE results at 6 months’ follow-up.
A new large Oreophryne species from the mountains of Papua Province, Indonesian New Guinea (Amphibia, Anura, Microhylidae)
Authors: Günther Rainer , Iskandar Djoko T. , Richards Stephen J.
Published: February 2023

The microhylid genusOreophrynereaches its greatest diversity in the New Guinea region, where more than 60 species have been documented to date. MostOreophryneare small (<30 mm SVL) and only three species,O. anthonyi,O. idenburgensisandO. inornata, exceed 40 mm SVL adult body size. Here we describe a fourth large species ofOreophrynethat was collected in 1998 from the mountains of Papua Province in western New Guinea. In having a cartilaginous connection between the procoracoid and scapula it is most similar toO. idenburgensis, a species known only from the mountains of central-western New Guinea but differs from that species in a suite of morphological characters including a broader head, a hidden (vs. visible) tympanum and a more pointed snout.
Three new species in Tetrastemma Ehrenberg, 1828 (Nemertea, Monostilifera) from sublittoral to upper bathyal zones of the northwestern Pacific
Authors: Hookabe Natsumi , Kohtsuka Hisanori , Fujiwara Yoshihiro , Tsuchida Shinji , Ueshima Rei
Published: February 2023

Monostiliferous nemerteans in the genus Tetrastemma Ehrenberg, 1828 are generally characterized as having four eyes, and they occur worldwide, from the intertidal zone to the deep-sea bottom. Recent extensive sampling of Tetrastemma has explored the high species diversity, including many undescribed forms, but phylogenic analysis has revealed non-monophyly of the genus. We herein describe three new species of the genus (T. albumsp. nov., T. personasp. nov., and T. shohoensesp. nov.) from northwestern Pacific waters based on specimens collected by dredging or by use of a remotely operated vehicle at depths of 116–455 m. Since anatomical and histological characters traditionally used in systematics of the genus are sometimes interspecifically uniform, a histology-free approach is applied for the species descriptions in this study. To confirm the generic affiliation of the new species, a molecular phylogenetic analysis based on partial sequences of cytochrome c oxidase subunit I, 16S rRNA, 18S rRNA, 28S rRNA, and histone H3 genes was performed. Our result shows that all three new species are nested in a subclade formed by species from the North Pacific and American Atlantic, inferring that geographic distribution does not reflect the cladogenesis of Tetrastemma. Furthermore, two Tetrastemma species with a cylindrical stylet basis, T. freyaeChernyshev et al., 2020 from off the coast of India and Hawaii and T. shohoensesp. nov. from Shoho Seamount, Japan, constitute a clade in the resulting tree.
A survey of the spider genus Dysdera Latreille, 1804 (Araneae, Dysderidae) in Iran, with fourteen new species and notes on two fossil genera
Authors: Zamani Alireza , Marusik Yuri M. , Szűts Tamás
Published: February 2023

The taxonomy of the Iranian species of the dysderid spider genus Dysdera Latreille, 1804 is revised. Currently, the only species of this genus known from Iran is D. pococki Dunin, 1985, albeit on the basis of a doubtful record. The following 14 species are described as new to science in this paper: D. achaemenessp. nov. (♀; Fars), D. bakhtiarisp. nov. (♂; Chaharmahal & Bakhtiari), D. damavandicasp. nov. (♂; Mazandaran), D. genoensissp. nov. (♂♀; Hormozgan), D. hormuzensissp. nov. (♀; Hormozgan), D. iranicasp. nov. (♂♀; Fars, Hormozgan), D. isfahanicasp. nov. (♂♀; Isfahan), D. mazerunisp. nov. (♀; Mazandaran), D. medessp. nov. (♂; Tehran), D. persicasp. nov. (♂♀; Golestan, Mazandaran), D. sagartiasp. nov. (♂♀; Tehran), D. tapuriasp. nov. (♂♀; Mazandaran), D. verkanasp. nov. (♂; Golestan), and D. xerxesisp. nov. (♂; Bushehr). Distribution records of all species are mapped. Also, the taxonomy of Mistura Petrunkevitch, 1971 and Segistriites Straus, 1967, two fossil genera currently considered in Dysderidae, is discussed and the latter is transferred to Segestriidae.
Agency beyond Action: Modernist Charactersas Interpreters and Readers
Authors: Hercend Olivier
Published: February 2023

