Sequential Addition Method Research Articles

Anodised TiO2 nanotubes as a scaffold for antibacterial silver nanoparticles on titanium implants

Medical grade titanium alloy is widely used for bone/dental implants, but the material alone has no innate antimicrobial properties that would reduce infection risk following surgery. However, silver nanoparticles (Ag NPs) are known to be antibacterial. This study investigated the growth of Ag NPs on titanium dioxide nanotubes (TiO2 NTs) on Ti-6Al-4V discs. The TiO2 NTs were grown on the Ti alloy using an electrochemical method, and then decorated with Ag NPs. The Ag NPs were synthesised by chemical reduction using δ-gluconolactone. A silver ammonia solution (silver nitrate + liquid ammonia) was used as the source of silver. Two separate approaches were used: (1) The δ-gluconolactone was mixed with the silver ammonia and then exposed to the TiO2 NTs (the ‘mixing method’), which produced micron-sized clusters of the Ag NPs. (2) The TiO2 NTs were exposed to the silver ammonia first and then to δ-gluconolactone (the ‘sequential addition method’), which resulted in the formation of nano-sized clusters of the nanoparticles. The Ag-TiO2 composites were confirmed by scanning electron microscopy and the elements analysed using energy dispersive X-ray spectroscopy (EDS). The composite coatings were exposed to a simulated body fluid for 24 h in order to determine the total Ag released. The release from the micron-sized clusters from the mixing method (14.6 ± 0.67 ppm) was higher than that from the nano-sized clusters (4.05 ± 0.36 ppm) when 0.015 M of silver ammonia was used. Additionally, Staphylococcus aureus, was cultured on the composite coatings for 24 h. Both the micron- and nano-sized clusters of the Ag NPs were found to be antibacterial using the Live/Dead assay. Overall, δ-gluconolactone was successfully used to reduce silver to Ag NPs on the surface of TiO2 NTs. The sequential addition method was the preferred method of synthesis because of its slower silver release, better coverage of the Ag-NPs on the TiO2 NTs and strong antibacterial properties.

Heat transfer simulations of selective laser melting process based on volumetric heat source with powder size consideration

Three-dimensional finite element heat transfer simulations with new volumetric heat source are performed to estimate the size of the melt pool cross-section during Selective Laser Melting (SLM). The simulations are based on a new volumetric heat source which takes into account the effect of the powder size distribution on the propagation of the laser energy through the depth of the metal powder layer. In modeling the volumetric heat source, a modified sequential addition method is used to construct the metal powder layer with different powder particle sizes and the absorptivity profile along the depth of the powder layer is then calculated by means of Monte Carlo ray-tracing simulations. It is shown that the peak melt pool temperature obtained in the present simulations (3005 K) is in better agreement with the experimental value than that obtained in previous simulation studies. Furthermore, the peak temperature is lower than the evaporation point of the powder particle layer, and is hence consistent with the stable melt track reported in experimental studies. To further confirm the validity of the proposed finite element heat transfer model, the simulation results obtained for the contact width between the melt pool and the substrate and the width of the powder-consumed band are compared with the experimental results and simulation findings presented in the literature. Finally, simulations are performed to predict the stability condition of a single scan melt track in the SLM process. The prediction results are shown to be consistent with the experimental findings.

Analysis of Scattering and Absorption Characteristics of Metal Powder Layer for Selective Laser Sintering

A modified sequential addition method is proposed for simulating the deposition of the metal powder layers used in selective laser sintering (SLS) process. The scattering characteristics of the deposited layers are analyzed by means of Monte Carlo ray-tracing simulations and a gray-level co-occurrence matrix (GLCM) method. The validity of the proposed modeling approach is demonstrated by comparing simulation results for the gray-scale properties of the scattered image and the absorption coefficient of the metal powder layer with the experimental results obtained using a scanned laser pico-projection (SLPP) detection method and the simulation findings presented in the literature, respectively. Further simulations are then performed to investigate the effect of the metal powder packing density on the scattering characteristics and absorption of metal powder layers. The results show that a higher packing density leads to a lower scattering effect and a greater absorptivity. In addition, as compared with the characteristics of scattering and absorption of metal powder layers with different size distributions, it is shown that a bimodal distribution of the powder particle size results in the lowest scattering effect and the highest absorptivity given an appropriate specification of distribution parameters for powder structures used in SLS.

