Glioblastomas with primitive neuronal component harbor a distinct methylation and copy‑number profle with inactivation of TP53, PTEN, and RB1

Glioblastoma IDH-wildtype presents with a wide histological spectrum. Some features are so distinctive that they are considered as separate histological variants or patterns for the purpose of classification. However, these usually lack defined (epi-)genetic alterations or profiles correlating with this histology. Here, we describe a molecular subtype with overlap to the unique histological pattern of glioblastoma with primitive neuronal component. Our cohort consists of 63 IDH-wildtype glioblastomas that harbor a characteristic DNA methylation profile. Median age at diagnosis was 59.5 years. Copy-number variations and genetic sequencing revealed frequent alterations in TP53, RB1 and PTEN, with fewer gains of chromosome 7 and homozygous CDKN2A/B deletions than usually described for IDH-wildtype glioblastoma. Gains of chromosome 1 were detected in more than half of the cases. A poorly differentiated phenotype with frequent absence of GFAP expression, high proliferation index and strong staining for p53 and TTF1 often caused misleading histological classification as carcinoma metastasis or primitive neuroectodermal tumor. Clinically, many patients presented with leptomeningeal dissemination and spinal metastasis. Outcome was poor with a median overall survival of only 12 months. Overall, we describe a new molecular subtype of IDH-wildtype glioblastoma with a distinct histological appearance and genetic signature.publishedVersio

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications

Rail vehicle dynamics

This book on the dynamics of rail vehicles is developed from the manuscripts for a class with the same name at TU Berlin. It is directed mainly to master students with pre-knowledge in mathematics and mechanics and engineers that want to learn more. The important phenomena of the running behaviour of rail vehicles are derived and explained. Also recent research results and experience from the operation of rail vehicles are included. One focus is the description of the complex wheel-rail contact phenomena that are essential to understand the concept of running stability and curving. A reader should in the end be able to understand the background of simulation tools that are used by the railway industry and universities today

On the influence of Freight Traffic Operational Conditions on Track Deterioration Cost

In order to increase the understanding of the running behaviour of freight wagons and the interaction between vehicles and track, a research project was started at KTH in 1996. The background to the initiation of the project were plans to increase axle load, loading gauge and speed of freight trains to make freight traffic on rail more competitive. In the present paper, the effect of different types of running gear and operational conditions on the track deterioration marginal cost in terms of settlement in the ballast, component fatigue and wear and RCF are investigated. Considerable differences in track deterioration cost per produced ton-km for the different types of running gear are observed. Axleload is an important parameter for settlement and component fatigue. Also the height of centre of gravity has significant influence on track deterioration, especially on track sections with high cant deficiency or cant excess.QC 20100802. Konferens: The International Heavy Haul ConferenceQC 20151223</p

On the influence of Freight Traffic Operational Conditions on Track Deterioration Cost

In order to increase the understanding of the running behaviour of freight wagons and the interaction between vehicles and track, a research project was started at KTH in 1996. The background to the initiation of the project were plans to increase axle load, loading gauge and speed of freight trains to make freight traffic on rail more competitive. In the present paper, the effect of different types of running gear and operational conditions on the track deterioration marginal cost in terms of settlement in the ballast, component fatigue and wear and RCF are investigated. Considerable differences in track deterioration cost per produced ton-km for the different types of running gear are observed. Axleload is an important parameter for settlement and component fatigue. Also the height of centre of gravity has significant influence on track deterioration, especially on track sections with high cant deficiency or cant excess.QC 20100802. Konferens: The International Heavy Haul ConferenceQC 20151223</p

Modelling of pantograph-catenary interaction around critical speed

The dynamic interaction of pantograph and catenary in electrified railway systems has considerable research attention, both in terms of simulation and of measurements. The simulation benchmark of 2015 proved a good base of agreement between established models, but also showed that deviations between the different models increase when the simulated system approaches critical speeds. From these deviations it can be concluded that some of the models in the benchmark better depict the system behaviour around critical speed than others. Therefore, this paper analyses and compares measurement data from the Green Train project in Sweden, which includes speed at and over critical level, to simulations performed with one of the participating models, the finite element (FE) based CaPaSIM model. Based on this comparison,modelling alternatives are implemented and tested in CaPaSIM, to examine if they improve the accuracy of the model in the speed range around critical speeds. These alternative modelling approaches are to a large extent based on previous studies in thefield, such as other models that  participated in the benchmark. The varied aspects include choice of element type for single components of the catenary and element mesh resolution. On the pantograph side, the effect of separately modelling independent flexible collector strips is studied. The modelling choices that prove to be most promising during the initial variation tests are presented and recommendations are given for further investigations of possible improvements.QC 20220822</p