Creep behavior comparison of CMW1 and palacos R-40 clinical bone cements

The restrained dynamic creep behaviors of two clinical bone cements, Palacos R-40 and CMW1 have been investigated at room temperature and body temperature. It was found that the two cements demonstrated significantly different creep deformations, with Palacos R-40 bone cement demonstrating higher creep strain than CMW1 bone cement at each loading cycle. For both cements, two stages of creep were identified with a higher creep rate during early cycling followed by a steady-state creep rate. The test temperature had a strong effect on the creep performance of the bone cements with higher creep rate observed at body temperature. The relationship between creep deformation and loading cycles can be expressed by single logarithmic model. The SEM examinations revealed that CMW1 bone cement is more sensitive to defects within the specimen especially to the defects at the edges of the specimen than Palacos R-40 bone cement. However, in the absence of micro-cracks or defects within the inner surface layer, the dynamic loading (at less than 10.6 MPa) is unlikely to produce micro-cracks in the CMW1 bone cement. The different behaviors between the two bone cements may be attributed to differences in chemical compositions and molecular weight distributions.     

Structural analysis of Si-substituted hydroxyapatite: zeta potential and X-ray photoelectron spectroscopy

The aim of this study was to determine the effect of the incorporation of silicon on the surface charge of hydroxyapatite (HA) and to assess surface structural changes of HA and Si–HA induced by dissolution in both static and dynamic systems. X-ray photoelectron spectroscopy (XPS) analysis showed that SiO₄ ^4– groups were substituted for PO₄ ^3– groups in the silicon-hydroxyapatite (Si–HA) lattice according to a previously proposed substitution mechanism without the formation of other crystalline phases, such as tricalcium phosphate or calcium oxide. The substituted silicon induced a decrease in the net surface charge and the isoelectric point of HA as determined by zeta potential (ZP) measurements. At physiological pH=7.4 the surface charge of Si–HA was significantly lowered compared to unmodified HA, i.e. –50±5 to –71±5 eV, caused by the presence of silicate groups in the HA lattice, which may account for a faster in vitro apatite formation using SBF testing. XPS results indicated that silicon seems to be preferentially leached out from Si–HA surface compared to other ionic species after dissolution studies in tris-buffer using a dynamic system.     

Material properties of various cements for use with vertebroplasty

The purpose of the current study was to measure the material properties of various cements prepared per manufacturers' recommendations and of cements modified according to compositions developed by clinicians with experience performing vertebroplasty. Cement was prepared, cast to form cylindrical specimens, and tested in compression. The optical density of specimens from the various cement preparations was measured. Batches of Simplex P and Cranioplastic cement were also prepared with increased concentrations of BaSO₄ (20% and 30%; and 10%, 20% and 30%, respectively) to evaluate the effect of additional BaSO₄. Compressive modulus values for polymethylmethacrylate cements ranged from 2–2.7 GPa; some differences were significant (p<0.05). Compared with polymethylmethacrylate cements, Orthocomp exhibited almost twice the compressive modulus and 2–3 times the strength values. Increasing the BaSO₄ concentration in Simplex P and Cranioplastic significantly (p<0.05) affected their material properties; however, it is unknown if these changes in material properties are clinically important. Optical density increased as a function of concentration of the opacifying agent added. The current study provides clinicians with information on changes in the material properties of bone cements when the compositions are altered in a manner consistent with the practice of vertebroplasty.     

Contact conductivity detection in poly(methyl methacrylate)-based microfluidic devices for analysis of mono- and polyanionic molecules

An on-column contact conductivity detector was developed for the analysis of various mono- and polyanionic compounds separated by electrophoresis chips fabricated in poly(methyl methacrylate) (PMMA) using hot embossing techniques from Ni electroforms. The detector consisted of a pair of Pt wires (127 microm diameter) with an end-to-end spacing of approximately 20 microm and situated within the fluidic channel. The waveform applied to the electrode pair was a bipolar pulse with a frequency of 5.0 kHz and was used to reduce the charging current from measurement so that the current recorded at the end of one pulse is more representative of the solution conductivity. Using the detector, separations of amino acids, peptides, proteins, and oligonucleotides were demonstrated. For the amino acids and peptides, free-solution zone electrophoresis was performed. A calibration plot for the amino acid alanine was found to be linear from approximately 10 to 100 nM in a carrier electrolyte consisting of 10 mM triethylamonium acetate. The concentration detection limit was found to be 8.0 nM, with the corresponding mass detection limit equal to 3.4 amol (injection volume = 425 pL). The protein separations with conductivity detection were performed using MEKC, in which the carrier electrolyte contained the anionic surfactant sodium dodecyl sulfate (SDS) above its cmc. Near baseline resolution was achieved in the PMMA microchip for a solution containing 8 different proteins. In the case of the DNA fragments, capillary electrochromatography was used with a C18-modified PMMA chip and a carrier electrolyte containing an ion-pairing agent.     

A fiber-optic fluorescence sensor for lithium ion in acetonitrile

A novel fiber-optic fluorescence sensor based on a controlled-release reagent for the determination of lithium ion in organic solvents is proposed. The fluorogenic indicator 2-(2-hydroxyphenyl)benzoxazole is contained in a mini-polyethylene tube as the reagent reservoir and is brought into contact with the analyte solution by diffusion across a poly(vinyl chloride) (PVC) membrane to form a strongly fluorescent complex at the membrane/solution interface. The fluorescence signals produced are measured via two joined optical fibers positioned closely to the backside of the PVC membrane for light illumination and collection. The sensor is useful for measuring Li+ at concentrations in acetonitrile ranging from 1.0 x 10(-6) to 1.0 x 10(-2) M with a detection limit of 3.0 x 10(-7) M. The steady-state response can be reached within seconds, and the signal changes are fully reversible. The sensor shows minimal interference effects from other alkali metal and alkaline earth metal cations and has good stability and durability when stored in acetonitrile solutions.     

