Time-series data from a hybrid finite element Large Eddy Simulation of flow over a backward-facing step.

In previous work, a Large Eddy Simulation turbulence (LES) algorithm was developed for finite element-based computational fluid dynamics, using a hybrid continuous-discontinuous Galerkin scheme. The test case for this was a backward-facing step, which is a well-known example with published experimental results for validation. The results of this simulation were used to produce temporal statistics, such as averaged velocity and Reynolds stress profiles, and time-series data.

Staggered immunization with mRNA vaccines encoding SARS-CoV-2 polymerase or spike antigens broadens the T cell epitope repertoire.

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope.

trehalose-6-phosphate synthase (tps1) promotes organ-specific virulence and fungal protection against multiple lines of host defenses.

Trehalose-6-phosphate synthase (TPS1) was identified as a virulence factor for and a promising therapeutic target. This study reveals previously unknown roles of TPS1 in evasion of host defenses during pulmonary and disseminated phases of infection. In the pulmonary infection model, TPS1-deleted () are rapidly cleared by mouse lungs whereas TPS1-sufficent WT (H99) and revertant (:) strains expand in the lungs and disseminate, causing 100% mortality.

Batf3-dependent orchestration of the robust Th1 responses and fungal control during cryptococcal infection, the role of cDC1.

While type I conventional dendritic cells (cDC1s) are vital for generating adaptive immunity against intracellular pathogens and tumors, their role in defense against fungal pathogen remains unclear. We investigated the role of the cDC1 subset in a fungus-restricting mouse model of cryptococcal infection. The cDC1 subset displayed a unique transcriptional signature with highly upregulated T-cell recruitment, polarization, and activation pathways compared to other DC subsets.

Establishing a mouse model of lung metastases using ultrasound-guided right heart ventricle injection.

We report a technique to generate a murine model of lung metastases by selectively injecting tumor cells into the right heart ventricle under ultrasound guidance. First, we describe cell preparation and reference animal preparation as previously described. We then detail the technique using a previously described 3D-printed instrument stabilization device.

Generation of liver metastases in a mouse model using ultrasound-guided intravenous injection.

Here, we present a protocol to generate a murine model of liver metastasis by directly injecting tumor cells into the portal vein under ultrasound guidance. We describe steps for animal and cell preparation and two techniques for injecting tumor cells. One technique is freehand, while the other technique is device-assisted using a 3D-printed prototype device.

and colonization on plastics influenced by temperature and strain variability.

Marine bacteria often exist in biofilms as communities attached to surfaces, like plastic. Growing concerns exist regarding marine plastics acting as potential vectors of pathogenic , especially in a changing climate. It has been generalized that and often attach to plastic surfaces.

Online Group Music-Making in Community Concert Bands: Perspectives From Conductors and Older Amateur Musicians.

At the beginning of the pandemic, many music ensembles had to stop their activities due to the confinement. While some found creative ways to start making music again with the help of technologies, the transition from "real" rehearsals to "online" rehearsals was challenging, especially among older amateur musicians. The aim of this case study was to examine the effects of this transition on three community band conductors and three older amateur musicians.

F-FDG PET Visualizes Systemic STING Agonist-Induced Lymphocyte Activation in Preclinical Models.

Stimulator of interferon genes (STING) is a mediator of immune recognition of cytosolic DNA, which plays important roles in cancer, cytotoxic therapies, and infections with certain pathogens. Although pharmacologic STING activation stimulates potent antitumor immune responses in animal models, clinically applicable pharmacodynamic biomarkers that inform of the magnitude, duration, and location of immune activation elicited by systemic STING agonists are yet to be described. We investigated whether systemic STING activation induces metabolic alterations in immune cells that can be visualized by PET imaging.

Purine nucleoside phosphorylase enables dual metabolic checkpoints that prevent T cell immunodeficiency and TLR7-associated autoimmunity.

Purine nucleoside phosphorylase (PNP) enables the breakdown and recycling of guanine nucleosides. PNP insufficiency in humans is paradoxically associated with both immunodeficiency and autoimmunity, but the mechanistic basis for these outcomes is incompletely understood. Here, we identify two immune lineage-dependent consequences of PNP inactivation dictated by distinct gene interactions.

Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells.

We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration of a phosphoproteomic analysis and a chemical genomics synergy screen reveals that IFN activates the replication stress response kinase ataxia telangiectasia and Rad3-related protein (ATR) in PDAC cells and sensitizes them to ATR inhibitors. IFN triggers cell-cycle arrest in S-phase, which is accompanied by nucleotide pool insufficiency and nucleoside efflux.

