bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen evolution from water using CdS as photosensitizer
Authors: Oncescu Tatiana , Contineanu M. , Meahcov Lucia
Published: March 2007

Colloidal chemical approaches are increasingly utilised for the preparation and stabilization of
semiconductor nanoparticles.We prepared a colloidal CdS in excess of Na2S using a method described in the literature and determined
the particle size from its absorption spectrum by Brus equation. A diameter of about 50Å was calculated.
For the stabilization of colloid we choosed from various tested polymers a 1% in weight copolymer (1/1),
styrene/maleic anhydride. As redox catalyst we used colloidal Pt obtained “in situ” by irradiaton of PtCl6K2.
We established the role of each of the system partners as: CdS concentration, Na2S excess, Pt catalyst concentration,
the irradiation time, and the system temperature. We studied the influence of each participant
to the hydrogen evolution in order to optimize this system.The formation of nanosize composite particles Cd1−xZnxS showed an increasing of H2 amount generated
under irradiation, in comparison with CdS particles.The results obtained permitted us to calculate the turnover number (TO) of the system.
Thin film solar cells on glass by transfer of monocrystalline Si films
Authors: Bergmann R. B. , Rinke T. J. , Hausner R. M. , Grauvogl M. , Vetter M. , Werner J. H.
Published: March 2007

Thin film solar cells based on monocrystalline Si films are transferred to a glass superstrate.
Chemical vapor deposition serves to epitaxially deposit Si on quasi‐monocrystalline Si films obtained from
thermal crystallization of a double layer porous Si film on a Si wafer. A separation layer that forms during
this crystallization process allows one to separate the epitaxial layer on top of the quasi‐monocrystalline film
from the starting Si wafer. We presently achieve an independently confirmed solar cell conversion efficiency
of 9:26%. Ray tracing studies in combination with electrical device simulation indicate an efficiency potential
of around 17% using simple device processing and moderate assumptions on minority carrier lifetime and
surface recombination.
Photoinduced energy‐transfer in covalently and non‐covalently linked supramolecular arrays of metal polypyridyl complexes
Authors: Ward Michael D.
Published: March 2007

Photoinduced energy‐transfer has been studied between the component parts of two types of
multichromophoric array. In the first type the components (metal polypyridyl complexes) are covalently
linked by using the bridging ligand 2, 2′ : 3′, 2″ : 6″, 2′″‐quaterpyridine, which has two inequivalent bipyridyl
chelating sites in close proximity. Structural, redox and photophysical studies of the complexes based on this
ligand show how the properties of each metal fragment vary between the two inequivalent binding sites, and
show also how efficient inter‐component energy transfer can occur between components, with an example
of the antenna effect being demonstrated by energy transfer from three peripheral {Re(bipy)(CO)3CL}
fragments
to one central fragment. In the second type of supramolecular array, the mononuclear
complex component parts are held together by hydrogen‐bonding between peripheral adenine, thymine,
cytosine or guanine nucleobase groups. Thus a derivative with a pendant cytosine group
strongly associates in CH2CL2 solution with an complex bearing a pendant guanine group,
by Watson‐Crick base‐pair formation (Ka ≈ 5000M-1), and Ru → Os photoinduced energy‐transfer can occur
across the triple hydrogen‐bonded bridge.
C–H bond activation of benzene and thiophene by photochemically generated rhenocene cation
Authors: Ogino Hiroshi , Tobita Hiromi , Endo Kouji , Hashidzume Kiyonari
Published: March 2007

A cationic rhenocene‐acetonitrile adduct [Cp2Re(NCMe)](BF4)(1) reacted with an excess of benzene,
thiophene, 2‐methylthiophene, and pyrrole under UV irradiation to afford the C–H bond activation
products [Cp2Re(H)R]BF4 (R = phenyl, 2‐thienyl, 2‐(5‐methylthienyl), 2‐pyrrolyl) in high yields. In cases
of thiophene derivatives and pyrrole, α‐C–H bonds are selectively activated. A plausible mechanism involves
the photodissociation of acetonitrile from 1 to generate a coordinatively unsaturated rhenocene cation
. When 2,5‐dimethylthiophene and dibenzothiophene, having no α‐C–H bonds, were used as substrates,
products of the activation of other C–H bonds were formed first, but they isomerized to thermodynamically
more stable η11‐S‐coordinated complexes in refluxing acetone. On the other hand, irradiation
of the η1‐S‐coordinated complexes reproduced the original C–H bond activation products. Because of the
cationic character, [Cp2Re(H)R]BF4 were readily deprotonated by triethylamine to give neutral rhenocene
derivatives Cp2ReR. When R is thienyl or 2‐(5‐methylthienyl), treatment of Cp2ReR with HBF4 · Et2O and MeI resulted in protonation and methylation to give [Cp2Re(H)R]BF4 (R = and [Cp2Re(Me)R]I. Thermolysis of
[Cp2Re(Me)R]I
in the presence of PPh3 unexpectedly resulted in migration of R to the Cp ring to give [(2 thienyl C5H4)CpRe(PPh3)]I.
Fluorescence quenching of aromatic hydrocarbons by nitroxide radicals: a mechanismatic study
Authors: Fayed Tarek A. , Grampp Gunter , Landgraf Stephan
Published: March 2007