S’appuyant sur la distinction proposée par Bruno Latour, cet article s’intéresse à la façon dont les textes modernistes tendent à se détourner des moments d’action, pour focaliser l’attention sur les réseaux de « puissance d’agir » ( agency ) qui informent ces actions. Cette tendance, qui sous-tend de nombreux choix narratifs ou poétiques, décentre les personnages. Ceux-ci ne sont plus définis par leurs choix, mais constituent des points focaux sur lesquels s’exercent diverses influences antagoniques. Via les notions d’« interpellation » et de « contre-interpellation » développées par Jean-Jacques Lecercle, je défends l’idée que la force des personnages modernistes tient à ce statut décentré : ils sont contraints de construire leur identité dans un constant mouvement d’interprétation et de réappropriation de puissances d’agir externes. Ainsi, l’acte de lecture, en tant que confrontation au texte écrit mais aussi à d’autres agents et à des pressions sociales, constitue une scène paradigmatique : il représente la tension inhérente à la réception, mais aussi les potentialités créatives et expressives que celle-ci recèle, et que les personnages modernistes doivent intégrer pour s’affirmer dans leur propre histoire.
One-sided differentiability: a challenge for computer algebra systems
Authors: Ferres-López Enrique , Roanes-Lozano Eugenio , Martínez-Zarzuelo Angélica , Sánchez Fernando
Published: February 2023

Computer Algebra Systems (CASs) are extremely powerful and widely used digital tools. Focusing on differentiation, CASs include a command that computes the derivative of functions in one variable (and also the partial derivative of functions in several variables). We will focus in this article on real-valued functions of one real variable. Since CASs usually compute the derivative of real-valued functions as a whole, the value of the computed derivative at points where the left derivative and the right derivative are different (that we will call conflicting points) should be something like "undefined", although this isn't always the case: the output could strongly differ depending on the chosen CAS. We have analysed and compared in this article how some well-known CASs behave when addressing differentiation at the conflicting points of five different functions chosen by the authors. Finally, the ability for calculating one-sided limits of CASs allows to directly compute the result in these cumbersome cases using the formal definition of one-sided derivative, which we have also analysed and compared for the selected CASs. Regarding teaching, this is an important issue, as it is a topic of Secondary Education and nowadays the use of CASs as an auxiliary digital tool for teaching mathematics is very common.
Coordinated location-allocation of cruise ship emergency supplies under public health emergencies
Authors: Huang Liling , Tan Yong , Ye Jinzhu , Guan Xu
Published: February 2023

For the rapid development of the cruise industry, the cruise disaster relief supply chain has attracted extensive attention, especially because COVID-19 cases on international cruise ships occurred. In this paper, we propose an idea of coordination layout for cruise ship emergency supplies, the problem optimized two objective functions of maximizing coverage satisfaction and minimizing the total cost, addressing the low efficiency of resource utilization at the same. By applying to cruise ship emergency supplies layout of Northeast Asia cruise port group system, using expert scoring method and AHP to evaluate cruise port security vulnerability. The NSGA-II algorithm is used to solve the multi-objective programming model. A numerical example shows that the optimization design model and method are valid and feasible, and the algorithm is efficient for solving the above collaborative location and allocation problem of sectional reserves, which can also offer a variety of decision-making options.
Dynamics of a delayed reaction-diffusion predator-prey model with the effect of the toxins
Authors: Zhu Meiling , Xu Huijun
Published: February 2023

In this study, we investigate a delayed reaction-diffusion predator-prey system with the effect of toxins. We first investigate whether the internal equilibrium exists. We then provide certain requirements for the presence of Turing and Hopf bifurcations by examining the corresponding characteristic equation. We also study Turing-Hopf and Hopf bifurcations brought on by delays. Finally, numerical simulations that exemplify our theoretical findings are provided. The quantitatively obtained properties are in good agreement with the findings that the theory had predicted. The effects of toxins on the system are substantial, according to theoretical and numerical calculations.
Fast matrix exponential-based quasi-boundary value methods for inverse space-dependent source problems
Authors: Bazán Fermín S. V. , Bedin Luciano , Leem Koung Hee , Liu Jun , Pelekanos George
Published: February 2023

In this paper, we study the well-established quasi-boundary value methods for regularizing inverse state-dependent source problems, where the convergence analysis of three typical cases is presented in the framework of filtering regularization method under suitable source conditions. Interestingly, the quasi-boundary value methods can be interpreted as certain Lavrentiev-type regularization, which was not known in literature. As another major contribution, efficient numerical implementation based on matrix exponential in time is developed, which shows much improved computational efficiency than MATLAB's backslash solver based on the all-at-once space-time discretization scheme. Numerical examples are reported to illustrate the promising computational performance of our proposed algorithms based on matrix exponential techniques.
RiC-CM en construcción: del modelo descriptivo sintáctico (2016) al semántico armonizador (2021)
Authors: Llanes Padrón Dunia , Moro Cabero Manuela
Published: February 2023

