Artificial intelligence for dementia drug discovery and trials optimization.

Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress. Opportunities arise at multiple stages in the therapy pipeline and the growing availability of large medical data sets opens possibilities for big data analyses to answer key questions in clinical and therapeutic challenges. However, before this goal is reached, several challenges need to be overcome and only a multi-disciplinary approach can promote data-driven decision-making to its full potential. Herein we review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation.

Conceptual Developments of Aryldiazonium Salts as Modifiers for Gold Colloids and Surfaces.

Modified colloids and flat surfaces occupy an important place in materials science research due to their widespread applications. Interest in the development of modifiers that adhere strongly to surfaces relates to the need for stability under ambient conditions in many applications. Diazonium salts have evolved as the primary choice for the modification of surfaces. The term "diazonics" has been introduced in the literature to describe "the science and technology of aryldiazonium salt-derived materials". The facile reduction of diazonium salts via chemical or electrochemical processes, irradiation stimuli, or spontaneously results in the efficient modification of gold surfaces. Robust gold-aryl nanoparticles, where gold is connected to the aryl ring through bonding to carbon and films modified by using diazonium salts, are critical in electronics, sensors, medical implants, and materials for power sources. Experimental and theoretical studies suggest that gold-carbon interactions constructed via chemical reactions with diazonium salts are stronger than nondiazonium surface modifiers. This invited feature article summarizes the conceptual development of recent studies of diazonium salts in our laboratories and others with a focus on the surface modification of gold nanostructures, flat surfaces and gratings, and their applications in nanomedicine engineering, sensors, energy, forensic science, and catalysis.

Development of Latent Fingerprints via Aryldiazonium Tetrachloroaurate Salts on Copper Surfaces: An XPS Study.

Surface studies of developed fingerprints have aided in the elimination of criminal cases before moving to the court. The combination of X-ray photoelectron spectroscopy (XPS) with the aryldiazonium gold(III), 4-O2NC6H4N2+AuCl4-, surface modifier has been shown to be a novel approach in latent fingerprint detection and development for the quantification of film elements. The robust gold-aryl film was developed on the reducing chemicals excreted in the sebaceous fingerprints without the need for external stimuli and at a lesser extent after contacting the free metal surface. The concurrent reduction of the diazonium functional group and gold(III) from [AuCl4]- developed a robust gold-aryl film, which showed increasing gold(0) quantity in the time range of 30-120 min over copper coins and model flat sheets. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) support the presence of reduced gold on the top of the latent fingerprints and the presence of CuO resulting from the reaction of the diazonium salt with copper metal. This research combines the quantification of deposits using XPS, a surface-sensitive technique for chemical analysis, in addition to surface imaging.

Optimization of polyvinylidene fluoride (PVDF) membrane fabrication for protein binding using statistical experimental design.

Statistical experimental design was employed to optimize the preparation conditions of polyvinylidenefluoride (PVDF) membranes. Three variables considered were polymer concentration, dissolving temperature, and casting thickness, whereby the response variable was membrane-protein binding. The optimum preparation for the PVDF membrane was a polymer concentration of 16.55 wt%, a dissolving temperature of 27.5°C, and a casting thickness of 450 µm. The statistical model exhibits a deviation between the predicted and actual responses of less than 5%. Further characterization of the formed PVDF membrane showed that the morphology of the membrane was in line with the membrane-protein binding performance.

Comparison of harvesting methods for microalgae Chlorella sp. and its potential use as a biodiesel feedstock.

Three methods for harvesting Chlorella sp. biomass were analysed in this paper--centrifugation, membrane microfiltration and coagulation: there was no significant difference between the total amount of biomass obtained by centrifugation and membrane microfiltration, i.e., 0.1174 +/- 0.0308 and 0.1145 +/- 0.0268 g, respectively. Almost the same total lipid content was obtained using both methods, i.e., 27.96 +/- 0.77 and 26.43 +/- 0.67% for centrifugation and microfiltration, respectively. However, harvesting by coagulation resulted in the lowest biomass and lipid content. Similar fatty acid profiles were obtained for all of the harvesting methods, indicating that the main components were palmitic acid (C16:0), oleic acid (C18:1) and linoleic acid (C18:2). However, the amounts of the individual fatty acids were higher for microfiltration than for centrifugation and coagulation; coagulation performed the most poorly in this regard by producing the smallest amount of fatty acids (41.61 +/- 6.49 mg/g dw). The harvesting method should also be selected based on the cost benefit and energy requirements. The membrane filtration method offers the advantages of currently decreasing capital costs, a high efficiency and low maintenance and energy requirements and is thus the most efficient method for microalgae harvesting.

