3-hydroxybenzene 1,2,4-trisphosphate, a novel second messenger mimic and unusual substrate for type-I myo-inositol 1,4,5-trisphosphate 5-phosphatase: Synthesis and physicochemistry

3-Hydroxybenzene 1,2,4-trisphosphate 4 is a new myo-inositol 1,4,5-trisphosphate analogue based on the core structure of benzene 1,2,4-trisphosphate 2 with an additional hydroxyl group at position-3, and is the first noninositol based compound to be a substrate for inositol 1,4,5-trisphosphate 5-phosphatase. In physicochemical studies on 2, when three equivalents of protons were added, the (31)P NMR spectrum displayed monophasic behaviour in which phosphate-1 and phosphate-2 behaved independently in most of the studied pH range. For compound 4, phosphate-2 and phosphate-4 interacted with the 3-OH group, which does not titrate at physiological pH, displaying complex biphasic behaviour which demonstrated co-operativity between these groups. Phosphate-1 and phosphate-2 strongly interacted with each other and phosphate-4 experienced repulsion because of the interaction of the 3-OH group. Benzene 1,2,4-trisphosphate 2 is resistant to inositol 1,4,5-trisphosphate type I 5-phosphatase catalysed dephosphorylation. However, surprisingly, 3-hydroxybenzene 1,2,4-trisphosphate 4 was dephosphorylated by this 5-phosphatase to give the symmetrical 2,3-dihydroxybenzene 1,4-bisphosphate 16. The extra hydroxyl group is shown to form a hydrogen bond with the vicinal phosphate groups at -15 degrees C, and (1)H NMR titration of the ring and hydroxyl protons in 4 shows the OH proton to be strongly stabilized as soon as the phosphate groups are deprotonated. The effect of the phenolic 3-OH group in compound 4 confirms a critical role for the 6-OH group of the natural messenger in the dephosphorylation mechanism that persists even in radically modified analogues.     

Preparation of hot-pressed silicon-germanium ingots: Part I — Chill casting of silicon-germanium alloys

Large chill cast ingots of silicon-germanium produced from melts that were not stirred contained two major alloys, one rich in silicon and one rich in germanium, in addition to a composition continuum. While stirring produced little change in distribution of Si/Ge ratios, inductive stirring did result in ingots that varied in composition but in a more uniform manner. In all cases, dopants were uniformly distributed throughout the cast ingots.     

Evaluating "fast" micellar monolithic liquid chromatography for high-throughput quantitative structure-retention relationship screening

The recently introduced monolithic silica columns were tested for their use in micellar liquid chromatography. Micellar methods are utilized in high-throughput quantitative structure-retention relationships to estimate an indicator of the membrane permeability of drugs, namely, the octanol-water partition coefficient, log P. The monolithic column's ability to function at higher flow rates might be useful to speed up these chromatographic methods estimating the log P. Therefore, the elution behavior of diverse basic pharmaceutical substances was determined on a classical particle-based and a monolithic column, both with and without a micellar medium in the mobile phase. Utilizing among others principal component analysis, the extent to which these methods differ in retention characteristics was examined in the context of high-throughput determination of log P. Results indicate that combining monolithic columns with micellar media leads to faster log P and possibly even better permeability predictions.     

A linear programming formulation for an inventory management decision problem with a service constraint

Inventory systems with uncertainty go hand in hand with the determination of a safety stock level. The decision on the safety stock level is based on a performance measure, for example the expected shortage per replenishment period or the probability of a stock-out per replenishment period. The performance measure assumes complete knowledge of the probability distribution during lead time, which might not be available. In case of incomplete information regarding the lead-time distribution of demand, no single figure for the safety stock can de determined in order to satisfy a performance measure. However, an optimisation model may be formulated in order to determine a safety stock level which guarantees the performance measure under the worst case of lead-time demand, of which the distribution is known in an incomplete way. It is shown that this optimisation problem can be formulated as a linear programming problem.     

The use of time series forecasting in zone order picking systems to predict order pickers’ workload

In order to differentiate from competitors in terms of customer service, warehouses accept late orders while providing delivery in a quick and timely way. This trend leads to a reduced time to pick an order. This paper introduces workload forecasting in a warehouse context, in particular a zone picking warehouse. Improved workforce planning can contribute to an effective and efficient order picking process. Most order picking publications treat demand as known in advance. As warehouses accept late orders, the assumption of a constant given demand is questioned in this paper. The objective of this study is to present time series forecasting models that perform well in a zone picking warehouse. A real-life case study demonstrates the value of applying time series forecasting models to forecast the daily number of order lines. The forecast of order lines, along with order pickers’ productivity, can be used by warehouse supervisors to determine the daily required number of order pickers, as well as the allocation of order pickers across warehouse zones. Time series are applied on an aggregated level, as well as on a disaggregated zone level. Both bottom-up and top-down approaches are evaluated in order to find the best-performing forecasting method.     

