The transcription factor SOX11 is a potential tumor suppressor in myxoid liposarcomas: Analysis of function, target genes and mutation

Soft tissue sarcomas are a rare group of highly aggressive, histologically and genetically heterogeneous malignant tumors of mesenchymal origin. Liposarcomas are the most common type of sarcomas and are classified into the three types well-differentiated / dedifferentiated liposarcomas, pleomorphic liposarcomas and myxoid liposarcomas (MLS). MLS are characterized by a t(12;16)(q13;p11) translocation resulting in a FUS-DDIT3 fusion protein causing a block of differentiation during adipogenesis and malignant transformation. SOX11 is a neuronal transcription factor which is expressed during embryonic development of central and peripheral nervous system. In adult tissues SOX11 is rarely expressed. SOX11 expression is elevated in a variety of tumors but seems to exert different functions in tumorigenesis. Prior to this study a genome-wide expression profile of primary MLS samples identified SOX11 as the significant most upregulated gene in comparison to non-neoplastic adipose tissue. Additionally, SOX11 target genes in MLS were identified. The overexpression of SOX11 in the SOX11-negative MLS cell line MLS-1765 decreased migration, clonogenicity, and viability. In addition, the reduced cell growth is caused by decreased proliferation. However, overexpression of SOX11 had no influence on apoptosis and necrosis and on the phosphorylation profile of MLS-1765 cells. Also, SOX11 increased the sensitivity of MLS-1765 cells against treatment with the chemotherapeutic drugs dasatinib and trabectedin, but not against the standard first line treatment doxorubicin. The potential target genes LHX2, TMSB15A, CD24, NNAT, THEM6, TUBB2B und SOX11 were validated by qPCR. Positive correlation of gene expression with SOX11 in primary MLS and non-neoplastic adipose tissue and results from dual-luciferase reporter assays revealed that CD24 and LHX2 are putative direct target genes of SOX11. The treatment of T778 cells with histone deacetylase inhibitors indicated that the SOX11 expression in liposarcomas may be regulated via histone modifications. Sequencing of the chromosomal SOX11 gene locus identified a somatic heterozygous mutation (c.248T>A; SOX11T248A) in the tumor of a patient with MLS. According to in silico analyses the SOX11T248A mutation significantly affects folding of the HMG-box domain leading to a loss of DNA binding. Stable overexpression of SOX11T248A in MLS-1765 cells showed reduced ability to activate the downstream transcription of the seven SOX11 target genes and impaired the SOX11-mediated phenotypes proliferation and chemosensitivity against trabectedin. Taken together, this study obtained first evidence for a tumor suppressive role of SOX11, validated CD24 and LHX2 as potential SOX11 target genes and discovered a SOX11 loss-of-function mutation

Hyperfine Interactions in Charm and Bottom Systems

Hyperfine interactions in the light meson and baryon sectors are generalized to the charm and bottom systems. It is pointed out that an attempt to increase the value of the wave function at the origin to account for the unusual ratio of $\Lambda_{b}$ to the $B^0$ lifetimes could spoil the good agreement among the baryon and meson hyperfine mass-splitting. Including spin effects and taking phase space differences into account we predict that the decay rate of the $\Lambda_{b}$ can be increased relative to that of the $B^0$ meson by about 7%.Comment: 10 pages, plain Latex, no figures. A new isospin argument has been adde

Public support for worktime reductions in Switzerland in the context of a transition to a post-growth society

Work time reductions (WTRs) may contribute to a transition to a post-growth society. We analysed Swiss stakeholders’ perceptions of the effects of WTRs and their support for measures to implement them. It is assumed that public support will play a significant role in putting WTRs into practice. There is some scientific evidence that work time reductions (WTRs) have beneficial ecological, social, and economic effects that could contribute to a transition to a post-growth society. However, little research has been conducted on whether the occurrence of such desired effects is acknowledged: Do they form part of the public debate and is there any public support for WTRs? We conducted a two-round survey among Swiss stakeholder groups (N = 51/28) to identify what effects they believe WTRs have, and what measures to implement WTRs they would be most likely to support. Stakeholders perceived WTRs to have several beneficial social and economic effects, including effects that are relevant for a transition to a post-growth society. However, they did not assume that ecological effects occur. Measures voluntarily implemented on an organisational level by businesses were more popular than those implemented on a national policy or social partnership level. Certain incremental measures and/or those that are merely conducive to WTRs were uncontested. Other more direct and extensive measures were predominantly supported, but not uncontested

Glauber Phases in Non-Global LHC Observables: Resummation for Gluon-Initiated Processes

The resummation of the ''Glauber series'' in non-global LHC observables is extended to processes with gluons in the initial state. This series simultaneously incorporates large double-logarithmic corrections, the so-called ''super-leading logarithms'', together with higher-order exchanges of pairs of Glauber gluons associated with the large numerical factor $(i\pi)^2$. On a technical level, the main part of this work is devoted to the systematic reduction of the appearing color traces and construction of basis structures, which consist of thirteen elements for $gg$ and eleven elements for $qg$ scattering. Numerical estimates for wide-angle gap-between-jet cross sections at the parton level show that, in particular for $gg$ scattering at relatively small vetoes $Q_0$, the contribution involving four Glauber exchanges gives a sizeable correction and should not be neglected.Comment: 38 pages, 5 figure

