The Oxidation Stability, Light Absorbing Power, and Component of Humic Acids from Different Origins, and Their Mutal Relations

Toxin-antitoxin modules are necessary for the mode of action of several antibiotics. One of the most studied toxin-antitoxin modules is the quorum sensing - dependent MazEF system in Escherichia coli. The quorum sensing factor in this system is called the extracellular death factor (EDF), a linear pentapeptide with the sequence NNWNN. In spite of the extensive research on the mazEF system and the involvement of the quorum sensing factor EDF, the effect of EDF itself on bacteria has not yet been studied. In this research, we determined the effect of EDF and variants on cell growth in the Gram-negative bacterium E. coli and the Gram-positive Bacillus globigii. By aligning the zwf gene (from where EDF originates) of different bacterial species, we found 27 new theoretical variants of the peptide. By evaluating growth curves and light microscopy we found that three EDF variants reduced bacterial cell size in B. globigii, but not in E. coli. The D-peptides did not affect cell size, indicating that the effect is stereospecific. Peptides wherein tryptophan was substituted by alanine also did not affect cell size, which indicates that the effect seen is mediated by an intracellular target. © 2013 Springer Science+Business Media Dordrecht

Performance of a GridPix detector based on the Timepix3 chip

A GridPix readout for a TPC based on the Timepix3 chip is developed for future applications at a linear collider. The GridPix detector consists of a gaseous drift volume read out by a single Timepix3 chip with an integrated amplification grid. Its performance is studied in a test beam with 2.5 GeV electrons. The GridPix detector detects single ionization electrons with high efficiency. The Timepix3 chip allowed for high sample rates and time walk corrections. Diffusion is found to be the dominating error on the track position measurement both in the pixel plane and in the drift direction, and systematic distortions in the pixel plane are below 10 $\mu$m. Using a truncated sum, an energy loss (dE/dx) resolution of 4.1% is found for an effective track length of 1 m.Comment: To be published in Nuclear Instruments and Methods in Physics Research Section

Stalboekje varkens : natuurlijk gezond met kruiden en andere natuurproducten

Het streven om het gebruik van antibiotica terug te dringen vraagt om een ander management. Goede voeding, huisvesting en hygiëne zijn hierbij belangrijk. In dit boekje worden handvaten gegeven om met natuurlijke middelen de gezondheid van de dieren te bevorderen en zo ziektes te voorkomen. Tevens kunnen middelen worden ingezet om de ernst van de ziekte te reduceren. Doel is tevens om de dierenartsen te informeren over de mogelijkheden van natuurproducten en de wetenschappelijke onderbouwing hiervan inzichtelijk te make

ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach

Abstract Background Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy. Methods To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression. Results The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types. Conclusions This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1

Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups

Oceanic Controls on the Mass Balance of Wilkins Ice Shelf, Antarctica

Several Antarctic Peninsula (AP) ice shelves have lost significant fractions of their volume over the past decades, coincident with rapid regional climate change. Wilkins Ice Shelf (WIS), on the western side of the AP, is the most recent, experiencing a sequence of large calving events in 2008 and 2009. We analyze the mass balance for WIS for the period 1992-2008 and find that the averaged rate of ice-shelf thinning was similar to 0.8 m a(-1), driven by a mean basal melt rate of \u3c w(b)\u3e = 1.3 +/- 0.4 m a(-1). Interannual variability was large, associated with changes in both surface mass accumulation and \u3c w(b)\u3e. Basal melt rate declined significantly around 2000 from 1.8 +/- 0.4 m a(-1) for 1992-2000 to similar to 0.75 +/- 0.55 m a(-1) for 2001-2008; the latter value corresponding to approximately steady-state ice-shelf mass. Observations of ocean temperature T obtained during 2007-2009 by instrumented seals reveal a cold, deep halo of Winter Water (WW; T approximate to - 1.6 degrees C) surrounding WIS. The base of the WW in the halo is similar to 170 m, approximately the mean ice draft for WIS. We hypothesize that the transition in \u3c w(b)\u3e in 2000 was caused by a small perturbation (similar to 10-20 m) in the relative depths of the ice base and the bottom of the WW layer in the halo. We conclude that basal melting of thin ice shelves like WIS is very sensitive to upper-ocean and coastal processes that act on shorter time and space scales than those affecting basal melting of thicker West Antarctic ice shelves such as George VI and Pine Island Glacier

Elevation change of the Greenland Ice Sheet due to surface mass balance and firn processes, 1960–2014

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The Cryosphere 9 (2015): 2009-2025, doi:10.5194/tc-9-2009-2015.Observed changes in the surface elevation of the Greenland Ice Sheet are caused by ice dynamics, basal elevation change, basal melt, surface mass balance (SMB) variability, and by compaction of the overlying firn. The last two contributions are quantified here using a firn model that includes compaction, meltwater percolation, and refreezing. The model is forced with surface mass fluxes and temperature from a regional climate model for the period 1960–2014. The model results agree with observations of surface density, density profiles from 62 firn cores, and altimetric observations from regions where ice-dynamical surface height changes are likely small. In areas with strong surface melt, the firn model overestimates density. We find that the firn layer in the high interior is generally thickening slowly (1–5 cm yr−1). In the percolation and ablation areas, firn and SMB processes account for a surface elevation lowering of up to 20–50 cm yr−1. Most of this firn-induced marginal thinning is caused by an increase in melt since the mid-1990s and partly compensated by an increase in the accumulation of fresh snow around most of the ice sheet. The total firn and ice volume change between 1980 and 2014 is estimated at −3295 ± 1030 km3 due to firn and SMB changes, corresponding to an ice-sheet average thinning of 1.96 ± 0.61 m. Most of this volume decrease occurred after 1995. The computed changes in surface elevation can be used to partition altimetrically observed volume change into surface mass balance and ice-dynamically related mass changes.P. Kuipers Munneke received financial support from the Netherlands Polar Programme (NPP) of the Netherlands Institute for Scientific Research (NWO). ECMWF at Reading (UK) is acknowledged for use of the Cray supercomputing system. The J. E. Box contribution is supported by Det Frie Forskningsråd grant 4002-00234 and Geocenter Denmark