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Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based drug discovery, novel in vitro systems are needed that enable mechanical perturbation of cells in a format amenable to high throughput screening. Here, both a mechanical stretch device and 192-well silicone flexible linear stretch plate were designed and fabricated to meet high throughput technology needs for cell stretch-based applications. To demonstrate the utility of the stretch plate in automation and screening, cell dispensing, liquid handling, high content imaging, and high throughput sequencing platforms were employed. Using this system, an assay was developed as a biological validation and proof-of-concept readout for screening. A mechano-transcriptional stretch response was characterized using focused gene expression profiling measured by RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Gen sequencing. Using articular chondrocytes, a gene expression signature containing stretch responsive genes relevant to cartilage homeostasis and disease was identified. The possibility for integration of other stretch sensitive cell types (e.g., cardiovascular, airway, bladder, gut, and musculoskeletal), in combination with alternative phenotypic readouts (e.g., protein expression, proliferation, or spatial alignment), broadens the scope of high throughput stretch and allows for wider adoption by the research community. This high throughput mechanical stress device fills an unmet need in phenotypic screening technology to support drug discovery in mechanobiology-based disease areas. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)‐associated cancer continues to evade the immune system by promoting a suppressive tumor microenvironment. Therefore, immunotherapy appears to be a promising approach for targeting HPV‐associated tumors. We hypothesized that valproic acid (VA) as an epigenetic agent combined with avelumab may enhance the antitumor immunity in HPV‐associated solid tumors. We performed bulk RNA‐sequencing (RNA‐Seq) on total peripheral blood mononuclear cells (PBMCs) of seven nonresponders (NRs) and four responders (Rs). A total of 39 samples (e.g., pretreatment, post‐VA, postavelumab, and endpoint) were analyzed. Also, we quantified plasma analytes and performed flow cytometry. We observed a differential pattern in immune response following treatment with VA and/or avelumab in NRs vs. Rs. A significant upregulation of transcripts associated with NETosis [the formation of neutrophil extracellular traps (NETs)] and neutrophil degranulation pathways was linked to the presence of a myeloid‐derived suppressor cell signature in NRs. We noted the elevation of IL‐8/IL‐18 cytokines and a distinct transcriptome signature at the baseline and endpoint in NRs. By using the receiver operator characteristics, we identified a cutoff value for the plasma IL‐8/IL‐18 to discriminate NRs from Rs. We found differential therapeutic effects for VA and avelumab in NRs vs. Rs. Thus, our results imply that measuring the plasma IL‐8/IL‐18 and bulk RNA‐Seq of PBMCs may serve as valuable biomarkers to predict immunotherapy outcomes. [ABSTRACT FROM AUTHOR]

Students rely on rote knowledge to learn accounting concepts. However, this approach does not allow them to understanding the meta language of accounting. Meta language is simply the concepts and terms that are used in a profession and are easily understood by its users. Terms such as equity, assets, and balance sheet are part of the accounting meta language. The authors used a pre-test in upper level accounting courses at several universities over multiple semesters to evaluate students' understanding of the accounting meta language. The students' average scores on the pre-test were less than the anticipated average scores. The paper offers some suggestions on steps that can be used by educators to strengthen students' understanding of accounting meta language.

ESL is both a professional educational service and, particularly in post-compulsory contexts, a commercial activity. The effective management of ESL programs can secure quality outcomes for practitioners and students. Nevertheless, writings on ESL management do not figure prominently in the literature. In particular, the association between services management theory and ESL practice has enjoyed only limited recognition. This article highlights the association by exploring selected elements of service logic theory and their application to the management of post-compulsory ESL in a commercial context. The elements are the co-creation of student-perceived value during the service process; the significance of relational aspects of the service; and the capacity to generate memorable experiences that are also quality educational outcomes. The application of service logic to ESL not only accentuates the link between services management principles and what could be considered ESL management best practice, but also suggests that service logic can support and complement standard teaching and learning processes and precepts that are desirable in well-run ESL programs. Thus ESL managers' and instructors' acquaintance with the basics of service logic has the potential to enhance the effectiveness of how they provide service.

BackgroundWhole-genome sequencing represents a powerful experimental tool for pathogen research. We present methods for the analysis of small eukaryotic genomes, including a streamlined system (called Platypus) for finding single nucleotide and copy number variants as well as recombination events.ResultsWe have validated our pipeline using four sets of Plasmodium falciparum drug resistant data containing 26 clones from 3D7 and Dd2 background strains, identifying an average of 11 single nucleotide variants per clone. We also identify 8 copy number variants with contributions to resistance, and report for the first time that all analyzed amplification events are in tandem.ConclusionsThe Platypus pipeline provides malaria researchers with a powerful tool to analyze short read sequencing data. It provides an accurate way to detect SNVs using known software packages, and a novel methodology for detection of CNVs, though it does not currently support detection of small indels. We have validated that the pipeline detects known SNVs in a variety of samples while filtering out spurious data. We bundle the methods into a freely available package.