Final Assembly of the Helmholtz Zentrum Berlin Series Connected Hybrid Magnet System

The final assembly of the Series Connected Hybrid magnet system for the Helmholtz Zentrum Berlin for Materials and Energy HZB has occurred with the integration of the superconducting cold mass, cryostat, resistive Florida Bitter coils, and the cryogenic, chilled water, power, and control subsystems. The hybrid magnet consists of a 13 T superconducting Nb3Sn CICC coil and a set of 12 T resistive, water cooled coils at 4.4 MW. Much of the cryostat and cold mass functional requirements were dictated by the electromagnetic interactions between the superconducting and resistive coils. This includes the radial decentering and axial aligning forces from normal operations and a 1.1 MN fault load. The system assembly was an international achievement with the cold mass being completed at the NHMFL in the USA, cryostat to cold mass interfaces made at Criotec Impianti in Italy, and final assembly at the HZB in German

Systems theory of Smad signaling

Transforming Growth Factor-beta (TGF-beta) signalling is an important regulator of cellular growth and differentiation. The principal intracellular mediators of TGF-beta signalling are the Smad proteins, which upon TGF-beta stimulation accumulate in the nucleus and regulate transcription of target genes. To investigate the mechanisms of Smad nuclear accumulation, we developed a simple mathematical model of canonical Smad signalling. The model was built using both published data and our experimentally determined cellular Smad concentrations (isoforms 2, 3, and 4). We found in mink lung epithelial cells that Smad2 (8.5-12 x 10^4 molecules/cell) was present in similar amounts to Smad4 (9.3-12 x 10^4 molecules/cell), while both were in excess of Smad3 (1.1-2.0 x 10^4 molecules/cell). Variation of the model parameters and statistical analysis showed that Smad nuclear accumulation is most sensitive to parameters affecting the rates of RSmad phosphorylation and dephosphorylation and Smad complex formation/dissociation in the nucleus. Deleting Smad4 from the model revealed that rate-limiting phospho-R-Smad dephosphorylation could be an important mechanism for Smad nuclear accumulation. Furthermore, we observed that binding factors constitutively localised to the nucleus do not efficiently mediate Smad nuclear accumulation if dephosphorylation is rapid. We therefore conclude that an imbalance in the rates of R-Smad phosphorylation and dephosphorylation is likely an important mechanism of Smad nuclear accumulation during TGF-beta signalling.Comment: To appear in IEE Proceedings Systems Biology. 12 pages of text, 36 pages tota

Cancer tissue classification using supervised machine learning applied to maldi mass spectrometry imaging

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.Paul Mittal, Mark R. Condina, Manuela Klingler-Hoffmann, Gurjeet Kaur, Martin K. Oehler, Oliver M. Siebe

Partial clustering prevents global crystallization in a binary 2D colloidal glass former

A mixture of two types of super-paramagnetic colloidal particles with long range dipolar interaction is confined by gravity to a flat interface of a hanging water droplet. The particles are observed by video microscopy and the dipolar interaction strength is controlled via an external magnetic field. The system is a model system to study the glass transition in 2D, and it exhibits partial clustering of the small particles. This clustering is strongly dependent on the relative concentration $\xi$ of big and small particles. However, changing the interaction strength $\Gamma$ reveals that the clustering does not depend on the interaction strength. The partial clustering scenario is quantified using Minkowski functionals and partial structure factors. Evidence that partial clustering prevents global crystallization is discussed

The motion of a fluid-rigid disc system at the zero limit of the rigid disc radius

We consider the two-dimensional motion of the coupled system of a viscous incompressible fluid and a rigid disc moving with the fluid, in the whole plane. The fluid motion is described by the Navier-Stokes equations and the motion of the rigid body by conservation laws of linear and angular momentum. We show that, assuming that the rigid disc is not allowed to rotate, as the radius of the disc goes to zero, the solution of this system converges, in an appropriate sense, to the solution of the Navier-Stokes equations describing the motion of only fluid in the whole plane. We also prove that the trajectory of the centre of the disc, at the zero limit of its radius, coincides with a fluid particle trajectory.Comment: 29 pages, 0 figure

Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG-positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

Background:There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples.Methods:About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold >3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample.Results:We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC).Conclusions:We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression

Prospects for the CERN Axion Solar Telescope Sensitivity to 14.4 keV Axions

The CERN Axion Solar Telescope (CAST) is searching for solar axions using the 9.0 T strong and 9.26 m long transverse magnetic field of a twin aperture LHC test magnet, where axions could be converted into X-rays via reverse Primakoff process. Here we explore the potential of CAST to search for 14.4 keV axions that could be emitted from the Sun in M1 nuclear transition between the first, thermally excited state, and the ground state of 57Fe nuclide. Calculations of the expected signals, with respect to the axion-photon coupling, axion-nucleon coupling and axion mass, are presented in comparison with the experimental sensitivity.Comment: 4 pages, 1 figure. Submitted to Nucl. Instr. and Meth.

Regularity issues in the problem of fluid structure interaction

We investigate the evolution of rigid bodies in a viscous incompressible fluid. The flow is governed by the 2D Navier-Stokes equations, set in a bounded domain with Dirichlet boundary conditions. The boundaries of the solids and the domain have H\"older regularity $C^{1, \alpha}$, $0 < \alpha \le 1$. First, we show the existence and uniqueness of strong solutions up to collision. A key ingredient is a BMO bound on the velocity gradient, which substitutes to the standard $H^2$ estimate for smoother domains. Then, we study the asymptotic behaviour of one $C^{1, \alpha}$ body falling over a flat surface. We show that collision is possible in finite time if and only if $\alpha < 1/2$