α-Glucosidase, α-amylase inhibition kinetics,in vitro gastro-intestinal digestion,and apoptosis inducing abilities of Ficus microcarpa L. f. and Ficus racemosa L. fruit polysaccharides

Food Science and Biotechnology - A rich source of nutrients, figs have a number of clinically validated benefits. This study aimed to evaluate the in vitro simulated gastrointestinal digestion, and...     

Description of the thermodynamic properties and fluid-phase behavior of aqueous solutions of linear,branched, and cyclic amines

The SAFT-γ Mie group-contribution equation of state is used to represent the fluid-phase behavior of aqueous solutions of a variety of linear, branched, and cyclic amines. New group interactions are developed in order to model the mixtures of interest, including the like and unlike interactions between alkyl primary, secondary, and tertiary amine groups (NH₂, NH, N), cyclic secondary and tertiary amine groups (cNH, cN), and cyclic methine-amine groups (cCHNH, cCHN) with water (H₂O). The group-interaction parameters are estimated from appropriate experimental thermodynamic data for pure amines and selected mixtures. By taking advantage of the group-contribution nature of the method, one can describe the fluid-phase behavior of mixtures of molecules comprising those groups over broad ranges of temperature, pressure, and composition. A number of aqueous solutions of amines are studied including linear, branched aliphatic, and cyclic amines. Liquid–liquid equilibria (LLE) bounded by lower critical solution temperatures (LCSTs) have been reported experimentally and are reproduced here with the SAFT-γ Mie approach. The main feature of the approach is the ability not only to represent accurately the experimental data employed in the parameter estimation, but also to predict the vapor–liquid, liquid–liquid, and vapor–liquid–liquid equilibria, and LCSTs with the same set of parameters. Pure compound and binary phase diagrams of diverse types of amines and their aqueous solutions are assessed in order to demonstrate the main features of the thermodynamic and fluid-phase behavior.     

Activity-Directed Synthesis: A Flexible Approach for Lead Generation

Activity-directed synthesis (ADS) is a structure-blind, functional-driven molecular discovery approach. In this Concept, four case studies highlight the general applicability of ADS and showcase its flexibility to support different medicinal chemistry strategies. ADS deliberately harnesses reactions with multiple possible outcomes, and allows many chemotypes to be evaluated in parallel. Resources are focused on bioactive molecules, which emerge in tandem with associated synthetic routes. Some of the future challenges for ADS are highlighted, including the realisation of an autonomous molecular discovery platform. The prospects for ADS to become a mainstream lead generation approach are discussed.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Indoor heterogeneous photochemistry of furfural drives emissions of nitrous acid

People spend approximately 80% of their time indoor, making the understanding of the indoor chemistry an important task for safety. The high surface-area-to-volume ratio characteristic of indoor environments leads the semi-volatile organic compounds (sVOCs) to deposit on the surfaces. Using a long path absorption photometer (LOPAP), this work investigates the formation of nitrous acid (HONO) through the photochemistry of adsorbed nitrate anions and its enhancement by the presence of furfural. Using a high-resolution proton-transfer-reaction time-of-flight mass spectrometer (PTR-TOF-MS), this work also investigates the surface emissions of VOCs from irradiated films of furfural and a mix of furfural and nitrate anions. Among the emitted VOCs, 2(5H)-furanone/2-Butenedial was observed at high concentrations, leading to maleic anhydride formation after UV irradiation. Moreover, the addition of potassium nitrate to the film formed NO_x and HONO concentrations up to 10 ppb, which scales to ca. 4 ppb for realistic indoor conditions. This work helps to understand the high levels of HONO and NO_x measured indoors.     

Role of Metabolism in Bone Development and Homeostasis

Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies.     

A closed-form solution for the distribution of the sum of Nakagami-m random phase vectors

The distribution of the modulus of the sum of random phase vectors, is of great practical importance in several applications which deal with sums of sinusoidal signals (wireless multipath transmissions, radars, optical communications, etc). In this letter, simple closed-form expressions are presented for the probability density function (PDF), the cumulative distribution function (CDF), the moment generating function (MGF) and the moments of the envelope distribution of the sum of L non-identical random Nakagami-m phase vectors with integer fading parameters. Moreover, the average over this distribution of the Gaussian Q-function and of the squared Q-function, are also presented in closed-form     

Managing Fashion Goods Inventories: Dynamic Recourse for Retailers with Outlet Stores

The proliferation of both online and bricks and mortar outlet stores underscores the observation that secondary markets are readily accessible to retailers of short-life-cycle products. These secondary markets provide recourse channels for retailers to sell excess inventory of out-of-favor items at reduced prices when overstocking occurs in a primary market. We study the problem of determining when a retailer should terminate its primary selling season by selling remaining inventory on a secondary market. The retailer has a single opportunity to procure prior to a primary selling season consisting of multiple periods. Demand in each period is random, but correlated. At the end of each period, any remaining inventory incurs a holding cost. Then, based upon the current level of inventory and the cumulative demand-to-date, the retailer decides either to terminate the primary selling season by selling all or part of the remaining inventory on a secondary market, or to extend the current primary selling season by another period. We develop structural properties of the optimal policy for determining when to terminate the primary selling season, and we develop corresponding implications for procurement.     

On trading wavelengths with fibers: a cost-performance based study

We consider the effect of multiple fibers on wavelength division multiplexing networks without wavelength conversion. We study networks with dynamic wavelength routing and develop accurate analytical models to compare various possible options using single- and multiple-fiber networks. We use results of an analytical model and simulation-based studies to evaluate the blocking performance and cost of multifiber networks. The number of fibers required providing high performance in multifiber networks and their costs are compared. A case is made for using multiple fibers in each link with fewer wavelengths instead of using a single fiber with many wavelengths. In particular, we show that a network with four fibers per link and with four wavelengths on each fiber without any wavelength conversion on any node yields similar same performance as the networks with one fiber per link and 16 wavelengths per fiber on each link and with full wavelength conversion capability on all nodes. In addition, the multifiber network may also offer the cost advantage depending on the relative cost of components. We develop a parametric cost model to show that multiple fibers in each link are an attractive option. Finally, such multifiber networks also has fault tolerance, with respect to a single fiber failure, already built into the system.