Dynamics of railway freight vehicles

This paper summarises the historical development of railway freight vehicles and how vehicle designers have tackled the difficult challenges of producing running gear which can accommodate the very high tare to laden mass of typical freight wagons whilst maintaining stable running at the maximum required speed and good curving performance. The most common current freight bogies are described in detail and recent improvements in techniques used to simulate the dynamic behaviour of railway vehicles are summarised and examples of how these have been used to improve freight vehicle dynamic behaviour are included. A number of recent developments and innovative components and sub systems are outlined and finally two new developments are presented in more detail: the LEILA bogie and the SUSTRAIL bogie

Supersymmetrization of the Radiation Damping

We construct a supersymmetrized version of the model to the radiation damping \cite{03} introduced by the present authors \cite{ACWF}. We dicuss its symmetries and the corresponding conserved Noether charges. It is shown this supersymmetric version provides a supersymmetric generalization of the Galilei algebra obtained in \cite{ACWF}. We have shown that the supersymmetric action can be splited into dynamically independent external and internal sectors.Comment: 9 page

Jacobson generators, Fock representations and statistics of sl(n+1)

The properties of A-statistics, related to the class of simple Lie algebras sl(n+1) (Palev, T.D.: Preprint JINR E17-10550 (1977); hep-th/9705032), are further investigated. The description of each sl(n+1) is carried out via generators and their relations, first introduced by Jacobson. The related Fock spaces W_p (p=1,2,...) are finite-dimensional irreducible sl(n+1)-modules. The Pauli principle of the underlying statistics is formulated. In addition the paper contains the following new results: (a) The A-statistics are interpreted as exclusion statistics; (b) Within each W_p operators B(p)_1^\pm, ..., B(p)_n^\pm, proportional to the Jacobson generators, are introduced. It is proved that in an appropriate topology the limit of B(p)_i^\pm for p going to infinity is equal to B_i^\pm, where B_i^\pm are Bose creation and annihilation operators; (c) It is shown that the local statistics of the degenerated hard-core Bose models and of the related Heisenberg spin models is p=1 A-statistics.Comment: LaTeX-file, 33 page

DNA methylation-based profiling of bone and soft tissue tumours: a validation study of the 'DKFZ Sarcoma Classifier'

Diagnosing bone and soft tissue neoplasms remains challenging because of the large number of subtypes, many of which lack diagnostic biomarkers. DNA methylation profiles have proven to be a reliable basis for the classification of brain tumours and, following this success, a DNA methylation-based sarcoma classification tool from the Deutsches Krebsforschungszentrum (DKFZ) in Heidelberg has been developed. In this study, we assessed the performance of their classifier on DNA methylation profiles of an independent data set of 986 bone and soft tissue tumours and controls. We found that the 'DKFZ Sarcoma Classifier' was able to produce a diagnostic prediction for 55% of the 986 samples, with 83% of these predictions concordant with the histological diagnosis. On limiting the validation to the 820 cases with histological diagnoses for which the DKFZ Classifier was trained, 61% of cases received a prediction, and the histological diagnosis was concordant with the predicted methylation class in 88% of these cases, findings comparable to those reported in the DKFZ Classifier paper. The classifier performed best when diagnosing mesenchymal chondrosarcomas (CHSs, 88% sensitivity), chordomas (85% sensitivity), and fibrous dysplasia (83% sensitivity). Amongst the subtypes least often classified correctly were clear cell CHSs (14% sensitivity), malignant peripheral nerve sheath tumours (27% sensitivity), and pleomorphic liposarcomas (29% sensitivity). The classifier predictions resulted in revision of the histological diagnosis in six of our cases. We observed that, although a higher tumour purity resulted in a greater likelihood of a prediction being made, it did not correlate with classifier accuracy. Our results show that the DKFZ Classifier represents a powerful research tool for exploring the pathogenesis of sarcoma; with refinement, it has the potential to be a valuable diagnostic tool

Symmetries of field theories on the non-commutative plane

New developments on the symmetries of non-relativistic field theoretical models on the non commutative plane are reviewed. It is shown in particular that Galilean invariance strongly restricts the admissible interactions. Moreover, if a scalar field is coupled to a Chern - Simons gauge field, a geometrical phase emerges for vortex - like solutions, transformed by Galilei boosts.Comment: Reference corrected. Talk presented by LM at the International Workshop Nonlinear Physics: Theory and Experiment III. Gallipoli, (Lecce, Italy) 2004. To appear in Theor. Math. Phys. Latex 9 page

A subset of pediatric-type thalamic gliomas share a distinct DNA methylation profile, H3K27me3 loss and frequent alteration of EGFR

Background: Malignant astrocytic gliomas in children show a remarkable biological and clinical diversity. Small in-frame insertions or missense mutations in the epidermal growth factor receptor gene (EGFR) have recently been identified in a distinct subset of pediatric-type bithalamic gliomas with a unique DNA methylation pattern. Methods: Here, we investigated an epigenetically homogeneous cohort of malignant gliomas (n = 58) distinct from other subtypes and enriched for pediatric cases and thalamic location, in comparison with this recently identified subtype of pediatric bithalamic gliomas. Results EGFR gene amplification was detected in 16/58 (27%) tumors, and missense mutations or small in-frame insertions in EGFR were found in 20/30 tumors with available sequencing data (67%; 5 of them co-occurring with EGFR amplification). Additionally, 8 of the 30 tumors (27%) harbored an H3.1 or H3.3 K27M mutation (6 of them with a concomitant EGFR alteration). All tumors tested showed loss of H3K27me3 staining, with evidence of overexpression of the EZH inhibitory protein (EZHIP) in the H3 wildtype cases. Although some tumors indeed showed a bithalamic growth pattern, a significant proportion of tumors occurred in the unilateral thalamus or in other (predominantly midline) locations. Conclusions: Our findings present a distinct molecular class of pediatric-type malignant gliomas largely overlapping with the recently reported bithalamic gliomas characterized by EGFR alteration, but additionally showing a broader spectrum of EGFR alterations and tumor localization. Global H3K27me3 loss in this group appears to be mediated by either H3 K27 mutation or EZHIP overexpression. EGFR inhibition may represent a potential therapeutic strategy in these highly aggressive gliomas

Genetic and epigenetic characterization of posterior pituitary tumors

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets