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.

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.

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.

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.

Preparation of magnetic, macro-reticulated cross-linked chitosan for tetracycline removal from aquatic systems.

A novel adsorbent, magnetic, macro-reticulated cross-linked chitosan (MRC) was synthesised for the removal of tetracycline (TC) from water using a source of biogenic waste (gastropod shells) as a pore-forming agent. The insertion of crosslinks into the chitosan frame was confirmed by FTIR analysis, while the stability of the MRC was demonstrated via a stability test performed in an acidic solution. The enhanced porosity of the MRC was confirmed by the evaluation of its porosity, a swelling test and the determination of its specific surface area. The time-concentration profile of the sorption of TC onto the MRC demonstrated that equilibrium was attained relatively quickly (120 min), and the data obtained fitted a pseudo second order (r(2)>0.99) kinetic equation better than a pseudo first order or reversible first order kinetic equation. The optimisation of process variables indicated that the sorption of TC onto the MRC was favoured at a low solution pH and that the presence of organics (simulated by the addition of humic acid) negatively impacted the magnitude of TC removal. The area of coverage of TC on the MRC (2.51 m(2)/g) was low compared to the specific surface area of the MRC (47.95 m(2)/g). The value of the calculated energy of adsorption of TC onto the MRC was 100 kJ/mol, which is far above the range of 1-16 kJ/mol stipulated for physical adsorption.

Electrophoretic interactions between nitrocellulose membranes and proteins: Biointerface analysis and protein adhesion properties.

Protein adsorption onto membrane surfaces is important in fields related to separation science and biomedical research. This study explored the molecular interactions between protein, bovine serum albumin (BSA), and nitrocellulose films (NC) using electrokinetic phenomena and the effects of these interactions on the streaming potential measurements for different membrane pore morphologies and pH conditions. The data were used to calculate the streaming ratios of membranes-to-proteins and to compare these values to the electrostatic or hydrophobic attachment of the protein molecules onto the NC membranes. The results showed that different pH and membrane pore morphologies contributes to different protein adsorption mechanisms. The protein adsorption was significantly reduced under conditions where the membrane and protein have like-charges due to electrostatic repulsion. At the isoelectric point (IEP) of the protein, the repulsion between the BSA and the NC membrane was at the lowest; thus, the BSA could be easily attached onto the membrane/solution interface. In this case, the protein was considered to be in a compact layer without intermolecular protein repulsions.

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.

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.

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.

Interaction of isothermal phase inversion and membrane formulation for pathogens detection in water.

The aim of this study was to explore the utilization of polymeric membrane for bio-sensing application in most efficient and rapid way. Customization of membrane formulation via phase separation study to modify its morphologies and properties enable the detection of different pathogens in a specific manner. Experimental findings (FESEM, through-pore distribution, porosity, capillary flow test and protein binding test) verified the predictions of faster capillary flow time and higher membrane's protein binding by the addition of cellulose acetate and nitrocellulose to the membrane casting dope, respectively. Throughout the phase separation study, the potential phase behavior was investigated, which was correlating various membrane structures to its performances for potential pathogens detection in water.

A comparative study on the membrane based palm oil mill effluent (POME) treatment plant.

The discharge of palm oil mill effluent (POME) causes serious pollution problems and the membrane based POME treatment is suggested as a solution. Three different designs, namely Design A, B and C distinguished by their different types and orientations of membrane system are proposed. The results at optimum condition proved that the quality of the recovered water for all the designs met the effluent discharge standards imposed by the Department of Environment (DOE). The economic analysis at the optimum condition shows that the total treatment cost for Design A was the highest (RM 115.11/m(3)), followed by Design B (RM 23.64/m(3)) and Design C (RM 7.03/m(3)). In this study, the membrane system operated at high operating pressure with low membrane unit cost is preferable. Design C is chosen as the optimal design for the membrane based POME treatment system based on the lowest total treatment cost.

Sustainable biocatalytic synthesis of L-homophenylalanine as pharmaceutical drug precursor.

