Classification of vacuum arc breakdowns in a pulsed DC system

11 pages, 13 figuresUnderstanding the microscopic phenomena behind vacuum arc ignition and generation is crucial for being able to control the breakdown rate, thus improving the effectiveness of many high-voltage applications where frequent breakdowns limit the operation. In this work, statistical properties of various aspects of breakdown, such as the number of pulses between breakdowns, breakdown locations and crater sizes are studied independently with almost identical pulsed dc systems at the University of Helsinki and in CERN. In high-gradient experiments, copper electrodes with parallel plate capacitor geometry, undergo thousands of breakdowns. The results support the classification of the events into primary and secondary breakdowns, based on the distance and number of pulses between two breakdowns. Primary events follow a power law on the log-log scale with the slope alpha approximate to 1.30, while the secondaries are highly dependent on the pulsing parameters.Peer reviewe

Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer

Background. Fibronectin type III domain-containing (FNDC) proteins fulfill manifold functions in tissue development and regulation of cellular metabolism. FNDC4 was described as anti-inflammatory factor, upregulated in inflammatory bowel disease (IBD). FNDC signaling includes direct cell-cell interaction as well as release of bioactive peptides, like shown for FNDC4 or FNDC5. The G-protein-coupled receptor 116 (GPR116) was found as a putative FNDC4 receptor. We here aim to comprehensively analyze the mRNA expression of FNDC1, FNDC3A, FNDC3B, FNDC4, FNDC5, and GPR116 in nonaffected and affected mucosal samples of patients with IBD or colorectal cancer (CRC). Methods. Mucosa samples were obtained from 30 patients undergoing diagnostic colonoscopy or from surgical resection of IBD or CRC. Gene expression was determined by quantitative real-time PCR. In addition, FNDC expression data from publicly available Gene Expression Omnibus (GEO) data sets (GDS4296, GDS4515, and GDS5232) were analyzed. Results. Basal mucosal expression revealed higher expression of FNDC3A and FNDC5 in the ileum compared to colonic segments. FNDC1 and FNDC4 were significantly upregulated in IBD. None of the investigated FNDCs was differentially expressed in CRC, just FNDC3A trended to be upregulated. The GEO data set analysis revealed significantly downregulated FNDC4 and upregulated GPR116 in microsatellite unstable (MSI) CRCs. The expression of FNDCs and GPR116 was independent of age and sex. Conclusions. FNDC1 and FNDC4 may play a relevant role in the pathobiology of IBD, but none of the investigated FNDCs is regulated in CRC. GPR116 may be upregulated in advanced or MSI CRC. Further studies should validate the altered FNDC expression results on protein levels and examine the corresponding functional consequences

Effect of dc voltage pulsing on high-vacuum electrical breakdowns near Cu surfaces

14 pages, 11 figures. Published in Physical Review Accelerators and BeamsVacuum electrical breakdowns, also known as vacuum arcs, are a limiting factor in many devices that are based on application of high electric fields near their component surfaces. Understanding of processes that lead to breakdown events may help mitigating their appearance and suggest ways for improving operational efficiency of power-consuming devices. Stability of surface performance at a given value of the electric field is affected by the conditioning state, i.e. how long the surface was exposed to this field. Hence, optimization of the surface conditioning procedure can significantly speed up the preparatory steps for high-voltage applications. In this article, we use pulsed dc systems to optimize the surface conditioning procedure of copper electrodes, focusing on the effects of voltage recovery after breakdowns, variable repetition rates as well as long waiting times between pulsing runs. Despite the differences in the experimental scales, ranging from 10^-4 s between pulses, up to pulsing breaks of 10^5 s, the experiments show that the longer the idle time between the pulses, the more probable it is that the next pulse produces a breakdown. We also notice that secondary breakdowns, i.e. those which correlate with the previous ones, take place mainly during the voltage recovery stage. We link these events with deposition of residual atoms from vacuum on the electrode surfaces. Minimizing the number of pauses during the voltage recovery stage reduces power losses due to secondary breakdown events improving efficiency of the surface conditioning.Peer reviewe

Galleria melonella as an experimental in vivo host model for the fish-pathogenic oomycete Saprolegnia parasitica

Our work is supported by the University of Aberdeen (AW, PvW); BBSRC (BB/M026566/1 & BB/P020224/1: PvW); BBSRC (BB/N005058/1 & BB/J018333/1: FT & PvW); NERC (NE/P010873/1: PvW). We would like to acknowledge Joan Wilson and Bill Mathieson at NHS Grampian Biorepository (Aberdeen, Scotland) for help with histological experiments and Kevin McKenzie and his team at the Microscopy Core facility at the University of Aberdeen for assistance with microscopy and histology.Peer reviewedPublisher PD