Kinetic studies and thermodynamics of oil extraction and transesterification of Chlorella sp. for biodiesel production.

In this work, a mixture of chloroform and methanol (1:1, v/v) was applied to oil extraction from Chlorella sp. at 30, 40, 50 and 60 degrees C for 150 min extraction times. Kinetic studies revealed that the values of n and the rate constants were found to depend strongly on temperature. The activation energy was Ea = 38.893 kJ/mol, and the activation thermodynamic parameters at 60 degrees C were ΔS≠ = -180.190 J/mol , ΔH≠ = 36.124k J/mol and ΔG≠ = 96.128k J/mol. Both ΔH and ΔS yielded positive values, whereas ΔG was negative at 60 degrees C, indicating that this process is endothermic, irreversible and spontaneous. The acidic transesterification process was also investigated by gas chromatographic analysis of the microalgae fatty acid methyl esters (biodiesel) at different temperatures and reaction times. The fatty acid profile indicated that the main components were palmitic, linoleic and linolenic acids. The concentration of linolenic acid increased and oleic acid decreased as the temperature increased. Two-hour transesterification is the best reaction time for biodiesel production because it produces the highest percentage of unsaturated fatty acids (74%). These results indicate the potential of Chlorella sp. to produce biodiesel of good quality.

Potential of nanofiltration and low pressure reverse osmosis in the removal of phosphorus for aquaculture.

Aquaculture activities in developing countries have raised deep concern about nutrient pollution, especially excess phosphorus in wastewater, which leads to eutrophication. NF, NF90, NF450 and XLE membranes were studied to forecast the potential of nanofiltration and low pressure reverse osmosis in the removal of phosphorus from aquaculture wastewater. Cross-sectional morphology, water contact angle, water permeability and zeta potential of these membranes were first examined. Membrane with higher porosity and greater hydrophilicity showed better permeability. Membrane samples also commonly exhibited high zeta potential value in the polyphosphate-rich solution. All the selected membranes removed more than 90% of polyphosphate from the concentrated feed (75 mg/L) at 12 bar. The separation performance of XLE membrane was well maintained at 94.6% even at low pressure. At low feed concentration, more than 70.0% of phosphorus rejection was achieved using XLE membrane. The formation of intermolecular bonds between polyphosphate and the acquired membranes probably had improved the removal of polyphosphate at high feed concentration. XLE membrane was further tested and its rejection of polyphosphate reduced with the decline of pH and the addition of ammonium nitrate.

Fouling mitigation in humic acid ultrafiltration using polysulfone/SAPO-34 mixed matrix membrane.

Although ultrafiltration (UF) membranes are applicable in wastewater and water treatment, most UF membranes are hydrophobic and susceptible to severe fouling by natural organic matter. In this work, polysulfone (PSf) membrane was blended with silicaluminophosphate (SAPO) nanoparticles, SAPO-34, to study the effect of SAPO-34 incorporation in humic acid (HA) fouling mitigation. The casting solution was prepared by blending 5-20 wt% of SAPO-34 nanoparticles into the mixture of PSf, 1-methyl-2-pyrrolidinone and polyvinyl alcohol at 75 °C. All membrane samples were then prepared using the phase inversion method. Blending SAPO-34 zeolite into PSf membranes caused augmentation in surface hydrophilicity and pore size, leading to higher water permeation. In the HA filtration test, mixed matrix membranes (MMMs) with SAPO-34 zeolite showed reduced HA fouling initiated from pore blocking. The MMM with 20 wt% SAPO-34 loading exhibited the highest increment of water permeation (83%) and maintained about 75% of permeate flux after 2.5 h. However, the SAPO-34 fillers agglomerated in the PSf matrix and induced macrovoid formation on the membrane surface when excessive zeolite was added.