Over the past decade, L-homophenylalanine is extensively used in the pharmaceutical industry as a precursor for production of angiotensin-converting enzyme (ACE) inhibitor, which possesses significant clinical application in the management of hypertension and congestive heart failure (CHF). A number of chemical methods have been reported thus far for the synthesis of L-homophenylalanine. However, chemical methods generally suffer from process complexity, high cost, and environmental pollution. On the other hand, enantiomerically pure L-homophenylalanine can be obtained elegantly and efficiently by employing biocatalytic methods, where it appears to be the most attractive process in terms of potential industrial applications, green chemistry and sustainability. Herein we review the biocatalytic synthesis of vital L-homophenylalanine as potentially useful intermediate in the production of pharmaceutical drugs in environmentally friendly conditions, using membrane bioreactor for sustainable biotransformation process. One envisages the future prospects of developing an integrated membrane bioreactor system with improved performance for L-homophenylalanine production.

Removal of disperse dye from aqueous solution using waste-derived activated carbon: optimization study.

The purpose of this work is to obtain optimal preparation conditions for activated carbons prepared from rattan sawdust (RSAC) for removal of disperse dye from aqueous solution. The RSAC was prepared by chemical activation with phosphoric acid using response surface methodology (RSM). RSM based on a three-variable central composite design was used to determine the effect of activation temperature (400-600 degrees C), activation time (1-3h) and H(3)PO(4):precursor (wt%) impregnation ratio (3:1-6:1) on C.I. Disperse Orange 30 (DO30) percentage removal and activated carbon yield were investigated. Based on the central composite design, quadratic model was developed to correlate the preparation variables to the two responses. The most influential factor on each experimental design responses was identified from the analysis of variance (ANOVA). The optimum conditions for preparation of RSAC, which were based on response surface and contour plots, were found as follows: temperature of 470 degrees C, activation time of 2h and 14min and chemical impregnation ratio of 4.45.

Preparation of oil palm empty fruit bunch-based activated carbon for removal of 2,4,6-trichlorophenol: optimization using response surface methodology.

The effects of three preparation variables: CO(2) activation temperature, CO(2) activation time and KOH:char impregnation ratio (IR) on the 2,4,6-trichlorophenol (2,4,6-TCP) uptake and carbon yield of the activated carbon prepared from oil palm empty fruit bunch (EFB) were investigated. Based on the central composite design, two quadratic models were developed to correlate the three preparation variables to the two responses. The activated carbon preparation conditions were optimized using response surface methodology by maximizing both the 2,4,6-TCP uptake and activated carbon yield within the ranges studied. The optimum conditions for preparing activated carbon from EFB for adsorption of 2,4,6-TCP were found as follows: CO(2) activation temperature of 814 degrees C, CO(2) activation time of 1.9h and IR of 2.8, which resulted in 168.89 mg/g of 2,4,6-TCP uptake and 17.96% of activated carbon yield. The experimental results obtained agreed satisfactorily with the model predictions. The activated carbon prepared under optimum conditions was mesoporous with BET surface area of 1141 m(2)/g, total pore volume of 0.6 cm(3)/g and average pore diameter of 2.5 nm. The surface morphology and functional groups of the activated carbon were respectively determined from the scanning electron microscopy and Fourier transform infrared analysis.

Adsorption isotherms, kinetics, thermodynamics and desorption studies of 2,4,6-trichlorophenol on oil palm empty fruit bunch-based activated carbon.

The adsorption characteristics of 2,4,6-trichlorophenol (TCP) on activated carbon prepared from oil palm empty fruit bunch (EFB) were evaluated. The effects of TCP initial concentration, agitation time, solution pH and temperature on TCP adsorption were investigated. TCP adsorption uptake was found to increase with increase in initial concentration, agitation time and solution temperature whereas adsorption of TCP was more favourable at acidic pH. The adsorption equilibrium data were best represented by the Freundlich and Redlich-Peterson isotherms. The adsorption kinetics was found to follow the pseudo-second-order kinetic model. The mechanism of the adsorption process was determined from the intraparticle diffusion model. Boyd plot revealed that the adsorption of TCP on the activated carbon was mainly governed by particle diffusion. Thermodynamic parameters such as standard enthalpy (DeltaH degrees ), standard entropy (DeltaS degrees ), standard free energy (DeltaG degrees ) and activation energy were determined. The regeneration efficiency of the spent activated carbon was high, with TCP desorption of 99.6%.