Metabolite biomarker discovery for metabolic diseases by flux analysis

Metabolites can serve as biomarkers and their identification has significant importance in the study of biochemical reaction and signalling networks. Incorporating metabolic and gene expression data to reveal biochemical networks is a considerable challenge, which attracts a lot of attention in recent research. In this paper, we propose a promising approach to identify metabolic biomarkers through integrating available biomedical data and disease-specific gene expression data. A Linear Programming (LP) based method is then utilized to determine flux variability intervals, therefore enabling the analysis of significant metabolic reactions. A statistical approach is also presented to uncover these metabolites. The identified metabolites are then verified by comparing with the results in the existing literature. The proposed approach here can also be applied to the discovery of potential novel biomarkers. © 2012 IEEE.published_or_final_versio

Regulation of notch sensitivity of lattice materials by strut topology

We propose a local reinforcement technique for lattices in the vicinity of a stress-raiser such as a notch, in order to elevate the macroscopic strength and ductility. A spatially non-uniform waviness distribution of sinusoidally-shaped struts is assumed in the vicinity of the notch, and the sensitivity of macroscopic tensile response to strut waviness distribution is studied by finite element analysis. Optimized lattice structures are determined in order to maximise the macroscopic tensile strength or ductility from these various strut waviness distributions. Both hexagonal and triangular lattices are studied as these geometries are representative of bending-dominated and stretching-dominated lattices, respectively

The Influence of Strut Waviness on the Tensile Response of Lattice Materials

Abstract Recent advances in additive manufacturing methods make it possible, for the first time, to manufacture complex micro-architectured solids that achieve desired stress versus strain responses. Here, we report experimental measurements and associated finite element (FE) calculations on the effect of strut shape upon the tensile response of two-dimensional (2D) lattices made from low-carbon steel sheets. Two lattice topologies are considered: (i) a stretching-dominated triangular lattice and (ii) a bending-dominated hexagonal lattice. It is found that strut waviness can enhance the ductility of each lattice, particularly for bending-dominated hexagonal lattices. Manufacturing imperfections such as undercuts have a small effect on the ductility of the lattices but can significantly reduce the ultimate tensile strength. FE simulations provide additional insight into these observations and are used to construct design maps to aid the design of lattices with specified strength and ductility.</jats:p

Discovery of metabolite biomarkers: flux analysis and reaction-reaction network approach

published_or_final_versio

An assessment of the J-integral test for a metallic foam

An assessment is made of the J-integral test procedure for initial crack growth in an open-cell aluminium alloy foam by combining finite element (FE) simulations with experiment. It is found experimentally that a zone of randomly failed struts develops ahead of the primary crack tip, and is comparable in size to that of the plastic zone. Hence, a crack tip J-field is absent at the initiation of crack growth from the primary crack tip. This implies that the measured J_IC value and the J versus crack extension Da curve cannot be treated as material properties despite the fact that the specimen size meets the usual criteria for J validity. The toughness tests were performed on a single-edge notched bend specimen, and crack extension was measured by the direct current potential drop method, by digital image correlation and by X-ray computed tomography. The crack growth resistance of the foam is associated with two distinct zones of plastic dissipation: (i) a bulk plastic zone emanating from the crack tip (containing a cluster of randomly failed struts), and (ii) a crack bridging zone behind the advancing crack tip. The applicability of a cohesive zone model to predict the fracture response is explored for the observed case of large scale bridging. To do so, FE simulations are performed by replacing the discrete lattice of the open-cell metallic foam by a compressible, elastic-plastic hardening solid while the fracture process zone in the foam is represented by a cohesive zone, as characterised by a tensile traction versus separation law. A detailed comparison of the cohesive zone model with experimental observations reveals that it is possible to capture the load versus displacement response but not the details of the fracture process zone using a single set of process zone parameters

Removal of antibiotics (sulfamethazine, tetracycline and chloramphenicol) from aqueous solution by raw and nitrogen plasma modified steel shavings

© 2017 Elsevier B.V. The removal of sulfamethazine (SMT), tetracycline (TC) and chloramphenicol (CP) from synthetic wastewater by raw (M3) and nitrogen plasma modified steel shavings (M3-plN2) was investigated using batch experiments. The adsorption kinetics could be expressed by both pseudo-first-order kinetic (PFO) and pseudo-second-order kinetic (PSO) models, where correlation coefficient r2 values were high. The values of PFO rate constant k1p and PSO rate constant k2p decreased as SMT-M3 > SMT-M3-plN2 > TC-M3-plN2 > TC-M3 > CP-M3 > CP-M3-plN2 and SMT-M3 > SMT-M3-plN2 > TC-M3 > TC-M3-plN2 > CP-M3 > CP-M3-plN2, respectively. Solution pH, adsorbent dose and temperature exerted great influences on the adsorption process. The plasma modification with nitrogen gas cleaned and enhanced 1.7-fold the surface area and 1.4-fold the pore volume of steel shavings. Consequently, the removal capacity of SMT, TC, CP on the adsorbent rose from 2519.98 to 2702.55, 1720.20 to 2158.36, and 2772.81 to 2920.11 μg/g, respectively. Typical chemical states of iron (XPS in Fe2p3 region) in the adsorbents which are mainly responsible for removing antibiotics through hydrogen bonding, electrostatic and non- electrostatic interactions and redox reaction were as follows: Fe3O4/Fe2 +, Fe3O4/Fe3 +, FeO/Fe2 + and Fe2O3/Fe3 +

