Structural characterization of heparins from different commercial sources

Seven commercial heparin active pharmaceutical ingredients and one commercial low molecular weight from different manufacturers were characterized with a view profiling their physicochemical properties. All heparins had similar molecular weight properties as determined by polyacrylamide gel electrophoresis (M _N, 10–11 kDa; M _W, 13–14 kDa; polydispersity (PD), 1.3–1.4) and by size exclusion chromatography (M _N, 14–16 kDa; M _W, 21–25 kDa; PD, 1.4–1.6). one-dimensional ¹H- and ¹³C-nuclear magnetic resonance (NMR) evaluation of the heparin samples was performed, and peaks were fully assigned using two-dimensional NMR. The percentage of glucosamine residues with 3-O-sulfo groups and the percentage of N-sulfo groups and N-acetyl groups ranged from 5.8–7.9%, 78–82%, to 13–14%, respectively. There was substantial variability observed in the disaccharide composition, as determined by high performance liquid chromatography (HPLC)-mass spectral analysis of heparin lyase I–III digested heparins. Heparin oligosaccharide mapping was performed using HPLC following separate treatments with heparin lyase I, II, and III. These maps were useful in qualitatively and quantitatively identifying structural differences between these heparins. The binding affinities of these heparins to antithrombin III and thrombin were evaluated by using a surface plasmon resonance competitive binding assay. This study provides the physicochemical and activity characterization necessary for the appropriate design and synthesis of a generic bioengineered heparin.     

Hyphenated techniques for the analysis of heparin and heparan sulfate

The elucidation of the structure of glycosaminoglycan has proven to be challenging for analytical chemists. Molecules of glycosaminoglycan have a high negative charge and are polydisperse and microheterogeneous, thus requiring the application of multiple analytical techniques and methods. Heparin and heparan sulfate are the most structurally complex of the glycosaminoglycans and are widely distributed in nature. They play critical roles in physiological and pathophysiological processes through their interaction with heparin-binding proteins. Moreover, heparin and low-molecular weight heparin are currently used as pharmaceutical drugs to control blood coagulation. In 2008, the health crisis resulting from the contamination of pharmaceutical heparin led to considerable attention regarding their analysis and structural characterization. Modern analytical techniques, including high-performance liquid chromatography, capillary electrophoresis, mass spectrometry, and nuclear magnetic resonance spectroscopy, played critical roles in this effort. A successful combination of separation and spectral techniques will clearly provide a critical advantage in the future analysis of heparin and heparan sulfate. This review focuses on recent efforts to develop hyphenated techniques for the analysis of heparin and heparan sulfate.     

A novel, ultra sensible biosensor built by layer-by-layer covalent attachment of a receptor for diagnosis of tumor growth

In the presented research, a novel, ultra sensitive biosensor for the impedimetric detection of vascular endothelial growth factor (VEGF) is introduced. The human vascular endothelial growth factor receptor 1 (VEGF-R1, Flt-1) was used as a biorecognition element for the first time. The immobilization of VEGF-R1 on glassy carbon electrodes was carried out using layer-by-layer covalent attachment of VEGF-R1. The electrochemical properties of the layers constructed on the electrodes were characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The differences in electron transfer resistance (R_et) between the working solution and the biosensor surface, recorded by the redox probe K₃[Fe(CN)₆]/K₄[Fe(CN)₆], confirmed the binding of VEGF to VEGF-R1. The new biosensor allowed a detection limit of 100 fg mL⁻¹ with a linear range of 100–600 fg mL⁻¹ to be obtained. The biosensor also exhibited good repeatability (with a correlation coefficient of 1.95%), and reproducibility.     

Assembly of nanoparticles at the contact line of a drying droplet under the influence of a dipped tip

The manipulation of colloidal nanoparticles (NPs) in a drying droplet has critical importance not only for several industrial applications but also their assembly into patterns on surfaces. The influence of a tip with hydrophilic or hydrophobic surfaces dipped into a drying droplet on hydrophilic or hydrophobic surfaces on the behavior of 98 nm latex NPs was investigated. The formation of concentric rings on hydrophilic glass surfaces regardless of the surface chemistry of the dipped tip was observed. On the other hand, no pattern formation on hydrophobic surfaces was observed with the insertion of the tip. With a hydrophilic tip, the concentric rings were formed due to stick-slip motion of the solvent contact line resulting from competition between pinning and capillary forces while the capillary effect was not effective until the surface of the tip was changed by adherent NPs making the tip surface available for water adherence with a hydrophobic tip, which results in the pulling of droplet towards the tip. It is also found that the tip thickness and suspension concentration significantly influences the formation of concentric rings on surfaces. This simple procedure can be used to influence the distribution or assembly of NPs in the droplet area.     