Weak Decays in the light--front Quark Model

We study the form factors of heavy--to--heavy and heavy--to--light weak decays using the light--front relativistic quark model. For the heavy--to--heavy B \ra D^{(\ast)} semileptonic decays we calculate the corresponding Isgur--Wise function for the whole kinematic region. For the heavy--to--light B\ra P and B\ra V semileptonic decays we calculate the form factors at $q^2 = 0$; in particular, we have derived the dependence of the form factors on the $b$--quark mass in the m_b \ra \infty limit. This dependence can not be produced by extrapolating the scaling behavior of the form factors at $q^2_{max}$ using the single--pole assumption. This shows that the $q^2$ dependence of the form factors in regions far away from the zero--recoil could be much more complicated than that predicted by the single--pole assumption.Comment: 24 pages, Latex, Postscript figure included at the en

Graph neural networks for materials science and chemistry

Machine learning plays an increasingly important role in many areas of chemistry and materials science, being used to predict materials properties, accelerate simulations, design new structures, and predict synthesis routes of new materials. Graph neural networks (GNNs) are one of the fastest growing classes of machine learning models. They are of particular relevance for chemistry and materials science, as they directly work on a graph or structural representation of molecules and materials and therefore have full access to all relevant information required to characterize materials. In this Review, we provide an overview of the basic principles of GNNs, widely used datasets, and state-of-the-art architectures, followed by a discussion of a wide range of recent applications of GNNs in chemistry and materials science, and concluding with a road-map for the further development and application of GNNs

Interplay of Na+ Balance and Immunobiology of Dendritic Cells

Local Na+ balance emerges as an important factor of tissue microenvironment. On the one hand, immune cells impact on local Na+ levels. On the other hand, Na+ availability is able to influence immune responses. In contrast to macrophages, our knowledge of dendritic cells (DCs) in this state of affair is rather limited. Current evidence suggests that the impact of increased Na+ on DCs is context dependent. Moreover, it is conceivable that DC immunobiology might also be influenced by Na+-rich-diet-induced changes of the gut microbiome

The rare decay b--> s gluon beyond leading logarithms

We calculate the alpha_s virtual corrections to the decay width for b --> s gluon in the standard model. Also the corresponding order alpha_s bremsstrahlung corrections are systematically calculated in this paper. The combined result is free of infrared and collinear singularities, in accordance with the KLN theorem. Taking into account the existing next-to-leading logarithmic (NLL) result for the Wilson coefficient C_8^(eff), a complete NLL result for the branching ratio B(b -> s gluon) is derived. Numerically, we obtain B^(NLL)=(5.0 +/- 1.0) * 10^{-3}, which is more than a factor of two larger than the leading logarithmic result B^(LL)=(2.2 +/- 0.8) * 10^{-3}.Comment: 14 pages including 5 postscript figures; uses epsfi

Mapping the O-Mannose Glycoproteome in Saccharomyces cerevisiae

O-Mannosylation is a vital protein modification conserved from fungi to humans. Yeast is a perfect model to study this post-translational modification, because in contrast to mammals O-mannosylation is the only type of O-glycosylation. In an essential step toward the full understanding of protein O-mannosylation we mapped the O-mannose glycoproteome in baker's yeast. Taking advantage of an O-glycan elongation deficient yeast strain to simplify sample complexity, we identified over 500 O-glycoproteins from all subcellular compartments for which over 2300 O-mannosylation sites were mapped by electron-transfer dissociation (ETD)-based MS/MS. In this study, we focus on the 293 O-glycoproteins (over 1900 glycosylation sites identified by ETD-MS/MS) that enter the secretory pathway and are targets of ER-localized protein O-mannosyltransferases. We find that O-mannosylation is not only a prominent modification of cell wall and plasma membrane proteins, but also of a large number of proteins from the secretory pathway with crucial functions in protein glycosylation, folding, quality control, and trafficking. The analysis of glycosylation sites revealed that O-mannosylation is favored in unstructured regions and β-strands. Furthermore, O-mannosylation is impeded in the proximity of N-glycosylation sites suggesting the interplay of these types of post-translational modifications. The detailed knowledge of the target proteins and their O-mannosylation sites opens for discovery of new roles of this essential modification in eukaryotes, and for a first glance on the evolution of different types of O-glycosylation from yeast to mammals

Removal of hydrogen from Ti VT 1-0 under action of accelerated electrons

The process of hydrogen removal from titanium of VT1-0 grade under the action of accelerated electrons has been studied experimentally. The irradiation was carried out by an electron beam with energies of 25-40 keV during 15-60 min. The information on the hydrogen content in samples from titanium of VT1-0 grade has been obtained both before and after irradiation with accelerated electrons. The activation energy of hydrogen desorption from titanium has been calculated. It was found that the increase of the time and the energy of an irradiation lead to the decrease of the residual hydrogen content in the titanium samples