The fluorescence quenching of phenanthrene (Phen), 9‐cyanophenanthrene (CPhen), 9‐cyanoanthracene
(CA), perylene (Per), 9,10‐dicyanoanthracene (DCA), and 9,10‐diphenylanthracene (DPA) using
stable nitroxide radicals as quenchers has been studied by steady state and flash photolysis measurements.
Both linearity and deviation from linearity in the Stern‐Volmer plots have been observed. The active sphere
model was used to discuss the upward curvature of the Stern‐Volmer plots in case of Per, DCA, and DPA.
The bimolecular quenching rate constant (kq) of Phen, CPhen and CA was found to be diffusion controlled
while in other cases it is lower than the diffusion limit. On the basis of flash photolysis measurements as
well as the overlap between the emission spectra of hydrocarbons and the absorption spectra of radicals,
a resonance energy transfer mechanism is taken place in case of Per, DPA, DCA, and CA. For Phen and
CPhen where the energy gap between the first excited singlet and the nearest lower triplet state is small,
an induced intersystem crossing was suggested. Finally, the quenching process was discussed in terms of
the free energy dependence (ΔG) of the electron transfer from nitroxide radicals to the excited hydrocarbons.
Stratified filtered sampling in stochastic optimization
Authors: Rush Robert , Mulvey John M. , Mitchell John E. , Willemain Thomas R.
Published: March 2007

We develop a methodology for evaluating a decision strategy
generated by a stochastic optimization model. The methodology is
based on a pilot study in which we estimate the distribution of
performance associated with the strategy, and define an appropriate
stratified sampling plan. An algorithm we call filtered search
allows us to implement this plan efficiently. We demonstrate the
approach's advantages with a problem in asset / liability management
for an insurance company.
Analysis of singly ordered two-way contingency tables
Authors: Rayner J. C.W. , Best D. J.
Published: March 2007

Pearson's statistic is investigated for nominal-ordinal two-way contingency tables in
which we wish to test for identical rows. The statistic is expressed as a sum, the first summand of
which is a statistic given by Yates (1948), and examines location effects for the nominal category.
The second and subsequent summands reflect the corresponding moments: for example, dispersion,
skewness, kurtosis etc. The summands are shown to be weakly optimal in that they are score statistics.
Flexible plate and foundation modelling
Authors: Hosking R. J.
Published: March 2007

In the most common mathematical model for a moving load on a
continuously- supported flexible plate, the plate is assumed thin and
elastic. An exception is the inclusion of viscoelasticity in the
theory for the response of a floating ice plate, where the deflexion at
the critical load speed corresponding to the minimum phase speed of
hybrid flexural-gravity waves consequently approaches a steady state.
This is in contrast to the elastic theory, where the response is
predicted to grow continuously at this critical load speed. In the
theory for a floating ice plate, the dominant pressure due to the
underlying water is inertial, introduced via a velocity potential
and the Bernoulli equation (assuming non-cavitation at the
plate-water interface). On the other hand, the classical Winkler
representation used in early railway engineering analysis
corresponds to retaining a term which is generally negligible in the
ice plate context. Critical load speeds are consequently predicted
to be much higher, at wavelengths correspondingly much lower, for
commonly accepted railway engineering parameters. Other models might
be considered.
Modelling fluid flow and heat transfer in a saturated porous medium
Authors: Nield D. A.
Published: March 2007

Since the days of Darcy, many refinements have been made to the
equations used to model single-phase fluid flow and heat transfer in a
saturated porous medium, to allow for such basic things as inertial
effects, boundary friction and viscous dissipation, and also
additional effects such as those due to rotation or a magnetic
field. These developments are reviewed.
Can we prevent the next epidemic? The elimination of childhood diseases by mass vaccination
Authors: Roberts M. G.
Published: March 2007

Recently in New Zealand there have been outbreaks of measles and
pertussis every six and five years respectively. A model has been
used to compare the dynamics of these diseases, and to determine the
optimum ages at which children should be vaccinated against them.
Whereas measles could be eliminated by giving the second vaccination
at five years instead of eleven, it is difficult to devise a
practical scheme that would eliminate pertussis. It is then
necessary to consider vaccination schemes in the light of the
age-structure of future epidemics as well as their timing.
One sample tests for the location of modes of nonnormal data
Authors: Carolan Anthony M. , Rayner J. C. W.
Published: March 2007

There are few techniques available for testing if modes take speciﬁed values. We show that standard tests of location such as the t-test and the Wilcoxon test, which test for the mean and median respectively, can perform poorly as tests for modes when the data is other than unimodal and symmetric. Carolan and Rayner [1] proposed a score test of location for symmetric nonnormal data. We consider a family of distributions similar to those considered by Carolan and Rayner [1] and propose a test for the mode or modes of data from multimodal or skewed distributions and demonstrate by way of simulations that it is reasonably effective.
Growing bubbles rising in line
Authors: Harper John F.
Published: March 2007

