Premix Solution Research Articles

Light Chain of Factor VIII Is Sufficient for Accelerating Cleavage of von Willebrand Factor by ADAMTS13 Metalloprotease

We previously demonstrated that coagulation factor VIII (FVIII) accelerates proteolytic cleavage of von Willebrand factor (VWF) by A disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS13) under fluid shear stress. In this study, the structural elements of FVIII required for the rate-enhancing effect and the biological relevance of this cofactor activity are determined using a murine model. An isolated light chain of human FVIII (hFVIII-LC) increases proteolytic cleavage of VWF by ADAMTS13 under shear in a concentration-dependent manner. The maximal rate-enhancing effect of hFVIII-LC is ∼8-fold, which is comparable with human full-length FVIII and B-domain deleted FVIII (hFVIII-BDD). The heavy chain (hFVIII-HC) and the light chain lacking the acidic (a3) region (hFVIII-LCΔa3) have no effect in accelerating VWF proteolysis by ADAMTS13 under the same conditions. Although recombinant hFVIII-HC and hFVIII-LCΔa3 do not detectably bind immobilized VWF, recombinant hFVIII-LC binds VWF with high affinity (K(D), ∼15 nM). Moreover, ultra-large VWF multimers accumulate in the plasma of fVIII(-/-) mice after hydrodynamic challenge but not in those reconstituted with either hFVIII-BDD or hFVIII-LC. These results suggest that the light chain of FVIII, which is not biologically active for clot formation, is sufficient for accelerating proteolytic cleavage of VWF by ADAMTS13 under fluid shear stress and (patho) physiological conditions. Our findings provide novel insight into the molecular mechanism of how FVIII regulates VWF homeostasis.

Gelcasting of BeO

Aqueous gel-casting of beryllia using polyelectrolyte NH4PAA as a dispersant has been investigated. The effects of the dispersant amount, pH values on the surface properties of BeO powders in aqueous solvent were studied and high solids loading BeO suspension (45 vol.%) was developed. A premix solution containing 15-20 wt.% of AM monomer can provide enough mechanical strength for the green body obtained from 45 vol.% BeO suspension. SEM photography indicates that BeO ceramics with homogeneous microstructure can be fabricated. The thermal conductivity of sintered green body is 182.1±10 W/(m.K). Gelcasting is a suitable process to form BeO ceramic parts.

Process dependant setting behavior of aqueous gelcast AlN slurries

In this study, AlN powder modified to improve anti-hydrolysis property with aluminum dihydrogen phosphate and phosphoric acid by mechanical milling was applied to prepare M-AlN gelcasting slurry. The effect of various parameters such as concentration of monomer and crosslinker, amount of initiator, solid content and temperature on the idle time was discussed for low-toxic N,N-dimethylacrylamide and N,N′-methylenbisacrylamide (DMAA and MBAM) system. The results suggested that the idle time of M-AlN gelcasting slurries decreased with increasing concentration of monomer and crosslinker, amount of initiator, temperature and the volume fraction of M-AlN. The calculated activation energy of 52.5vol.% M-AlN was 29.46kJ/mol. The M-AlN green body with optimum bulk density and maximum flexural strength was obtained when the amount of APS was 1.2wt.% (on the monomers base), polymerization temperature was 65°C, and polymerization time was 60min for constant DMAA and MBAM (10wt.%, 1wt.% in the premix solution, respectively) in 52.5vol.% M-AlN slurry. The bulk density of AlN sintered ceramic is greater than 3.27g/cm3, which presents relative density value of 99.3% of theoretical.

Pharmaceutical development and preliminary clinical testing of an oral solid dispersion formulation of docetaxel (ModraDoc001)

For use in chronic oral chemotherapeutic regimens, the potent anticancer drug docetaxel needs a solid oral dosage form. Because docetaxel has a very low permeability and a very low aqueous solubility (biopharmaceutical classification system class IV), a pharmacokinetic booster was combined with a newly developed solid dispersion formulation to improve the oral bioavailability of docetaxel. The best performing solid dispersion was a 1/9/1 w/w/w ternary mixture of docetaxel, polyvinylpyrrolidone (PVP)-K30 and sodium lauryl sulphate (SLS). In a phase I clinical trial, with ritonavir as pharmacokinetic booster, the docetaxel premix solution (TAXOTERE) was pharmacokinetically evaluated against the solid dispersion formulation filled into hard gelatin capsules (ModraDoc001 15 mg capsules). There were no significant differences between the pharmacokinetic parameters of docetaxel after administration of docetaxel premix solution or ModraDoc001 15 mg capsules, although there was a trend towards a higher and more variable exposure to docetaxel after oral administration of docetaxel premix solution (513 ± 219 vs. 790 ± 669 ng h/mL). The low inter-individual variability of docetaxel exposure (44%), the dosing accuracy, and the absence of ethanol and polysorbate are major advantages of ModraDoc001 15 mg capsules over docetaxel premix solution.

An assessment of the effectiveness of 5-methylthioninhydrin within dual action reagents for latent fingerprint development on paper substrates

A critical investigation of 5-methylthioninhydrin (5MTN) is presented as a 'dual action' formulation component for the development of latent finger marks on paper substrates. Preparation of a dual action reagent was performed by combining proportions of 5MTN and zinc chloride (ZnCl(2)) in a pre-mixed solution. Developed prints (deposited on filter paper substrates) could be subsequently visualised in both colour and fluorescence modes. Finger mark quality was graded using a quartered print approach for a number of reagent compositions to deliver an optimised formulation recipe. To fully appraise 5MTN in comparison to currently employed chemistries, this reagent was evaluated against three alternative amino acid selective reagents, ninhydrin, 1,8-diazafluorenone (DFO) and 1,2-indandione/ZnCl(2). Six common paper types were used for this purpose and split depletion finger marks from six donors were collected. Finger mark sets were also left for two days or two weeks to show the effect of ageing on development quality. For the first time, it was shown that 5MTN/ZnCl(2) is effective as a 'dual action' reagent under the United Kingdom climate conditions. However, results presented herein show that the existing recommended chemistries and the 1,2 indandione/ZnCl(2) process are all more effective than this new latent finger mark enhancement reagent. In a preliminary sequencing study, we show the effectiveness of the existing DFO-ninhydrin sequence over dual action reagents.

Composition-space premixed flamelet solution with differential diffusion for in situ flamelet-generated manifolds

Canonical flame problems have been widely used in the combustion literature to tabulate detailed chemistry. Prior to three-dimensional flame simulations, reference laminar premixed flames are usually solved in physical-space, and, diffusion flames in either physical, or, mixture fraction space. Composition-space solutions would be convenient for premixed flame also, because all the points are relevant for chemistry, as a result of the zoom inside the flame zone; however, differential diffusion is not always easy to introduce with accuracy in these moving-frame coordinate systems, parameterized by their physical-space gradients (or scalar dissipation rates). A projection is discussed in this paper that ensures that differential diffusion is properly accounted for, in any composition-space coordinates, thus allowing for perfect matching between physical- and composition-space solutions, even for premixed flames. Both a diffusion velocity correction, which is necessary to properly conserve mass with Fick’s law, and a differential diffusion effect between the composition-space moving with the flow and fast diffusing species, are introduced. A procedure for rapidly building converged composition-space solutions for premixed flamelets is then proposed and tested. It provides the framework for an efficient in situ calculation of complex chemistry with differential diffusion, to be applied to three-dimensional unsteady flame simulations. The objective is to avoid building a priori look-up tables, whose range of validity is strongly limited by their boundary conditions, which are fixed once for all, therefore lacking of generic character, specifically when pressure, composition and enthalpy of fresh gases are varying in space and time.

Hypersensitivity pneumonitis due to high-dose colistin aerosol therapy

We report a case of hypersensitivity pneumonitis, possibly due to aerosolized colistin therapy for severe multi-resistant Gram-negative pneumonia. Microbiological eradication was achieved with colistin therapy, which was stopped after 12 days in view of rising eosinophilia and possible lung fibrosis. The eosinophil count started to normalize 3 days after stopping colistin therapy and the patient was eventually weaned to minimal ventilatory support.

Ageing of trisiloxane solutions

Surfactants are commonly employed in numerous industrial applications and everyday products due to their enhancing wetting abilities. Trisiloxane surfactants in particular have proved to be matchless in reducing the surface tension of the liquid and consequently in enhanced wetting on even highly hydrophobic surfaces. In many practical applications trisiloxanes are frequently used as water-based solution. For convenience and reduced cost they are often pre-mixed with water and left for long periods of time in aqueous environment. We provide evidence that ageing of trisiloxane surfactants in water solutions may lead to loss of their interfacial activity. A mechanism for the observed behaviour is suggested and the phenomenon quantified. Along with a detailed explanation of the problem, we shed light on the dynamics of the process and provide some limitations of pre-mixed solutions.

Neutrally Charged Gas/Liquid Interface by a Catanionic Langmuir Monolayer

Surface-sensitive synchrotron X-ray scattering and spectroscopic experiments were performed to explore the characteristics of Langmuir monolayers of oppositely charged mixed amphiphiles. A premixed (molar 1:1 stearic acid/stearylamine) solution was spread as a monolayer at the gas/liquid interface on pure water and on mono- and divalent salt solutions, revealing that the negatively charged carboxyl groups and positively charged amine groups are miscible into one another and tend to bond together to form a nearly neutral surface. Similar control experiments on pure stearic acid (SA) and stearylamine (ST) were also conducted for comparison. Due to the strong bonding, hexagonal structures in small domains with acyl-chains normal to the liquid surface are formed at zero surface pressures, that is, at molecular areas much larger than those of the densely packed acyl chains. In-plane X-ray diffraction indicates that the catanionic surface is highly ordered and modifies the structure of the water surface and thus can serve as a model system for interactions of an amino acid template with solutes.

Hydrolysis-Induced Aqueous Gelcasting of Magnesium Aluminate Spinel

This paper reports on the synthesis of magnesium aluminate spinel (MAS) powders and consolidation of MAS ceramics by hydrolysis-induced aqueous gelcasting (GCHAS). The MAS powders surface passivated against hydrolysis were dispersed in an aqueous–organic premix solution using suitable dispersants. The consolidation of green bodies occurred under ambient conditions by adding a polymerization initiator, a catalyst, and AlN (0–4.06 wt%) as a cosetting agent. Green samples with exceptionally high green strength (∼21 MPa) were obtained in the presence of 4.06 wt% AlN. Sintered (1650°C, 1 h) MAS ceramics consolidated by GCHAS exhibited mechanical properties that are comparable to those consolidated by dry pressing.

Impact of Computerized Order Entry and Pre-mixed Dialysis Solutions for Continuous Veno-Venous Hemodiafiltration on Selection of Therapy for Acute Renal Failure

To investigate the impacts of availability of pre-mixed solutions and computerized order entry on nephrologists' choice of the initial mode of renal replacement therapy in acute renal failure. We studied 898 patients with acute renal failure in 3 consecutive eras: era 1 (custom-mixed solution; n = 309), era 2 (pre-mixed commercial solution; n = 324), and era 3 (post-computerized order entry; n = 265). The proportion of patients treated with renal replacement therapy and the time from consult to initiation of continuous renal replacement therapy was similar in the 3 eras. Following introduction of the pre-mixed solution, the proportion of patients treated with continuous renal replacement therapy increased (20% vs. 33%; p < 0.05), it was initiated at a lower serum creatinine (353 ± 123 μmol/L vs. 300 ± 80 μmol/L; p < 0.05) and in older patients (53 ± 12 vs. 61 ± 14 years; p < 0.05). There was a progressive increase in the use of continuous veno-venous hemodialysis (18% vs. 79% vs. 100%; p < 0.05) and in the total prescribed flow rate (1,382 ± 546 vs. 2,324 ± 737 vs. 2,900 ± 305 mL/hr 3; p < 0.05). There was no significant impact on mortality. The availability of a pre-mixed solution increases the likelihood of initiating continuous renal replacement therapy in acute renal failure, initiating it at a lower creatinine and for older patients, use of continuous veno-venous hemodialysis and higher prescribed continuous renal replacement therapy dose. Computerized order entry implementation is associated with an additional increase in the use of continuous veno-venous hemodialysis, higher total prescribed dialysis dose, and use of CRRT among an increasing number of patients not on mechanical ventilation. The effect of these changes on patient survival is not significant.

TriSilanolPhenyl POSS–polyimide nanocomposites: Structure–properties relationship

Polyhedral Oligomeric Silsesquioxane (POSS)–polyimide (PI) thin films were synthesized from pre-mixed solution of oxydianiline–pyromellitic dianhydryde (ODA–PMDA) and TriSilanolPhenyl (TSP) POSS. POSS–PI polymerization reaction kinetics was studied using Fourier Transform Infrared (FTIR) spectroscopy. The POSS–PI films were then investigated by tensile tests, followed by surface morphology examination using Atomic Force Microscopy (AFM) and Environmental Scanning Electron Microscopy (ESEM). An interdisciplinary approach was applied for establishing a relation between POSS–PI composites chemical microstructure properties and failure mechanisms. Inter molecular POSS–POSS interaction by either phase separation, or chemical POSS–POSS condensation reaction were observed as key factors, affecting the nanocomposite mechanical properties via formation of aggregates. The amount and density of these aggregates were shown to be composition dependent. A model based on formation and coalescence of voids during tensile tests was suggested for understanding the effect of the POSS content on the POSS–PI mechanical response.

Hydrolysis-induced aqueous gelcasting for near-net shape forming of ZTA ceramic composites

A new near-net shape forming process called “hydrolysis-induced aqueous gelcasting” (GCHAS) is reported in this paper for the consolidation of ZTA composites, ZTA-30 (70 wt.% Al 2O 3 + 30 wt.% ZrO 2) and ZTA-60 (40 wt.% Al 2O 3 + 60 wt.% ZrO 2). For comparison purposes, ceramics having the same chemical compositions were also consolidated by hydrolysis-assisted solidification (HAS). All the starting suspensions contained a solids loading of 50 vol.%. In the precursor powder mixtures, 1–5 wt.% of Al 2O 3 was replaced by equivalent amounts of AlN to enhance or promote or co-promote the consolidation of suspensions by HAS or by GCHAS, respectively. The suspensions for GCHAS were prepared by dispersing the ZTA powder precursor mixtures in a premix solution of 20 wt.% MAM (methacrylamide), MBAM (methylenebisacrylamide) and NVP ( n-vinylpyrrolidinone) in 3:1:3 ratio in de-ionized water. Ceramics consolidated via GCHAS exhibited superior mechanical properties after consolidation and after sintering for 1 h at 1600 °C in comparison to those consolidated by HAS.

Aqueous Gelcasting Process for β‐Si4Al2O2N6 Ceramics

Dense β‐Si4Al2O2N6 ceramics were obtained from α‐Si3N4, α‐Al2O3, AlN, and Y2O3 upon sintering (for 4 h at 1675°C) green bodies consolidated by an aqueous gelcasting and a conventional dry‐powder processing route. The as‐purchased AlN powder was treated with H3PO4 and Al(H2PO4)3 and dispersed in aqueous‐organic premix solution along with α‐Si3N4, α‐Al2O3, and Y2O3 powder with the help of a commercial amino alcohol‐based cationic (Dolapix A88) dispersing agent to obtain suspensions with 45–50 vol% solids loading for gelcasting purpose. The gelcat β‐Si4Al2O2N6 exhibited superior hardness (1423±6 Hv), fracture toughness (3.95±0.3 MPa·m1/2), and coefficient of thermal expansion (3.798 × 10−6/°C between 30° and 1000°C) in comparison with the ceramic consolidated by conventional dry‐powder pressing route, which exhibited only 1317±5 Hv, 3.30±0.2 MPa·m1/2 and 3.532 × 10−6/°C between 30° and 700°C.

Electrical conductivity of gelcast alumina sintered under inert atmosphere

Electrically conductive alumina ceramic has been successfully fabricated by sintering of dried gelcast alumina in an inert atmosphere. The process was developed similar to the conventional gelcasting method except for varying the amount of monomer in the premix solution. The sintering treatment was carried out in argon gas from 1100 °C to 1700 °C. Van der Pauw's method was used to measure the electrical resistivity. The results showed that increasing monomer addition and sintering treatment were significantly affecting in lowering electrical resistance. Using the lowest monomer addition and increased sintering treatment, the measured electrical resistivities were in the range from 1.94 Ω-cm to 0.37 Ω-cm. The material exhibited ohmic behavior and rendered two regimes of Arrhenius profile in the plot of electrical conductivity against increasing temperature from 20 °C to 600 °C. All conduction processes were governed by the presence of carbon that caused the alumina grains in polygonal morphology typical of densification. Furthermore, physical tests were conducted to describe the electrical conduction behavior of the material.

Gelcasting of SiC using epoxy resin as gel former

Epoxy resin was used as gel former in SiC gelcasting. A hardener as cross-linker causes a nucleophilic addition reaction of epoxy resin instead of free radical reaction of the acrylamide-based gel former system to avoid oxygen and mould materials (plastic and rubber) inhibition. The gelling behavior of premix solution and slurry was investigated by the change of elastic modulus (G′) changing during gelling. Data show 3.4 wt% hardener in 15 wt% epoxy resin solution to be the optimized content to obtain gel with high-G′. Both the polymerization process and the gelation process depend greatly on temperature, which is beneficial for mixing and casting. Green bodies fabricated with epoxy resin show that rubber do not inhibit in the process.

Dual Fingerprint Reagents with Enhanced Sensitivity: 5‐Methoxy‐ and 5‐Methylthioninhydrin

"Dual fingerprint reagents" are chemical formulations which produce with latent fingerprints in a single step, impressions that are both colored and fluorescent. Pre-mixed solutions of the two commercially available ninhydrin analogues, 5-methoxyninhydrin (MN) and 5-methylthioninhydrin (MTN) with zinc or cadmium salts, are true dual reagents. They are much more sensitive than the parent dual reagent, ninhydrin/ZnCl(2). The main advantage of the new formulations is that they can be used at room temperature, with no need to cool the sample to liquid nitrogen temperature. At 0.05% concentration, which is 10-fold lower than the common ninhydrin working solution, MTN/ZnCl(2) is as sensitive as DFO in the fluorescence mode and considerably more sensitive in the color mode. MTN is also slightly cheaper than DFO.

Rheological Properties and Gelcasting Behavior of Ultrafine ZrO&lt;sub&gt;2&lt;/sub&gt; Suspension

Ultrafine ZrO2 suspension with stable high solid loading was prepared, and ZrO2 ceramic materials with uniform structures were fabricated through gelcasting. Zeta potential of the ultrafine ZrO2 suspensions with A-type dispersant, triammonium citrate, and without dispersant was measured. The influencing factors on suspension flowability as the content of dispersant, pH value, solid loading, and milling time were studied in detail. And the optimum premixed solution/initiator (APS)/catalyst (TEMED) ratio for gelcasting was investigated. The results showed that A-type dispersant was suitable for dispersing of ultrafine ZrO2 particles in aqueous premixed solutions; the optimized content of dispersant was 2%~2.5% of ZrO2 volume; ZrO2 suspension displayed a minimum viscosity at pH 10.66; the upper limit of solid loading was 54vol.%; and the appropriate milling time was 12 hours. When premixed solution/initiator (APS)/catalyst (TEMED) ratio was 100/1/0.5, ZrO2 suspension has a better gelcasting behavior.

Study on the gel casting of fused silica glass

Slip casting process is usually applied for the forming of fused silica products. Segregation always occurs and it will results in density deviation. By using gel casting process, green is fabricated by means of in situ polymerization with a three-dimensional network, holding the particles together and eliminating the tendency of migration. To prepare gel casting slurries, premix solutions were composed of acrylamide and N,N′-methylenebisacrylamide. Solid loading was kept 60% and the average particle size of silica powder 8–8.5 μm. Lactic acid was introduced as a dispersant to regulate the pH value 3–4. Mechanism of the dispersant was investigated by studying ζ-potential at different pH. Ammonium persulfate (NH4)2S2O4 was added as an initiator. Gelation took place with the help of initiator at 50–60 °C. Nanometer silica was introduced to boost sinterability so that the density and bending strength of fused silica ceramics have been increased to 2.1 g/cm3 and 40 Mpa, respectively.

Gelcasting of Alumina Using Epoxy Resin as a Gelling Agent

A water‐soluble epoxy resin and hardener system for gelcasting of ceramics was developed. Polymerization of the system is a nucleophilic addition reaction, and not affected by oxygen. Therefore, this gelcasting system can be carried out in an air atmosphere. The ceramic slurries were prepared by mixing the aqueous premix solution of epoxy resin with alumina powder and dispersant. For cross‐linking, a polyamine hardener was added. Both the rheological properties of the slurries and the gelling behaviors of the aqueous premix solutions were evaluated. The slurry with a solid loading of 80 wt% is optimized for gelcasting. The flexural strength of the sintered ceramics is 335±47 MPa with 98% of theoretical density.