One of the key aspects of computational systems biology is the investigation on the dynamic biological processes within cells. Computational models are often required to elucidate the mechanisms and principles driving the processes because of the nonlinearity and complexity. The models usually incorporate a set of parameters that signify the physical properties of the actual biological systems. In most cases, these parameters are estimated by fitting the model outputs with the corresponding experimental data. However, this is a challenging task because the available experimental data are frequently noisy and incomplete. In this paper, a new hybrid optimization method is proposed to estimate these parameters from the noisy and incomplete experimental data. The proposed method, called Swarm-based Chemical Reaction Optimization, integrates the evolutionary searching strategy employed by the Chemical Reaction Optimization, into the neighbouring searching strategy of the Firefly Algorithm method. The effectiveness of the method was evaluated using a simulated nonlinear model and two biological models: synthetic transcriptional oscillators, and extracellular protease production models. The results showed that the accuracy and computational speed of the proposed method were better than the existing Differential Evolution, Firefly Algorithm and Chemical Reaction Optimization methods. The reliability of the estimated parameters was statistically validated, which suggests that the model outputs produced by these parameters were valid even when noisy and incomplete experimental data were used. Additionally, Akaike Information Criterion was employed to evaluate the model selection, which highlighted the capability of the proposed method in choosing a plausible model based on the experimental data. In conclusion, this paper presents the effectiveness of the proposed method for parameter estimation and model selection problems using noisy and incomplete experimental data. This study is hoped to provide a new insight in developing more accurate and reliable biological models based on limited and low quality experimental data.
Metabolic engineering involves the modification and alteration of metabolic pathways to improve the production of desired substance. The modification can be made using in silico gene knockout simulation that is able to predict and analyse the disrupted genes which may enhance the metabolites production. Global optimization algorithms have been widely used for identifying gene knockout strategies. However, their productions were less than theoretical maximum and the algorithms are easily trapped into local optima. These algorithms also require a very large computation time to obtain acceptable results. This is due to the complexity of the metabolic models which are high dimensional and contain thousands of reactions. In this paper, a hybrid algorithm of Cuckoo Search and Minimization of Metabolic Adjustment is proposed to overcome the aforementioned problems. The hybrid algorithm searches for the near-optimal set of gene knockouts that leads to the overproduction of metabolites. Computational experiments on two sets of genome-scale metabolic models demonstrate that the proposed algorithm is better than the previous works in terms of growth rate, Biomass Product Couple Yield, and computation time.
This study investigated consequent functional effects (mechanical and physical) on Gelatin/ CMC/Chitosan composite films from the addition of sorbitol. With glycerol as a plasticizer, solutions for Gelatin/CMC/Chitosan composite films containing graduated sorbitol concentrations (0%, 5%, 10%, 15%, 20%, 25% and 30%), were cast on a petri dish and oven dried at 45˚C. The fabricated films were then characterized for tensile strength, elongation at break (EAB) and puncture resistance (mechanical properties); as well as film thickness, water vapor permeability (WVP), thermal properties, light transmittance and transparency (UV and visible light transmission), biodegradability, and X-ray diffraction (physical properties). Results indicated that by increasing sorbitol concentration, melting point and tensile strength decreased overall (p
FK506-binding protein35 of Plasmodium knowlesi (Pk-FKBP35) is a member of peptidyl prolyl cis-trans isomerase (PPIase) and is considered as a promising avenue of antimalarial drug target development. This protein is organized into the N-terminal domain responsible for PPIase catalytic activity followed and the tetratricopeptide repeat domain for its dimerization. The protease-coupling and protease-free assays are known to be the common methods for investigating the catalytic properties of PPIase. Earlier, the protease-coupling assay was used to confirm the catalytic activity of Pk-FKBP35 in accelerating cis-trans isomerization of the peptide substrate. This report is aimed to re-assess the catalytic and substrate specificity of Pk-FKBP35 using an alternative method of a protease-free assay. The result indicated that while Pk-FKBP35 theoretically contained many possible cleavage sites of chymotrypsin, experimentally, the catalytic domain was relatively stable from chymotrypsin. Furthermore, under protease-free assay, Pk-FKBP35 also demonstrated remarkable PPIase catalytic activity with kcat/KM of 4.5 + 0.13 × 105 M−1 s−1, while the kcat/KM of active site mutant of D55A is 0.81 + 0.05 × 105 M−1 s−1. These values were considered comparable to kcat/KM obtained from the protease-coupling assay. Interestingly, the substrate specificities of Pk-FKBP35 obtained from both methods are also similar, with the preference of Pk-FKBP35 towards Xaa at P1 position was Leu>Phe>Lys>Trp>Val>Ile>His>Asp>Ala>Gln>Glu. Altogether, we proposed that protease-free and protease-coupling assays arereliable for Pk-FKBP35.