The sequential addition and migration method to generate representative volume elements for the homogenization of short fiber reinforced plastics

We present an algorithm for generating volume elements of short fiber reinforced plastic microstructures for prescribed fourth order fiber orientation tensor, fiber aspect ratio and solid volume fraction. The algorithm inserts fibers randomly into an existing microstructure, and removes the resulting overlap systematically based on a gradient descent method. In contrast to existing methods, large fiber aspect ratios (up to 150) and large volume fractions (60 vol% for isotropic orientation and aspect ratio of 33) can be reached. We study the effective linear elastic properties of the resulting microstructures, depending on fiber orientation, volume fraction as well as aspect ratio, and examine the size of a corresponding representative volume element.

On the behaviour of Eu oxo-species in molten NaBr–NaI (0.77:0.23) mixture at 973 K

ABSTRACTThe interaction of Eu2O3 with molten NaBr–NaI (0.77:0.23) mixture at 973 K was studied by sequential addition method with the use of YSZ membrane oxygen electrode for controlling of course of the process. The Red-Ox process is accompanied with formation of EuO in the melt. The total solubility of EuO (sum of concentration of Eu2+, O2–, non-dissociated EuO) in the molten NaBr–NaI at 973 K (mole fraction 2.7 × 10–4) is considerably lower than in pure NaI melt (4.2 × 10–4), which can be explained using the ‘hole’ model by reduction of a number of holes of comparable with EuO particle size because of addition of smaller bromide ion to the iodide melt.The solubility of EuO is appreciably affected by its dispersity and the value of surface energy causing these solubility changes is estimated as 37 J m–2.

Biotransformation of prochiral sulfides into (R)-sulfoxides using immobilized Gordonia terrae IEGM 136 cells

Biotransformation of methyl phenyl sulfide (MPS) into optically active (R)-sulfoxide was optimized using Gordonia terrae IEGM 136 cells immobilized into cryogel of polyvinyl alcohol. Biotransformation time of 0.5g/L MPS was shortened from 144 to 24h in comparison with free cells. Immobilized Gordonia cells were resistant to high (up to 1.5g/L) sulfide concentrations and catalyzed its complete bioconversion into (R)-sulfoxide (95% ee) within 72h. Using a sequential addition method, the total load of MPS reached 4.25g/L. At that, MPS bioconversion was 96.9% and the enantiomeric excess (ee) value of the target (R)-sulfoxide was as high as 96%. Possible reuse of immobilized cells for MPS biotransformation was experimentally proved. The obtained biocatalyst showed a high activity towards ethyl phenyl sulfide, benzyl methyl sulfide, methyl p-tolyl sulfide and formed corresponding (R)-sulfoxides with 77–95% ee. Putative pathways for sulfide oxidation by Gordonia cells were proposed.

Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both cancer cells and cancer stem cells.

Electrochemiluminescence Quenching by Halide Ions at Bipolar Electrodes

Quenching of Ru(bpy)32+ electrochemiluminescence (ECL) by Cl−, Br−, and I− ions was studied as a function of halide concentration in a bipolar electrochemical cell. All of the halides investigated showed similar qualitative behavior: above a critical concentration, ECL intensity was found to decrease linearly as the halide ion concentration was increased, due to dynamic quenching of Ru(bpy)32+ ECL. Stern-Volmer slopes (KSV) of 0.111±0.003, 4.2±0.3, and 6.2±0.3 mM−1 were measured for Cl−, Br− and I−, respectively. The magnitude of KSV correlates with halide ion oxidation potential, consistent with an electron transfer quenching mechanism. Using the bipolar platform described herein, aqueous, halide-containing solutions could be quantified rapidly using the sequential standard addition method. The lower detection limit is determined by a complex mechanism involving the competitive electrooxidation of halide ions and the ECL co-reactants, as well as the passivation of the surface of the bipolar electrode, and was found to be 0.20±0.01, 0.08±0.01 and 10±1 mM, respectively, for I−, Br−, and Cl−. The performance of the bipolar ECL quenching assay is comparable to previously published fluorescence quenching methods for the determination of halide ions, while being much simpler and less expensive to implement.