Experimental and theoretical investigation of phosphorus in-situ doping of germanium epitaxial layers

We investigate phosphorus in-situ doping characteristics in germanium (Ge) during epitaxial growth by spreading resistance profiling analysis. In addition, we present an accurate model for the kinetics of the diffusion in the in-situ process, modeling combined growth and diffusion events. The activation energy and pre-exponential factor for phosphorus (P) diffusion are determined to be 1.91 eV and 3.75 × 10^?5 cm²/s. These results show that P in-situ doping diffusivity is low enough to form shallow junctions for high performance Ge devices.     

HEAT TRANSFER COEFFICIENTS FOR TUBES SUBMERGED IN CIRCULATING FLUIDIZED BED

Convective heat transfer coefficients were measured experimentally for a tube immersed vertically in a circulating fluidized bed. Circulating fluidized beds operate in the dilute transport regime of two-phase (solid/gas) flow. The dominant mechanism for heat transfer to surfaces is particle-induced convection. In this study, experiments were carried out in a circulating fluidized bed of15 cm diameter and 11 m height. An instrumented tube of 9.5 mm diameter and 1.3 m length was placed vertically at the centeriine of the fluidized bed to measure convective heat transfer coefficients at several different elevations in the bed. Three types of particles, with mean diameters ranging from 68 to 2S1 urn, were used in the experiments at superficial gas velocities in the range of 1.3 to 8.2 m/s. Results showed that the convective heat transfer coefficients with solid/gas two-phase circulation were two to three times greater than those for single-phase gas convection at the same velocity. For a given gas velocity, the coefficients increased with increasing solid mass flux, but decreased with elevation. It was demonstrated that the heat transfer coefficients for the immersed tube and for the bed wall could be correlated with different functional dependence on the two-phase suspension density.     

Non-cooperative joint replenishment under asymmetric information

We consider jointly replenishing n ex-ante identical firms that operate under an EOQ like setting using a non-cooperative game under asymmetric information. In this game, each firm, upon being privately informed about its demand rate (or inventory cost rate), submits a private contribution to an intermediary that specifies how much it is willing to pay for its replenishment per unit of time and the intermediary determines the maximum feasible frequency for the joint orders that would finance the fixed replenishment cost. We show that a Bayesian Nash equilibrium exists and characterize the equilibrium in this game. We also show that the contributions are monotone increasing in each firm’s type. We finally conduct a numerical study to compare the equilibrium to solutions obtained under independent and cooperative ordering, and under full information. The results show that while information asymmetry eliminates free-riding in the contributions game, the resulting aggregate contributions are not as high as under full information, leading to higher aggregate costs.     

ZnO–TiO2 nanocomposites formed under submerged DC arc discharge: preparation,characterization and photocatalytic properties

A rutile TiO₂ (α-TiO₂) and hexagonal wurtzite ZnO nanocomposite was directly and synchronously synthesized via arc discharge method submerged in de-ionized water. In correlation with the detailed characterization of the morphology, and crystalline structure of the prepared ZnO–TiO₂ nanocomposites, the UV–visible and photoluminescence properties were studied. X-ray diffraction and transmission electron microscopy investigations revealed the co-existence of α-TiO₂ and hexagonal wurtzite ZnO phases with the ZnO and α-TiO₂ nanoparticles are in nanorod and nanospheres morphologies, respectively. The diameters of the synthesized nanocomposite particles are in the range of 5–70 nm. Interestingly, the as-prepared ZnO–TiO₂ nanocomposite shows better photocatalytic activity for photodegradation of the methylene blue dye than both of pure ZnO and TiO₂ nanocatalyts. This work would explore feasible routes to synthesize efficient metal or/and metal oxide nanocomposites for degrading organic pollutants, gas sensing or other related applications.     

Modular photoinduced grafting onto approach by ketene chemistry

A modular approach for the synthesis of graft copolymers by the combination of reversible addition–fragmentation chain‐transfer (RAFT) polymerization and photoinduced acylation processes is described. In the two‐step approach, first the copolymers of benzodioxinone containing monomer, namely, 4‐oxo‐2,2‐diphenyl‐4H‐benzo[d][1,3]dioxin‐7‐yl methacrylate (BDMA) and methyl methacrylate (MMA) in different feed ratios were prepared by RAFT polymerization. In the subsequent step, dichloromethane solutions of these copolymers (PMMA‐co‐PBDMA) were irradiated at λ = 300 nm in the presence of independently prepared hydroxyl functional polymers such as poly(ethylene glycol) (MeO‐PEG‐OH) and poly(?‐caprolactone) (PCL‐OH). Side‐chain esterification reaction between photochemically generated ketene groups and hydroxyl functionalities resulted in the formation graft copolymers. The intermediates and final graft copolymers were characterized by ¹H NMR, UV, IR, fluorescence, and GPC measurements. The success of the process was also confirmed by a model reaction using pyrene methanol. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 274–280