Modeling Alcohol Dehydrogenase Catalysis in Deep Eutectic Solvent/Water Mixtures

The use of oxidoreductases (EC1) in non-conventional reaction media has been increasingly explored. In particular, deep eutectic solvents (DESs) have emerged as a novel class of solvents. Herein, an in-depth study of bioreduction with an alcohol dehydrogenase (ADH) in the DES glyceline is presented. The activity and stability of ADH in mixtures of glyceline/water with varying water contents were measured. Furthermore, the thermodynamic water activity and viscosity of mixtures of glyceline/water have been determined. For a better understanding of the observations, molecular dynamics simulations were performed to quantify the molecular flexibility, hydration layer, and intraprotein hydrogen bonds of ADH. The behavior of the enzyme in DESs follows the classic dependence of water activity (a_W) in non-conventional media. At low a_W values (<0.2), ADH does not show any activity; at higher a_W values, the activity was still lower than that in pure water due to the high viscosities of the DES. These findings could be further explained by increased enzyme flexibility with increasing water content.     

Structure–Function Relationship of Retinal Ganglion Cells in Multiple Sclerosis

The retinal ganglion cells (RGC) may be considered an easily accessible pathophysiological site of degenerative processes in neurological diseases, such as the RGC damage detectable in multiple sclerosis (MS) patients with (HON) and without a history of optic neuritis (NON). We aimed to assess and interrelate RGC functional and structural damage in different retinal layers and retinal sites. We included 12 NON patients, 11 HON patients and 14 healthy controls for cross-sectional multifocal pattern electroretinography (mfPERG) and optical coherence tomography (OCT) measurements. Amplitude and peak times of the mfPERG were assessed. Macula and disc OCT scans were acquired to determine macular retinal layer and peripapillary retinal nerve fiber layer (pRNFL) thickness. In both HON and NON patients the foveal N2 amplitude of the mfPERG was reduced compared to controls. The parafoveal P1 peak time was significantly reduced in HON only. For OCT, parafoveal (pfGCL) and perifoveal (pGCL) ganglion cell layer thicknesses were decreased in HON vs. controls, while pRNFL in the papillomacular bundle sector (PMB) showed reductions in both NON and HON. As the mfPERG derived N2 originates from RGC axons, these findings suggest foveal axonal dysfunction not only in HON, but also in NON patients.     

Advanced Postirradiation Characterization of Nuclear Fuels Using Pulsed Neutrons

Methods for postirradiation characterization of bulk (cm³) irradiated materials or even spent nuclear fuels are sparse due to their extremely radioactive nature. While several methods exist to characterize smaller volumes (<?1 mm³) of such samples, selecting these volumes from larger samples is challenging. X-ray-based methods are prohibitive due to the strong γ-radiation from the sample flooding the detectors. Neutron-based methods available in the proximity of irradiation reactors allow for thermal neutron radiography or computed tomography using a small reactor source, but one cannot assess isotope distributions or microstructural features such as phases, texture, or strain from diffraction measurements due to flux limitations. We present herein a pathway to provide pulsed neutron characterization of bulk irradiated samples using time-of-flight neutron diffraction for microstructural characterization and energy-resolved neutron imaging for assessment of isotopic densities and distributions. Ultimately, laser-driven pulsed neutron sources may allow deployment of these techniques pool-side at irradiation reactors.

     

Impact of the Electromagnetic Brake Position on the Flow Structure in a Slab Continuous Casting Mold: An Experimental Parameter Study

Metallurgical and Materials Transactions B - Flow measurements are performed in a slab model for continuous casting of steel under the influence of a ruler type Electromagnetic Brake (EMBr). The...     

Relating video game exposure,sensation seeking,aggression and socioeconomic factors to school performance

ABSTRACT

The time displacement hypothesis has been widely used to explain the effects of media use on academic performance. This approach has been criticised for its monocausality and weak explanatory power. Utilising a combination of different theoretical perspectives is better suited than utilising only one. Considering displacement, excitement, attraction and third variable hypothesis, this paper argues that the relation between video game use and school performance is not the same for all types of gamers by considering the influence of socioeconomic, psychological and contextual factors. It investigates how gaming patterns (frequency, time of day) and psychological characteristics (sensation seeking, aggression) are related to academic performance for primary and secondary school students. Five hundred and seven students from five primary and four secondary schools in Singapore participated in a paper-pencil survey. Results showed support for a combination of displacement and third variable hypothesis, as overall time spent on video games was negatively associated with primary school children’s and active gamers’ school performances. There was no significant relationship for secondary school children. For primary school children who play games in the morning and afternoon, video game use was negatively associated with school performance. There was no support for the attraction and excitement hypotheses.     