An in vivo evaluation of amphiphilic, biodegradable peptide copolymers as siRNA delivery agents

A series of amphiphilic, biodegradable polypeptide copolymers were prepared for the delivery of siRNA (short interfering ribonucleic acid). The molecular weight (or polymer chain length) of the linear polymer was controlled by reaction stoichiometry for the 11.5, 17.2, and 24.6 kDa polypeptides, and the highest molecular weight polypeptide was prepared using a sequential addition method to obtain a polypeptide having a molecular weight of 38.6 kDa. These polymers were used to prepare polymer conjugate systems designed to target and deliver an apolipoprotein B (ApoB) siRNA to hepatocyte cells and to help delineate the effect of polymer molecular weight or polymer chain length on siRNA delivery in vivo. A clear trend in increasing potency was found with increasing molecular weight of the polymers examined (at a constant polymer:siRNA (w/w) ratio), with minimal toxicity found. Furthermore, the biodegradability of these polymer conjugates was examined and demonstrates the potential of these systems as siRNA delivery vectors.

Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: Mineralization and its effect on tumor targetability in vivo

The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery. In this study, to develop biostable nanoparticles with high tumor targetability, poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method. The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153.7±4.5nm) than bare PEG-HANPs (265.1±9.5nm), implying that mineralization allows the formation of compact nanoparticles. Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions (<pH6.5), their sizes increased rapidly due to dissolution of the inorganic minerals. Doxorubicin (DOX), chosen as the model anticancer drug, was effectively encapsulated into the bare and mineralized nanoparticles. For bare PEG-HANPs, DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution. On the other hand, DOX release from M-PEG-HANPs was pH-dependent: i.e. DOX was slowly released from nanoparticles under physiological condition (pH7.4), whereas its release rates were much higher at mildly acidic environments (<pH6.5). From in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs. The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice. Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs. Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.

Synthesis of stimuli-responsive PEO-based triblock copolymers and their applications for preparation of iron oxide nanoparticles

In this paper, the important and useful method for manufacturing superparamagnetic iron oxide nanoparticles stabilized by water-soluble poly(ethylene oxide) (PEO)-based triblock copolymers showing stimuli-responsive phase transition is introduced. Triblock copolymers, such as poly(ethylene oxide-b-N-vinylimidazole-b-3-(methacrylamino)phenylboronic acid) (PEO-b-PVIm-b-PMAPBA), poly(ethylene oxide-b-N-vinylpyrrolidone-b-3-(methacrylamino)phenylboronic acid) (PEO-b-PVP-b-PMAPBA), and poly(ethylene oxide-b-N-vinylimidazoleb-maleic acid) (PEO-b-PVIm-b-PMAc), were synthesized using the sequential monomer addition method via reversible addition fragmentation chain transfer (RAFT) radical block copolymerizations of the corresponding monomers, using PEO-based RAFT agent. After complete polymerization of N-vinylimidazole or N-vinylpyrrolidone in dimethylformamide (DMF) at 110 °C, 3-(methacrylamino)phenylboronic acid (MAPBA) was polymerized in DMF at 90 °C for 24 h, and N-phenylmaleimide was polymerized in dimethylsulfoxide (DMSO) at 110 °C for 28 h. All the block copolymers were water-soluble and efficient enough to stabilize the surface of nano-sized iron oxide particles in water. The nanoparticles were stable in neutral aqueous media for at least one month. The resulting products were characterized by a combination of 1H nuclear magnetic resonance spectroscopy (NMR), size exclusion chromatography, transmission electron microscopy (TEM), electron diffraction pattern, and phase transition behavior of the block copolymers using UV/visible spectrophotometer. Open image in new window

Deprotonation reaction of α-amino acid N-carboxyanhydride at 4-CH position by yttrium tris[bis(trimethylsilyl)amide

Reaction of yttrium tris[bis(trimethylsilyl)amide] [(TMSN)3Y] with equivalent L-alanine N-carboxyanhydride (ALA NCA) yields yttrium α-isocyanato carboxylate (II), yttrium ketenyl carbamate (III), and hexamethyldisilazane (V). The products indicate that 4-CH group of ALA NCA monomer is deprotonated in addition to 3-NH group, which has been neglected in NCA chemistry for decades. This result proves the acidity of 4-CH in NCA and provides the first direct evidence for racemization phenomenon of NCA in strong base in microscopic aspect. Rare earth tris[bis(trimethylsilyl)amide] (TMSN)3Ln (Ln = Sc, Y, La, Dy, and Lu) compounds are high efficient catalysts for ring-opening polymerizations of NCAs. Polypeptides can be produced in quantitative yields with narrow molecular weight distributions below 1.3, and block copolypeptides can be facilely prepared by sequential addition method. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Synthesis of PEO-based glucose-sensitive block copolymers and their application for preparation of superparamagnetic iron oxide nanoparticles

