Mice expressing HLA-DQ6α8β transgenes develop polychondritis spontaneously

Relapsing polychondritis (RP) is a human autoimmune disease of unknown etiology in which cartilaginous sites are destroyed by cyclic inflammatory episodes beginning, most commonly, during the fourth or fifth decade of life. We have previously described collagen-induced polychondritis that closely mirrors RP occurring in young (6–8 weeks old) HLA-DQ6αβ8αβ transgenic Aβ0 mice, following immunization with heterologous type II collagen (CII). We present evidence here that transgenic strains expressing the DQ6α8β transgene develop spontaneous polychondritis (SP) at the mouse equivalent of human middle age (4.5–6 months and 40–50 years old, respectively) and display polyarthritis, auricular chondritis and nasal chondritis – three of the most common sites affected in RP. Auricular chondritis in SP, like RP but unlike CII-induced polychondritis, exhibited a relapsing/remitting phenotype, requiring several inflammatory cycles before the cartilage is destroyed. Elevated serum levels of total IgG corresponded with the onset of disease in SP, as in RP and CII-induced polychondritis. No CII-specific immune response was detected in SP, however – more closely mirroring RP, in which as few as 30% of RP patients have been reported to have CII-specific IgG. CII-induced polychondritis displays a strong CII-specific immune response. SP also demonstrated a strong female preponderance, as some workers have reported in RP but has not observed in CII-induced polychondritis. These characteristics of SP allow for the examination of the immunopathogenesis of polychondritis in the absence of an overwhelming CII-specific immune response and the strong adjuvant-induced immunostimulatory influence in CII-induced polychondritis. This spontaneous model of polychondritis provides a new and unique tool to investigate both the initiatory events as well as the immunopathogenic mechanisms occurring at cartilaginous sites during the cyclic inflammatory assaults of polychondritis

CARACTERES ANATÔMICOS DE FOLHA DE Vernonanthura tweedieana (BAKER) H.ROB., ASTERACEAE

A espécie Vernonanthura tweedieana, anteriormente referida pelo basiônimo Vernonia tweediana, é denominada comumente de assa-peixe e empregada para tratar distúrbios respiratórios e como antimicrobiano na medicina popular. Este trabalho objetivou investigar a anatomia foliar dessa planta medicinal, a fim de subsidiar a identificação microscópica no controle de qualidade farmacognóstico. O material botânico foi coletado, identificado e preparado de acordo com técnicas usuais para observação em microscopia de luz e eletrônica de varredura. A folha é anfiestomática, exibindo estômatos anomocíticos em maior número na face abaxial. Ocorrem tricomas tectores e glandulares. Os primeiros são pluricelulares, unisseriados, com célula apical alongada. Os tricomas glandulares são capitados, com pedicelo curto e cabeça bicelular. A epiderme é unisseriada e o mesofilo é dorsiventral. A nervura central e o pecíolo são percorridos por vários feixes vasculares colaterais, dispostos lado a lado. Esses resultados são inéditos para a espécie e contribuem para a sua caracterização microscópica

Moral Mediators in the Metaverse: Exploring Artificial Morality through a Talking Cricket Paradigm

As technological innovations continue to shape our social interactions, the Metaverse introduces immersive experiences that reflect real-life practices, accessible by users through their avatars. However, these interactions also bring forth potential negative aspects, including discrimination and cyberbullying. While current automatic detection systems exist, educating users on appropriate behaviour remains crucial. Leveraging recent advancements in Artificial Intelligence, the paper focuses on creating virtual AI-controlled moral agents within the Metaverse to guide users in dealing with moral dilemmas. The research aims to understand how such agents impact users' perceptions and behaviours in ethically challenging virtual environments

Response to erlotinib in a patient with lung adenocarcinoma harbouring the EML4-ALK translocation: A case report.

Lung cancer is the leading cause of cancer-associated mortality worldwide, and the mainstay of treatment remains to be personalised therapy. Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKIs) have been reported to exert a significant impact in the treatment of non-small cell lung cancer (NSCLC), particularly in patients harbouring mutations in the EGFR gene. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) gene translocation has been described in a subset of patients with NSCLC and possesses potent oncogenic activity. This translocation represents one of the most novel molecular targets in the treatment of NSCLC. Patients who harbour the EML4-ALK rearrangement possess lung tumours that lack EGFR or K-ras mutations. The present study reports the case of a patient possessing the EML4-ALK rearrangement that was initially treated with erlotinib and achieved a lasting clinical response. To the best of our knowledge, the current study is the first report of a clinical response to EGFR-TKI in a patient with lung adenocarcinoma harbouring the EML4-ALK fusion gene, but no EGFR mutations. However, as the disease progressed, the ALK gene status of the tumour was investigated, and based upon a positive result, the patient was treated with crizotinib and achieved a complete response. In conclusion, the present study suggests that the EML4-ALK rearrangement is not always associated with resistance to EGFR-TKIs. Further studies are required to clarify the biological features of these tumours and to investigate the mechanisms underlying the primary resistance to EGFR-TKIs when the EML4-ALK rearrangement is present

Validation of an echo-Doppler decision model to predict left ventricular filling pressure in patients with heart failure independently of ejection fraction

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Molecular scale contact line hydrodynamics of immiscible flows

From extensive molecular dynamics simulations on immiscible two-phase flows, we find the relative slipping between the fluids and the solid wall everywhere to follow the generalized Navier boundary condition, in which the amount of slipping is proportional to the sum of tangential viscous stress and the uncompensated Young stress. The latter arises from the deviation of the fluid-fluid interface from its static configuration. We give a continuum formulation of the immiscible flow hydrodynamics, comprising the generalized Navier boundary condition, the Navier-Stokes equation, and the Cahn-Hilliard interfacial free energy. Our hydrodynamic model yields interfacial and velocity profiles matching those from the molecular dynamics simulations at the molecular-scale vicinity of the contact line. In particular, the behavior at high capillary numbers, leading to the breakup of the fluid-fluid interface, is accurately predicted.Comment: 33 pages for text in preprint format, 10 pages for 10 figures with captions, content changed in this resubmissio

Formalized Conceptual Spaces with a Geometric Representation of Correlations

The highly influential framework of conceptual spaces provides a geometric way of representing knowledge. Instances are represented by points in a similarity space and concepts are represented by convex regions in this space. After pointing out a problem with the convexity requirement, we propose a formalization of conceptual spaces based on fuzzy star-shaped sets. Our formalization uses a parametric definition of concepts and extends the original framework by adding means to represent correlations between different domains in a geometric way. Moreover, we define various operations for our formalization, both for creating new concepts from old ones and for measuring relations between concepts. We present an illustrative toy-example and sketch a research project on concept formation that is based on both our formalization and its implementation.Comment: Published in the edited volume "Conceptual Spaces: Elaborations and Applications". arXiv admin note: text overlap with arXiv:1706.06366, arXiv:1707.02292, arXiv:1707.0516

Genetic correlates of the development of theta event related oscillations in adolescents and young adults

The developmental trajectories of theta band (4–7 Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. Associations between the theta EROs and genotypic variants of 4 KCNJ6 single nucleotide polymorphisms (SNPs) were found to vary with age, sex, scalp location, and task modality. Three of the four KCNJ6 SNPs studied here were found to be significantly associated with the same theta EROs in adults in a previous family genome wide association study. Since measures of the P3 response have been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of genetic effects on its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions