Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

The effectiveness of adaptive versus non-adaptive learning with digital educational games

For the training of academic skills, digital educational games with integrated adaptivity are promising. Adaptive games are considered superior to non-adaptive games, because they constantly assess children's performance, and accordingly adapt the difficulty of the tasks corresponding to the children's individual level. However, empirical evidence with regard to the effectivity of adaptive compared to non-adaptive games is limited. A study was conducted with 191 children from the third year of Kinder garten who were enrolled in one of three conditions, that is, playing an adaptive version of the reading game (RG), a non-adaptive version of the RG or training with pen-and-paper exercises. In all three conditions, children trained emergent reading (phonological awareness and letter knowledge) once a week for 30 min over a period of 5 weeks. Children's performance on cognitive (phonological awareness, letter knowledge, reading fluency) and non-cognitive (motivation, self-concept) factors was assessed. Results revealed a significant improvement in phonological awareness and letter knowledge in all conditions. However, no differences between the conditions were observed with respect to children's improvement on phonological awareness and letter knowledge or on their post-test scores for reading fluency. With regard to motivation and self-concept, again, no differences in these non-cognitive factors were observed across conditions.     

Hybrid make-to-stock and make-to-order systems: a taxonomic review

Production planning and control (PPC) systems that employ aspects from both make-to-order (MTO) and make-to-stock (MTS) production control are known as hybrid MTS/MTO systems. While both MTO and MTS separately have been studied extensively, their combined use has received less attention. However, the literature on this topic is growing and this paper shows that the review performed in this paper is an important addition to the field. We categorise relevant literature according to a novel taxonomy and show that hybrid MTS/MTO production control can be used in different contexts. In addition, an overview of the modelling techniques and methods used in these papers is provided. Based on the reviewed literature, relevant research questions and directions for future research are identified. Finally, it is shown that hybrid MTS/MTO production control is prevalent in practice by discussing research with industrial applications. The paper contains an overview of research on hybrid MTS/MTO production control to be used as reference for researchers active in the field, and provides managerial insights and directions for future research on this topic.     

Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Dhh1 is a member of the SESA network

The correct separation of chromosomes during mitosis is necessary to prevent genetic instability and aneuploidy, which are responsible for cancer and other diseases, and it depends on proper centrosome duplication. In a recent study, we found that Smy2 can suppress the essential role of Mps2 in the insertion of yeast centrosome into the nuclear membrane by interacting with Eap1, Scp160, and Asc1 and designated this network as SESA (S my2, E ap1, S cp160, A sc1). Detailed analysis showed that the SESA network is part of a mechanism which regulates translation of POM34 mRNA. Thus, SESA is a system that suppresses spindle pole body duplication defects by repressing the translation of POM34 mRNA. In this study, we performed a genome-wide screening in order to identify new members of the SESA network and confirmed Dhh1 as a putative member. Dhh1 is a cytoplasmic DEAD-box helicase known to regulate translation. Therefore, we hypothesized that Dhh1 is responsible for the highly selective inhibition of POM34 mRNA by SESA.     

Color preferences for different topics in connection to personal characteristics

Studies on color preferences are dependent on the topic and the relationships with personal characteristics, particularly personality, but these are seldom studied in one population. Therefore a questionnaire was collected from 1095 Dutch people asking for color preferences about different topics and relating them to personal characteristics. Color preferences regarding different topics show different patterns and significant differences were found between gender, age, education and personality such as being technical, being emotional or being a team player. Also, different colors were mentioned when asked for colors that stimulate to be quiet, energetic, and able to focus or creative. Probably, due to unconsciousness of contexts, many people had no color preference, a result that in the literature seldom is mentioned. Blue was the overall favorite color; however, most males chose for blue (25%) while most females had no color preference (18%). Black was the overall favorite color for clothing, mainly chosen by females (40%), while males primarily chose blue (27%). For building interiors subjects preferred white. For moods, subjects preferred white for being quiet or being able to focus, red for being energetic and had no color preference for being creative. It is concluded that color preferences are dependent upon the topic, and personal characteristics. The findings are important for architects, interior designers, fashion designers and product designers to have a basic idea of preferred colors for different objects by different types of people. © 2013 Wiley Periodicals, Inc. Col Res Appl, 40, 62–71, 2015     

On the origin of strain hardening in glassy polymers

The influence of network density on the strain hardening behaviour of amorphous polymers is studied. The network density of polystyrene is altered by blending with poly(2,6-dimethyl-1,4-phenylene-oxide) and by cross-linking during polymerisation. The network density is derived from the rubber-plateau modulus determined by dynamic mechanical thermal analysis. Subsequently uniaxial compression tests are performed to obtain the intrinsic deformation behaviour and, in particular, the strain hardening modulus. At room temperature, the strain hardening modulus proves to be proportional to the network density, irrespective of the nature of the network, i.e. physical entanglements or chemical cross-links. With increasing temperature, the strain hardening modulus is observed to decrease. This decrease appears to be related to the influence of thermal mobility of the chains, determined by the distance to the glass-transition temperature (T−T_g).     

Calibrated Free-Space Microwave Measurements With an Ultrawideband Reflectometer-Antenna System

We present a 3-12 GHz compact mixer-based reflectometer (CMR) and horn antenna system, and demonstrate its use in detecting backscatter signals with a free space calibration procedure. We evaluate the frequency-domain performance of the CMR-antenna system for measuring the complex reflection coefficient of a dielectric slab and compare it with that of a commercial vector network analyzer (VNA)-antenna setup. Time-domain responses are also investigated, and show the effectiveness of this calibration method. This low-cost, compact system eliminates the need for traditional mechanical standards and a VNA, is effective in reducing reflection artifacts, and allows for flexibility in the placement of reference planes; thus it is well suited for array-based imaging applications     

Prediction of brittle-to-ductile transitions in polystyrene

In this study it is attempted to predict brittle-to-ductile transitions (BDTs) in polystyrene blends, induced either by an increase in temperature or by a decrease in inter-particle distance. A representative, two-dimensional volume element (RVE) of a polystyrene matrix with 20% circular voids, is deformed in tension. During deformation a hydrostatic-stress based craze-nucleation criterion [1] is evaluated. The simulations demonstrate that crazes initiate at low temperatures while a transition from crazing to shear yielding (BDT) is found around 75 °C. The numerical results correlate well with tensile tests on similar heterogeneous polystyrene. The presence of an absolute length, as experimentally found, is more difficult to explain. Near a free surface a T_g-depression is measured for polystyrene and also the resistance to indentation in polystyrene is lower than expected from bulk properties. Both observations are rationalised by an enhanced segmental mobility of chains near a free surface. As a consequence of these findings, an absolute length-scale could be incorporated in the numerical simulations. For simplicity, the length-scale is modelled by taking a temperature gradient over a thin layer near the internal free surfaces of the RVE. Deformation of the RVE with different absolute length-scales shows that indeed also the experimentally found brittle-to-ductile transition can be predicted if the ligament thickness between the inclusions (‘voids’) in polystyrene is below a critical value of ca. 15 nm.