Amphiphilic block copolymers were synthesized by reversible addition fragmentation chain transfer (RAFT) radical block polymerization of N-vinylimidazole and 3-(methacrylamido)phenylboronic acid using poly (ethylene oxide) (PEO)-based xanthate type of RAFT agent and 2,2′-azobisisobutyronitrile (AIBN) in dimethylformaide (DMF) at 90∼110 °C for 24 h. Poly(ethylene oxide-b-3-(methacrylamido)phenylboronic acid) and poly(ethylene oxide-b-N-vinylimidazole-b-3-(methacrylamido)phenylboronic acid) were prepared successfully through the sequential monomer addition method. Both block copolymers were found to exhibit glucose-responsive behavior via the feasibility test for complex formation with Alizarin Red S (ARS). The ratio of molecular weight of the poly(N-vinyimidazole) to the poly(3-(methacrylamido)phenylboronic acid) appeared to play an important role in the pH- & glucose-responsive behavior. The resulting block copolymers were used successfully as polymeric stabilizers to prepare water-soluble Fe3O4 nanoparticles. All the materials were characterized by the combination of 1H nuclear magnetic resonance (NMR), size exclusion chromatography (SEC), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and x-ray diffraction (XRD) analyses.

Effects of Different Reactive Oxyanionic Initiators on the Anionic Polymerizaition of n-Hexyl Isocyanate

Poly(n-hexyl isocyanate) was synthesized by anionic polymerization using various oxy-initiators, including sodium phenoxide (Na-PO), sodium benzhydroxide (Na-BH), and sodium methoxyphenylethoxide (Na-MPE). We optimized polymerization conditions. To confirm the living natures of the polymerization, we carried out various polymerizations changing mole ratio between monomers and initiators and a postpolymerization by sequential monomer addition method. Our results indicated that the anionic polymerization of n-hexyl isocyanate was not controlled using Na-PO and Na-MPE. However, Na-BH as an initiator is favorable for the living anionic polymerization of n-hexyl isocyanate because it has a dual function in the initiation and in the efficient prevetion of trimerization by reducing the reactivity at the growth chain ends. Polymers were thus synthesized with predictable molecular weights (MW), narrow molecular weight distributions (MWD), and high yields.

Processes of Europium Oxide Dissolution in Molten Alkali Metal Iodides

The interactions of Eu2+ with oxide ions and the processes accompanying dissolution of Eu2O3 in molten CsI and NaI at 700 °C were studied by a potentiometric method and sequential addition method with electrochemical control of the saturation. An electrochemical cell with a membrane oxygen electrode Pt(O2)|ZrO2(Y2O3) was used for determination of the equilibrium molality of O2−. The solubility products of EuO are equal to PEuO = 7.94·10−14 mol2·kg−2 in molten CsI and 2.24·10−9 mol2·kg−2 in molten NaI. In the latter melt EuO is referred to as a weak base since its dissociation constant is 2.0·10−6. The interaction of Eu2O3 with both molten iodides leads to the formation of EuO and O2− in the solutions, which contain approximately 4·10−4 mol·kg−1 EuO in CsI and 4·10−3 mol·kg−1 EuO in NaI melts, and the dissociation of EuO in the melts is suppressed. The behavior of Eu oxo-species in the iodide melts is subjected to predictions of the Pearson “hard” and “soft” acids and bases concept. The admixtures formed by Eu2O3 dissolution in the molten iodides essentially affect the luminescence properties of single crystals grown from the saturated solutions as compared with the pure iodides. The obtained thermodynamic data permit consideration of Eu2+ as a good scavenger for the CsI melt, but it is not available for molten NaI.

