bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogeology of the Oak Ridges Moraine aquifer system: implications for protection and management from the Duffins Creek watershed
Authors: Gerber Richard E , Howard Ken
Published: September 2002

The Oak Ridges Moraine aquifer feeds the headwaters of major rivers in the Greater Toronto Area and is an important source of domestic water supply. Recognizing the rapid rate of urban growth in the region, there is a concern that changing land use along the moraine must be strictly controlled if groundwater is to be adequately protected. To date, efforts to incorporate groundwater protection into the land use planning process have been hampered by an inadequate quantitative hydrogeological understanding of the aquifer system. Focusing on the Duffins Creek watershed, comprehensive hydrogeological studies including a numerical flow model now provide a quantitative insight into the hydrogeologic function of the moraine. These studies demonstrate that 60% of the entire basin groundwater discharge to streams occurs along the south flank of the moraine, and 60% of this headwater discharge occurs below the 275 m above sea level contour, one of the commonly accepted planning boundaries of the moraine. The remaining discharge is contributed by aquifers within and underlying deposits that extend to the south of the moraine. While 7580% of the watershed discharge to streams is received from the uppermost aquifer, 2025% is contributed by deeper aquifers underlying the extensive NorthernNewmarket till aquitard. This work shows that the moraine sediments represent just one component of a regional flow system that extends beyond the morphological boundary of the moraine. This has important implications for groundwater protection, as it demonstrates the need for management strategies that incorporate the regional groundwater flow system and not the moraine in isolation.
Analysis and reinterpretation of deformation features in the Rouge River valley, Scarborough, Ontario
Authors: Godin Laurent , Brown Richard L , Dreimanis Aleksis , Atkinson Gail M , Armstrong Derek K
Published: September 2002

Geometry and timing of deformation affecting Ordovician bedrock and overlying Pleistocene sediments in the Rouge River valley near Scarborough, Ontario, are analysed to evaluate whether or not the structures are a result of glacial action or neotectonic activity. Extensive data on local and regional ice-flow directions are used to evaluate the kinematic compatibility between the observed faults and folds and the local ice-flow directions. Jointing and multiple episodes of faulting affect both the Ordovician bedrock and the overlying Pleistocene sediments. At one site, the bedrock is displaced by a normal fault by a minimum of 1.2 m. Crosscutting relationships constrain the majority of the faulting in the Rouge River valley as being coeval with deposition of the lower Bowmanville till during the Nissouri phase (ca. 2315 ka), and possibly younger at one locality. The youngest regional ice-flow direction is northwestward; however, local ice-flow directions are highly variable. This can be explained by local perturbation enhanced by the presence of drumlinoid features in the area. Most deformation features are compatible with local and regional ice-flow directions. Glaciotectonic ice-push and ice-thrust deformation affected the Thorncliffe Formation after about 23 ka. Although some faults appear to be kinematically incompatible with ice-flow directions, six boreholes drilled to 52 m depth revealed only minor vertical offsets of bedrock strata in the uppermost 20 m, and an absence of obvious fault offsets deeper, precluding the possibility that the faults observed in the surface exposures were caused by deep-seated neotectonic stresses.
A STUDY ON SHEAR WAVE VELOCITY ESTIMATION AND FRACTURE DETECTION IN HTI MEDIA
Authors: DU QIZHEN , YANG HUIZHU , DONG YUAN
Published: September 2002

The paper presents estimates of the S-wave velocity and the crack density at which fractured reservoirs begin to play an important role in oil exploration. Transverse isotropy with a horizontal axis of symmetry (HTI) is the simplest azimuthally anisotropic model used to describe fractured reservoirs that contain parallel vertical cracks. A double profile concept is used to develop an equation for the P-S wave normal-moveout (NMO) velocity. The azimuthal NMO velocities of the P- and P-S waves can then be used to estimate the velocities of the S-waves and Thomsen's coefficient, γ. For multilayered media, a recursive equation is developed for the NMO velocity in each layer. The numerical results indicate that the S-wave NMO velocity can be accurately estimated using the P- and P-S wave NMO velocities in HTI media. An important parameter of fracture systems that can be measured from seismic data is the crack density which can be estimated using the NMO velocities of the P- and S-waves from horizontal reflectors. Therefore, fractures can be completely characterized by the joint inversion of P-waves and converted P-S waves in HTI media.
SIMULATION OF THE PROPAGATION OF ULTRASONIC PULSES IN NONLINEAR AND/OR ATTENUATIVE MEDIA
Authors: SCALERANDI M. , AGOSTINI V.
Published: September 2002

Computer simulation techniques, such as the Local Interaction Simulation Approach (LISA), allow us to predict accurately and efficiently the propagation of acoustic and ultrasonic waves or pulses in complex (heterogeneous and/or anisotropic) media. For a quantitative comparison with experimental results it is necessary to properly include in the model the attenuation and dispersion properties of the propagation medium. A spring model is used to derive heuristically the iteration equations, which yield stable and convergent simulations of the wave propagation even in the case of attenuative, dispersive and/or nonlinear media. To illustrate the procedure several examples of propagation of monochromatic waves and pulses are presented.
TIME-DOMAIN SIMULATION OF ACOUSTIC SOURCES OVER AN IMPEDANCE PLANE
Authors: JU H. B. , FUNG K.-Y.
Published: September 2002