Over many years the author and others have given theories for bubbles rising in line in a liquid. Theory has usually suggested that the bubbles will tend towards a stable distance apart, but experiments have often showed them pairing off and sometimes coalescing. However, existing theory seems not to deal adequately with the case of bubbles growing as they rise, which they do if the liquid is boiling, or is a supersaturated solution of a gas, or simply because the pressure decreases with height. That omission is now addressed, for spherical bubbles rising at high Reynolds numbers. As the flow is then nearly irrotational, Lagrange's equations can be used with Rayleigh's dissipation function. The theory also works for bubbles shrinking as they rise because they dissolve.
The joint determination of price, quality, and capacity: An application to supermarket operations
Authors: Boronico Jess S. , Panayides Alexandros
Published: March 2007

This paper focuses on a service provider who, faced with competition, must determine the optimal price and level of service quality to provide in order to maximize profits. Service quality and price are assumed to impact jointly on demand for services. Both demand and service quality impact on the cost of providing service. While a considerable literature exists on the impact of service quality on demand or cost, less work has focused on the explicit impact of service quality jointly on both demand for and the cost of providing services. A service quality constraint is appended to the formulation in order to guarantee that a declared service standard is met. Conditions are developed which characterize optimal solutions, together with comparative statics. Illustrative results are presented based on empirical data obtained from a supermarket study.
A case study of the residual-based cointegration procedure
Authors: Biondini Riccardo , Lin Yan-Xia , Mccrae Michael
Published: March 2007

The study of long-run equilibrium processes is a significant component of economic and finance theory. The Johansen technique for identifying the existence of such long-run stationary equilibrium conditions among financial time series allows the identification of all potential linearly independent cointegrating vectors within a given system of eligible financial time series. The practical application of the technique may be restricted, however, by the pre-condition that the underlying data generating process fits a finite-order vector autoregression (VAR) model with white noise. This paper studies an alternative method for determining cointegrating relationships without such a pre-condition. The method is simple to implement through commonly available statistical packages. This ‘residual-based cointegration’ (RBC) technique uses the relationship between cointegration and univariate Box-Jenkins ARIMA models to identify cointegrating vectors through the rank of the covariance matrix of the residual processes which result from the fitting of univariate ARIMA models. The RBC approach for identifying multivariate cointegrating vectors is explained and then demonstrated through simulated examples. The RBC and Johansen techniques are then both implemented using several real-life financial time series.
Discovery of functional and approximate functional dependencies in relational databases
Authors: King Ronald S. , Legendre James J.
Published: March 2007

This study develops the foundation for a simple, yet efficient method for uncovering functional and approximate functional dependencies in relational databases. The technique is based upon the mathematical theory of partitions defined over a relation's row identifiers. Using a levelwise algorithm the minimal non-trivial functional dependencies can be found using computations conducted on integers. Therefore, the required operations on partitions are both simple and fast. Additionally, the row identifiers provide the added advantage of nominally identifying the exceptions to approximate functional dependencies, which can be used effectively in practical data mining applications.
From classroom to online teaching: experiences in improving statistics education
Authors: Porter Anne , Griffiths David , Hedberg John
Published: March 2007

This study used reflective practitioner methodology to investigate how to improve the quality of statistical education. During the study, this methodology, curricula, pedagogical practices, assessment and a framework for learning to learn statistics were all developed as means of improving the quality of statistical education. Also documented was the move from being a classroom teacher of statistics to a teacher who is developing learning resources for online delivery to students. For a classroom teacher, flexible delivery has meant drawing on the sights, sounds, movement, quiet and live shows. By contrast, the online teacher feels the constraints of translating activity based programs to technologically based programs. As more students have chosen to rely on online materials rather than classroom activities, the focus of improving quality has been extended to the enrichment of online resources, so that the learning experience is not second to that of the classroom.
Supporting statistics in the workplace: experiences with two hospitals
Authors: Mortlock M. Y. , Spencer N. , Mengersen K.
Published: March 2007

This paper provides some reflections on the promotion of lifelong learning in statistics in the workplace. The initiative from which the reflections are drawn is a collaboration between a university and two public hospitals, of which one of the stated aims is to develop statistical skills among the hospitals' researchers. This is realized in the provision of ‘biostatistical clinics’ in which workplace teaching and learning of statistics takes place in one-on-one or small group situations. The central issue that is identified is the need to accommodate diversity: in backgrounds, motivations and learning needs of workplace learners (in this case medical researchers), in the workplace environments themselves and in the projects encountered. Operational issues for the statistician in providing such training are addressed. These considerations may reflect the experiences of the wider community of statisticians involved in service provision within a larger organization.
Considering ethnicity in teaching and learning statistics: should I worry about where my students come from?
Authors: Nur Darfiana , Mengersen Kerrie
Published: March 2007

