Morpholine As a Scaffold in Medicinal Chemistry: An Update on Synthetic Strategies

Morpholine is a frequently used heterocycle in medicinal chemistry and a privileged structural component of bioactive molecules. This is mainly due to its contribution to a plethora of biological activities as well as to an improved pharmacokinetic profile of such bioactive molecules. The synthesis of morpholines is a subject of much study due to their biological and pharmacological importance, with the last such review being published in 2013. Here, an overview of the main approaches toward morpholine synthesis or functionalization is presented, emphasizing on novel work which has not been reviewed so far. This review is an update on synthetic strategies leading to easily accessible libraries of bioactives which are of interest for drug discovery projects.     

A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

Effect of Drying Methods on Dyeing Capacity of Dyestuff Plant Materials

This article presents a study of the effect of drying methods on dyeing capacity of widespread European flora dyestuff plant materials. The natural colorants, derived from the selected plant materials, were applied on chemical pulp in order to examine their dyeability. In this work, three different drying methods were examined—the natural, the air-, and the freeze-drying method—in various conditions. The plant materials that were dried naturally show weak dyeing results in comparison with the air- and freeze-dried materials. Freeze drying significantly improved the dyeing capacity of dyestuff plant materials with high initial moisture content. On the other hand, air drying at low temperature and high relative humidity improved the dyeing capacity of plant materials with low initial moisture content.     

Optimal rate allocation for production and injection wells in an oil and gas field for enhanced profitability

An oil and gas field requires careful operational planning and management via production optimization for increased recovery and long-term project profitability. This article addresses the challenge of production optimization in a field undergoing secondary recovery by water flooding. The field operates with limited processing capacity at the surface separators, pipeline pressure constraints, and water injection constraints; an economic indicator (net present value, NPV) is used as the objective function. The formulated optimization framework adequately integrates slow-paced subsurface dynamics using reservoir simulation, and fast-paced surface dynamics using sophisticated multiphase flow simulation in the upstream facilities. Optimization of this holistic long-term model is made possible by developing accurate second-order polynomial proxy models at each time step. The resulting formulation is solved as a nonlinear program using commercially available solvers. A comparative analysis is performed using MATLAB's fmincon solver and the IPOPT solver for their robustness, speed, and convergence stability in solving the proposed problem. By implementing two synthetic case studies, our mathematical programming approach determines the optimal production and injection rates of all wells and further demonstrates considerable improvement to the NPV obtained by simultaneously applying the tools of streamline, reservoir, and surface facility simulation for well rate allocation via systematic NLP optimization.     

Effects of Genetic, Pre- and Post-Harvest Factors on Phenolic Content and Antioxidant Capacity of White Asparagus Spears

The effects of genetic, pre-harvest (season of harvest, spear diameter, spear portion and spear tip color) and post-harvest factors (storage and domestic preparation practices, e.g., peeling and cooking) on total phenolic, flavonoid and ascorbic acid content of white asparagus spears and their correlation with antioxidant capacity (DPPH and FRAP) were studied. Results showed that genetic material was important for the total phenolic content but not season of harvest, spear diameter or storage. Violet spear tips and apical spear portions showed the largest amount of total phenolics. Peeling did not affect total phenolics in fresh asparagus, whereas it reduced their content in stored asparagus, while cooking resulted in an increase in both fresh and stored asparagus. However, the soluble extract of total phenolics and flavonoids were minor and the missing significance of phenolics and flavonoids in antioxidant capacity of white asparagus spears depends on these small amounts.     

Endogenous microflora in turbid virgin olive oils and the physicochemical characteristics of these oils

Cloudy olive oil, the fresh olive juice, is an intermediate form before full precipitation of freshly produced olive oil. Some consumers prefer it because they consider it as more natural and less processed. The cloudy form can persist for several months. The oil is a sort of dispersion/suspension system which can be also described as a micro‐emulsion/suspension. Water micro‐droplets were found to have a size ranging from 1 to 5 µm. Cloudiness is due to the low water content and the presence of natural emulsifiers in the oil. The suspension is formed by solid particles (5–60 µm) deriving from the olive fruit. They are present in small amounts (12–460 mg/kg oil). In the newly produced olive oil, containing 0.17–0.49% water, a number of microorganisms of different types (bacteria, yeasts, moulds) were found to survive, but at very low concentrations (<3 log cfu/mL oil). They originate from the exterior of the fruit (epiphytic microflora) and their presence is considered natural. Their enzyme activities do not seem to affect the quality of the final product.     

Estimation of multiple, time-varying motions using time-frequency representations and moving-objects segmentation.

We extend existing spatiotemporal approaches to handle time-varying motions estimation of multiple objects. It is shown that multiple, time-varying motions estimation is equivalent to the instantaneous frequency estimation of superpositioned FM sinusoids. Therefore, we apply established signal processing tools, such as time-frequency representations to show that for each time instant, the energy is concentrated along planes in the 3-D space: spatial frequencies-instantaneous frequency. Using fuzzy C-planes, we estimate indirectly the instantaneous velocities. Furthermore, adapting existing approaches to our problem, we attain the identification of the moving objects. The experimental results verify the effectiveness of our methodology.     

A Cross Layer Scheduling Framework for Supporting Bursty Data Applications in WCDMA Networks

In future wireless networks multimedia applications are expected to finally dominate the overall traffic volume. Shared channels are more suitable for the transmission of this type of traffic, as they are able to periodically adjust their transmission rate. In this paper, we introduce a cross-layer framework for WCDMA based networks which aims to make the packet scheduling procedure more efficient. In addition to that, we further propose a traffic scheduling scheme which serves the connections not only according to their delay sensitivity, but also according to the predicted state of their wireless channel. The efficiency of the proposed scheme, in terms of average packet delay and channel utilization is verified via simulations.