Fluorescence detection in capillary zone electrophoresis using a charge-coupled device with time-delayed integration

A fluorescence detection system for capillary zone electrophoresis is described in which a charged-coupled device (CCD) views a 2-cm section of an axially illuminated capillary column. The CCD is operated in two readout modes: a snapshot mode that acquires a series of images in wavelength and capillary position, and a time-delayed integration mode that allows long exposure times of the moving analyte zones. By use of the latter mode, the ability to differentiate a species based on both its fluorescence emission and migration rate is demonstrated for fluorescein and sulforhodamine 101. The detection limit for fluorescein isothiocyanate (FITC) is 1.2 X 10(-20) mol; detection limits for FITC-amino acids are in the (2-8) X 10(-20) mol range.     

Erosion characteristics of an erodible tablet incorporated in a time-delayed capsule device

A time-delayed oral drug delivery device was investigated in which an erodible tablet (ET), sealing the mouth of an insoluble capsule, controlled the lag-time prior to drug release. The time-delayed capsule (TDC) lag-time may be altered by manipulation of the excipients used in the preparation of the ET. Erosion rates and drug release profiles from TDCs were investigated with four different excipient admixtures with lactose: calcium sulphate dihydrate (CSD), dicalcium phosphate (DCP), hydroxypropylmethyl cellulose (HPMC; Methocel® K100LV grade) and silicified microcrystalline cellulose (SMCC; Prosolv® 90 grade). Additionally, the compressibility of different insoluble coated capsules was tested at different moisture levels to determine their overall integrity and suitability for oral delivery. Erosion rates of CSD, DCP, and SMCC displayed a nonlinear relationship to their concentration, while HPMC indicated rapid first-order erosion followed by zero-order erosion, the onset of which was dependent on the HPMC concentration. Capsule integrity was confirmed to be most suitable for oral delivery when the insoluble ethyl cellulose coat was applied to a hard gelatin capsule using an organic spray coating process. T_50% drug release times varied between 245 (± 33.4) and 393 (± 40.8) minutes for 8% and 20% DCP, respectively, T_50% release times of 91 (± 22.1) and 167 (± 34.6) were observed for 8% and 20% CSD; both formulations showed incidence of premature drug release. The SMCC formulations showed high variability due to lamination effects. The HPMC formulations had T_50% release times of 69 (± 13.9), 213 (± 25.4), and 325 (± 30.3) minutes for 15%, 24%, and 30% HPMC concentrations respectively, with no premature drug release. In conclusion, HPMC showed the highest reproducibility for a range of time-delayed drug release from the assembled capsule formulation. The method of capsule coating was confirmed to be important by investigation of the overall capsule integrity at elevated humidity levels. The erosion characteristics of ETs containing HPMC may be described by gravimetric loss. The novel time-delayed capsule device presented in this study may be assembled to include an erodible tablet with a known concentration of HPMC. A variety of suitable drugs for targeted chronopharmaceutical therapy can beincorporated into such a device, ultimately improving drug efficacy and patient compliance, and reducing harmful side effects.     

Interface of an array of five capillaries with an array of one-nanoliter wells for high-resolution electrophoretic analysis as an approach to high-throughput chemical cytometry

We report a system that allows the simultaneous aspiration of one or more cells into each of five capillaries for electrophoresis analysis. A glass wafer was etched to create an array of 1-nL wells. The glass was treated with poly(2-hydroxyethyl methacrylate) to control cell adherence. A suspension of formalin-fixed cells was placed on the surface, and cells were allowed to settle. The concentration of cells and the settling time were chosen so that there was, on average, one cell per well. Next, an array of five capillaries was placed so that the tip of each capillary was in contact with a single well. A pulse of vacuum was applied to the distal end of the capillaries to aspirate the content of each well into a capillary. Next, the tips of the capillaries were placed in running buffer and potential was applied. The cells lysed upon contact with the running buffer, and fluorescent components were detected at the distal end of the capillaries by laser-induced fluorescence. The electrophoretic separation efficiency was outstanding, generating over 750,000 theoretical plates (1,800,000 plates/m). In this example, AtT-20 cells were used that had been treated with TMR-G(M1). The cells were allowed to metabolize this substrate into a series of products before the cells were fixed. The number of cells found in each well was estimated visually under the microscope and was described by a Poisson distribution with mean of 0.98 cell/well. This system provides an approach to high-throughput chemical cytometry.     