Este articulo analiza los dos borradores de Record in Context (RiC), un modelo conceptual (MC) para la descripción archivística elaborado por el Internacional Council of Archives (ICA). Se estudian diferentes elementos de las versiones del modelo para la comprensión de su estructura: principios teóricos, entidades, atributos y relaciones. RiC-CM se plantea como la alternativa para la representación, el acceso, el uso y la interoperabilidad de los recursos archivísticos en los tiempos posmodernos. El análisis permite comprender el papel de RiC en la integración y unificación de los esquemas descriptivos de archivos, bibliotecas, museos e instituciones culturales con la finalidad de lograr un acceso distribuido y entrelazado del patrimonio cultural mundial.
Persistence and Proliferation: Integrating Community-Engaged Scholarship into 59 Departments, 7 Units, and 1 University Academic Promotion and Tenure Policies
Authors: Janke Emily , Jenkins Isabelle , Quan Melissa , Saltmarsh John
Published: February 2023

Choosing how to recognize community-engaged scholarship in promotion and tenure policies so that it is assessed accurately and fairly remains a relatively new and ongoing challenge for institutions of higher education. This case study examines how one U.S. research university integrated recognition of community-engaged scholarship across all levels of policy, including university, unit, and department. The terms used within and across policies reveal that while some terms were perpetuated across policies, many more terms proliferated across policies. Using organizational change and signaling theories, as well as the Democratic Civic Engagement Framework, analysis raises questions and insights regarding the use of both specificity and ambiguity when choosing and defining terms, and the use of terms across faculty roles of teaching, research/creative activity, and service to signal and address legitimacy of community-engaged scholarship within a larger context of institutional values. 
Coups de pieds en talons hauts : politiques du corps et performancescapes dans les scènes drag et ballroom grecques contemporaines
Authors: Koutsougera Natalia , Kontou Amalia Maria
Published: February 2023

Ces dernières années, dans la Grèce post-crise économique, les violences homophobes, transphobes de même que la haine de l’efféminé et du féminin se sont intensifiées. En parallèle, de nouvelles esthétiques médiatiques, de nouveaux codes visuels et de nouveaux impératifs hyperpolitiques ont émergé, cherchant à redéfinir les pratiques artistiques drag et queer. Dans ce cadre, ces dernières se sont mises à se jouer tout à la fois de la culture populaire nationale, des standards de beauté et de la politique dans une perspective quasi postmoderne et postironique. S’appuyant sur des références locales et internationales, les scènes grecques du drag et du ballroom subvertissent artistiquement les horizons d’attente de leurs publics, à l’aide « d’imaginaires alternatifs et chaotiques du genre » (Davies, 2012) et d’autoréférences populaires et culturelles qui « soulignent la fausseté du naturel » (Van de Port, 2012). Bien souvent, ces appropriations sont perçues comme « en guerre avec la grécité » (Ieropoulos, 2018) et incarnent l’archétype moderne du « déviant » et du blasphème aux yeux d’une société grecque chrétienne orthodoxe. Dans une veine similaire, les vogueur·euses portent des costumes étranges, déformant les images d’une féminité pop et extravagante, et s’adonnent publiquement à des mouvements de danse en talons hauts, dans une logique combative et excessive. Dans ce contexte, nous proposons une analyse des performances espiègles et hasardeuses qui ponctuent les scènes drag et ballroom d’Athènes, afin d’en révéler les configurations politiques et les rhizomes performatifs, qui s’étalent bien au-delà des interprétations et imaginaires de résistance inter et extracommunautaires.
« Est-ce qu’il fait gay ? » : Analyse des questions soulevées lors du casting de comédiens pour des personnages gays dans une websérie
Authors: Gay Déborah
Published: February 2023

À la fin des années 2010 est diffusée la saison 1 d’une websérie sur des militants LGBT. Lors des castings s’est posée la question du choix des comédiens, pour incarner des personnages gays. Ce choix dépend de plusieurs facteurs. D’une part, les responsables des castings ont chacun un regard propre sur ce qui fait un personnage LGBT fictionnel, en lien avec leur sexualité, leurs expériences, les normes de genre qu’ils adoptent et ce qu’ils attendent de la série. D’autre part, la question de la crédibilité et la volonté de portée universaliste de la websérie ont également des effets sur le choix des comédiens. Ces derniers peuvent aussi refuser de jouer le rôle d’un personnage gay, car le coût symbolique et économique à payer serait trop élevé, d’autant plus si le comédien est racisé. Dans cet article, nous nous intéressons au corps du comédien, tel qu’il a été discuté lors des réunions de préparation des castings et durant les castings eux-mêmes, auxquels j’ai pu assister dans le cadre d’une observation participante, ainsi que dans les discussions qui ont suivi.
Décrire, est-ce déjà juger ?
Authors: Jouanno Aubrie
Published: February 2023