In the past decade there has been strong interest in the special needs of overseas students attending Australian universities, with respect to teaching and learning. This paper reports on three action research studies that address the question of whether such issues remain in the teaching and learning of statistics in particular.
Robustness to non-normality of common tests for the many-sample location problem
Authors: Khan Azmeri , Rayner Glen D.
Published: March 2007

This paper studies the effect of deviating from the normal distribution assumption when considering the power of two many-sample location test procedures: ANOVA (parametric) and Kruskal-Wallis (non-parametric). Power functions for these tests under various conditions are produced using simulation, where the simulated data are produced using MacGillivray and Cannon's [10] recently suggested g-and-k distribution. This distribution can provide data with selected amounts of skewness and kurtosis by varying two nearly independent parameters.
A reduced load approximation accounting for link interactions in a loss network
Authors: Thompson M. R. , Pollett P. K.
Published: March 2007

This paper is concerned with evaluating the performance of loss networks. Accurate determination of loss network performance can assist in the design and dimen- sioning of telecommunications networks. However, exact determination can be difficult and generally cannot be done in reasonable time. For these reasons there is much interest in developing fast and accurate approximations. We develop a reduced load approximation that improves on the famous Erlang fixed point approximation (EFPA) in a variety of circumstances. We illustrate our results with reference to a range of networks for which the EFPA may be expected to perform badly.
SUR Models applied to an environmental situation with missing data
and censored values
Authors: Sparks Ross
Published: March 2007

This paper develops methodology for predicting faecal coliform values in
waterways when some of the data are missing, and some of the data are left-censored.
Such predictions are important in predicting when bathing is safe in specific areas of
Sydney harbor. The approach taken in the paper makes use of spatial information to
improve these predictions.
Comparison of efficient seasonal indexes
Authors: Ittig Peter T.
Published: March 2007

Estimates of a seasonal index in the standard manner (from a moving average)
introduce systematic error into the seasonal estimates if a trend is present. This
paper shows that a logarithmic modification of the standard moving average procedure
will cause it to be consistent with a trend and is an efficient alternative. This paper
also compares several other efficient seasonal indexing procedures appropriate for routine
business applications and shows some numerical results. The results indicate that
it is possible to achieve an improvement in the precision of the seasonal index, in the
seasonally adjusted data and in forecasts based upon this data, by considering logarithmic
alternatives to standard seasonal indexing procedures. This improvement may be
accomplished without a substantial increase in complexity or in the associated computational
burden. The opportunities for improvement are shown to be greatest when the
data contain substantial trend and seasonal aspects and when the trend has a percentage
form. Some suggestions for forecasters are offered.
Linear programs with an additional separable concave constraint
Authors: Kuno Takahito , Shi Jianming
Published: March 2007

In this paper, we develop two algorithms for globally optimizing a special
class of linear programs with an additional concave constraint. We assume that the
concave constraint is defined by a separable concave function. Exploiting this special
structure, we apply Falk-Soland's branch-and-bound algorithm for concave minimization
in both direct and indirect manners. In the direct application, we solve the problem
alternating local search and branch-and-bound. In the indirect application, we carry
out the bounding operation using a parametric right-hand-side simplex algorithm.
A wareness, belief, and communication reaching consensus
Authors: Fukuda Emiko , Matsuhisa Takashi , Sasanuma Hisato
Published: March 2007

This article studies graph-theoretical conditions under which communication will lead to consensus among players about their decisions in circumstances where there are more than tow players and they interact in pair without public announcement. It is shown that comsensus on their decisions can be guaranteed if the communication graph contains no cycle. Where none of the requirements for player's knowledge is imposed as in the standard model of knowledg with partitional information structure.
On the significance level of the multirelation coefficient
Authors: Dear Roger , Drezner Zvi
Published: March 2007

The concept of the multirelation coefficient is defined to describe the closeness of a set of variables to a linear relation. This concept extends the linear correlation between two variables to two or more variables. Parameters of a beta distribution are determined that are utilized to approximate significance levels of the multirelation coefficient for any given number of observations and variables. A generalized Student t distribution is defined. This distribution, which is termed the multirelated t distribution, reduces to the Student t distribution for two variables. It is useful in the determination of the significance level of the multirelation coefficient.
On the equiponderate equation xa+xb+x=xc+xd+1 and a representation of weight quadruplets
Authors: de Baets Bernard , de Meyer Hans
Published: March 2007

The equation xa+xb+x=xc+xd+1 considered in this paper is a particular
equiponderate equation. The number and location of the roots (w.r.t. x = 1) of this equation
are determined in case (a,b,c,d)∈]0,1[4. Based on these results, it is shown that any weight
quadruplet, a basic tool in fuzzy preference modelling, admits an interesting expression in terms
of Frank t-norms with reciprocal parameters.
Technical Note: An investigation of chaos in the
RL-diode circuit using the BDS test
Authors: Kasap R. , Kurt E.
Published: March 2007

