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Identification and characterization of antigen-specific t-cells in viral infections

Identification and characterization of CD8+ T-cells is important to determine their role in protecting and clearing viral infections. Here we provide details of the peptide-MHC (pMHC) tetramers-based approach to identify antigen-specific T-cells in human and murine samples. This method provides ex vivo quantifica-tion and functional characterization of T-cells reactive to specific viral antigens d

Dynamics of a Staphylococcus aureus infective endocarditis simulation model

Infective endocarditis (IE) is a serious infection of the inner surface of heart, resulting from minor lesions in the endocardium. The damage induces a healing reaction, which leads to recruitment of fibrin and immune cells. This sterile healing vegetation can be colonized during temporary bacteremia, inducing IE. We have previously established a novel in vitro IE model using a simulated IE vegeta

Alternative translation and retrotranslocation of cytosolic C3 that detects cytoinvasive bacteria

Complement C3 was originally regarded as a serum effector protein, although recent data has emerged suggesting that intracellular C3 can also regulate basic cellular processes. Despite the growing interest in intracellular C3 functions, the mechanism behind its generation has not been demonstrated. In this study we show that C3 can be expressed from an alternative translational start site, resulti

Inflammatory Animal Models of Parkinson's Disease

Accumulating evidence suggests that microglia and peripheral immune cells may play determinant roles in the pathogenesis of Parkinson's disease (PD). Consequently, there is a need to take advantage of immune-related models of PD to study the potential contribution of microglia and peripheral immune cells to the degeneration of the nigrostriatal system and help develop potential therapies for PD. I

EFFECTS OF INTERNAL COOLANT CROSSFLOW ON FILM-COOLING PERFORMANCE OF DOUBLE-JET AND CYLINDRICAL HOLES

In this paper, the effects of internal coolant crossflow on double-jet holes were simulated and compared with two rows of cylindrical holes under three blowing ratios (M = 0.5, 1.0, and 1.5), with an established and validated turbulence model. The results show that double-jet holes can provide better film cooling performance for the three different blowing ratios compared with cylindrical holes. A

EDGE : The sensitivity of ultra-faint dwarfs to a metallicity-dependent initial mass function

Motivated by the observed bottom-light initial mass function (IMF) in faint dwarfs, we study how a metallicity-dependent IMF affects the feedback budget and observables of an ultra-faint dwarf galaxy. We model the evolution of a low-mass 8 × 108 M⊙) dark matter halo with cosmological, zoomed hydrodynamical simulations capable of resolving individual supernovae explosions, which we complement with

Artificial intelligence in women's cancers : innovation and challenges in clinical translation

Artificial intelligence (AI) is set to transform the care of women with cancer. From early detection via digital phenotyping to diagnosis, treatment, and follow-up, innovative AI applications are rapidly emerging across the cancer care continuum. AI-assisted mammographic screening for breast cancer has been clinically translated, and AI-based contouring in radiotherapy is streamlining treatment pl

First-in-human study of intravenous bispecific CTLA-4 × OX40 antibody (ATOR-1015) in advanced solid malignancies

Background: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), was the first approved checkpoint inhibitor; however, its use is hampered by treatment-related adverse events (TRAEs). ATOR-1015 is a bispecific antibody targeting CTLA-4 and OX40 designed to direct the effect to the tumor microenvironment and thereby improve the response rate and reduce TRA

Environmental Human Rights Defenders, Biodiversity and the Right to a Healthy Environment in the Transition Away from Fossil Fuels

we propose to fully integrate EHRDs rights in the roadmap for phasing out fossil fuels with the aim to uphold a pace that is required to catalyse climate justice for the most affected peoples and territories. A phase-out fossil fuel roadmap should consider the central role they have in protecting life on Earth, safeguarding the climate and environment, thriving biodiversity and leading pathways to

Early Pharmacodynamic Changes Measured Using RNA Sequencing of Peripheral Blood from Patients in a Phase I Study with Mitazalimab, a Potent CD40 Agonistic Monoclonal Antibody

CD40-targeting therapies can enhance the dendritic cell priming of tumor-specific T cells and repolarize intratumoral macrophages to alleviate the tumoral immunosuppressive environment and remodel the extracellular matrix. Mitazalimab is a potent agonistic CD40 monoclonal IgG1 antibody currently under clinical development. This study used RNA sequencing of blood samples from a subset of patients f

Tetraploidization Increases the Motility and Invasiveness of Cancer Cells

Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and in

Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen : patient-level meta-analysis of randomised trials

BACKGROUND: As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen.METHODS: We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21,4

Researching Social Resilience in the Context of Migrants’ Life Transition: A Qualitative Methodological Mosaic

Migration is a psychosocial challenge, and migrants' transitory experiences in host countries are shaped by a combination of linked environmental factors. The absence of social aspects of resilience, as well as disciplinary limitations and biases, hinder the methodological rigor and flexibility needed to investigate social resilience as a phenomenon that occurs at the intersection of social, cultu

Causal effect of adiposity measures on blood pressure traits in 2 urban swedish cohorts : A mendelian randomization study

BACKGROUND: Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. METHODS AND RESULTS: In this study, we used 4 different genetic risk scores (GRS; GRS-BMI 565, GRS-WHR 324, GRS-VAT 208,

Experiences of becoming widowed in old age–a cross-countries study with qualitative interviews from Denmark and quantitative measures of association in a Swedish sample

Purpose: Becoming widowed is a stressful health-threatening event causing major life changes. We explored how widowed people experience becoming widowed and examined if these experiences are quantitatively associated with widowhood. Methods: A multi-methods study using an exploratory sequential mixed-methods approach including a qualitative descriptive study with widowed people from Denmark and a

Innovatively processed quinoa (Chenopodium quinoa Willd.) food : chemistry, structure and end-use characteristics

BACKGROUND: Quinoa (Chenopodium quinoa Willd.) flour and processed traditional Peruvian quinoa breakfast foods were studied to evaluate the effect of extrusion and post-processing on protein properties, morphology and nutritional characteristics (amino acids and dietary fibers). RESULTS: The extrusion increased quinoa protein crosslinking and aggregation observed by size exclusion high-performance

The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms

Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 Å resolution, as well as a model of the full-length luminal protein obtained by a combinati

Rational Design of Bright Long Fluorescence Lifetime Dyad Fluorophores for Single Molecule Imaging and Detection

Increasing demand for detecting single molecules in challenging environments has raised the bar for the fluorophores used. To achieve better resolution and/or contrast in fluorescence microscopy, it is now essential to use bright and stable dyes with tailored photophysical properties. While long fluorescence lifetime fluorophores offer many advantages in time-resolved imaging, their inherently low