L’exercice de l’autorité parentale fait aujourd’hui l’objet d’une régulation par les pouvoirs publics chargés de protéger les enfants « en danger ou en risque de l’être ». Une fois confiés à l’aide sociale à l’enfance, la justice doit évaluer à intervalles réguliers si les enfants peuvent retourner chez leurs parents ou, au contraire, rester placés. Mais comment une juge peut-elle déterminer si l’enfant encourt toujours un (potentiel) danger dans sa famille alors même qu’il ne s’y trouve plus ? Cet article retrace le processus de construction collectif d’une décision de renouvellement d’une assistance éducative en prenant appui sur les deux dispositifs centraux du processus judiciaire : le rapport envoyé aux juges et les audiences. En s’attachant à reconstituer une ethnographie de l’action publique, l’exposé montre comment la décision de justice se forme à l’issue d’une construction collective du jugement sur les usagers dans laquelle leur parole n’a que peu de chance d’émerger autrement que médiée par les discours institutionnels.
L’œil à la page de Jean-Claude Passeron.
Authors: Vallet Pascal
Published: February 2023

Cet article examine la formule de recherche de L’œil à la page, une enquête réalisée en 1979 par le Groupe Interuniversitaire de Documentation et d’Enquêtes Sociologiques (GIDES) qui avait pour objectif d’étudier l’implantation de matériel audiovisuel dans huit bibliothèques municipales et dont les comptes rendus prirent la forme d’un rapport et d’un livre. Tout à la fois enquête de commande et recherche à visée pédagogique, elle fut aussi pour Jean-Claude Passeron, son directeur scientifique, l’occasion de tester empiriquement Le Métier de sociologue et de préparer l’écriture de (Les) mots de la sociologie. À ce titre, elle peut être considérée comme l’une des bases empiriques du Raisonnement sociologique. Pour cette raison, cette enquête est prise entre deux bornes théoriques : d’une part, celle que constitue le Métier de sociologue qui en est la matrice conceptuelle et, d’autre part, Le raisonnement sociologique, considéré dès sa publication comme une contribution majeure à la réflexion sur l’épistémologie des sciences sociales. Grâce à cette description qui s’appuie sur le livre, le rapport et les archives de l’enquête, cet article met en évidence un style de pensée scientifique et saisit l’articulation du Métier de Sociologue au Raisonnement sociologique, pour mieux en comprendre et faire comprendre l’épistémologie.
Barriers to capacity building amongst physicians in the Sri Lankan health sector - a point of view
Authors: Ariyananda P. L.
Published: February 2023

No abstract available
Carpal tunnel syndrome with shoulder symptoms; is it a different entity? A prospective cohort study comparing recovery patterns following decompression
Authors: Ekanayake G. N. S. , Manilgama S. R.
Published: February 2023

Background: Carpal tunnel syndrome (CTS) may present with atypical proximal symptoms other than hand symptoms.Among proximal symptoms, shoulder symptoms are most distant to the site of compression and leads to a battery of investigations to exclude other pathologies. The recovery patterns of proximal symptoms have not been studied following carpal tunnel decompression.
Methods: A prospective cohort study was conducted to compare the recovery patterns between subgroup-A; CTS patients (n=55) with shoulder symptoms, with subgroup-B; patients (n=55) without shoulder symptoms. A pre-tested questionnaire was administered prior and after the surgery and information was gathered on day-7, day-14 and day-21.
Results: Of 110 patients, 81.8% were females. The mean age(+SD) of the total population was 49.2(+10.6), that of subgroup-A was 48.7(+10.3), and subgroup-B was 49.7(+11) years. They were predominantly right-handed (82.7%), 73% had their dominant hand affected while 74.5% were affected bilaterally at presentation. All had hand symptoms: numbness in 94.5%, pain in 85.4%, tingling of hand in 66.3% and all-three symptoms in 57.2%. In subgroup-A, pain was the predominant shoulder symptom which appeared before hand symptoms in 34.5%, after in 47.3% and simultaneously in 18.2%. It was aching-type in 91%. The pain radiated proximally (neck and scapula) in 61.8% and to the arm in 81.8%. The recovery rates (RR) of hand symptoms following decompression on day-7 were 41.8% in subgroup-A and 40.0% in subgroup-B. RR of hand symptoms in subgroup-A and subgroup-B on day-14 were 72.7% and 70.9%, while on day-21 were 83.6%and 85.5% respectively. RR of shoulder symptoms in subgroup-A were 38.2% on day-7, 65.4% on day-14, and 78.2% on day-21.
Conclusions: Near identical RR of hand and shoulder symptoms were seen between the two subgroups after decompression, which indicates CTS with shoulder symptoms is not a different entity.
Developing synbiotic bacterial therapeutics to treat food allergy
Authors: Hesser Lauren A. , Hubbell Jeffrey A , Nagler Cathryn
Published: February 2023

