Scaling language model size yields diminishing returns for single-message political persuasion.

Large language models can now generate political messages as persuasive as those written by humans, raising concerns about how far this persuasiveness may continue to increase with model size. Here, we generate 720 persuasive messages on 10 US political issues from 24 language models spanning several orders of magnitude in size. We then deploy these messages in a large-scale randomized survey experiment ( = 25,982) to estimate the persuasive capability of each model.

The Exoproteome and Surfaceome of Toxigenic 1737 and Its Response to Iron Restriction and Growth on Human Hemoglobin.

Toxin-producing strains are the etiological agents of the severe upper respiratory disease, diphtheria. A global phylogenetic analysis revealed that biotype gravis is particularly lethal as it produces diphtheria toxin and a range of other virulence factors, particularly when it encounters low levels of iron at sites of infection. To gain insight into how it colonizes its host, we have identified iron-dependent changes in the exoproteome and surfaceome of strain 1737 using a combination of whole-cell fractionation, intact cell surface proteolysis, and quantitative proteomics.

Dnmt3a-dependent DNA methylation enforces lineage commitment and preserves functionality of memory Th1 and Tfh cells.

Following acute viral infection, naïve CD4+ T cells differentiate into T follicular helper (Tfh) and T helper 1 (Th1) cells that generate long-lived memory cells. However, it is unclear how memory Tfh and Th1 cells maintain their lineage commitment. We demonstrate that Tfh and Th1 lineages acquire distinct Dnmt3a-dependent DNA methylation programs that are preserved into memory.

Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction.

Co-formulation of the rF1V plague vaccine with depot-formulated cytokines enhances immunogenicity and efficacy to elicit protective responses against aerosol challenge in mice.

This study evaluated a depot-formulated cytokine-based adjuvant to improve the efficacy of the recombinant F1V (rF1V) plague vaccine and examined the protective response following aerosol challenge in a murine model. The results of this study showed that co-formulation of the Alhydrogel-adsorbed rF1V plague fusion vaccine with the depot-formulated cytokines recombinant human interleukin 2 (rhuIL-2) and/or recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) significantly enhances immunogenicity and significant protection at lower antigen doses against a lethal aerosol challenge. These results provide additional support for the co-application of the depot-formulated IL-2 and/or GM-CSF cytokines to enhance vaccine efficacy.

OCA-B/Pou2af1 is sufficient to promote CD4 T cell memory and prospectively identifies memory precursors.

The molecular mechanisms leading to the establishment of immunological memory are inadequately understood, limiting the development of effective vaccines and durable antitumor immune therapies. Here, we show that ectopic OCA-B expression is sufficient to improve antiviral memory recall responses, while having minimal effects on primary effector responses. At peak viral response, short-lived effector T cell populations are expanded but show increased and expression, while memory precursor effector cells show increased expression of , and on a per-cell basis.

Effector-Phase IL-2 Signals Drive Th1 Effector and Memory Responses Dependently and Independently of TCF-1.

Following viral infection, CD4+ T cell differentiation is tightly regulated by cytokines and TCR signals. Although most activated CD4+ T cells express IL-2Rα after lymphocytic choriomeningtis virus infection, by day 3 postinfection, only half of activated T cells maintain expression. IL-2Rα at this time point distinguishes precursors for terminally differentiated Th1 cells (IL-2Rαhi) from precursors for Tfh cells and memory T cells (IL-2Rαlo) and is linked to strong TCR signals.

Multimodal analysis of disinformation and misinformation.

The use of disinformation and misinformation campaigns in the media has attracted much attention from academics and policy-makers. Multimodal analysis or the analysis of two or more semiotic systems-language, gestures, images, sounds, among others-in their interrelation and interaction is essential to understanding dis-/misinformation efforts because most human communication goes beyond just words. There is a confluence of many disciplines (e.

Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection.

Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction.

Tet2 deletion in CD4+ T cells disrupts Th1 lineage commitment in memory cells and enhances T follicular helper cell recall responses to viral rechallenge.

Following viral clearance, antigen-specific CD4+ T cells contract and form a pool of distinct Th1 and Tfh memory cells that possess unique epigenetic programs, allowing them to rapidly recall their specific effector functions upon rechallenge. DNA methylation programing mediated by the methylcytosine dioxygenase Tet2 contributes to balancing Th1 and Tfh cell differentiation during acute viral infection; however, the role of Tet2 in CD4+ T cell memory formation and recall is unclear. Using adoptive transfer models of antigen-specific wild type and knockout CD4+ T cells, we find that Tet2 is required for full commitment of CD4+ T cells to the Th1 lineage and that in the absence of Tet2, memory cells preferentially recall a Tfh like phenotype with enhanced expansion upon secondary challenge.

Immunogen-Specific Strengths and Limitations of the Activation-Induced Marker Assay for Assessing Murine Antigen-Specific CD4+ T Cell Responses.

The activation-induced marker (AIM) assay is a cytokine-independent technique to identify Ag-specific T cells based on the upregulated expression of activation markers after Ag restimulation. The method offers an alternative to intracellular cytokine staining in immunological studies, in which limited cytokine production makes the cell subsets of interest difficult to detect. Studies of lymphocytes in human and nonhuman primates have used the AIM assay to detect Ag-specific CD4+ and CD8+ T cells.

