The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.
View Article and Find Full Text PDFMetabolite accumulation in the tumor microenvironment fosters immune evasion and limits the efficiency of immunotherapeutic approaches. Methylthioadenosine phosphorylase (MTAP), which catalyzes the degradation of 5'-deoxy-5'methylthioadenosine (MTA), is downregulated in many cancer entities. Consequently, MTA accumulates in the microenvironment of MTAP-deficient tumors, where it is known to inhibit tumor-infiltrating T cells and NK cells.
View Article and Find Full Text PDFEx vivo expansion of human CD34+ hematopoietic stem and progenitor cells remains a challenge due to rapid differentiation after detachment from the bone marrow niche. In this study, we assessed the capacity of an inducible fusion protein to enable sustained ex vivo proliferation of hematopoietic precursors and their capacity to differentiate into functional phagocytes. We fused the coding sequences of an FK506-Binding Protein 12 (FKBP12)-derived destabilization domain (DD) to the myeloid/lymphoid lineage leukemia/eleven nineteen leukemia (MLL-ENL) fusion gene to generate the fusion protein DD-MLL-ENL and retrovirally expressed the protein switch in human CD34+ progenitors.
View Article and Find Full Text PDFThis simulation study investigated to what extent departures from construct similarity as well as differences in the difficulty and targeting of scales impact the score transformation when scales are equated by means of concurrent calibration using the partial credit model with a common person design. Practical implications of the simulation results are discussed with a focus on scale equating in health-related research settings. The study simulated data for two scales, varying the number of items and the sample sizes.
View Article and Find Full Text PDFIn recent years, machine learning methods have become increasingly popular prediction methods in psychology. At the same time, psychological researchers are typically not only interested in making predictions about the dependent variable, but also in learning which predictor variables are relevant, how they influence the dependent variable, and which predictors interact with each other. However, most machine learning methods are not directly interpretable.
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