In this paper, RL-diode circuit driven by a sinusoidal voltage is employed to obtain nonlinear experimental data. The BDS test statistic is used to analyse these data. According to
the results of the analysis for the first differenced order data, chaotic structure has been found for
each e
values.
Classroom Note: A note on calculating steady state results for an M/M/k queuing system when the ratio of the arrival rate to the service rate is large
Authors: Pasternack Barry Alan , Drezner Zvi
Published: March 2007

The formulas for calculating steady state results for the M/M/k queuing system are
well known. Computational difficulties, however, can arise in using these formulas in situations in
which the ratio of the arrival rate to the service rate is high. In this paper we consider a recursive
approach for calculating steady state results which avoid such computational difficulties. As an
additional benefit, such formulas are far easier to program into a spreadsheet package than the
traditional formulas presented in most management science texts.
Distributions of occupation times of Brownian motion with drift
Authors: Pechtl Andreas
Published: March 2007

The purpose of this paper is to present a survey of recent developments concerning
the distributions of occupation times of Brownian motion and their applications in mathematical
finance. The main result is a closed form version for Akahori's generalized arc-sine law which can
be exploited for pricing some innovative types of options in the Black & Scholes model. Moreover
a straightforward proof for Dassios' representation of the α
-quantile of Brownian motion with drift
shall be provided.
Some applications of occupation times of Brownian motion with
drift in mathematical finance
Authors: Pechtl Andreas
Published: March 2007

In the last few years new types of path-dependent options called corridor options
or range options have become well-known derivative instruments in European options markets.
Since the payout profiles of those options are based on occupation times of the underlying security
the purpose of this paper is to provide closed form pricing formulae of Black & Scholes type for
some significant representatives. Alternatively we demonstrate in this paper a relatively simple
derivation of the Black & Scholes price for a single corridor option – based on a static portfolio representation – which does not make use of the distribution of occupation times (of Brownian
motion). However, knowledge of occupation times' distributions is a more powerful tool.
Global properties of the three-dimensional
predator-prey Lotka-Volterra systems
Authors: Korobeinikov A. , Wake G. C.
Published: March 2007

The global properties of the classical three-dimensional Lotka-Volterra two prey-one
predator and one prey-two predator systems, under the assumption that competition can
be neglected, are analysed with the direct Lyapunov method. It is shown that, except for a
pathological case, one species is always driven to extinction, and the system behaves asymptotically
as a two-dimensional predator-prey Lotka-Volterra system. The same approach can be easily
extended to systems with many prey species and one predator, or many predator species and one
prey, and the same conclusion holds. The situation considered is common for New Zealand wild life,
where indigenous and introduced species interact with devastating consequences for the indigenous
species. According to our results the New Zealand indigenous species are definitely driven to
extinction, not only in consequence of unsuccessful competition, but even when competition is
absent. This result leads to a better understanding of the mechanism of natural selection, and
gives a new insight into pest control practice.
Classroom Note: Numerical solutions of Nagumo's equation
Authors: Iqbal M.
Published: March 2007

Nagumo's equation is a third order non-linear ordinary differential equation
d3udx3−cd2udx2+f′(u)dudx−(b/c)u=0
where f(u)=u(1−u)(u−α)
, 0<α<1
. In this paper we
have developed a technique to determine those values of the parameters a,b
and c
which permit
non-constant bounded solutions.
Automated bone marrow analysis using the CD4000 automated haematology analyser
Authors: Yamamura Ryousuke , Yamane Takahisa , Hino Masayuki , Ohta Kensuke , Koh Ki-Ryang , Tsuda Izumi , Takubo Takayuki , Tatsumi Noriyuki
Published: March 2007

At present, bone marrow analysis is performed microscopically, but is time consuming and labour intensive. No automated methods have been successfully applied to classification of bone marrows cells because automated blood cell analysers have been incapable of identifying erythroblasts. The present study was designed to evaluate automated analysis of bone marrow aspirates with the CELL‐DYN 4000 (CD4000) haematology analyser, which enables automated determination of erythroblast counts in both the normal mode (haemolytic time; 11.5s) and the resistant RBC mode (34.0s). The percentages of subpopulations including lymphocytes, neutrophils and erythroblasts were obtained with the CD4000, and as a reference, differential counts by microscopic observation of May–Grünwald–Giesa‐stained films of bone marrow aspirates were performed (n=98). Significant correlations (P < 0.01) between the results obtained with the two methods were observed for total nucleated cell count and lymphocytes, neutrophils, erythroblasts and myeloid/erythroid (M/E) ratio. However, there were biases in the average percentages of erythroblasts, lymphocytes and M/E ratio obtained using the normal mode with the CD4000 toward values lower than those obtained with the microscopic method. Using the RBC resistant mode with the CD4000, the average percentages of erythroblasts, lymphocytes and M/E ratio approximated those obtained with the microscopic method. In conclusion, the CD4000 in resistant RBC mode is more useful for analysis of bone marrow aspirates than is the normal mode, because the former better approximates the M/E ratio than the latter.
Performance characteristics of a low‐cost, field‐deployable miniature CCD spectrometer
Authors: Coles Simon , Nimmo Malcolm , Worsfold Paul J.
Published: March 2007