A semi-quantitative approach to risk analysis, as an alternative to QRAs

In quantitative risk analysis (QRA) risk is quantified using probabilities and expected values, for example expressed by PLL values, FAR values, IR values and F–N curves. The calculations are tedious and include a strong element of arbitrariness. The value added by the quantification can certainly be questioned. In this paper, we argue that such analyses often are better replaced by semi-quantitative analyses, highlighting assessments of hazards and barriers, risk influencing factors (RIFs) and safety improvement measures. The assessments will be based on supporting information produced by risk analysts, including hard data and analyses of failure causes and mechanisms, barrier performance, scenario development, etc. The approach acknowledges that risk cannot be adequately described and evaluated simply by reference to summarising probabilities and expected values. There is a need for seeing beyond the standard probabilistic risk results of a QRA. Key aspects to include are related to uncertainties in phenomena and processes, and manageability factors. Such aspects are often ignored in standard QRAs.     

Tuning in to a single molecule: vibrational spectroscopy with atomic resolution

It has recently been shown that the scanning tunneling microscope can be used to obtain the vibrational spectrum of a single molecule on a surface. The ability to obtain both spatial and precise energetic information with angstrom-scale resolution should lead to an enhancement in our ability to understand and engineer surfaces at the atomic level.     

Study of electron-phonon interactions in a single molecule covalently connected to two electrodes

Presented here is a study of electron-phonon interactions in a single molecule junction where the molecule is covalently connected to two electrodes. In this system, vibration modes in a single molecule junction are measured by sweeping the bias voltage between the two electrodes and recording the differential conductance while the strain in the junction is changed by separating the two electrodes. This unique approach allows changes in conductance to be compared to changes in the configuration of a single molecule junction. This system opens a new door for characterizing single molecule junctions and a better understanding of the relationship between molecular conductance, electron-phonon interactions, and configuration.     

How to make an autonomous robot as a partner with humans: design approach versus emergent approach

In this paper, we discuss what factors are important to realize an autonomous robot as a partner with humans. We believe that it is important to interact with people without boring them, using verbal and non-verbal communication channels. We have already developed autonomous robots such as AIBO and QRIO, whose behaviours are manually programmed and designed. We realized, however, that this design approach has limitations; therefore we propose a new approach, intelligence dynamics, where interacting in a real-world environment using embodiment is considered very important. There are pioneering works related to this approach from brain science, cognitive science, robotics and artificial intelligence. We assert that it is important to study the emergence of entire sets of autonomous behaviours and present our approach towards this goal.     

Microbuckling elastic modelling approach of a single carbon fibre embedded in an epoxy matrix

Carbon fibre alignment defect inside of an epoxy matrix is examined by the use of microscopy and video recording. The initiation and the growth of a fibre waviness defect was monitored during the cure of the matrix. The observations established that fibre defect appears during the hot stage of the epoxy matrix thermosetting reaction. The objective is to evaluate the possibility of a fibre microbuckling mechanism to explain the observations. A first elastic microbuckling model is proposed. Analytical expressions of the necessary elastic load for the appearance of a fibre buckling instability and its associated wavelength are established. The compressive load applied onto the fibre has been evaluated by using finite elements calculations based on mechanical characteristics of the materials. Comparison between the critical microbuckling load and the applied load onto the carbon fibre during the cure is in coherence with the observations. The associated wavelength is discussed.     

Exploring Web keyword analysis as an alternative to link analysis: a multi-industry case

The study explored the feasibility of using Web keyword analysis as an alternative to link analysis and tested the feasibility in a multi-industry environment. The keyword is the organization??s name, in this case the company name. American companies from five industries were included in the study. The study found that the Web visibility of a company as measured by the number of Webpages on which the company name appears correlates with the company??s business measures (revenue, profits, and assets). The correlation coefficients are similar to that between the inlink counts and the business measures. This suggests that the keyword count (searched by the company name) could replace inlink count as an alternative indicator of some commonly used business measures. The co-word (the co-occurrence of the names of two companies on Webpages) count was used as a measure of the relatedness of the two companies. Multidimensional scaling (MDS) analysis was applied to the co-word matrices and generated MDS maps that showed relationships among companies in a multi-industry context. Keyword data were collected from three different types of Websites (general Websites, blog sites, and Web news sites) and results were compared. The study found blog sites to be the better source to collect data for this type of study. The comparison of MDS maps generated from co-link data and the blog co-word data showed that the co-word analysis is as effective as co-link analysis in mapping business relationships. The value of the study is not limited to the business sector as the co-word method could be applied to analysing relationships among other types of organizations.     