The recent generational rise in the incidence of food allergies has been correlated to adverse changes in the commensal microbiome, particularly depletion of potentially protective bacteria. By correlating the abundance of fecal bacteria with functional data sets between healthy and food allergic human cohorts, we have identified candidate bacteria for live biotherapeutics. Ruminococcus bromii is more abundant in healthy adult twins than their allergic counterparts and is a keystone species for the initial stages of resistant starch consumption. Anaerostipes caccae is comparatively abundant in healthy infants and uses the intermediate products of starch or fiber digestion to produce butyrate. We have observed cross-feeding between R. bromii and A. caccae in vitro and are now investigating their therapeutic potential. Monocolonization of germ free mice with A. caccae mimics the protective effects of the replete healthy microbiome in a model of food allergy. Our hypothesis is that A. caccae will not provide the same protection to a microbially replete host without the aid of additional factors (e.g. R. bromii). In mice colonized with the dysbiotic fecal bacteria of a cow’s milk allergic (CMA) infant, A. caccae colonizes but does not produce measurable butyrate, even when supplemented with potato starch. We predict that treating CMA-colonized mice with the combination therapy of potato starch, R. bromii, and A. caccae will increase luminal butyrate and influence the local gut immune environment. Our synbiotic strategy of combining protective bacteria with their preferred substrate(s) will address the current limitations of live biotherapeutics and provide insight into the microbiome/immune interactions relevant to food allergy.
Interleukin-1β secretion induced by mucosal-associated gut commensal bacteria promotes intestinal barrier repair
Authors: Wu Wan-Jung , Kim Myunghoo , Morales Fatima Beatriz Saldana , Ruiz Daniel Fernando Zegarra , Hill Andrea , Song Hyo Won , Norwood Kendra , Diehl Gretchen
Published: February 2023

It is known that the gut commensal bacteria support intestinal epithelial barrier integrity. However, how specific microbes regulate barrier integrity is not fully understood. We and others find that barrier repair in models of colitis requires the microbiota and asked whether individual microbes are sufficient to replace functions of the total microbiota. We identified a mouse commensal E. coli that protects mice from enhanced damage in the absence of the microbiota in a mouse model of infectious colitis. Surprisingly, the protective E. coli induced IL-1β production by intestinal macrophages in vivo. Such IL-1β secretion activated type 3 innate lymphoid cells (ILC3) and induced IL-22 production that triggered epithelial barrier repair. In addition to mouse commensal E. coli, we also identified a subset of human E. coli isolates that offered protection utilizing the same cellular and molecular pathways. Together, we reveal a novel mechanism that select intestinal commensal bacteria activate inflammatory pathways to support gut barrier repair and maintain barrier integrity.
A single cell sequencing approach to understand the nature of myeloid-derived suppressor cells in tumor-bearing mice
Authors: Abdulla Osama Azeldeen , Wilson Kiesha , Nagarkatti Prakash , Nagarkatti Mitzi
Published: February 2023

Peripheral T Cell Lymphoma (PTCL), a type of non-Hodgkin’s lymphoma, is a heterogeneous group of mature T cells that have undergone transformation into a malignant form. The tumor microenvironment (TME) is very heterogeneous and is comprised of different cell types. Myeloid-derived suppressor cells (MDSC) are one of the vital components of the TME. Further, MDSC are associated with tumor growth, angiogenesis and enhanced metastasis. The aim of this study was to compare MSDCs isolated from TME and splenic MDSCs from tumor-bearing hosts (TBHs) as well as splenic MDSCs from naïve mice by using single cell RNA sequencing (scRNASeq). For this reason, C57BL/6 mice were injected with 1×106 EL4 cancer cells subcutaneously to induce tumor growth and 14 days later, cells were isolated from these three tissues, and flow cytometry and scRNASeq were performed. The flow cytometry results showed an increase in MDSC recruitment in the spleens from TBHs in comparison with spleens from naïve mice. scRNASeq analysis showed most of the genes upregulated in MDSCs from TME and spleen of TBHs were responsible for generation, recruitment and proliferation of MDSCs (Lgals5, CXCL10, Alox5ap, CCL6, IL1b, S100A8/A9/A11, CCL4, CCL5). Furthermore, we found several genes overexpressed in MDSCs promoted the proliferation and migration of cancer cells as well as tumor formation (Lyz2, Plac8, Ifitm3, Vim, S100A6, Crip1). In addition, we found some genes have anti-tumor effects by suppressing T and B cells (Lgals5, Ly6c2). In summary, these studies demonstrated that MDSCs from TME and spleens of TBHs have unique features for inducing immunosuppression, as well as recruitment and expansion of MDSCs in TBHs, which make these cells critical for target for immunotherapy.
Cellular and humoral immune responses in adults receiving an inactivated mammalian cell-based influenza vaccine
Authors: Yu Esther Dawen , Grifoni Alba , Sutherland Aaron , Voic Hannah , Wang Eric , Frazier April , Jimenez-Truque Natalia , Yoder Sandra , Welsh Sabrina , Wooden Stacey , Koff Wayne , Creech Buddy , Sette Alessandro , Antunes Ricardo da Silva
Published: February 2023