Spontaneous organic cocoa bean box fermentations in Brazil are characterized by a restricted species diversity of lactic acid bacteria and acetic acid bacteria

Spontaneous organic cocoa bean box fermentations were carried out on two different farms in Brazil. Physical parameters, microbial growth, bacterial species diversity [mainly lactic acid bacteria (LAB) and acetic acid bacteria (AAB)], and metabolite kinetics were monitored, and chocolates were produced from the fermented dry cocoa beans. The main end-products of the catabolism of the pulp substrates (glucose, fructose, and citric acid) by yeasts, LAB, and AAB were ethanol, lactic acid, mannitol, and/or acetic acid. Lactobacillus fermentum and Acetobacter pasteurianus were the predominating bacterial species of the fermentations as revealed through (GTG)₅-PCR fingerprinting of isolates and PCR-DGGE of 16S rRNA gene PCR amplicons of DNA directly extracted from fermentation samples. Fructobacillus pseudoficulneus, Lactobacillus plantarum, and Acetobacter senegalensis were among the prevailing species during the initial phase of the fermentations. Also, three novel LAB species were found. This study emphasized the possible participation of Enterobacteriaceae in the cocoa bean fermentation process. Tatumella ptyseos and Tatumella citrea were the prevailing enterobacterial species in the beginning of the fermentations as revealed by 16S rRNA gene-PCR-DGGE. Finally, it turned out that control over a restricted bacterial species diversity during fermentation through an ideal post-harvest handling of the cocoa beans will allow the production of high-quality cocoa and chocolates produced thereof, independent of the fermentation method or farm.     

The effect of family climate on risky driving of young novices: The moderating role of attitude and locus of control

The aim of the study was to examine the relative importance of young novice drivers’ family climate on their driving behavior. A sample of young novice drivers (N = 171) between the age of 17 and 24, who held their permanent (or temporary) driver's license for no longer than one year, participated. The questionnaire included items related to the participants’ family climate, 3 socio-cognitive determinants (i.e., attitude, locus of control and social norm), and risky driving behaviors. We expected both family climate and the socio-cognitive determinants to exert a direct effect on risky driving. Furthermore we hypothesized that the socio-cognitive determinants would moderate the impact of family climate on risky driving. The results showed that the effect of family climate on risky driving only originated from one single factor (i.e., noncommitment). Besides that, the results confirmed the importance of the three socio-cognitive determinants to the degree that attitude, locus of control, and social norm significantly predicted the self-reported risky driving. In line of what we hypothesized, attitude moderated the relationship between noncommitment and risky driving. Lastly, we found an unexpected three-way interaction which indicated that locus of control moderated the relation between noncommitment and risky driving only when young drivers’ attitude was risk-supportive. We recommend scholars and practitioners to take into account the interaction between external sources of influence (such as an individual's family climate) and more personally oriented dispositions (such as an individual's attitude, social norm and locus of control) when trying to explain and change young novices’ risky driving.     

WEBEXPIR: Windowless target electron beam experimental irradiation

The windowless target electron beam experimental irradiation (WEBEXPIR) program was set-up as part of the MYRRHA/XT-ADS R&D effort on the spallation target design to investigate the interaction of a proton beam with a liquid lead-bismuth eutectic (LBE) free surface. In particular, possible free surface distortion or shockwave effects in nominal conditions and during sudden beam on/off transient situations, as well as possible enhanced evaporation were assessed. An experiment was conceived at the IBA TT-1000 Rhodotron, where a 7 MeV electron beam was used to simulate the high power deposition at the MYRRHA/XT-ADS LBE free surface. The geometry and the LBE flow characteristics in the WEBEXPIR set-up were made as representative as possible of the actual situation in the MYRRHA/XT-ADS spallation target. Irradiation experiments were carried out at beam currents of up to 10 mA, corresponding to 40 times the nominal beam current necessary to reproduce the MYRRHA/XT-ADS conditions. Preliminary analyses show that the WEBEXPIR free surface flow was not disturbed by the interaction with the electron beam and that vacuum conditions stayed well within the design specifications.     

Preparation of hot-pressed silicon-germanium ingots: Part II - Reduction of chill cast material

Nine different reduction techniques were evaluated for reducing Si-Ge chill cast alloys. Planetary ball milling with agate vessels and balls proved best for producing large quantities of high purity Si-Ge alloy powders. With the planetary ball mill Si-rich alloys were more difficult to reduce than Ge-rich alloys and the addition of dopant (boron or phosphorus) decreased the grinding time necessary for comparable particle size distributions.