Efficient Local Resorting Techniques with Space Filling Curves Applied to the Tsunami Simulation Model TsunAWI

The OpenMP-parallel model TsunAWI for the simulation of tsunami propagation and inundation discretizes the shallow water quations on an unstructured linear conforming-nonconforming finite element grid. The data access to the variables on the unstructured grid is crucial for the computational performance. A reordering of the unknowns at elements, nodes, and edges along a space filling curve (SFC) guarantees data locality on all levels of the memory hierarchy, thus reducing cash misses and false sharing. The SFC resorting algorithm is presented and its influence on the serial and OpenMP parallel computation times of TsunAWI is compared to other common resorting algorithms like reverse Cuthill-McKee and minimum degree ordering

Operational tsunami modelling with TsunAWI – recent developments and applications

In this article, the tsunami model TsunAWI (Alfred Wegener Institute) and its application for hindcasts, inundation studies, and the operation of the tsunami scenario repository for the Indonesian tsunami early warning system are presented. TsunAWI was developed in the framework of the German-Indonesian Tsunami Early Warning System (GITEWS) and simulates all stages of a tsunami from the origin and the propagation in the ocean to the arrival at the coast and the inundation on land. It solves the non-linear shallow water equations on an unstructured finite element grid that allows to change the resolution seamlessly between a coarse grid in the deep ocean and a fine representation of coastal structures. During the GITEWS project and the following maintenance phase, TsunAWI and a framework of pre- and postprocessing routines was developed step by step to provide fast computation of enhanced model physics and to deliver high quality results

Definition of the Surgical Case Complexity in the Treatment of Soft Tissue Tumors of the Extremities and Trunk

BACKGROUND: We intend to establish a complexity score for soft tissue tumor surgeries to compare the complexities of different soft tissue tumor surgeries and to ultimately assign affected patients to appropriate treatments. METHODS: We developed a soft tissue tumor complexity score (STS-SCS) based on three pillars: in addition to patient-related factors, tumor biology and surgery-associated parameters were taken into account. The STS-SCS was applied to our sampling group of 711 patients. RESULTS: The minimum STS-SCS was 4, the maximum score was 34 and the average score 11.4 ± 5.9. The scores of patients with malignant diagnoses were notably higher and more widely scattered than those of patients with benign or intermediate malignant tumors. To better categorize the complexities of individual surgeries, we established four categories using the collected data as a reference dataset. Each of the categories contained approximately one-quarter of the registered patients. DISCUSSION: The STS-SCS allows soft tissue tumor surgeries to be retrospectively evaluated for their complexity and forms the basis for the creation of a prospective concept to provide patients with the right intervention in the right geographic location, which can lead to better results and provision of the most cost-effective overall treatment

Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes

Aim: To elucidate the impact of liraglutide on the kinetics of apolipoprotein (apo) B48- and apoB100-containing triglyceride-rich lipoproteins in subjects with type 2 diabetes (T2D) after a single fat-rich meal. Materials and Methods: Subjects with T2D were included in a study to investigate postprandial apoB48 and apoB100 metabolism before and after 16 weeks on 1.8 mg/day liraglutide (n = 14) or placebo (n = 4). Stable isotope tracer and compartmental modelling techniques were used to determine the impact of liraglutide on chylomicron and very low-density lipoprotein (VLDL) production and clearance after a single fat-rich meal. Results: Liraglutide reduced apoB48 synthesis in chylomicrons by 60% (p <.0001) and increased the triglyceride/apoB48 ratio (i.e. the size) of chylomicrons (p <.001). Direct clearance of chylomicrons, a quantitatively significant pathway pretreatment, decreased by 90% on liraglutide (p <.001). Liraglutide also reduced VLDL1-triglyceride secretion (p = .017) in parallel with reduced liver fat. Chylomicron-apoB48 production and particle size were related to insulin sensitivity (p = .015 and p <.001, respectively), but these associations were perturbed by liraglutide. Conclusions: In a physiologically relevant setting that mirrored regular feeding in subjects with T2D, liraglutide promoted potentially beneficial changes on postprandial apoB48 metabolism. Using our data in an integrated metabolic model, we describe how the action of liraglutide in T2D on chylomicron and VLDL kinetics could lead to decreased generation of remnant lipoproteins.Peer reviewe

Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping

Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases

Tsunami-Simulation für das indonesische Fühwarnsystem

Nach dem verheerenden Tsunami im Indischen Ozean 2004 wurde das internationale Kooperationsprojekt ''German-Indonesian Tsunami Early Warning System'' ins Leben gerufen und das Frühwarnzentrum am Amt für Meteorologie, Klimatologie und Geophysik in Jakarta aufgebaut. Auf deutscher Seite wurde das Projekt vom Helholtz-Zentrum Potsdam, Deutsches Geoforschungszentrum geleitet. Die Warnung nach einem starken Erdbeben basiert auf einer Datenbank möglicher Tsunamiszenarien, so dass schnell die Gefährdung der Küsten abgeschätzt werden kann. Im Vorfeld dienen detailiierte Überflutungsrechnungen als Basis für Evakuierungspläne. Der Vortrag stellt den Aufbau des Warnsystems mit einem Schwerpunkt auf der Rolle der Tsunami-Simulation vor. Neben den physikalischen und numerischen Grundlagen des Simulationsmodells TsunAWI wird die Einbettung der Tsunami-Szenariendatenbank beleuchtet. Wie kommt man von der Simulation zur konkreten Warnung, wie werden Szenarien zu vorhandenen Messdaten ausgewählt? Außerdem wird die Erarbeitung von Evakuierungsplänen am Beispiel von Bali kurz vorgestellt

Deep Phenotyping of CD11c+ B Cells in Systemic Autoimmunity and Controls

Circulating CD11c+ B cells are a key phenomenon in certain types of autoimmunity but have also been described in the context of regular immune responses (i.e., infections, vaccination). Using mass cytometry to profile 46 different markers on individual immune cells, we systematically initially confirmed the presence of increased CD11c+ B cells in the blood of systemic lupus erythematosus (SLE) patients. Notably, significant differences in the expression of CD21, CD27, and CD38 became apparent between CD11c- and CD11c+ B cells. We observed direct correlation of the frequency of CD21-CD27- B cells and CD21-CD38- B cells with CD11c+ B cells, which were most pronounced in SLE compared to primary Sjögren's syndrome patients (pSS) and healthy donors (HD). Thus, CD11c+ B cells resided mainly within memory subsets and were enriched in CD27-IgD-, CD21-CD27-, and CD21-CD38- B cell phenotypes. CD11c+ B cells from all donor groups (SLE, pSS, and HD) showed enhanced CD69, Ki-67, CD45RO, CD45RA, and CD19 expression, whereas the membrane expression of CXCR5 and CD21 were diminished. Notably, SLE CD11c+ B cells showed enhanced expression of the checkpoint molecules CD86, PD1, PDL1, CD137, VISTA, and CTLA-4 compared to HD. The substantial increase of CD11c+ B cells with a CD21- phenotype co-expressing distinct activation and checkpoint markers, points to a quantitative increased alternate (extrafollicular) B cell activation route possibly related to abnormal immune regulation as seen under the striking inflammatory conditions of SLE which shows a characteristic PD-1/PD-L1 upregulation

Defining the landscape of circular RNAs in neuroblastoma unveils a global suppressive function of MYCN

Circular RNAs (circRNAs) are a regulatory RNA class. While cancer-driving functions have been identified for single circRNAs, how they modulate gene expression in cancer is not well understood. We investigate circRNA expression in the pediatric malignancy, neuroblastoma, through deep whole-transcriptome sequencing in 104 primary neuroblastomas covering all risk groups. We demonstrate that MYCN amplification, which defines a subset of high-risk cases, causes globally suppressed circRNA biogenesis directly dependent on the DHX9 RNA helicase. We detect similar mechanisms in shaping circRNA expression in the pediatric cancer medulloblastoma implying a general MYCN effect. Comparisons to other cancers identify 25 circRNAs that are specifically upregulated in neuroblastoma, including circARID1A. Transcribed from the ARID1A tumor suppressor gene, circARID1A promotes cell growth and survival, mediated by direct interaction with the KHSRP RNA-binding protein. Our study highlights the importance of MYCN regulating circRNAs in cancer and identifies molecular mechanisms, which explain their contribution to neuroblastoma pathogenesis