Current evaluation of influenza vaccines focuses mainly on humoral response to surface hemagglutinin (HA), although both CD4 and CD8 T cell responses have been reported, to both HA and other viral proteins. We conducted a comprehensive functional analysis on the pre-existing and vaccine-induced immune responses to Flucelvax, a tetravalent mammalian cell-based influenza vaccine which in addition to HA contains additional viral proteins (NA, M1, M2, NP, NEP, NS1, PA, PB1, and PB2). Longitudinal samples of peripheral blood mononuclear cells from a cohort of 10 participants, were stimulated by pools of peptides overlapping individual influenza viral protein components. We examined both humoral and cellular responses, intra-vaccine interference, type-specific immunodominance patterns of responses and cytokine polarization. In addition to serological responses, our results demonstrated vaccine-induced CD4 and CD8 responses that were still present after 90 days post vaccination, a balanced immunogenicity across all 4 included viral strains, as well as unchanged type-specific immunodominance patterns and cytokine polarization post-vaccination. Our results demonstrated distinct CD4 reactivities mostly directed to HA/NA (neuraminidase) proteins in Influenza B strains, but similar CD8 responses to both influenza A and B viruses preferentially targeting the more conserved core viral proteins. The present study suggests that Flucelvax induces, both humoral, CD4 and CD8 cellular immunity, balanced across four different influenza strains and targeting HA and multiple additional viral antigens.
The immunological perturbations induced by ongoing blood-stage infection during Plasmodium GAP (Genetically Attenuated Parasites) vaccination
Authors: Patel Hardik , Minkah Nana K. , Sheikh Amina A. , Reynolds Laura , Vaughan Ashley M. , Kappe Stefan H.I.
Published: February 2023

Plasmodium sporozoites (SPZ) are transmitted by mosquito bite, infect the liver, grow and differentiate as intrahepatocytic liver stages (LS) and ultimately form the first generation of red blood cell-infectious merozoites, which initiate the symptomatic blood stage infection. Immunization with replication-deficient radiation attenuated SPZ vaccine has shown to confer sterilizing immunity in animal models by preventing parasite growth into the liver before onset of symptomatic blood stage infection. This attenuated SPZ vaccine has undergone clinical testing and it was observed that sterilizing immunity was achieved high in malaria naïve subjects but lower in malaria pre-exposed subjects residing in malaria-endemic regions. Previous studies in rodent models indicate that the ongoing blood stage infection suppresses protection after immunization with replication deficient irradiated SPZ. We have shown that replication competent late liver stage arresting genetically attenuated parasites (RC-GAP) immunization confer superior protection when compared to irradiated SPZ. However, whether the blood stage infection would also affect the RC-GAP parasite vaccine mediated protective immunity by altering specific immune responses remains unknown. Here, we show that ongoing homologous blood stage infection during Plasmodium yoelii RC-GAP immunization suppress the vaccine mediated immunity in Balb/c mice. Our data suggest that the reduction in protection was associated with the perturbations of long-lived Ag specific antibody as well as tissue resident memory CD8 T cell (TRMs) responses generated against pre-erythrocytic SPZ and LS stages.
Roles of Fc receptor γ chain in inducing protective immune responses after F virus-like particles prime and FI-RSV boost against respiratory syncytial virus infection
Authors: Hwang Hye Suk , Kang Sang-Moo
Published: February 2023

The roles of Fc receptor (FcR) in protection or in inflammatory disease after RSV vaccination and infection remain unknown. Virus-like particles containing RSV fusion proteins (RSV F-VLPs) induce T-helper type 1 antibody responses and protection against RSV. Heterologous RSV F VLP prime and inactivated RSV (FI-RSV) boost vaccination was reported to be effective in providing protection without inflammatory disease. Here we investigated whether the FcRγ chain is important for immune protection by heterologous F VLP and FI-RSV vaccination using FcRγ chain knockout (−/−) mouse model. RSV F-VLP prime and FI-RSV boosted FcRγ−/− mice were not well protected, as shown by higher lung viral titers upon RSV virus challenge compared to RSV F-VLP prime-immunized wild-type mice. RSV F-VLP and FI-RSV immunization of FcRγ−/− mice induced significantly lower levels of neutralizing activity and interferon γ-producing CD8 T cells in bronchoalveolar lavage cells than those in in wild-type mice. In addition, FcRγ−/− mice displayed a trend of enhancing lung histopathology after RSV vaccination and infection. This study suggests that the FcR γ chain plays an important role in antiviral protection and CD8 T cell responses in RSV F-VLP and FI-RSV vaccination after RSV infections.
Resident Memory CD8+ T cells in the respiratory tract prevent transmission of respiratory viruses
Authors: Uddback Ida Elin Maria , Mattingly Cameron , Thomas Jeronay , Kost Kirsten Nicole , Li Zheng-Rong Tiger , Thomsen Allan R , Scharer Christopher D. , Christensen Jan Pravsgaard , Kohlmeier Jacob E
Published: February 2023