Miniature spectrometers incorporating array detectors are becoming a viable, low‐cost option for field and process deployments. The performance characteristics of one such instrument are reported and compared with those of a conventional benchtop instrument. The parameters investigated were wavelength repeatability, photometric linearity, instrumental noise (photometric precision) and instrumental drift.
Automation — down to the nuts and bolts
Authors: Fix Sr Robert J. , Rowe Jannell M. , McConnell Bain C.
Published: March 2007

Laboratories that once viewed automation as an expensive luxury are now looking to automation as a solution to increase sample throughput, to help ensure data integrity and to improve laboratory safety. The question is no longer, ‘Should we automate?’, but ‘How should we approach automation?’ A laboratory may choose from three approaches when deciding to automate: (1) contract with a third party vendor to produce a turnkey system, (2) develop and fabricate the system in‐house or (3) some combination of approaches (1) and (2). The best approach for a given laboratory depends upon its available resources. The first lesson to be learned in automation is that no matter how straightforward an idea appears in the beginning, the solution will not be realized until many complex problems have been resolved. Issues dealing with sample vessel manipulation, liquid handling and system control must be addressed before a final design can be developed. This requires expertise in engineering, electronics, programming and chemistry. Therefore, the team concept of automation should be employed to help ensure success. This presentation discusses the advantages and disadvantages of the three approaches to automation. The development of an automated sample handling and control system for the STAR™ System focused microwave will be used to illustrate the complexities encountered in a seemingly simple project, and to highlight the importance of the team concept to automation no matter which approach is taken. The STAR™ System focused microwave from CEM Corporation is an open vessel digestion system with six microwave cells. This system is used to prepare samples for trace metal determination. The automated sample handling was developed around a XYZ motorized gantry system. Grippers were specially designed to perform several different functions and to provide feedback to the control software. Software was written in Visual Basic 5.0 to control the movement of the samples and the operation and monitoring of the STAR™ microwave. This software also provides a continuous update of the system′s status to the computer screen. The system provides unattended preparation of up to 59 samples per run.
Case study of the automation options and decisions made in implementing a high‐throughput cell based screen using the FLIPR™
Authors: Hook Derek J.
Published: March 2007

This case study examines the automation and process change options available to emerging discovery/development stage pharmaceutical companies when considering implementing sophisticated high‐throughput screens. Generally there are both financial and personnel constraints that have to be addressed when implementing state‐of‐the‐art screening technology in smaller companies which generally are not as significant as in large pharmaceutical companies. When NPS Pharmaceuticals considered installing a Molecular Devices FLIPR™ for high‐throughput cell based screening it became clear that, to make the best decision, the whole screening process at NPS Pharmaceuticals from screen development and validation, tissue culture, compound distribution, data handling and screening had to be re‐examined to see what automation options were possible and which, if any, made sense to implement. Large scale automated systems were not considered due to their cost and the lack of in‐house engineering infrastructure to support such systems. The current trend towards workstation based laboratory automation suggested that a minimalist approach to laboratory automation, coupled with improved understanding of the physical process of screening, would yield the best approach. Better understanding of the work flow within the Biomolecular Screening team enabled the group to optimize the process and decide what support equipment was needed. To install the FLIPR™, train users, set up the tissue culture protocols for cell supply, establish high‐throughput screening database protocols, integrate compound distribution and re‐supply and validate the pharmacology on four cell based screens took the team 3 months. The integration of the screening team at the primary, secondary and tertiary screening stages of the target discovery project teams at NPS has enabled us to incorporate minimal automation into the Biomolecular Screening Group whilst retaining an enriching work environment. This is reflected in our current consistent throughput of 64 96‐well microplates per day on the FLIPR™, a figure that is comparable with that achieved within most major pharmaceutical companies. This case study suggests that process optimization coupled with modern stand alone automated workstations can achieve significant throughput in a resource constrained environment. Significantly greater throughput could be achieved by coupling the process improvement techniques described above with 384‐well microplate technology.
An industrial engineering approach to laboratory automation for high throughput screening
Authors: Menke Karl C.
Published: March 2007

Across the pharmaceutical industry, there are a variety of approaches to laboratory automation for high throughput screening. At Sphinx Pharmaceuticals, the principles of industrial engineering have been applied to systematically identify and develop those automated solutions that provide the greatest value to the scientists engaged in lead generation.
Drug discovery from Nature: automated high‐quality sample preparation
Authors: Thiericke Ralf
Published: March 2007