Investigating membrane morphology and quantity of immobilized protein for the development of lateral flow immunoassay.

This study was aimed at gaining a quantitative understanding of the effect of protein quantity and membrane pore structure on protein immobilization. The concentration of immobilized protein was measured by staining with Ponceau S and measuring its color intensity. In this study, both membrane morphology and the quantity of deposited protein significantly influenced the quantity of protein immobilization on the membrane surface. The sharpness and intensity of the red protein spots varied depending on the membrane pore structure, indicating a dependence of protein immobilization on this factor. Membranes with smaller pores resulted in a higher color density, corresponding to enhanced protein immobilization and an increased assay sensitivity level. An increased of immobilized volume has a significant jagged outline on the protein spot but, conversely, no difference in binding capacity.

Adsorption isotherm and kinetic modeling of 2,4-D pesticide on activated carbon derived from date stones.

In this work, the adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) on activated carbon derived from date stones (DSAC) was studied with respect to pH and initial 2,4-D concentration. The experimental data were analyzed by the Freundlich isotherm, the Langmuir isotherm, and the Temkin isotherm. Equilibrium data fitted well with the Langmuir model with maximum adsorption capacity of 238.10 mg/g. Pseudo-first and pseudo-second-order kinetics models were tested with the experimental data, and pseudo-first-order kinetics was the best for the adsorption of 2,4-D by DSAC with coefficients of correlation R(2)>or=0.986 for all initial 2,4-D concentrations studied. The results indicated that the DSAC is very effective for the adsorption of 2,4-D from aqueous solutions.

Fatty acid profile from immobilised Chlorella vulgaris cells in different matrices.

The immobilisation of Chlorella vulgaris 211/11B entrapped in combinations of natural matrices to simplify the harvesting process was demonstrated in this study. Three combinations of matrices composed of calcium alginate (CA) and sodium alginate (SA), sodium carboxymethyl cellulose (CMC) and SA, and mixed matrices (SA, CA, and CMC) were investigated. The number of cells grown for each immobilised matrix to microalgae volume ratios (0.2:1-1:1) were explored and compared with using SA solely as a control. The optimum volume ratios obtained were 1:1 for SA, 0.3:1 for CA and SA, 1:1 for CMC and SA, and 0.3:1 for mixed matrices. The immobilised microalgae of mixed matrices exhibited the highest number of cells with 1.72 × 109 cells/mL at day 10 and 30.43% of oil extraction yield followed by CA and SA (24.29%), CMC and SA (13.00%), and SA (6.71%). Combining SA, CA, and CMC had formed a suitable structure which improved the growth of C. vulgaris and increased the lipid production compared to the immobilisation using single matrix. Besides, the fatty acids profile of the oil extracted indicates a high potential for biodiesel production.

Sorption equilibrium and kinetics of basic dye from aqueous solution using banana stalk waste.

The sorption of basic dye from aqueous solutions by banana stalk waste (BSW), an abundant agricultural waste in Malaysia, was studied in a batch system with respect to pH and initial dye concentration. Sorption isotherm of methylene blue (MB) onto the BSW was determined at 30 degrees C with the initial concentrations of MB in the range of 50-500 mg/L. At pH 2.0, the sorption of dye was not favorable, while the sorption at other pHs (4.0-12.0) was remarkable. Equilibrium data were fitted to the Langmuir, Freundlich and Temkin isotherm models. The equilibrium data were best represented by the Langmuir isotherm model, with maximum monolayer adsorption capacity of 243.90 mg/g. The sorption kinetic data were analyzed using pseudo-first-order, pseudo-second-order and intraparticle diffusion models. It was found that the pseudo-second-order kinetic model was the best applicable model to describe the sorption kinetics. The results showed that BSW sorbent was a promising for the removal of MB from aqueous solutions.