In-channel electrochemical detection for microchip capillary electrophoresis using an electrically isolated potentiostat

A new electrode configuration for microchip capillary electrophoresis (CE) with electrochemical (EC) detection is described. This approach makes it possible to place the working electrode directly in the separation channel. The "in-channel" EC detection was accomplished without the use of a decoupler through the utilization of a specially designed, electrically isolated potentiostat. The effect of the working electrode position on the separation performance (in terms of plate height and peak skew) of poly(dimethylsiloxane)-based microchip CEEC devices was evaluated by comparing the more commonly used end-channel configuration with this new in-channel approach. Using catechol as the test analyte, it was found that in-channel EC detection decreased the total plate height by a factor of 4.6 and lowered the peak skew by a factor of 1.3. A similar trend was observed for the small, inorganic ion nitrite. Furthermore, a fluorescent and electrochemically active amino acid derivative was used to directly compare the separation performance of in-channel EC detection to that of a widely used laser-induced fluorescence (LIF) detection scheme. In this case, it was found that the plate height and peak skew for both detection schemes were essentially equal, and the separation performance of in-channel EC detection is comparable to LIF detection.     

High-throughput method for the production and analysis of large natural product libraries for drug discovery

High-throughput methods were applied to the production, analysis, and characterization of libraries of natural products in order to accelerate the drug discovery process for high-throughput screening in the pharmaceutical and biotechnology industries. Library production integrates automated flash chromatography, solid-phase extraction, filtration, and high-throughput parallel four-channel preparative high-performance liquid chromatography to obtain the libraries in 96- or 384-well plates. Libraries consist of purified fractions with approximately one to five compounds per well. Libraries are analyzed prior to biological screening by a high-throughput parallel eight-channel liquid chromatography-evaporative light scattering detection-mass spectrometry system to determine the molecular weight, number, and quantity of compounds in a fraction. After biological screening, active fractions are rapidly purified at the microgram level and individual compounds are rescreened for confirmation of activity. Structures of active compounds are elucidated by NMR spectroscopy and mass spectrometry. Utilization of a novel microcoil probe allows NMR data to be gathered on 50 microg. As a demonstration, a library was made from the stem bark of Taxus brevifolia. Biological screening in the National Cancer Institute's in vitro panel of three cancer cell lines demonstrates that the process enables the discovery of active anticancer compounds not detected in the flash fractions from which the library originates.     

Metal complexation of thiacrown ether macrocycles by electrospray ionization mass spectrometry

In the present study, electrospray ionization mass spectrometry is used to evaluate the metal-binding selectivities of an array of novel caged macrocycles for mercury(II), lead(II), cadmium(II), and zinc(II) ions. In homogeneous methanol/chloroform solutions as well as extractions of metals from aqueous solution by macrocycles in chloroform, it is found that the type of heteroatom (S, O, N), cavity size, and presence of other substituents influence the metal selectivities. Several of the macrocycles in this study bind mercury ion very selectively and efficiently in the presence of many other metal ions and have an avidity toward mercury that was tunable by the size and combination of heteroatoms in the macrocycle ring and the number of cage groups attached. The extraction mechanism was further investigated by determining the variation in extraction selectivity as a function of the counterions of the mercury salts.     

Self-organizing continuous attractor networks and path integration: one-dimensional models of head direction cells

Some neurons encode information about the orientation or position of an animal, and can maintain their response properties in the absence of visual input. Examples include head direction cells in rats and primates, place cells in rats and spatial view cells in primates. 'Continuous attractor' neural networks model these continuous physical spaces by using recurrent collateral connections between the neurons which reflect the distance between the neurons in the state space (e.g. head direction space) of the animal. These networks maintain a localized packet of neuronal activity representing the current state of the animal. We show how the synaptic connections in a one-dimensional continuous attractor network (of for example head direction cells) could be self-organized by associative learning. We also show how the activity packet could be moved from one location to another by idiothetic (self-motion) inputs, for example vestibular or proprioceptive, and how the synaptic connections could self-organize to implement this. The models described use 'trace' associative synaptic learning rules that utilize a form of temporal average of recent cell activity to associate the firing of rotation cells with the recent change in the representation of the head direction in the continuous attractor. We also show how a nonlinear neuronal activation function that could be implemented by NMDA receptors could contribute to the stability of the activity packet that represents the current state of the animal.     

Self-organizing continuous attractor networks and path integration: two-dimensional models of place cells

Single-neuron recording studies have demonstrated the existence of neurons in the hippocampus which appear to encode information about the place where a rat is located, and about the place at which a macaque is looking. We describe 'continuous attractor' neural network models of place cells with Gaussian spatial fields in which the recurrent collateral synaptic connections between the neurons reflect the distance between two places. The networks maintain a localized packet of neuronal activity that represents the place where the animal is located. We show for two related models how the representation of the two-dimensional space in the continuous attractor network of place cells could self-organize by modifying the synaptic connections between the neurons, and also how the place being represented can be updated by idiothetic (self-motion) signals in a neural implementation of path integration.