Secondary metabolites from plants, animals and microorganisms have been proven to be an outstanding source for new and innovative drugs and show a striking structural diversity that supplements chemically synthesized compounds or libraries in drug discovery programs. Unfortunately, extracts from natural sources are usually complex mixtures of compounds:: often generated in time consuming and for the most part manual processes. As quality and quantity of the provided samples play a pivotal role in the success of high‐throughput screening programs this poses serious problems. In order to make samples of natural origin competitive with synthetic compound libraries, we devised a novel, automated sample preparation procedure based on solid‐phase extraction (SPE). By making use of a modified Zymark RapidTrace® SPE workstation an easy‐to‐handle and effective fractionation method has been developed which allows the generation of highquality samples from natural origin, fulfilling the requirements of an integration into high‐throughput screening programs.
The planning and establishment of a sample preparation laboratory for drug discovery
Authors: Dufresne Claude
Published: March 2007

Nature has always been a productive source of new drugs. With the advent of high‐throughput screening, it has now become possible to rapidly screen large sample collections. In addition to seeking greater diversity from natural product sources (micro‐organisms, plants, etc.), fractionation of the crude extracts prior to screening is becoming a more important part of our efforts. As sample preparation protocols become more involved, automation can help to achieve and maintain a desired sample throughput. To address the needs of our screening program, two robotic systems were designed. The first system processes crude extracts all the way to 96‐well plates, containing solutions suitable for screening in biological and biochemical assays. The system can dissolve crude extracts, fractionate them on solid‐phase extraction cartridges, dry and weigh each fraction, re‐dissolve them to a known concentration, and prepare mother plates. The second system replicates mother plates into a number of daughter plates.
The Zymark BenchMate™. A compact, fully‐automated solution‐phase reaction work‐up facility for multiple parallel synthesis
Authors: Hamlin Gordon A.
Published: March 2007

The rapid growth of multiple parallel synthesis in our laboratories has created a demand for a robust, easily accessed automated system for solution‐phase reaction work‐up, since the manual work‐up of large numbers of small‐scale reactions is both time‐consuming and tedious, and is a rate limiting step in the generation of large numbers of compounds for test. Work‐up in chemical organic synthesis consists of a series of post‐reaction operations designed using differential chemical properties to remove excess reagent or starting material, reagent products and, where possible reaction by‐products. Careful consideration of post‐reaction operations as a clean‐up step can obviate the requirement for purification. Generally, work‐up can be resolved into four operations: filtration, solvent addition (dilution, trituration), washing and separation (partition) and it is the selection and ordering of these four basic operations that constitutes a chemical work‐up. Following the proven success of centralized Zymate robotic systems in the compilation, execution and work‐up of complex reaction sequences, a centralized chemical work‐up service has been in operation for over 12 months. It now seemed prudent that the needs of multiple parallel synthesis would be better served by the development of a compact, automated system, capable of operating in a standard chemistry laboratory fume‐hood. A Zymark BenchMate platform has been configured to perform the four basic operations of chemical solution work‐up. A custom‐built filtration station, incorporating an integrated tipping facility for the sample tube has also been developed. Compilation of each work‐up is through a set of Visual Basic procedure screens, each dedicated to a particular work‐up scenario. Methods are compiled at the chemist′s own PC and transferred to the BenchMate via a diskette.
Implementation of and experiences with new automation
Authors: Mahmud Ifte , Kim David
Published: March 2007

In an environment where cost, timeliness, and quality drives the business, it is essential to look for answers in technology where these challenges can be met. In the Novartis Pharmaceutical Quality Assurance Department, automation and robotics have become just the tools to meet these challenges. Although automation is a relatively new concept in our department, we have fully embraced it within just a few years. As our company went through a merger, there was a significant reduction in the workforce within the Quality Assurance Department through voluntary and involuntary separations. However the workload remained constant or in some cases actually increased. So even with reduction in laboratory personnel, we were challenged internally and from the headquarters in Basle to improve productivity while maintaining integrity in quality testing. Benchmark studies indicated the Suffern site to be the choice manufacturing site above other facilities. This is attributed to the Suffern facility employees′ commitment to reduce cycle time, improve efficiency, and maintain high level of regulatory compliance. One of the stronger contributing factors was automation technology in the laboratoriess, and this technology will continue to help the site′s status in the future. The Automation Group was originally formed about 2 years ago to meet the demands of high quality assurance testing throughput needs and to bring our testing group up to standard with the industry. Automation began with only two people in the group and now we have three people who are the next generation automation scientists. Even with such a small staff,we have made great strides in laboratory automation as we have worked extensively with each piece of equipment brought in. The implementation process of each project was often difficult because the second generation automation group came from the laboratory and without much automation experience. However, with the involvement from the users at ‘get‐go’, we were able to successfully bring in many automation technologies. Our first experience with automation was SFA/SDAS, and then Zymark TPWII followed by Zymark Multi‐dose. The future of product testing lies in automation, and we shall continue to explore the possibilities of improving the testing methodologies so that the chemists will be less burdened with repetitive and mundane daily tasks and be more focused on bringing quality into our products.
Automated analyser for monitoring trace amounts of volatile chloro‐organic compounds in recirculated industrial water
Authors: Janicki Wacław , Chrzanowski Wojciech , Wasik Andrzej , Przyk Elżbieta , Namieśnik Jacek
Published: March 2007