ICRS-Filter: A randomized direct search algorithm for constrained nonconvex optimization problems

This work presents a novel algorithm and its implementation for the stochastic optimization of generally constrained Nonlinear Programming Problems (NLP). The basic algorithm adopted is the Iterated Control Random Search (ICRS) method of Casares and Banga (1987) with modifications such that random points are generated strictly within a bounding box defined by bounds on all variables. The ICRS algorithm serves as an initial point determination method for launching gradient-based methods that converge to the nearest local minimum. The issue of constraint handling is addressed in our work via the use of a filter based methodology, thus obviating the need for use of the penalty functions as in the basic ICRS method presented in Banga and Seider (1996),which handles only bound constrained problems. The proposed algorithm, termed ICRS-Filter, is shown to be very robust and reliable in producing very good or global solutions for most of the several case studies examined in this contribution.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.cherd.2015.12.00

Analytical, Optimal, and Sparse Optimal Control of Traveling Wave Solutions to Reaction-Diffusion Systems

This work deals with the position control of selected patterns in reaction-diffusion systems. Exemplarily, the Schl\"{o}gl and FitzHugh-Nagumo model are discussed using three different approaches. First, an analytical solution is proposed. Second, the standard optimal control procedure is applied. The third approach extends standard optimal control to so-called sparse optimal control that results in very localized control signals and allows the analysis of second order optimality conditions.Comment: 22 pages, 3 figures, 2 table

Dual abrogation of Mnk and mTOR; a novel therapeutic approach for the treatment of aggressive cancers

Targeting the translational machinery has emerged as a promising therapeutic option for cancer treatment. Cancer cells require elevated protein synthesis for cell growth and exhibit augmented activity to meet the increased metabolic demand. Eukaryotic translation initiation factor 4E (eIF4E) is necessary for mRNA translation, its availability and phosphorylation are regulated by the PI3K/AKT/mTOR and Mnk1/2 pathways, respectively. The phosphorylated form of eIF4E drives the expression of oncogenic proteins including those involved in metastasis. This article will review the role of eIF4E in cancer, its regulation, and discuss the benefit of dual-inhibition of upstream pathways. The discernible interplay between the Mnk1/2 and mTOR signaling pathways provides a novel therapeutic opportunity to target aggressive migratory cancers through the development of hybrid molecules

Terminalia bentzoë, a Mascarene Endemic Plant, Inhibits Human Hepatocellular Carcinoma Cells Growth In Vitro via G0/G1 Phase Cell Cycle Arrest

Tropical forests constitute a prolific sanctuary of unique floral diversity and potential medicinal sources, however, many of them remain unexplored. The scarcity of rigorous scientific data on the surviving Mascarene endemic taxa renders bioprospecting of this untapped resource of utmost importance. Thus, in view of valorizing the native resource, this study has as its objective to investigate the bioactivities of endemic leaf extracts. Herein, seven Mascarene endemic plants leaves were extracted and evaluated for their in vitro antioxidant properties and antiproliferative effects on a panel of cancer cell lines, using methyl thiazolyl diphenyl-tetrazolium bromide (MTT) and clonogenic cell survival assays. Flow cytometry and comet assay were used to investigate the cell cycle and DNA damaging effects, respectively. Bioassay guided-fractionation coupled with liquid chromatography mass spectrometry (MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopic analysis were used to identify the bioactive compounds. Among the seven plants tested, Terminaliabentzoë was comparatively the most potent antioxidant extract, with significantly (p &lt; 0.05) higher cytotoxic activities. T. bentzoë extract further selectively suppressed the growth of human hepatocellular carcinoma cells and significantly halted the cell cycle progression in the G0/G1 phase, decreased the cells’ replicative potential and induced significant DNA damage. In total, 10 phenolic compounds, including punicalagin and ellagic acid, were identified and likely contributed to the extract’s potent antioxidant and cytotoxic activities. These results established a promising basis for further in-depth investigations into the potential use of T. bentzoë as a supportive therapy in cancer management