Indoles are amongst the most important class of heteroaromatics in organic chemistry, being commonly found in biologically active natural products and therapeutically useful compounds. The synthesis of indoles is therefore important and several methods for their synthesis that make use of silver(I) catalysts and reagents have been developed in recent years. This Focus Review contains, to the best of our knowledge, a comprehensive coverage of silver-mediated indole forming reactions since the first reaction of this type was reported in 2004.
Various production methods have been developed for graphene production, but each of them falls short in either the economic or quality aspect. In this paper, we present the flame deposition method, a modified chemical vapor deposition (CVD) that uses an open-flame. In this method, resulting carbon deposits were found to be graphitic in nature, thereby suggesting multilayer graphene growth in a very short reaction time of 5 min. Furthermore, the deposits were transferred onto a cyanoacrylate plastic substrate and its sheet resistance was measured to be 81 ohm/square. The results showed that open-flame deposition exhibits high potential for low-cost, low-energy and high-quality production of graphene.
Moisture susceptibiltiy is one of the common types of pavement failure found in asphaltic pavements.
Climatic factor such as temperature and moisture has a profound effect on the durability of hot mix
asphalt pavements. Couple with high traffic loads/stresses made stripping of pavement materials
inevitable. Thus, it has become necessary to improve the efficiency of the design of hot mix asphalt
(HMA) for better performance and safe riding comfort. This study investigates and discusses the findings
on the stripping performance of dense graded Superpave mixes using two type of binder; un-modified
binder and rubber polymer modified binder (RPM) using Superpave mix design (AASHTO TP4)
procedure. The RPM binder consists of 4% of both rubber crumb and EVA polymer. Modified Lottman
and Resilient Modulus tests were used to evaluate the stripping performance in these mixtures and this
study also documents the effect of different temperature on tensile strength ratio (TSR) and resilient
modulus ratio (RMR) on the HMA mixtures. Experimental evidences show that the RPM binder mixes
were found to have significantly improved the resistance to moisture damage compared to unmodified
binder mixtures. The RPM binder application may able to alleviate problems related to aggregate
stripping and potholes on our road. Statistical analysis showed good correlation between resilient
modulus and tensile strength ratio.
This study presents the sensitivity of graphene nanoribbon (GNR) when exposed to ammonia gas at room temperature. Alumina were used as a substrate and coated with GNR as sensing film for ammonia gas detection. Four different concentration of GNR in the category of maximum, high, low, and minimum were prepared. Each category of GNR will be dispersed on alumina substrate with area of 1cm2 and 4cm2. 30nm of gold contacts are sputtered on both ends of the sensing film. The ammonia gas can be detected by measuring the changes in resistance. The GNR as ammonia sensor shows good responses at room temperature. In repeatability test, maximum GNR shows least variation when exposed to ammonia with the value of 1.01% (4cm2) and 2.12% (1cm2). In a sensitivity test, 0.25% to 1.00% of ammonia gas was used and tested on maximum GNR. Maximum GNR on 4cm2 substrate shows higher sensitivity as compared to 1cm2. Reaction time of GNR on ammonia gas decreased as the concentration of ammonia increased. Larger surface area of sensing element required lesser reaction time.
This study explores optimization of resistance load (R-Load) of four silicon nanowire transistor (SiNWT)-based static random-access memory (SRAM) cell. Noise margins and inflection voltage of butterfly characteristics with static power consumption of SRAM cell are used as limiting factors in this optimization. Range of R-Load used in this study was 20-1000 KΩ with Vdd = 1 V. Results indicate that optimization depends critically on resistance load value. The optimized range of R-Load is 100-200 KΩ.
Using radiolabelled peptides that bind, with high affinity and specificity, to receptors on tumour cells is one of the most promising fields in modern molecular imaging and targeted radionuclide therapy (1). In the emergence of molecular imaging and nuclear medicine diagnosis and therapy, albeit theranostic, radiolabelled peptides have become vital tools for in vivo visualisation and monitoring physiological and biochemical processes on molecular and cellular levels (2). This approach may benefit patients in the era of personalised medicine.
Over two hundred bacteria were isolated from the halosphere, rhizosphere and endophyte of Malaysian maize plantation and screened for phytases activity. Thirty isolates with high detectable phytase activity were chosen for media optimization study and species identification. Ten types of bacterial phytase producers have been discovered in this study, which provides opportunity for characterization of new phytase(s) and various commercial and environmental applications. The majority of the bacterial isolates with high detectable phytase activity were of endophyte origin and 1.6% of the total isolates showed phytase activity of more than 1 U/ml. Most of the strains produced extra-cellular phytase and Staphylococcus lentus ASUIA 279 showed the highest phytase activity of 1.913 U/ml. All 30 species used in media optimization study exhibit favorable enzyme production when 1% rice bran was included in the growth media.