Specific feedback makes medical students better communicators

Background: Feedback is regarded a key element in teaching communication skills. However, specific aspects of feedback have not been systematically investigated in this context. Therefore, the aim of this study was to investigate the effectiveness of communication skills training (CST) integrating specific, structured and behavioral feedback. Methods: We condensed best practice recommendations for feedback in a CST for undergraduate medical students and compared the effect of specific, structured and behavior-orientated feedback (intervention group CST-behav) to general, experience-orientated feedback (CST- exp. as our control group) in a randomized controlled trial (RCT). We investigated changes on communication skills evaluated by independent raters, and evaluated by standardized patients (SP). To do that, every student was video-recorded in a pre and post assessment. Results: Sixty-six undergraduate medical students participated voluntarily in our study. Randomization did not result in equally skilled groups at baseline, so valid inter-group comparisons were not possible. Therefore, we analyzed the results of 34 students of our intervention group (CST-behav). Five out of seven domains in communication skills as evaluated by independent raters improved significantly, and there was a significant change in the global evaluation by SP. Conclusions: Although we were unable to make between-group comparisons, the results of the within group pre-post evaluation suggest that specific feedback helps improve communication skills

Cell entry of a host-targeting protein of oomycetes requires gp96

The animal-pathogenic oomycete Saprolegnia parasitica causes serious losses in aquaculture by infecting and killing freshwater fish. Like plant-pathogenic oomycetes, S. parasitica employs similar infection structures and secretes effector proteins that translocate into host cells to manipulate the host. Here, we show that the host-targeting protein SpHtp3 enters fish cells in a pathogen-independent manner. This uptake process is guided by a gp96-like receptor and can be inhibited by supramolecular tweezers. The C-terminus of SpHtp3 (containing the amino acid sequence YKARK), and not the N-terminal RxLR motif, is responsible for the uptake into host cells. Following translocation, SpHtp3 is released from vesicles into the cytoplasm by another host-targeting protein where it degrades nucleic acids. The effector translocation mechanism described here, is potentially also relevant for other pathogen-host interactions as gp96 is found in both animals and plants.This work is supported by the [European Community’s] Seventh Framework Programme [FP7/2007–2013] under grant agreement no. [238550] (L.L., J.D.-U., C.J.S., P.v.W.); BBSRC [BBE007120/1, BB/J018333/1 and BB/G012075/1] (F.T., I.d.B., C.J.S., S.W., P.v.W.); Newton Global Partnership Award [BB/N005058/1] (F.T., P.v.W.), the University of Aberdeen (A.D.T., T.R., C.J.S., P.v.W.) and Deutsche Forschungsgemeinschaft [CRC1093] (P.B., T.S.). We would like to acknowledge the Ministry of Higher Education Malaysia for funding INA. We would like to thank Brian Haas for his bioinformatics support. We would like to acknowledge Neil Gow and Johannes van den Boom for critical reading of the manuscript. We would like to acknowledge Svetlana Rezinciuc for technical help with pH-studies

Thermal Fluid-Structure-Interaction - Experimental and Numerical Analysis

In the present paper the thermal fluid-structure-interaction is experimentally and numerically investigated. Therefore, the interaction phenomena is modeled by the Reynolds-averaged Navier-Stokes equations and the nonlinear Fourier heat conduction equation are used for the fluid and the solid phase, respectively. The simulation is performed using a partitioned approach using the finite volume method for the fluid domain, the finite element method for the solid domain and Runge-Kutta integration schemes for the time domain. Furthermore, as a basis for the understanding of thermal fluid-structure-interaction and also for the veri cation and validation of the applied continuum mechanical models and numerical methods, respectively, a fundamental wind tunnel experiment is presented

Experimental and Numerical Aspects of a Thermal Fluid-Structure Phenomenon

A fundamental research experiment for thermal fluid-structure-interaction for the verification of a partitioned approach with non-linear material properties is examined. In the following, a specimen is heated as well as cooled within a wind tunnel. The thermal fluid-structure-interaction is first experimentally investigated and subsequently numerically validated. For the numerical simulation, two existing programs (a fluid and a structure code) are coupled using a partitioned approach

A pi-Halogen Bond of Dibenzofuranones with the Gatekeeper Phe113 in Human Protein Kinase CK2 Leads to Potent Tight Binding Inhibitors

Human protein kinase CK2 is an emerging target for neoplastic diseases. Potent lead structures for human CK2 inhibitors are derived from dibenzofuranones. Two new derivatives, 7,9-dichloro-1,2-dihydro-8-hydroxy-4-[(4-methoxyphenylamino)-methylene]dibenzo[b,d]furan-3(2H)-one (4a) and (E)-1,3-dichloro-6-[(4-methoxyphenylimino)-methyl]dibenzo[b,d]furan-2,7-diol (5) were tested for inhibition of CK2 and induction of apoptosis in LNCaP cells. Both turned out to be tight binding inhibitors, with IC50 values of 7 nM (4a) and 5 nM (5) and an apparent K-i value of 0.4 nM for both. Compounds 4a and 5 reduced cellular CK2 activity, indicating cell permeability. Cell viability was substantially impaired in LNCaP cells, as well as apoptosis was induced, which was not appearing in non-neoplastic ARPE-19 cells. Co-crystallization of 4a and 5 revealed an unexpected pi-halogen bond of the chloro substituent at C9 with the gatekeeper amino acid Phe113, leading to an inverted binding mode in comparison to parent compound 4b, with the Cl at C6 instead, which was co-crystallized as a control. This indicates that the position of the chloro substituent on ring A of the dibenzofuran scaffold is responsible for an inversion of the binding mode that enhances potency