An automated analyser of volatile chloro‐organic compounds in water was constructed and tested using standard mixtures of dichloromethane and dichloroethane. It was based on continuous, countercurrent gas stripping of the liquid sample followed by periodic trapping of the analytes on two traps alternately connected to the bubbler outlet, and thermal desorption. When one trap performed adsorption, the other underwent desorption and cooling. Analytes were detected by an ECD detector. Integration, calibration, calculations and overall operating cycle control was performed by a microcomputer. The instrument guarantees a 0.02 ppm Cl (w/w) detection limit, a 0—2 ppm detection range and 2 months of autonomous operation. Results are reported every 13 min.
To robotize chemistry laboratories. An example of organic synthesis: 2‐Boc‐amino‐N‐hydroxy‐3‐phenyl‐propionamide
Authors: Christophe G. , Chapelant L. , Bostyn S. , Porte C. , Delacroix A. , D′Orchymont H.
Published: March 2007

The paper describes the development of periodic modules used for the peptide synthesis of hydroxamic acid. A powder conveyor using the principle of positive weighing distribution is described. Purification is provided using automatic filtration and a liquid—liquid extraction module separation device. Device quality is improved using failure mode and effects analysis.
Automated system to acquire fluorescence, polarization and anisotropy maps within liquid flows
Authors: Quintella Cristina M. , Gonçalves Cristiane C. , Pepe Iuri , Lima Angelo M. V. , Musse Ana Paula S.
Published: March 2007

Maps of polarization and anisotropy can be helpful for flow analysis systems (FIA, CFA, etc.) with reactions dependent on the intermolecular alignment as well as for dispersion control. Maps can be acquired manually, but when a scan over a sample area is required, the acquisition becomes tiresome and has low precision. The paper describes an automatic flexible system for high‐precision sample positioning with closed loop self control, remote data acquisition and storage controlled by a BASIC program. The system was developed to acquire maps up to 850 mm2 of the sample (liquid flows, solids, interfaces, etc.), with up to 100 μm2 precision. To evaluate the equipment, performance is presented as the scan of a thin liquid film of monoethylene glycol (MEG) flowing on borosilicate. Tests were performed with and without surfactantes at submicellar concentrations: two concentrations of sodium dodecyl sulphate (SDS) and one of polyethylene oxide (PEO). For pure MEG, the intermolecular alignment initially increased, then decreased. When SDS was added, both polarization and anisotropy only increased progressively with the flow. This might be explained by the surfactant decrease of interfacial interaction. When PEO was added, both polarization and anisotropy decreased pronouncedly over the entire map, which might be due to macromolecular aggregates within the bulk generating misaligned molecular domains. The system presented as sample positioning repeatability of 0.1% and a high polarization reproducibility (error margin < 6 in 1000).
Integrated luminometer for the determination of trace metals in seawater using fluorescence, phosphorescence and chemiluminescence detection
Authors: Worsfold P. J. , Achterberg E. P. , Bowie A. R. , Cannizzaro V. , Charles S. , Costa J. M. , Dubois F. , Pereiro R. , San Vicente B. , Sanz-Medel A. , Vandeloise R. , Donckt E. Vander , Wollast P. , Yunus S.
Published: March 2007

The paper describes an integrated luminometer able to perform fluorescence (FL), room temperature phosphorescence (RTP) and chemiluminescence (CL) measurements on seawater samples. The technical details of the instrumentation are presented together with flow injection (FI) manifolds for the determination of cadmium and zinc (by FL), lead (RTP) and cobalt (CL). The analytical figures of merit are given for each manifold and results are presented for the determination of the four trace metals in seawater reference materials (NASS‐5, SLEW‐2) and Scheldt estuarine water samples.
Analytical evaluation of two automatic methods to measure blood CK‐MB mass and troponin I
Authors: Galán Amparo , Curos Antonio , Duran Jordi , Corominas Augusto , Valle Vicente
Published: March 2007

The lack of standardization of methods to measure cardiac markers for coronaria ischaemia, particularly troponin, led us to perform an analytical evaluation of two new immunoassays to quantify CK‐MB mass and troponin I using the Dimension R×L automatic analyser. The reliability and analytical intervals of the methods were studied as well as reference values (0.010— 0.228 μg l-1 for troponin I, 0.20—3.90 mg μg l-1 for CK‐MB mass) and cuto¡ values (0.77 μg l-1 for troponin I, 5 μg l-1 for CK‐MB mass) established. The cutoff values were established from 37 patients with acute myocardial infarction and from 20 with unstable angina. The absence of method cross‐reactivity was corroborated using myocardial, brain and skeletal muscle tissue. Both methods were highly specific and showed good reliability and practicability in the diagnosis of coronaria ischaemia after 6 h of precordial pain.