No association of dysbindin with symptom factors of schizophrenia in an Irish case–control sample

Robust associations between the dysbindin gene (DTNBP1) and schizophrenia have been demonstrated in many but not all samples, and evidence that this gene particularly predisposes to negative symptoms in this illness has been presented. The current study sought to replicate the previously reported negative symptom associations in an Irish case-control sample. Association between dysbindin and schizophrenia has been established in this cohort, and a factor analysis of the assessed symptoms yielded three factors, Positive, Negative, and Schneiderian. The sequential addition method was applied using UNPHASED to assess the relationship between these symptom factors and the high-risk haplotype. No associations were detected for any of the symptom factors indicating that the dysbindin risk haplotype does not predispose to a particular group of symptoms in this sample. Several possibilities, such as differing risk haplotypes, may explain this finding.

Synthesis of new pH-sensitive poly(ethylene oxide-b-maleic acid) from modification of poly(ethylene oxide-b-N-phenylmaleimide)

A new and useful poly(ethylene oxide)-based pH-sensitive block copolymer is introduced. Poly(ethylene oxide-b-N-phenylmaleimide) was first synthesized by anionic polymerization of N-phenylmaleimide (N-PMI) using mixed alkali metal polymeric alkoxide by sequential monomer addition method in the mixture of benzene/THF/ DMSO (10/5/3, v/v/v) at room temperature. Reductive deimidation of the resulting block copolymer was performed using hydrazine monohydrate leading to the formation of the corresponding pH-sensitive poly(ethylene oxide-bmaleic acid).

Enhancing trends of intensity signal of trace level Hf in zirconium oxide using AES sequential addition method

A sensitive, rapid and simple method to detect Hf at trace level in Zr has been described. It is based on the sequential addition of sample after each pre excitation period, in presence of graphite as buffer. The improvement with respect to the other published procedures lies in the use of solid powdered sample, omitting the step of wet chemistry or use of any optical filter. The enhancing trends of intensity curves were also studied for various stages. The coefficient of variation was found to be within the range 6 - 12% for different batches of samples. The detection limit was found to be 30 µgg-1. The improved sensitivity, accuracy and rapidity make it suitable for routine evaluation of Hf using emission spectroscopy. Key words: Hafnium, zirconium, intensity, AES.

Use of phenotypic covariates in association analysis by sequential addition of cases

Optimal use of phenotype information is important in complex disease gene mapping. We describe a method, sequential addition, for the analysis of case-control data by taking into account of a quantitative trait that is measured in cases but not in controls. The method also provides an estimate of the best phenotype definition for future studies. We demonstrate proof of principle, using an example of incorporation of age-at-onset data into a study of a small sample for association between APOE and late-onset Alzheimer's disease. The sequential addition method finds evidence of association when conventional case-control methods fail. We also illustrate the use of the method for taking account of a dimensional measure of psychosis in a study of the schizophrenia susceptibility gene, dysbindin, in bipolar disorder.

Atom Transfer Radical Block Copolymerization of 2‐(N,N‐Dimethylamino)ethyl Methacrylate and 2‐Hydroxyethyl Methacrylate

AbstractBlock copolymerization of 2‐(N,N‐dimethylamino)ethyl methacrylate (DMAEMA) with 2‐hydroxyethyl methacrylate (HEMA) via atom transfer radical polymerization (ATRP) was studied in methanol using a macroinitiator method and a “one‐pot” sequential addition method. The polymerization sequence of the two monomers strongly affected the block copolymer formation. When DMAEMA was used as the first monomer, both methods produced block copolymer samples containing significant amounts of DMAEMA homopolymer chains, because of the elimination of active halogen chain‐ends during the preparation of polyDMAEMA. Well‐controlled block copolymers with various block lengths were obtained via the macroinitiator method when polyHEMA was used as macroinitiator to initiate the polymerization of DMAEMA. The sequential addition method, in which HEMA was polymerized first with 90% conversion and DMAEMA was subsequently added, also yielded controlled block copolymers when the polymerization was carried out at room temperature with the DMAEMA conversion below 60%. Increasing the temperature to 60 °C promoted the copolymerization rate but the reaction suffered from gel formation. The addition of water to the system accelerated the polymerization rate, but led to the loss of the system livingness.Gel permeation chromatograms of poly(HEMA‐b‐DMAEMA). The samples were prepared in methanol at room temperature with different block molecular weights using the macroinitiator method.magnified imageGel permeation chromatograms of poly(HEMA‐b‐DMAEMA). The samples were prepared in methanol at room temperature with different block molecular weights using the macroinitiator method.