Smooth muscle mineralocorticoid receptor as an epigenetic regulator of vascular ageing.

Aims: Vascular stiffness increases with age and independently predicts cardiovascular disease risk. Epigenetic changes, including histone modifications, accumulate with age but the global pattern has not been elucidated nor are the regulators known. Smooth muscle cell-mineralocorticoid receptor (SMC-MR) contributes to vascular stiffness in ageing mice.

STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [F]FLT PET imaging.

Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these agents is the lack of noninvasive pharmacodynamic biomarkers that indicate increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity, but whether IFN signaling-induced alterations in tumor cell metabolism can be detected using PET has not been investigated.

Creative Collaboration and Collaborative Creativity: A Systematic Literature Review.

Studies of creativity emerging from cultural psychology and social psychology perspectives challenge individualist conceptions of creativity to argue that social interaction, communication, and collaboration are key elements in creativity. In recent work creative collaboration has been proposed to be "distributed" between audiences, materials, embodied actions, and the historico-socio-cultural affordances of the creative activity and environment, thus expanding the potentialities of creative collaboration beyond instances of direct human interaction and engagement. Music performance, improvisation and composition may be viewed as exemplary "laboratories" of creative collaboration through the combined elements of audiences, materials, embodied actions and historico-socio-cultural affordances and constraints.

Behavioral Auditory Processing in Children and Young Adults with Autism Spectrum Disorder.

Background: Auditory-processing deficits are common in children and adults who are diagnosed with autism spectrum disorder (ASD). These deficits are evident across multiple domains as exhibited by the results from subjective questionnaires from parents, teachers, and individuals with ASD and from behavioral auditory-processing testing.

Purpose: Few studies compare subjective and behavioral performance of adults and children diagnosed with ASD using commercially available tests of auditory processing.

Measuring the Impacts of Extra-Musical Elements in Guitar Music Playing: A Pilot Study.

Philosophers, composers, and musicians have long argued whether instrumental music finds meaning in its formal structure and musical content (Hanslick, 1986) or through reference to extra-musical elements, like narratives, emotions, or memories (Meyer, 1956). While the use of extra-musical elements appears grounded in individual musicians' priorities for performance and teaching (Héroux, 2018), the impact of emotional indications on expressivity has not previously been studied in a large-scale experiment. The aim of this pilot study was to construct the methodology for a larger project to study the impact of the use of extra-musical elements on the sound results of guitarists.

Defining HLA-II Ligand Processing and Binding Rules with Mass Spectrometry Enhances Cancer Epitope Prediction.

Increasing evidence indicates CD4 T cells can recognize cancer-specific antigens and control tumor growth. However, it remains difficult to predict the antigens that will be presented by human leukocyte antigen class II molecules (HLA-II), hindering efforts to optimally target them therapeutically. Obstacles include inaccurate peptide-binding prediction and unsolved complexities of the HLA-II pathway.

Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma.

BET-bromodomain inhibition (BETi) has shown pre-clinical promise for MYC-amplified medulloblastoma. However, the mechanisms for its action, and ultimately for resistance, have not been fully defined. Here, using a combination of expression profiling, genome-scale CRISPR/Cas9-mediated loss of function and ORF/cDNA driven rescue screens, and cell-based models of spontaneous resistance, we identify bHLH/homeobox transcription factors and cell-cycle regulators as key genes mediating BETi's response and resistance.

Next-generation characterization of the Cancer Cell Line Encyclopedia.

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR-Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers.

Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate.

Oxygen sensing is central to metazoan biology and has implications for human disease. Mammalian cells express multiple oxygen-dependent enzymes called 2-oxoglutarate (OG)-dependent dioxygenases (2-OGDDs), but they vary in their oxygen affinities and hence their ability to sense oxygen. The 2-OGDD histone demethylases control histone methylation.

Using Music Technology Creatively to Enrich Later-Life: A Literature Review.

A growing body of evidence has demonstrated significant social and emotional benefits of music-making amongst senior citizens. However, several as-yet unresolved age-related barriers to "musicking" have been identified. Positioned within the emergent field of gerontechnology, concerned with the interface between aging and technology research, this review of literature thus explores the potential for music technologies to function as a vehicle for creative musical opportunities in later-life.

A phosphoproteomic signature in endothelial cells predicts vascular toxicity of tyrosine kinase inhibitors used in CML.

Newer CML kinase inhibitors increase ischemia risk and are toxic to endothelial cells where they produce a proteomic toxicity signature. This phosphoproteomic EC toxicity signature predicts bosutinib to be safe, providing a potential screening tool for safer drug development.

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP).