A positioning sensor for tonometric applications

In this paper we present a sensor, which is designed for application in a tonometer, an instrument for the measurement of intraocular pressure. The sensor measures diameter and position of a part of the eye globe that is flattened by the tonometer. The sensor principle is based on a change in resistance of four resistor arrays due to contact with a metallized foil, which flattens a part of the eye globe. In spite of some problems with the contact resistance between the resistor contact arrays and the metallized foil, it may be concluded that the positioning sensor can be used to improve existing tonometers

The tonometric sensor, a new device for the measurement of intraocular pressure

In this paper we present a new sensor for the measurement of intraocular pressure. We have applied the indentation principle, in which the eye is indented by exerting a force on it, while the size of the indented area is monitored. To measure the force we have used a commercial force sensor. The sensor to measure the indentation of the eye has been developed in our laboratories. We have performed measurements using an experimental set-up; these show that an accuracy of 90% will be possible if the sensor is designed in the proper way

Catalytic in vivo protein knockdown by small-molecule PROTACs

The current predominant therapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy, often leading to adverse side effects. Here, we describe major improvements to the proteolysis targeting chimeras (PROTACs) method, a chemical knockdown strategy in which a heterobifunctional molecule recruits a specific protein target to an E3 ubiquitin ligase, resulting in the target's ubiquitination and degradation. These compounds behave catalytically in their ability to induce the ubiquitination of super-stoichiometric quantities of proteins, providing efficacy that is not limited by equilibrium occupancy. We present two PROTACs that are capable of specifically reducing protein levels by >90% at nanomolar concentrations. In addition, mouse studies indicate that they provide broad tissue distribution and knockdown of the targeted protein in tumor xenografts. Together, these data demonstrate a protein knockdown system combining many of the favorable properties of small-molecule agents with the potent protein knockdown of RNAi and CRISPR

Melken in Amerika

Resultaten van een Wagenings afstudeerproject, waarbij een vergelijking werd opgesteld om te bepalen welke bedrijfsontwikkelingsstrategie voor een Nederlandse melkveehouder het meest interessant is: blijven boeren in Nederland of emigreren naar de V.S. en zo ja, naar welk gebied

Macrofauna in de verontreinigde waterbodem van de Rijn/Maas-delta

Door middel van monsternemingen en statistische analyses is onderzoek gedaan naar de correlaties tussen fysische variabelen en verontreinigingen (zware metalen, organochloorpesticiden, PCB's, PAK's) in het sediment, de sedimenttoxiciteit bepaald door bioassays, en de variantie in soortensamenstelling van de bodembewonende macrofauna in Brabantsche Biesbosch, Dordtsche Biesbosch, Hollands Diep, Nieuwe Merwede en Haringvlie

Programming Heterogeneous Parallel Machines Using Refactoring and Monte-Carlo Tree Search

Funding: This work was supported by the EU Horizon 2020 project, TeamPlay, Grant Number 779882, and UK EPSRC Discovery, Grant Number EP/P020631/1.This paper presents a new technique for introducing and tuning parallelism for heterogeneous shared-memory systems (comprising a mixture of CPUs and GPUs), using a combination of algorithmic skeletons (such as farms and pipelines), Monte–Carlo tree search for deriving mappings of tasks to available hardware resources, and refactoring tool support for applying the patterns and mappings in an easy and effective way. Using our approach, we demonstrate easily obtainable, significant and scalable speedups on a number of case studies showing speedups of up to 41 over the sequential code on a 24-core machine with one GPU. We also demonstrate that the speedups obtained by mappings derived by the MCTS algorithm are within 5–15% of the best-obtained manual parallelisation.Publisher PDFPeer reviewe

Different carbon sources result in differential activation of sigma B and stress resistance in Listeria monocytogenes

Listeria monocytogenes is an important food-borne pathogen that is ubiquitous in the environment. It is able to utilize a variety of carbon sources, to produce biofilms on food-processing surfaces and to survive food preservation–associated stresses. In this study, we investigated the effect of three common carbon sources, namely glucose, glycerol and lactose, on growth and activation of the general stress response Sigma factor, SigB, and corresponding phenotypes including stress resistance. A fluorescent reporter coupled to the promoter of lmo2230, a highly SigB-dependent gene, was used to determine SigB activation via quantitative fluorescence spectroscopy. This approach, combined with Western blotting and fluorescence microscopy, showed the highest SigB activation in lactose grown cells and lowest in glucose grown cells. In line with this observation, lactose grown cells showed the highest resistance to lethal heat and acid stress, the highest biofilm formation, and had the highest adhesion/invasion capacity in Caco-2-derived C2Bbe1 cell lines. Our data suggest that lactose utilisation triggers a strong SigB dependent stress response and this may have implications for the resistance of L. monocytogenes along the food chain

A single point mutation in the Listeria monocytogenes ribosomal gene rpsU enables SigB activation independently of the stressosome and the anti-sigma factor antagonist RsbV

Microbial population heterogeneity leads to different stress responses and growth behavior of individual cells in a population. Previously, a point mutation in the rpsU gene (rpsUG50C) encoding ribosomal protein S21 was identified in a Listeria monocytogenes LO28 variant, which leads to increased multi-stress resistance and a reduced maximum specific growth rate. However, the underlying mechanisms of these phenotypic changes remain unknown. In L. monocytogenes, the alternative sigma factor SigB regulates the general stress response, with its activation controlled by a series of Rsb proteins, including RsbR1 and anti-sigma factor RsbW and its antagonist RsbV. We combined a phenotype and proteomics approach to investigate the acid and heat stress resistance, growth rate, and SigB activation of L. monocytogenes EGDe wild type and the ΔsigB, ΔrsbV, and ΔrsbR1 mutant strains. While the introduction of rpsUG50C in the ΔsigB mutant did not induce a SigB-mediated increase in robustness, the presence of rpsUG50C in the ΔrsbV and the ΔrsbR1 mutants led to SigB activation and concomitant increased robustness, indicating an alternative signaling pathway for the SigB activation in rpsUG50C mutants. Interestingly, all these rpsUG50C mutants exhibited reduced maximum specific growth rates, independent of SigB activation, possibly attributed to compromised ribosomal functioning. In summary, the increased stress resistance in the L. monocytogenes EGDe rpsUG50C mutant results from SigB activation through an unknown mechanism distinct from the classical stressosome and RsbV/RsbW partner switching model. Moreover, the reduced maximum specific growth rate of the EGDe rpsUG50C mutant is likely unrelated to SigB activation and potentially linked to impaired ribosomal function