Equilibrium modeling and kinetic studies on the adsorption of basic dye by a low-cost adsorbent: coconut (Cocos nucifera) bunch waste.

In this paper, the ability of coconut bunch waste (CBW), an agricultural waste available in large quantity in Malaysia, to remove basic dye (methylene blue) from aqueous solution by adsorption was studied. Batch mode experiments were conducted at 30 degrees C to study the effects of pH and initial concentration of methylene blue (MB). Equilibrium adsorption isotherms and kinetics were investigated. The experimental data were analyzed by the Langmuir, Freundlich and Temkin models of adsorption. The adsorption isotherm data were fitted well to Langmuir isotherm and the monolayer adsorption capacity was found to be 70.92 mg/g at 30 degrees C. The kinetic data obtained at different concentrations have been analyzed using a pseudo-first-order, pseudo-second-order equation and intraparticle diffusion equation. The experimental data fitted very well the pseudo-second-order kinetic model.

Adsorption of basic dye on high-surface-area activated carbon prepared from coconut husk: equilibrium, kinetic and thermodynamic studies.

Adsorption isotherm and kinetics of methylene blue on activated carbon prepared from coconut husk were determined from batch tests. The effects of contact time (1-30 h), initial dye concentration (50-500 mg/l) and solution temperature (30-50 degrees C) were investigated. Equilibrium data were fitted to Langmuir, Freundlich, Temkin and Dubinin-Radushkevich isotherm models. The equilibrium data were best represented by Langmuir isotherm model, showing maximum monolayer adsorption capacity of 434.78 mg/g. The kinetic data were fitted to pseudo-first-order, pseudo-second-order and intraparticle diffusion models, and was found to follow closely the pseudo-second-order kinetic model. Thermodynamic parameters such as standard enthalpy (DeltaH degrees), standard entropy (DeltaS degrees) and standard free energy (DeltaG degrees) were evaluated. The adsorption interaction was found to be exothermic in nature. Coconut husk-based activated carbon was shown to be a promising adsorbent for removal of methylene blue from aqueous solutions.

Preparation of activated carbon from coconut husk: optimization study on removal of 2,4,6-trichlorophenol using response surface methodology.

Activated carbon was prepared from coconut husk using physicochemical activation method which consisted of potassium hydroxide (KOH) treatment and carbon dioxide (CO(2)) gasification. The effects of three preparation variables (CO(2) activation temperature, CO(2) activation time and KOH:char impregnation ratio) on the 2,4,6-trichlorophenol (2,4,6-TCP) uptake and activated carbon yield were investigated. Based on the central composite design, two quadratic models were developed to correlate the preparation variables to the two responses. From the analysis of variance (ANOVA), the most influential factor on each experimental design response was identified. The activated carbon preparation conditions were optimized by maximizing both the 2,4,6-TCP uptake and activated carbon yield. The predicted 2,4,6-TCP uptake and carbon yield from the models agreed satisfactorily with the experimental values. The optimum conditions for preparing activated carbon from coconut husk for adsorption of 2,4,6-TCP were found as follow: CO(2) activation temperature of 750 degrees C, CO(2) activation time of 2.29 h and KOH:char impregnation ratio of 2.91, which resulted in 191.73 mg/g of 2,4,6-TCP uptake and 20.16 % of activated carbon yield.

The role of pH in nanofiltration of atrazine and dimethoate from aqueous solution.

This study examined the performance of nanofiltration membranes to retain atrazine and dimethoate in aqueous solution under different pH conditions. Four nanofiltration membranes, NF90, NF200, NF270 and DK are selected to be examined. The operating pressure, feed pesticide and stirring rate were kept constant at 6x10(5) Pa, 10 mg/L and 1000 rpm. It was found that increasing the solution's pH increased atrazine and dimethoate rejection but reduced the permeate flux performance for NF200, NF270 and DK. However, NF90 showed somewhat consistent performance in both rejection and permeate flux regardless of the solution's pH. NF90 maintained above 90% of atrazine rejection and approximately 80% of dimethoate rejection regardless of the changes in solution's pH. Thus, NF90 is deemed the more suitable nanofiltration membrane for atrazine and dimethoate retention from aqueous solution compared to NF200, NF270 and DK.