Tissue-resident memory CD8+ T cells (TRM) in the respiratory tract reduce viral replication and limit pathology following respiratory virus infections. In infection with heterosubtypic influenza viruses, where pre-existing antibodies does not proved sterilizing immunity, TRM are critical for protection. However, in addition to protecting the host against disease vaccine programs are also designed to limit viral spread in a population. Due to the lack of an animal model to study the effect of TRM on transmission through longitudinal tracking, and with immunological parameters easily identified and manipulated available, this hasn’t been studied before. To solve these issues, we used a luciferase expressing Sendai virus, a natural mouse parainfluenza virus that readily transmits via the aerosol and contact routes, as well as a recombinant influenza virus expressing the immunodominant Sendai NP324-332/Kb epitope to generate SenNP+ memory CD8+ T cells. By utilizing IVIS imaging to non-invasively measure Sendai virus infection over time, we found that mice with pre-existing SenNP+ TRM in the respiratory system don’t transmit Sendai virus to naïve mice when co-housed. In contrast, mice with pre-existing circulating SenNP+ effector memory CD8+ T cells, but no TRM, failed to prevent transmission of Sendai virus to naïve mice when co-housed. In addition, we found that the prevention of transmission was dependent on the production of IFNγ. These findings demonstrates notably that antigen specific lung TRM contributes to herd immunity by preventing respiratory virus transmission. This underscores the importance, and potential, of TRMs generated by vaccines for protection against respiratory viruses.
Systematic examination of antigen-specific recall T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile
Authors: Law Jaclyn C , Koh Wan Hon , Budylowski Patrick , Lin Jonah , Yue FengYun , Abe Kento T , Rathod Bhavisha , Girard Melanie , Li Zhijie , Rini James M , Mubareka Samira , McGeer Allison , Chan Adrienne K , Gingras Anne-Claude , Watts Tania H , Ostrowski Mario A
Published: February 2023

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. In this study, we investigated human T cell recall responses to fully glycosylated spike trimer, recombinant N protein, as well as to S, N, M, and E peptide pools in the early convalescent phase and compared them with influenza-specific memory responses from the same donors. All subjects showed SARS-CoV-2–specific T cell responses to at least one Ag. Both SARS-CoV-2–specific and influenza-specific CD4+ T cell responses were predominantly of the central memory phenotype; however SARS-CoV-2–specific CD4+ T cells exhibited a lower IFN-γ to TNF ratio compared with influenza-specific memory responses from the same donors, independent of disease severity. SARS-CoV-2–specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. We observed granzyme B+/IFN-γ+, CD4+, and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ T cell responses predominating over CD8+ T cell responses. Peripheral T follicular helper (pTfh) responses to S or N strongly correlated with serum neutralization assays as well as receptor binding domain–specific IgA; however, the frequency of pTfh responses to SARS CoV-2 was lower than the frequency of pTfh responses to influenza virus. Overall, T cell responses to SARS-CoV-2 are robust; however, CD4+ Th1 responses predominate over CD8+ T cell responses, have a more inflammatory profile, and have a weaker pTfh response than the response to influenza virus within the same donors, potentially contributing to COVID-19 disease. Work is in progress to assess long-term T cell immunity 6 months to 1 year after SARS-CoV-2 infection.
The ATP-Exporting Hemichannel Pannexin-1 Promotes CD8+ T Cell Memory Establishment
Authors: Vardam-Kaur Trupti , Peng Changwei , Wanhainen Kelsey , Jameson Stephen C , Silva Henrique Borges da
Published: February 2023

Release of extracellular ATP (eATP) by dying cells is often identified as a "danger signal" by immune cells. However, eATP export by healthy cells is common, and a major transmembrane ATP exporter is the Pannexin 1 (Panx1) molecule. CD8+ T cells express Panx1 during thymic development, at steady-state and during immune response. However, the role of Panx1 on CD8+ T cell-mediated immune response is not well defined. Here, we used genetic and pharmacological ablation tools to address this question. T cell-specific Panx1 deletion does not affect CD8+ T cell thymic development or effector responses to viral infection (LCMV). In contrast, memory CD8+ T cell establishment is impaired by either pharmacological inhibition or CD8-specific Panx1 deletion. Using a tamoxifen-controlled, conditional Panx1 knockout LCMV-specific (P14) CD8+ T cell system, we found that both memory CD8+ T cell generation and survival rely on Panx1. In vitro data further supports these findings: two Panx1 inhibitors, 10Panx and Probenecid, reduce the expression of the central memory marker CD62L. Panx1-deficient CD8+ T cells develop a memory-like phenotype in response to IL-15, but fail to engage mitochondrial respiration and present decreased mitochondrial membrane potential, suggesting Panx1 promotes optimal mitochondrial function. These defects are partially reverted with exogenous eATP. Collectively, our data indicates that cell-intrinsic Panx1-mediated eATP export favors memory CD8+ T cell differentiation. We are currently testing whether CD8-intrinsic Panx1 controls memory CD8+ T cell generation solely as an autocrine eATP source, or if Panx1 also serves as a “rheostat” controlling intracellular ATP levels in antigen-responding CD8+ T cells.
Impacts of vitamin A deficiency on mucosal immunity to respiratory syncytial virus infection
Authors: Hong Suyeon , McGill Jodi L
Published: February 2023