Mass spectrometry and the cellular surfaceome

The collection of exposed plasma membrane proteins, collectively termed the surfaceome, is involved in multiple vital cellular processes, such as the communication of cells with their surroundings and the regulation of transport across the lipid bilayer. The surfaceome also plays key roles in the immune system by recognizing and presenting antigens, with its possible malfunctioning linked to disease. Surface proteins have long been explored as potential cell markers, disease biomarkers, and therapeutic drug targets. Despite its importance, a detailed study of the surfaceome continues to pose major challenges for mass spectrometry-driven proteomics due to the inherent biophysical characteristics of surface proteins. Their inefficient extraction from hydrophobic membranes to an aqueous medium and their lower abundance compared to intracellular proteins hamper the analysis of surface proteins, which are therefore usually underrepresented in proteomic datasets. To tackle such problems, several innovative analytical methodologies have been developed. This review aims at providing an extensive overview of the different methods for surfaceome analysis, with respective considerations for downstream mass spectrometry-based proteomics.     

The Adhesion‐Enhanced Contact Electrification and Efficiency of Triboelectric Nanogenerators

In the present work, the contact electrification of polymers that differ in adhesion strength is studied. Electrical current is measured along with adhesion in macroscale contacting‐separation experiments. Additionally, local adhesion and roughness are studied with atomic force microscopy to get deeper insight into relations between surface properties and electrification. Measurements reveal that higher surface charge is formed on more adhesive surfaces, thus confirming covalent bond cleavage as a mechanism for contact electrification of polymers. Investigated materials possess enhanced contact electrification making them attractive candidates for the conversion of mechanical energy to electrical in triboelectric nanogenerator devices.     

Modeling project criticality in IT project portfolios

Today's IT project portfolios (ITPP) contain many projects and varied interdependencies. Depending on a project's criticality to the ITPP, a failure can have massive consequences. However, existing methods usually only assess overall project portfolio risk and do not account for the criticality of single projects and their dependencies. Applying Bayesian network modeling to ITPPs, we bridge this gap and extend the current body of knowledge for the information systems and project management literatures. Our new method analyzes single projects' criticality in a portfolio context by considering both transitive dependencies and different dependency types in an integrated way. Since we demonstrate that single projects' criticality can vary substantially, being aware of which projects are critical is a key success factor for ITPP management. For practitioners, our method provides a straightforward procedure to enhance ITPP risk management.     

Adaptive retrieval practice with multiple-choice questions in the university classroom

Retrieval practice promotes retention more than restudying (i.e., the testing effect) and is applied to many educational settings. However, little research has investigated means to enhance this effect in educational settings. Theoretical accounts assume retrieval practice to be the most effective whenever retrieval is difficult but successful. Therefore, we developed a novel retrieval practice procedure, which adapts to learners' abilities and can be applied irrespective of learning content. This adaptive procedure aims to make retrieval gradually easier whenever students provide an incorrect answer. In a field experiment, students read book chapters as part of a weekly university course. In three consecutive weeks, they then practiced reading assignments by (a) adaptive testing, (b) non-adaptive testing and (c) restudy. In Week 4, a surprise criterial test took place. Restudy outperformed both testing conditions, whereas adaptive testing performed equally well as non-adaptive testing. However, exploratory analyses revealed that with increasing retention intervals, the superiority of restudy disappeared. Furthermore, whenever participants fully read the assignments and retention intervals increased, adaptive testing outperformed non-adaptive testing. In sum, adaptive retrieval practice did not prove to be generally superior, but retention interval and students' preparation for class might be conditions rendering adaptive retrieval useful in educational settings.     

Dichloroacetate Radiosensitizes Hypoxic Breast Cancer Cells

Mitochondrial metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways can potentially sensitize tumors with limited treatment options, such as triple-negative breast cancer (TNBC), to chemo- and/or radiotherapy. Dichloroacetate (DCA) is a specific inhibitor of the pyruvate dehydrogenase kinase (PDK), which leads to enhanced reactive oxygen species (ROS) production. ROS are the primary effector molecules of radiation and an increase hereof will enhance the radioresponse. In this study, we evaluated the effects of DCA and radiotherapy on two TNBC cell lines, namely EMT6 and 4T1, under aerobic and hypoxic conditions. As expected, DCA treatment decreased phosphorylated pyruvate dehydrogenase (PDH) and lowered both extracellular acidification rate (ECAR) and lactate production. Remarkably, DCA treatment led to a significant increase in ROS production (up to 15-fold) in hypoxic cancer cells but not in aerobic cells. Consistently, DCA radiosensitized hypoxic tumor cells and 3D spheroids while leaving the intrinsic radiosensitivity of the tumor cells unchanged. Our results suggest that although described as an oxidative phosphorylation (OXPHOS)-promoting drug, DCA can also increase hypoxic radioresponses. This study therefore paves the way for the targeting of mitochondrial metabolism of hypoxic cancer cells, in particular to combat radioresistance.