Search Results (5)

This study delves into the polemical exchange between the 19th-century Ottoman scholar Harputlu İshak Hoca (d. 1892) and the protestant missionary Karl Gottlieb Pfander (d. 1865). By examining the historical context surrounding their controversy, this research sheds light on the interaction between the Ottoman state and British and American missionaries, particularly during the expansion of missionary activities in Anatolia. This paper also explores the responses of the Ottoman authorities to the missionary printing activities and the impact of the Church Missionary Society’s work on societal and governmental levels. Furthermore, it provides an analysis of Pfander’s Mizan ul-haqq (The Balance of Truth) and Harputlu’s Şemsü’l-hakîkat (The Sun of Truth) and Ziyâü’l-kulûb (The Light of Hearts), portraying them as not only engaging in interreligious polemics but also as creators of textual products that reflect the complex historical realities of their time. This research underscores the Ottoman scholars’ close attention and prompt responses to missionary literature. Full article

On-tissue enzymatic digestion is a prerequisite for MALDI mass spectrometry imaging (MSI) and spatialomic analysis of tissue proteins and their N-glycan conjugates. Despite the more widely accepted importance of N-glycans as diagnostic and prognostic biomarkers of many diseases and their potential as pharmacodynamic markers, the crucial sample preparation step, namely on-tissue digestion with enzymes like PNGaseF, is currently mainly carried out by specialized laboratories using home-built incubation arrangements, e.g., petri dishes placed in an incubator. Standardized spatially confined enzyme digests, however, require precise control and possible regulation of humidity and temperature, as high humidity increases the risk of analyte dislocation and low humidity compromises enzyme function. Here, a digestion device that controls humidity by cyclic ventilation and heating of the slide holder and the chamber lid was designed to enable controlled micro-condensation on the slide and to stabilize and monitor the digestion process. The device presented here may help with standardization in MSI. Using sagittal mouse brain sections and xenografted human U87 glioblastoma cells in CD1 nu/nu mouse brain, a device-controlled workflow for MALDI MSI of N-glycans was developed. Full article

Immune response control is critical as excessive cytokine production can be detrimental and damage the host. Interleukin-10 (Il-10), an anti-inflammatory cytokine produced primarily by macrophages, is a key regulator that counteracts and controls excessive inflammatory response. Il-10 expression is regulated through the transcription factor c-Maf. Another regulator of Il-10 production is p35, an activator of the cyclin-dependent kinase 5 (Cdk5), which decreases Il-10 production in macrophages, thus increasing inflammation. However, Cdk5 regulation of c-Maf and the involvement of Il-10 production in macrophages has not yet been investigated. We used in vitro primary bone marrow-derived macrophages (BMDMs) lacking Cdk5, stimulated them with lipopolysaccharid (LPS) and observed increased levels of c-Maf and Il-10. In an in vivo mouse model of LPS-induced endotoxemia, mice lacking Cdk5 in macrophages showed increased levels of c-Maf and elevated levels of Il-10 in lungs as well as in plasma, resulting in ameliorated survival. Taken together, we identified Cdk5 as a potential novel regulator of Il-10 production through c-Maf in macrophages under inflammatory conditions. Our results suggest that inhibition of Cdk5 enhances the c-Maf-Il-10 axis and thus potentiates improvement of anti-inflammatory therapy. Full article

Clustering is an important task in data mining that has become more challenging due to the ever-increasing size of available datasets. To cope with these big data scenarios, a high-performance clustering approach is required. Sparse grid clustering is a density-based clustering method that uses a sparse grid density estimation as its central building block. The underlying density estimation approach enables the detection of clusters with non-convex shapes and without a predetermined number of clusters. In this work, we introduce a new distributed and performance-portable variant of the sparse grid clustering algorithm that is suited for big data settings. Our computed kernels were implemented in OpenCL to enable portability across a wide range of architectures. For distributed environments, we added a manager–worker scheme that was implemented using MPI. In experiments on two supercomputers, Piz Daint and Hazel Hen, with up to 100 million data points in a ten-dimensional dataset, we show the performance and scalability of our approach. The dataset with 100 million data points was clustered in 1198 $\mathrm{s}$ using 128 nodes of Piz Daint. This translates to an overall performance of 352 $\mathrm{TFLOPS}$ . On the node-level, we provide results for two GPUs, Nvidia’s Tesla P100 and the AMD FirePro W8100, and one processor-based platform that uses Intel Xeon E5-2680v3 processors. In these experiments, we achieved between 43% and 66% of the peak performance across all computed kernels and devices, demonstrating the performance portability of our approach. Full article

DNA replication differs from most other processes in biology in that any error will irreversibly change the nature of the cellular progeny. DNA replication initiation, therefore, is exquisitely controlled. Deregulation of this control can result in over-replication characterized by repeated initiation events at the same replication origin. Over-replication induces DNA damage and causes genomic instability. The principal mechanism counteracting over-replication in eukaryotes is a division of replication initiation into two steps—licensing and firing—which are temporally separated and occur at distinct cell cycle phases. Here, we review this temporal replication control with a specific focus on mechanisms ensuring the faultless transition between licensing and firing phases. Full article