The magnitude of the germinal center B cell and T follicular helper cell response predicts long-lasting antibody titers to plague vaccination.

The development of a safe and effective vaccine against , the causative organism for plague disease, remains an important global health priority. Studies have demonstrated effective immune-based protection against plague challenge that is induced by plague antigen subunit vaccination in an aqueous alhydrogel formulation; however, whether these candidate vaccines in this formulation and presentation, induce long-lasting immunological memory in the form of durable cellular and antibody recall responses has not been fully demonstrated. In this study, we analyzed germinal center T follicular helper and germinal center B cell responses following F1V and F1 + V plague subunit immunization of mice with vaccines formulated in various adjuvants.

Erratum to: Use of a MAIT-Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of O1 Vaccination.

[This corrects the article DOI: 10.20411/pai.v7i1.

Use of a MAIT-Activating Ligand, 5-OP-RU, as a Mucosal Adjuvant in a Murine Model of O1 Vaccination.

Background: Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in the mucosa with capacity for B-cell help. We hypothesize that targeting MAIT cells, using a MAIT-activating ligand as an adjuvant, could improve mucosal vaccine responses to bacterial pathogens such as .

Methods: We utilized murine models of vaccination to test the adjuvant potential of the MAIT-activating ligand, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU).

Tet2 coordinates with Foxo1 and Runx1 to balance T follicular helper cell and T helper 1 cell differentiation.

In response to various types of infection, naïve CD4 T cells differentiate into diverse helper T cell subsets; however, the epigenetic programs that regulate differentiation in response to viral infection remain poorly understood. Demethylation of CpG dinucleotides by Tet methylcytosine dioxygenases is a key component of epigenetic programing that promotes specific gene expression, cellular differentiation, and function. We report that following viral infection, Tet2-deficient CD4 T cells preferentially differentiate into highly functional germinal center T follicular helper (T) cells that provide enhanced help for B cells.

A subset of follicular helper-like MAIT cells can provide B cell help and support antibody production in the mucosa.

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that aid in protection against bacterial pathogens at mucosal surfaces through the release of inflammatory cytokines and cytotoxic molecules. Recent evidence suggests that MAIT cells can also provide B cell help. In this study, we describe a population of CXCR5 T follicular helper (Tfh)–like MAIT cells (MAITfh) that have the capacity to provide B cell help within mucosal lymphoid organs.

Measuring the Volatility of the Political agenda in Public Opinion and News Media.

Recent election surprises, regime changes, and political shocks indicate that political agendas have become more fast-moving and volatile. The ability to measure the complex dynamics of agenda change and capture the nature and extent of volatility in political systems is therefore more crucial than ever before. This study proposes a definition and operationalization of volatility that combines insights from political science, communications, information theory, and computational techniques.

Protein Immunization Induces Memory CD4 T Cells That Lack Th Lineage Commitment.

Acute viral infection generates lineage-committed Th1 and T follicular helper (Tfh) memory cells that recall their lineage-specific functions following secondary challenge with virus. However, the lineage commitment of effector and memory Th cells in vivo following protein vaccination is poorly understood. In this study, we analyzed effector and memory CD4 T cell differentiation in mice () following adjuvanted glycoprotein immunization compared with acute lymphocytic choriomeningitis virus infection.

Cytokine-skewed Tfh cells: functional consequences for B cell help.

CD4 follicular helper T (Tfh) cells play a vital role in providing help for B cells undergoing selection and differentiation into activated antibody-secreting cells in mammalian germinal centers (GCs). Increasing evidence suggests that Tfh cells are a heterogeneous population that generates cytokine-skewed immune responses - a reflection of the microenvironment during differentiation. This has important ramifications for Tfh-mediated B cell help.

Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis.

Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses.

Estimating Traffic Disruption Patterns with Volunteered Geographic Information.

Accurate understanding and forecasting of traffic is a key contemporary problem for policymakers. Road networks are increasingly congested, yet traffic data is often expensive to obtain, making informed policy-making harder. This paper explores the extent to which traffic disruption can be estimated using features from the volunteered geographic information site OpenStreetMap (OSM).

Diagnosing the performance of human mobility models at small spatial scales using volunteered geographical information.

Accurate modelling of local population movement patterns is a core, contemporary concern for urban policymakers, affecting both the short-term deployment of public transport resources and the longer-term planning of transport infrastructure. Yet, while macro-level population movement models (such as the gravity and radiation models) are well developed, micro-level alternatives are in much shorter supply, with most macro-models known to perform poorly at smaller geographical scales. In this paper, we take a first step to remedy this deficit, by leveraging two novel datasets to analyse where and why macro-level models of human mobility break down.

Using immersive virtual reality to improve the beliefs and intentions of influenza vaccine avoidant 18-to-49-year-olds: Considerations, effects, and lessons learned.

Objective: Only one-third of adults 18-49 years old in the United States receive a recommended annual influenza vaccination. This study examined whether supplementing vaccine information statements (VIS) with an immersive virtual reality (VR), short video or electronic pamphlet story designed to convey the community immunity benefits of influenza vaccination would improve influenza vaccine avoidant participants' influenza-related perceptions as well as their influenza vaccination-related beliefs, confidence and intentions.

Method: A one-way between-subjects experimental design compared the effects of adding a supplemental education experience prior to VIS exposure with flu vaccine avoidant 18-to-49-year-olds.