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

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

Anisotropic scale invariant cosmology

We study a possibility of anisotropic scale invariant cosmology. It is shown that within the conventional Einstein gravity, the violation of the null energy condition is necessary. We construct an example based on a ghost condensation model that violates the null energy condition. The cosmological solution necessarily contains at least one contracting spatial direction as in the Kasner solution. Our cosmology is conjectured to be dual to, if any, a non-unitary anisotropic scale invariant Euclidean field theory. We investigate simple correlation functions of the dual theory by using the holographic computation. After compactification of the contracting direction, our setup may yield a dual field theory description of the winding tachyon condensation that might solve the singularity of big bang/crunch of the universe.Comment: 12 pages, v2: reference adde

Particle-seawater interaction of neodymium in the North Atlantic

Dissolved neodymium (Nd) isotopes (expressed as εNd) have been widely used as a water mass tracer in paleoceanography. However, one aspect of the modern biogeochemical cycle of Nd that has been sparsely investigated is the interplay between dissolved and particulate phases in seawater. We here present the first regional data set on particulate Nd isotope compositions (εNdp) and concentrations ([Nd]p) from five stations in the western North Atlantic Ocean along the GEOTRACES GA02 transect, in conjunction with previously published dissolved Nd isotope compositions (εNdd) and concentrations ([Nd]d)1. Key observations and interpretations from our new particulate data set include the following: (1) A low fractional contributions of [Nd]p to the total Nd inventory per volume unit of seawater (~5%), with significant increases of up to 45% in benthic boundary layers. (2) Increasing Nd concentrations in suspended particulate matter ([Nd]SPM) and fractions of lithogenic material with water depth, suggesting the removal of Nd poor phases. (3) Different provenances of particulates in the subpolar and subtropical gyres as evidenced by their Nd isotope fingerprints reaching from εNdp ≈ -20 near the Labrador Basin (old continental crust), over εNdp ≈ -4 between Iceland and Greenland (young mafic provenance), to values of εNdp ≈-13 in the subtropics (similar to African dust signal). (4) Vertical heterogeneity of εNdp, as well as large deviations from ambient seawater values in the subpolar gyre, indicate advection of lithogenic particles in this area. (5) Vertically homogenous εNdp values in the subtropical gyre, indistinguishable from εNdd values, are indicative of predominance of vertical particulate supply. The process of reversible scavenging only seems to influence particulate signatures below 3 km. Overall, we do not find evidence on enhanced particle dissolution, often invoked to explain the observed increase in dissolved Nd in the North Atlantic

Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup.

Embryonal rhabdomyosarcoma (ERMS) of the uterus has recently been shown to frequently harbor DICER1 mutations. Interestingly, only rare cases of extrauterine DICER1-associated ERMS, mostly located in the genitourinary tract, have been reported to date. Our goal was to study clinicopathologic and molecular profiles of DICER1-mutant (DICER1-mut) and DICER1-wild type (DICER1-wt) ERMS in a cohort of genitourinary tumors. We collected a cohort of 17 ERMS including nine uterine (four uterine corpus and five cervix), one vaginal, and seven urinary tract tumors. DNA sequencing revealed mutations of DICER1 in 9/9 uterine ERMS. All other ERMS of our cohort were DICER1-wt. The median age at diagnosis of patients with DICER1-mut and DICER1-wt ERMS was 36 years and 5 years, respectively. Limited follow-up data (available for 15/17 patients) suggested that DICER1-mut ERMS might show a less aggressive clinical course than DICER1-wt ERMS. Histological features only observed in DICER1-mut ERMS were cartilaginous nodules (6/9 DICER1-mut ERMS), in one case accompanied by foci of ossification. Recurrent mutations identified in both DICER1-mut and DICER1-wt ERMS affected KRAS, NRAS, and TP53. Copy number analysis revealed similar structural variations with frequent gains on chromosomes 2, 3, and 8, independent of DICER1 mutation status. Unsupervised hierarchical clustering of array-based whole-genome DNA methylation data of our study cohort together with an extended methylation data set including different RMS subtypes from genitourinary and extra-genitourinary locations (n = 102), revealed a distinct cluster for DICER1-mut ERMS. Such tumors clearly segregated from the clusters of DICER1-wt ERMS, alveolar RMS, and MYOD1-mutant spindle cell and sclerosing RMS. Only one tumor, previously diagnosed as ERMS arising in the maxilla of a 6-year-old boy clustered with DICER1-mut ERMS of the uterus. Subsequent sequencing analysis identified two DICER1 mutations in the latter case. Our results suggest that DICER1-mut ERMS might qualify as a distinct subtype in future classifications of RMS

Diffuse Glioneuronal tumour with Oligodendroglioma‐like features and Nuclear Clusters (DGONC) – a molecularly‐defined glioneuronal CNS tumour class displaying recurrent monosomy 14

Aims: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. Patients and methods: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. Results: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. Conclusions: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters

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