Magnetophoretic velocity modulation mass analysis of a single microparticle in an atmosphere

A new principle of the magnetophoretic velocity modulation mass analysis of microparticles, which can determine simultaneously the mass and magnetic susceptibility of a single microparticle, has been proposed, and the measurement system was constructed by applying a magnetophoretic force on a falling microparticle through a magnetic field gradient in an atmosphere. A polystyrene microparticle as a test particle adsorbed on a glass plate was selectively knocked off by a pulsed Nd:YAG laser impact into a narrow gap of pole pieces of permanent magnets having a magnetic field gradient with a maximum intensity of 850 T2 m(-1). The falling particle was irradiated by a He-Ne laser, and the scattered light was detected through a slit array mask as a function of time. A bundle of spiked signals of scattered light intensity was analyzed to obtain velocities, which gave acceleration and deceleration of the falling particle. On the basis of the equation of motion under the magnetic field gradient, the mass and magnetic susceptibility of the test particle were reasonably determined.     

Social network analysis as a field of invasions: bibliographic approach to study SNA development

Scientometrics - In this paper, the results of a study on the development of social network analysis (SNA) and its evolution over time, using the analysis of bibliographic networks are presented....     

Two-phase, all-magnetic shift registers that can be operated with a single pulse driver in the 0 to 5 KC range

Two-phase, all-magnetic shift registers have been designed and operated using either two pulse drivers or a single pulse driver and a dc source. The theory of operation of a one-core-per-bit register and a two-core-per-bit register is presented. Experimental information is given that demonstrates the significant operating characteristics of the circuits.     

An implementation of the stiffness derivative method as a discrete analytical sensitivity analysis and its application to mixed mode in LEFM

In this work, an improvement in the stiffness derivative method based on a shape design sensitivity analysis is proposed, so that the error inherent in the finite difference procedure is avoided. For a global estimation of G from a given finite element solution, this approach is shown to be equivalent to the well-known J-integral when the latter is numerically implemented through its equivalent domain integral. However, it is verified that its direct application to 2D mixed mode problems of linear elastic fracture mechanics through the field decomposition technique yields estimates for G_I and G_II which are in general more accurate for the proposed method. The importance of the velocity field is also remarked and some suggestions for its choice are given.     

Heavy traffic analysis of a single vehicle loop in an automated storage and retrieval system

We consider an automated storage/retrieval system in which cargo moves between the storage/retrieval machines and the system entrance/exit stations through a single automated vehicle loop. Past studies indicated that the cargo waiting time in the loop is affected by the dispatching rules, which govern the sequence of the cargo to be handled. In this paper, we show that the loop configuration, which has received little research attention, also has a big impact on the cargo waiting time. When the first-come-first-served dispatching rule is used, we derive the relationship between the number of stations and the ratio of the average cargo retrieval time to the average cargo storage time. When the first-encountered-first-served dispatching rule is used, we show that even the arrangement of the input channel and the output channel of a station can have significant impact on the cargo waiting time. Furthermore, we derive a formula for the vehicle visit rate for each station under heavy traffic conditions. This formula helps to explain the phenomenon that the waiting times at different stations can be very different even when the loop is symmetrically designed and the cargo arrival rates to the stations are similar. In addition to analytical models, we use simulations to evaluate the performance of different loop configurations. Our research suggests that a substantial improvement can be achieved by making proper adjustments to the loop configuration.     