A mutation is ultimately essential for adaptive evolution in all populations. It arises all the time, but is mostly fixed by enzymes. Further, most do consider that the evolution mechanism is by a natural assortment of variations in organisms in line for random variations in their DNA, and the suggestions for this are overwhelming. The altering of the construction of a gene, causing a different form that may be communicated to succeeding generations, produced by the modification of single base units in DNA, or the deletion, insertion, or rearrangement of larger units of chromosomes or genes. This altering is called a mutation. In this paper, a mathematical model is introduced to this reality. The model describes the time and space for the evolution. The tool is based on a complex domain for the space. We show that the evolution is distributed with the hypergeometric function. The Boundedness of the evolution is imposed by utilizing the Koebe function.
Eukaryotic cells contain translation-associated mRNA surveillance pathways which prevent the production of potentially toxic proteins from aberrant mRNA translation events. We found that loss of mRNA surveillance pathways in mutants deficient in nonsense-mediated decay (NMD), no-go decay (NGD) and nonstop decay (NSD) results in increased protein aggregation. We have isolated and identified the proteins that aggregate and our bioinformatic analyses indicates that increased aggregation of aggregation-prone proteins is a general occurrence in mRNA surveillance mutants, rather than being attributable to specific pathways. The proteins that aggregate in mRNA surveillance mutants tend to be more highly expressed, more abundant and more stable proteins compared with the wider proteome. There is also a strong correlation with the proteins that aggregate in response to nascent protein misfolding and an enrichment for proteins that are substrates of ribosome-associated Hsp70 chaperones, consistent with susceptibility for aggregation primarily occurring during translation/folding. We also identified a significant overlap between the aggregated proteins in mRNA surveillance mutants and ageing yeast cells suggesting that translation-dependent protein aggregation may be a feature of the loss of proteostasis that occurs in aged cell populations.
Indiscriminate application of organophosphate (OP) pesticides has led to environmental pollution and severe health problems. The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. A total of 28 male Sprague-Dawley rats were divided into four groups; control group, TRF-supplemented group, FNT-treated group and TRF+FNT group. TRF (200 mg/kg) was supplemented 30 minutes prior to FNT (20 mg/kg) administration, both orally for 28 consecutive days. Following 28 days of treatment, plasma biochemical changes and liver morphology were evaluated. The body and absolute liver weights were significantly elevated in TRF+FNT group compared to FNT group. TRF administration significantly decreased the total protein level and restored the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in TRF + FNT group. In contrast, total bilirubin level, γ-glutamyltranferase (GGT) and cholinesterase activity in TRF + FNT group did not significantly differ from FNT group. Administration of TRF also prevented FNT-induced morphological changes of liver as observed by electron microscope. In conclusion, TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT.
Solvothermal synthesis is the most preferable preparation technique of metal-organic frameworks (MOFs) that consists of reactants mixing, ultrasonication, solvothermal reaction, product washing, and solvent evacuation. Owing to fast reaction kinetics in solvothermal reaction, this technique allows for production of uniform MOF particles with high crystallinity, high phase purity, and small particle sizes. However, it exhibits some difficulties of washing processes that may involve the blockage of pores due to incomplete removal of reactive medium from MOF products. The present study proposes an improvement of washing processes by introducing centrifugal separations with optimized parameters at two different stages: after reaction and after product washing. Nickel‑based MOF‑74 was synthesized as the experimental material for this purpose. The quality of the produced sample was evaluated by gas adsorption performance using CO2 at 1 bar and 25 °C. The final sample of the optimized synthesis routes was able to adsorb 5.80 mmol/g of CO2 uptake, which was competitive with literature data and significantly higher than the sample of the basic synthesis. Fourier‑transform infrared spectroscopy (FTIR) and powder X‑ray diffraction (PXRD) analysis revealed that the sample displayed much higher crystallinity structure and was clean from impurities after centrifugations. The outcome indicated the success of separation between MOF products and reactive medium during washing processes, leading to the effective pore activation of MOFs.
