Laser-induced asymmetric faceting and growth of a nano-protrusion on a tungsten tip

Irradiation of a sharp tungsten tip by a femtosecond laser and exposed to a strong DC electric field led to reproducible surface modifications. By a combination of field emission microscopy and scanning electron microscopy, we observed asymmetric surface faceting with sub-ten nanometer high steps. The presence of faceted features mainly on the laser-exposed side implies that the surface modification was driven by a laser-induced transient temperature rise on a scale of a couple of picoseconds in the tungsten tip apex. Moreover, we identified the formation of a nano-tip a few nanometers high located at one of the corners of a faceted plateau. The results of simulations emulating the experimental conditions are consistent with the experimental observations. The presented technique would be a new method to fabricate a nano-tip especially for generating coherent electron pulses. The features may also help to explain the origin of enhanced field emission, which leads to vacuum arcs, in high electric field devices such as radio-frequency particle accelerators.Peer reviewe

The Compact Linear Collider (CLIC) - 2018 Summary Report

The Compact Linear Collider (CLIC) is a TeV-scale high-luminosity linear $e^+e^-$ collider under development at CERN. Following the CLIC conceptual design published in 2012, this report provides an overview of the CLIC project, its current status, and future developments. It presents the CLIC physics potential and reports on design, technology, and implementation aspects of the accelerator and the detector. CLIC is foreseen to be built and operated in stages, at centre-of-mass energies of 380 GeV, 1.5 TeV and 3 TeV, respectively. CLIC uses a two-beam acceleration scheme, in which 12 GHz accelerating structures are powered via a high-current drive beam. For the first stage, an alternative with X-band klystron powering is also considered. CLIC accelerator optimisation, technical developments and system tests have resulted in an increased energy efficiency (power around 170 MW) for the 380 GeV stage, together with a reduced cost estimate at the level of 6 billion CHF. The detector concept has been refined using improved software tools. Significant progress has been made on detector technology developments for the tracking and calorimetry systems. A wide range of CLIC physics studies has been conducted, both through full detector simulations and parametric studies, together providing a broad overview of the CLIC physics potential. Each of the three energy stages adds cornerstones of the full CLIC physics programme, such as Higgs width and couplings, top-quark properties, Higgs self-coupling, direct searches, and many precision electroweak measurements. The interpretation of the combined results gives crucial and accurate insight into new physics, largely complementary to LHC and HL-LHC. The construction of the first CLIC energy stage could start by 2026. First beams would be available by 2035, marking the beginning of a broad CLIC physics programme spanning 25-30 years

Genetically encoded Ca2+ -sensor reveals details of porcine endothelial cell activation upon contact with human serum.

The activation of the endothelial surface in xenografts is still a poorly understood process and the consequences are unpredictable. The role of Ca2+ -messaging during the activation of endothelial cells is well recognized and routinely measured by synthetic Ca2+ -sensitive fluorophors. However, these compounds require fresh loading immediately before each experiment and in particular when grown in state-of-the-art 3D cell culture systems, endothelial cells are difficult to access with such sensors. Therefore, we developed transgenic pigs expressing a Ca2+ -sensitive protein and examined its principal characteristics. Primary transgenic endothelial cells stimulated by ATP showed a definite and short influx of Ca2+ into the cytosol, whereas exposure to human serum resulted in a more intense and sustained response. Surprisingly, not all endothelial cells reacted identically to a stimulus, rather activation took place in adjacent cells in a timely decelerated way and with distinct intensities. This effect was again more pronounced when cells were stimulated with human serum. Finally, we show clear evidence that antibody binding alone significantly activated endothelial cells, whereas antibody depletion dramatically reduced the stimulatory potential of serum. Transgenic porcine endothelial cells expressing a Ca2+ -sensor represent an interesting tool to dissect factors inducing activation of porcine endothelial cells after exposure to human blood or serum

Synthesis and SAR of Tetracyclic Inhibitors of Protein Kinase CK2 Derived from Furocarbazole W16

The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2 alpha(2)beta(2) and its monomeric subunits CK2 alpha and CK2 beta. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)-3 a)) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide (9) and N-methylimide (10) substructure. The enantiomer (-)-3 a (K-i=4.9 mu M) of the lead compound (+)-3 a (K-i=31 mu M) showed a more than sixfold increased inhibition of the CK2 alpha/CK2 beta interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (-)-3 a did not show an increased enzyme inhibition of the CK2 alpha(2)beta(2) holoenzyme, the CK2 alpha subunit or the mutated CK2 alpha ' (C336S) subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (-)-9 a (K-i=3.6 mu M) and the N-methylimide (+)-10 a (K-i=2.8 mu M) represent the most promising inhibitors of the CK2 alpha/CK2 beta interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (+/-)-12, with a carboxy moiety in the 4-position, displays the highest CK2 alpha/CK2 beta interaction inhibition (K-i=1.8 mu M) of this series of compounds

Feedback in medical education - a workshop report with practical examples and recommendations

Background: As a teaching method, feedback is an integral part of medical education. However, there is a lack of a uniform theoretical basis or generally recognized guidelines for its specific design. Against this background, the aim of this article is to discuss conceptual considerations and empirical findings regarding feedback using various practical examples. Procedure and conceptual considerations: Building on the results of a workshop of the Committee for Communicative and Social Competences of the Society for Medical Education (GMA), this article first explains central conceptual considerations and empirical results on the topic of feedback. A particular focus is on various variables that influence the effect of feedback. This includes the feedback source, the frequency of feedback, starting points of feedback, the connection between feedback and reflection as well as the motivation and meta-cognitive skills of the feedback recipient. Practical examples: The implementation of feedback in practice is illustrated using eight examples from the field of medical and dental education. They stem from various settings and the focus is on formative oral feedback. It will become evident that the focus is more on the givers of feedback than the recipients of feedback. Instructions for recipients of feedback on how to reflect on it is still the exception. Discussion: Many of the relevant aspects for the effect of feedback described in the literature are already taken into account in the practical examples discussed. In conclusion, seven recommendations are made for implementing feedback in practice

LAUNCHING COSMIC-RAY-DRIVEN OUTFLOWS FROM THE MAGNETIZED INTERSTELLAR MEDIUM

We present a hydrodynamical simulation of the turbulent, magnetized, supernova (SN)-driven interstellar medium (ISM) in a stratified box that dynamically couples the injection and evolution of cosmic rays (CRs) and a self-consistent evolution of the chemical composition. CRs are treated as a relativistic fluid in the advection-diffusion approximation. The thermodynamic evolution of the gas is computed using a chemical network that follows the abundances of H+, H, H-2, CO, C+, and free electrons and includes (self-) shielding of the gas and dust. We find that CRs perceptibly thicken the disk with the heights of 90% (70%) enclosed mass reaching greater than or similar to 1.5 kpc (greater than or similar to 0.2 kpc). The simulations indicate that CRs alone can launch and sustain strong outflows of atomic and ionized gas with mass loading factors of order unity, even in solar neighborhood conditions and with a CR energy injection per SN of 10(50) erg, 10% of the fiducial thermal energy of an SN. The CR-driven outflows have moderate launching velocities close to the midplane (less than or similar to 100 km s(-1)) and are denser (rho similar to 10(-24)-10(-26) g cm(-3)), smoother, and colder than the (thermal) SN-driven winds. The simulations support the importance of CRs for setting the vertical structure of the disk as well as the driving of winds