Human respiratory syncytial virus (RSV) is a leading cause of severe acute lower respiratory tract disease in infants and young children worldwide. Vitamin A (VA) deficiency (VAD) is one of the most prevalent nutrition-related health problems globally. Acute childhood infections have been linked to an increased risk of VAD, while conversely, VAD leads to increased susceptibility to severe respiratory infections. To date, however, the impact of VAD on RSV infection specifically, or on adaptive immune responses in the respiratory tract, remains unexplored. Here, we used the BALB/c mouse model to determine the impact of VAD on RSV infection and lung virus-specific CD8 T cell immunity. Groups of VA sufficient (VAS) and VAD mice were infected with RSV strain A2. On day 8 after infection, antigen-specific CD8 T cell responses were evaluated using tetramer and intracellular cytokine staining and ELISA assays for IFNγ secretion in cell supernatants. Although no changes in morbidity and mortality were observed between groups, CD8 T cells from VAD animals showed significantly impaired production of IFNγ, suggesting changes in the Th1 balance of the lungs in the context of VAD. Future experiments will focus on changes in the innate and adaptive immune systems in the lungs during VAD and downstream effects on the response to RSV infection.
Defects in the CD8+ T cell response to arthritogenic alphaviruses
Authors: Bullock Christopher B , Davenport Bennett J , Morrison Thomas E , Miller Mark J , Diamond Michael S
Published: February 2023

Arthritogenic alphaviruses have infected millions of people globally. Following acute infection, symptoms of joint pain, swelling, and stiffness can last for months or even years, likely due to persistence of viral RNA and antigen, which also is seen in mice. Intriguingly, wild-type and CD8−/− mice show a similar lack of clearance of viral RNA. Despite this, a mechanism for this CD8+ T cell evasion has not been identified. We hypothesized that there are defects in the generation, function, and migration of the CD8+ T cells after infection with Ross River virus (RRV), a prototype, arthritogenic alphavirus. To study the antigen-specific response, we used a genetically modified RRV expressing the lymphocytic choriomeningitis virus (LCMV)-derived gp33 peptide. Compared to LCMV infection, in which CD8+ T cells are required for viral clearance, RRV infection generates fewer gp33-specific CD8+ T cells in the spleen and draining lymph node, especially at early times after infection. Antigen-specific CD8+ T cells from the draining lymph node at 5 days after RRV infection express much less granzyme B than in LCMV-infected mice. In vivo cytolysis assays showed a qualitative difference in CD8+ T cell killing of targets especially when variant peptides were used for pulsing. Finally, intravital imaging revealed that while both RRV and LCMV infection recruit CD8+ T cells and retain them in an antigen specific manner near infected cells, CD8+ T cells appear to have less contact with RRV than LCMV-infected cells. Identification of a specific defect in the CD8+ T cell response to arthritogenic alphaviruses would increase our understanding of viral immune evasion and provide a target for therapy of these debilitating infections.
Endothelial immune surveillance by intravascular antigen-experienced CD8+ T cells as a novel mechanism of antiviral adaptive immunity
Authors: Barreiro Olga , Loughhead Scott M , Pallis Paris , Eljalby Mahmoud , Zwijnenburg Ton , Collado Victor , Ziegler Carly , Yosef Nir , Shalek Alex , Gerlach Carmen , von Andrian Ulrich H
Published: February 2023

Following acute infection, pathogen-specific CD8+ T cells proliferate and divide in a heterogeneous manner, giving rise to effector and memory T cells with distinct migratory patterns. This migratory division of labor ensures that the host is efficiently scanned for ongoing or recurring infections. Recent evidence suggests that the presumed migratory behavior of the classical effector memory T cell subset needs revision. Here, we report that terminally differentiated effector and effector memory T cells adhere to and patrol the endothelium, while less differentiated T cells migrate into peripheral tissues. Interestingly, patrolling T cells have been observed at vascular beds such as the dermal microvasculature, where they concentrate in arterioles and preferentially migrate against the blood flow. Patrolling T cells survey the endothelium in the search for cognate antigen and, once encountered, cease their migration and establish long-lived interactions with peptide-presenting endothelial cells without inducing cytotoxicity. Finally, single-cell RNA-Seq analysis of patrolling CD8+ T effector cells and blockade experiments to prevent patrolling have unveiled a key and unexpected role for patrolling in the generation and maintenance of the intravascular CD8+ CX3CR1high KLRG-1+ effector memory T cell subset, which in turn is relevant for long-term protective immunity.