Dimethoate and atrazine retention from aqueous solution by nanofiltration membranes.

In order to produce sufficient food supply for the ever-increasing human population, pesticides usage is indispensable in the agriculture sector to control crop losses. However, the effect of pesticides on the environment is very complex as undesirable transfers occur continually among different environmental sections. This eventually leads to contamination of drinking water source especially for rivers located near active agriculture practices. This paper studied the application of nanofiltration membrane in the removal of dimethoate and atrazine in aqueous solution. Dimethoate was selected as the subject of study since it is being listed as one of the pesticides in guidelines for drinking water by World Health Organization. Nevertheless, data on effectiveness of dimethoate rejection using membranes has not been found so far. Meanwhile, atrazine is classified as one of the most commonly used pesticides in Malaysia. Separation was done using a small batch-type membrane separation cell with integrated magnetic stirrer while concentration of dimethoate and atrazine in aqueous solution was analyzed using high performance liquid chromatography (HPLC). Four nanofiltration membranes NF90, NF200, NF270 and DK were tested for their respective performance to separate dimethoate and atrazine. Of all four membranes, NF90 showed the best performance in retention of dimethoate and atrazine in water.

Optimization of basic dye removal by oil palm fibre-based activated carbon using response surface methodology.

Oil palm fibre was used to prepare activated carbon using physiochemical activation method which consisted of potassium hydroxide (KOH) treatment and carbon dioxide (CO(2)) gasification. The effects of three preparation variables: the activation temperature, activation time and chemical impregnation (KOH:char) ratio on methylene blue (MB) uptake from aqueous solutions and activated carbon yield were investigated. Based on the central composite design (CCD), a quadratic model and a two factor interaction (2FI) model were respectively developed to correlate the preparation variables to the MB uptake and carbon yield. From the analysis of variance (ANOVA), the significant factors on each experimental design response were identified. The optimum activated carbon prepared from oil palm fibre was obtained by using activation temperature of 862 degrees C, activation time of 1h and chemical impregnation ratio of 3.1. The optimum activated carbon showed MB uptake of 203.83 mg/g and activated carbon yield of 16.50%. The equilibrium data for adsorption of MB on the optimum activated carbon were well represented by the Langmuir isotherm, giving maximum monolayer adsorption capacity as high as 400mg/g at 30 degrees C.

Porous (PVDF-HFP/PANI/GO) ternary hybrid polymer electrolyte membranes for lithium-ion batteries.

A poly(vinylidene co-hexafluoropropylene) (PVDF-HFP) membrane is functionalized with polyaniline (PANI) and graphene oxide (GO) nanoparticles. The obtained PVDF-HFP polymer electrolyte membranes (PEMs) have been characterized and implemented in lithium-ion batteries. As a result, the PVDF-HFP/PANI membrane shows the highest ionic conductivity (IC) of 1.04 × 10-3 mS cm-1 compared to pristine PVDF-HFP and PVDF-HFP/PANI/GO ternary membrane; however, PANI addition decreases the tensile strength of the PVDF-HFP membrane from 4.2 MPa to 2.8 MPa. Therefore, GO is introduced to recover the reduced mechanical strength of the PVDF-HFP/PANI membrane. The obtained PVDF-HFP/PANI/GO ternary membrane shows a remarkable improvement in tensile strength of up to 8.8 MPa; however, slight reduction is observed in the ionic conductivity of 6.64 × 10-4 mS cm-1. Furthermore, the PVDF-HFP/PANI/GO ternary membrane exhibits outstanding thermal and mechanical stabilities, improved morphology, highest electrolyte uptake (367.5%) and an excellent porosity of around 89%. Moreover, the PVDF-HFP/PANI/GO ternary PEM has been successfully applied in a lithium-ion battery, which can retain over 95% capacity after 30 cycles. Therefore, the proposed PVDF-HFP/PANI/GO ternary membrane can be a promising candidate as a separator in future lithium-ion batteries.