Development of miracle medicines from sialic acids

Sialic acids are electronegatively charged C9-sugars and are considered to play important roles in higher animals and some microorganisms. Denoting their significance, understanding and exploiting the complexity of the sialic acids has been referred to as the “the third language of life”. In essence, “sialic acid derivatives possess a harmonious shape and good balance between two opposing hydrophilic and hydrophobic parts, meaning that they should display various kinds of potentially unique and possibly conflicting physiological activities (glycolipoids)”. Consequently, there are good omens that unprecedented ‘miracle’ medicines could be developed from sialic acid derivatives. In this review, the first problem, the preparation of sialic acids, is covered, the synthesis of sialic acid derivatives and confirmation of their structures obviously being of critical significance. In addition we needed to confirm their precise stereochemistry and a hydrolysis method has been developed for confirmation of the anomeric position. Several of the compounds have already demonstrated interesting bioactivity

Data analytics and optimization for assessing a ride sharing system

Ride-sharing schemes attempt to reduce road traffic by matching prospective passengers to drivers with spare seats in their cars. To be successful, such schemes require a critical mass of drivers and passengers. In current deployed implementations, the possible matches are based on heuristics, rather than real route times or distances. In some cases, the heuristics propose infeasible matches; in others, feasible matches are omitted. Poor ride matching is likely to deter participants from using the system. We develop a constraint-based model for acceptable ride matches which incorporates route plans and time windows. Through data analytics on a history of advertised schedules and agreed shared trips, we infer parameters for this model that account for 90% of agreed trips. By applying the inferred model to the advertised schedules, we demonstrate that there is an imbalance between riders and passengers. We assess the potential benefits of persuading existing drivers to switch to becoming passengers if appropriate matches can be found, by solving the inferred model with and without switching. We demonstrate that flexible participation has the potential to reduce the number of unmatched participants by up to 80%

Size Matters: Microservices Research and Applications

In this chapter we offer an overview of microservices providing the introductory information that a reader should know before continuing reading this book. We introduce the idea of microservices and we discuss some of the current research challenges and real-life software applications where the microservice paradigm play a key role. We have identified a set of areas where both researcher and developer can propose new ideas and technical solutions.Comment: arXiv admin note: text overlap with arXiv:1706.0735

Characteristics of LPG-diesel dual fuelled engine operated with rapeseed methyl ester and gas-to-liquid diesel fuels

AbstractA Liquefied Petroleum Gas (LPG)-diesel dual fuelled combustion experimental study was carried out to understand the impact of the properties of the direct injection diesel fuels, such as rapeseed methyl ester (RME) and gas-to-liquid (GTL), on combustion characteristics, engine performance and emissions. The experimental results showed that up to 60% of liquid fuel replacement by LPG was reached while keeping engine combustion variability within the acceptable range and obtaining clear benefits in the soot-NOx trade-off. However, the amount of LPG was limited by adverse effects in engine thermal efficiency, HC and CO emissions. LPG–RME showed a good alternative to LPG-diesel dual fuelling, as better engine combustion variability, HC, CO and soot behaviour was obtained when compared to the other liquid fuels, mainly due to its fuel oxygen content. On the other hand, NOx emissions were the highest, but these can be balanced by the application of EGR. LPG–GTL dual fuelling resulted in the highest NOx emissions benefit over a wide range of engine operating conditions. The high cetane number and the absence of aromatic of GTL are the main parameters for the more favourable soot-NOx trade-off compared to LPG–ULSD (ultra low sulphur diesel) dual fuelling

The selective elimination of messenger RNA underlies the mitosis–meiosis switch in fission yeast

The cellular programs for meiosis and mitosis must be strictly distinguished but the mechanisms controlling the entry to meiosis remain largely elusive in higher organisms. In contrast, recent analyses in yeast have shed new light on the mechanisms underlying the mitosis–meiosis switch. In this review, the current understanding of these mechanisms in the fission yeast Schizosaccharomyces pombe is discussed. Meiosis-inducing signals in this microbe emanating from environmental conditions including the nutrient status converge on the activity of an RRM-type RNA-binding protein, Mei2. This protein plays pivotal roles in both the induction and progression of meiosis and has now been found to govern the meiotic program in a quite unexpected manner. Fission yeast contains an RNA degradation system that selectively eliminates meiosis-specific mRNAs during the mitotic cell cycle. Mmi1, a novel RNA-binding protein of the YTH-family, is essential for this process. Mei2 tethers Mmi1 and thereby stabilizes the transcripts necessary for the progression of meiosis

Membrane-enclosed multienzyme (MEME) synthesis of 2,7-anhydro-sialic acid derivatives

Naturally occurring 2,7-anhydro-alpha-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac) is a transglycosylation product of bacterial intramolecular trans-sialidases (IT-sialidases). A facile one-pot two-enzyme approach has been established for the synthesis of 2,7-anhydro-sialic acid derivatives including those containing different sialic acid forms such as Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The approach is based on the use of Ruminoccocus gnavus IT-sialidase for the release of 2,7-anhydro-sialic acid from glycoproteins, and the conversion of free sialic acid by a sialic acid aldolase. This synthetic method, which is based on a membrane-enclosed enzymatic synthesis, can be performed on a preparative scale. Using fetuin as a substrate, high-yield and cost-effective production of 2,7-anhydro-Neu5Ac was obtained to high-purity. This method was also applied to the synthesis of 2,7-anhydro-Neu5Gc. The membrane-enclosed multienzyme (MEME) strategy reported here provides an efficient approach to produce a variety of sialic acid derivatives