An asymptotic approach applied to a longitudinal crack in an adhesive layer

The problem of a crack within an adhesive layer which is bonded to two linear elastic half-planes under tensile loading is studied. Two cases are considered. One in which the adhesive is linear elastic and, the second in which it is taken to be elasto-plastic. For the linear elastic layer, the half-planes (adherends) are assumed to be both similar and dissimilar. When the adhesive is considerably more compliant than the adherends, a method of inner and outer asymptotic expansions is employed to determine a relationship between the corresponding stress intensity factors. Expansions are determined in three regions and matched. The inner expansion relates to a region whose distance from the crack tip is much less than the adhesive thickness. The intermediate expansion relates to a region whose size is governed by the decay length of the stress in that part of the adhesive in which its compliancy is significant. The outer expansion relates to a region whose distance from the crack tip is much less than the crack length, for example, but much greater than the adhesive thickness. This method may be employed to determine all field quantities in terms of the outer stress intensity factor. For a layer which is considerably stiffer than the adherends, a similar strategy for solving the problem is sketched. In addition, for dissimilar adherends, energy considerations are employed to verify the relationship between the inner and outer stress intensity factors. It is seen that the two expressions for the stress intensity factors are identical. The problem of oscillatory stress and displacement behavior is addressed.Next, the problem of a sufficiently compliant elasto-plastic adhesive between dissimilar adherends is examined. Matched asymptotic expansions are employed to determine the plastic zone size, as well as the crack tip opening displacement. Small scale yielding is assumed. A Dugdale-Barenblatt type model is employed with the elasticity of the layer accounted for. The yield stress is taken to be constant throughout the plastic zone.     

Development of an infrared hollow waveguide as a sensing device for detection of organic compounds in aqueous solutions

In this paper, a new detection method based on an infrared hollow waveguide is developed to detect semivolatile to nonvolatile organic compounds in aqueous solutions. The hollow waveguide is produced by chemical deposition of silver on the inner surface of a polyethylene tube. The surface of the silver layer is further coated with a hydrophobic film to attract organic compounds in aqueous solution. Samples were pumped through this hollow waveguide sampler and organic compounds were attracted onto the hydrophobic film. After removal of the residual water molecules in the hollow waveguide sampler, organic compounds can be sensed by conventional Fourier transform infrared (FT-IR) spectrometry. Theoretical aspects of this type of sampler are also presented. The derived analytical equations for this type of sampler were consistent with experimental data. Under the condition of constant hydrophobic film volume, high linearity (R(2) equal to 0.9993) between the concentration of analyte and the detected signal was obtained for concentrations in the range from 2.5 ppm to 50 ppb. By co-adding 100 scans with 4 cm(-)(1) resolution, the typical detection limit in this type of sensing method can be lower than 10 ppb. Several factors such as sampling flow rate, sampling time, and hydrophobic film volume were also investigated in this work.     

Aryl functionalization as a route to band gap engineering in single layer graphene devices

Chemical functionalization is a promising route to band gap engineering of graphene. We chemically grafted nitrophenyl groups onto exfoliated single-layer graphene sheets in the form of substrate-supported or free-standing films. Our transport measurements demonstrate that nonsuspended functionalized graphene behaves as a granular metal, with variable range hopping transport and a mobility gap ～0.1 eV at low temperature. For suspended graphene that allows functionalization on both surfaces, we demonstrate tuning of its electronic properties from a granular metal to a semiconductor in which transport occurs via thermal activation over a transport gap ～80 meV from 4 to 300 K. This noninvasive and scalable functionalization technique paves the way for CMOS-compatible band gap engineering of graphene electronic devices.     

Sensitivity and uncertainty analysis in optimization programs using an evolutionary approach: a maintenance application

Indirect-Grouping Maintenance Strategy requires the calculation of an optimum (global) according to a minimization program P. However the model on which the optimal is based may be incomplete in the sense that important uncertainties have not been considered. In order to evaluate the effects of the uncertainty of the parameters or how the uncertainty is propagated in the optimization program, the decision-maker needs to evaluate the range of variation of program P.In this work an innovative two step evolutionary approach to analyze uncertainties in Indirect-Grouping Maintenance Strategies is presented. The proposed approach combines the two proven techniques of Cellular Evolutionary Strategies (CES) and Evolutionary Strategies (ES) for the optimization problem. The approach does not guarantee the global optimum, but the experiments show that the results are very close to the real one. The examples presented confirm that the approach produces very good approximations for the range of the minimum when there is uncertainty in the model parameters and can be used as a tool for uncertainty/sensitivity analysis in other areas.