In our efforts to develop druggable diphenyl ethers as potential antitubercular agents, a series of novel diphenyl ether derivatives (5a-f, 6a-f) were designed and synthesized. The representative compounds showed promising in vitro activity against drug-susceptible, isoniazid-resistant, and multidrug-resistant strains of Mycobacterium tuberculosis with MIC values of 1.56 μg/ml (6b), 6.25 μg/ml (6a-d), and 3.125 μg/ml (6b-c), respectively. All the synthesized compounds exhibited satisfactory safety profile (CC50 > 300 μg/ml) against Vero and HepG2 cells. Reverse phase HPLC method was used to probe the physicochemical properties of the synthesized compounds. This series of compounds demonstrated comparatively low logP values. pKa values of representative compounds indicated that they were weak acids. Additionally, in vitro human liver microsomal stability assay confirmed that the synthesized compounds possessed acceptable stability under study conditions. The present study thus establishes compound 6b as the most promising antitubercular agent with acceptable drug-likeness.
Parasitic roundworms (nematodes) cause substantial morbidity and mortality in livestock animals globally, and considerable productivity losses to farmers. The control of these nematodes has relied largely on the use of a limited number of anthelmintics. However, resistance to many of these these anthelmintics is now widespread, and, therefore, there is a need to find new drugs to ensure sustained and effective treatment and control into the future.
A new technique was accepted to fill the porosity of Al coating applied by arc thermal spray process to enhance corrosion resistance performance in artificial ocean water. The porosity is the inherent property of arc thermal spray coating process. In this study, applied coating was treated with different concentrations of ammonium phosphate mono basic (NH4H2PO4: AP) solution thereafter dried at room temperature and kept in humidity chamber for 7d to deposit uniform film. The corrosion resistance of Al coating and treated samples have been evaluated using electrochemical impedance spectroscopy (EIS) and potentiodynamic techniques with exposure periods in artificial ocean water. Electrochemical techniques, X-ray diffraction (XRD), Raman spectroscopy, atomic force microscopy (AFM) and field emission-scanning electron microscopy (FE-SEM) indicated that phosphate ion would have been retarding corrosion of Al coating effectively. The formation of AHP (Ammonium Aluminum Hydrogen Phosphate Hydrate: NH4)3Al5H6(PO4)8.18H2O) on Al coating surface after treatment with AP is nano sized, crystalline and uniformly deposited but after exposure them in artificial ocean water, they form AHPH (Aluminum hydroxide phosphate hydrate Al3(PO4)2(OH)3(H2O)5) that is very protective, adherent, uniform and plate like morphology of corrosion products. The AHPH is sparingly soluble and adherent to surface and imparted improved corrosion resistance.
This research investigated the removal of lead (Pb(2+)) by a novel biochar derived from palm oil sludge (POS-char) by slow pyrolysis. Multistage optimizations with central composite design were carried out to firstly optimize pyrolysis parameters to produce the best POS-char for Pb(2+) removal and secondly to optimize adsorption conditions for the highest removal of Pb(2+). The optimum pyrolysis parameters were nitrogen flowrateof30mLmin(-1), heating rateof10°Cmin(-1), temperatureof500°C and timeof30min. The optimum Pb(2+) adsorption conditions were concentrationof200mgL(-1), timeof60min, dosageof0.3g and pH of 3.02. The various functional groups within POS-char played a vital role in Pb(2+) uptake. Regeneration was demonstrated to be feasible using hydrochloric acid. Adsorption equilibrium was best described by Freundlich model. At low concentration range, adsorption kinetic obeyed pseudo-first-order model, but at high concentration range, it followed pseudo-second-order model. Overall, the results highlighted that POS-char is an effective adsorbent for Pb(2+) removal.
Porous silicon (Si) is a low thermal conductivity material, which has high potential for thermoelectric devices. However, low output performance of porous Si hinders the development of thermoelectric performance due to low electrical conductivity. The large contact resistance from nonlinear contact between porous Si and metal is one reason for the reduction of electrical conductivity. In this paper, p- and n-type porous Si were formed on Si substrate by metal-assisted chemical etching. To decrease contact resistance, p- and n-type spin on dopants are employed to dope an impurity element into p- and n-type porous Si surface, respectively. Compared to the Si substrate with undoped porous samples, ohmic contact can be obtained, and the electrical conductivity of doped p- and n-type porous Si can be improved to 1160 and 1390 S/m, respectively. Compared with the Si substrate, the special contact resistances for the doped p- and n-type porous Si layer decreases to 1.35 and 1.16 mΩ/cm2, respectively, by increasing the carrier concentration. However, the increase of the carrier concentration induces the decline of the Seebeck coefficient for p- and n-type Si substrates with doped porous Si samples to 491 and 480 μV/K, respectively. Power factor is related to the Seebeck coefficient and electrical conductivity of thermoelectric material, which is one vital factor that evaluates its output performance. Therefore, even though the Seebeck coefficient values of Si substrates with doped porous Si samples decrease, the doped porous Si layer can improve the power factor compared to undoped samples due to the enhancement of electrical conductivity, which facilitates its development for thermoelectric application.