An implicit high-order compact unconditionally stable finite-difference time-domain (FDTD) method is proposed here for numerical solution of point sources over an impedance plane. In this method, the linearized Euler equations are split into three directional sets and twelve simple wave components, or six when equivalent sources are adopted with no mean flow. Each component is solved using a fourth-order Padé approximant in space and second-order trapezoidal integration in time. The concept of reflection coefficient is used and algebraically modeled to develop time-domain impedance-equivalent boundary conditions. Comparisons with established methods for reflections of harmonic or impulsive sources demonstrate the applicability of this method for general impedance value, source type, or their arbitrary distributions. Examples of using typical wool felt and grass ground impedances are given to illustrate its practicality and effectiveness. This method provides a means through which time-domain theories and procedures for in-situ characterization of impedance surfaces can be developed.
COMPUTING THE INFLUENCE OF DOPPLER DUE TO SOURCE/RECEIVER MOTION IN A PARABOLIC EQUATION MODEL
Authors: SMITH KEVIN B.
Published: September 2002

A numerical method for computing the influence of Doppler due to source/receiver platform motion in a parabolic equation model is introduced. Both source/receiver speeds and angles of motion in the vertical plane are included in the specification of the motion. By necessity, it is shown that the source function must be defined in the vertical wavenumber domain. Furthermore, the source amplitude spectrum must be defined prior to the calculation, in contrast to previous implementations which would allow for application of variable spectra in post-processing. Examples are given for simple environments demonstrating the expected influence of Doppler due to source motion.
A PERTURBATIVE APPROACH TO ACOUSTIC SCATTERING FROM A VIBRATING BOUNDED OBSTACLE
Authors: MARIANI FRANCESCA , RECCHIONI MARIA CRISTINA , ZIRILLI FRANCESCO
Published: September 2002

In this paper we study a mathematical model to describe a three dimensional acoustic scattering problem associated to a "vibrating" obstacle that is a bounded simply connected domain contained in the three dimensional real Euclidean space whose shape changes in time. In particular we propose a numerical method based on a perturbation series and the operator expansion method to solve the mathematical model considered. This method makes possible to obtain highly parallelizable algorithms able to compute the solution of the problem considered order by order in perturbation theory, and able to obtain the required solution of the scattering problem summing up the perturbation series. Really impressive speed up factors are observed and reported when the algorithm is executed on the Chiba Cluster, a parallel machine of the Argonne National Laboratory, USA. We validate the mathematical model and the numerical method proposed solving some test problems. The quantitative character of the numerical results obtained is established. The results obtained on the test problems are discussed both from the numerical and the physical point of view. In particular we show that the Doppler spectrum associated to the far field patterns of the scattered acoustic fields depends mainly from the incoming wave and from the excited vibrational modes (Figs. 9–13). The website: shows some Applets relative to the numerical examples.
APPLYING CHAOS TO MANUFACTURING PROCESS OPTIMIZATION
Authors: DESSERT PATRICK E. , JAMES SCOTT D.
Published: September 2002

We have applied the principles of chaos theory to optimizing the manufacturing process. A simulation system was created in which multiple parameters were modified to denote the effect of chaotic changes on the net profit derived.

The companies that are successful in modeling their manufacturing systems in a simplistic manner can look forward to increased profit, better control and simpler manufacturing systems.

Finding and selecting the correct set of parameters to subject to chaotic changes is time consuming. There are countless operating parameters that could be selected and the interaction of those parameters may have varying degrees of success on trying to optimize the manufacturing process. Certain parametric interactions may increase revenue, while other interactions may actually do the inverse.
A STUDY ON VIRTUAL ENTERPRISE COALITION WITH MULTI-AGENT TECHNOLOGY IN AGILE MANUFACTURING ENVIRONMENT
Authors: KAIHARA TOSHIYA , FUJII SUSUMU
Published: September 2002

There is a growing recognition that current manufacturing enterprises must be agile, and the use of virtual enterprise (VE) is becoming increasingly prevalent in recent years. It is a very important and difficult activity in forming a virtual enterprise to select appropriate business partners, because each enterprise considers not only pursuing its profit but also sharing the risk to join the virtual enterprise. At first we propose a VE coalition algorithm based on multi-agent paradigm. Then we develop a computer simulation model to evaluate the proposed method by forming a virtual enterprise through multiple negotiations amongst several potential members in the negotiation domain. Finally, we clarify the coalition dynamism with the negotiation process. The effectiveness of the proposed concept in the agile manufacturing is discussed with several simulation experiments.
DISTRIBUTED VIRTUAL MANUFACTURING FOR DEVELOPMENT OF MODULAR MACHINE SYSTEMS
Authors: OLOFSGÅRD PETTER , NG AMOS , MOORE PHILIP , PU JUNSHENG , WONG CHI BUI , VIN LEO DE
Published: September 2002

To support all phases of an agile modular manufacturing machine life cycle with CAE and Virtual Manufacturing tools, a number of different engineering applications (e.g. specialist software based tools) are typically used for design, simulation, analysis, programming, control and monitoring of a machine. These applications mainly exist today as small applications islands where each of them manages their own data.

When a manufacturing machine is designed, simulated, programmed, analyzed, tested, or operated, the information, connected to that specific machine, used and generated by each application island is stored separately by each application. These application islands often use different storage technologies. Each one of the applications has an information structure to separate the information connected to each machine; however, they do not necessarily use the same information structure.

Another issue concerning these applications is the functionality that is implemented in them to manage information; namely, processes such as store, retrieve, search, permissions, etc. The functionality for one process is the same in all applications that has the process implemented. But the implementation of the process functionality may differ, due to misinterpretation of the functionality specification and regular implementation bugs, which could lead to problem with integrity and consistency of the data. Applications that make use of newer information technologies, such as databases and software development tools can simplify the implementation of the functionality but each application still has to implement their own version of the functionality.

This paper presents a research investigation focused on the development of a distributed integration platform that supports the whole life cycle of agile modular machine systems, which includes the design, simulation, programming, analysis, machine operation and re-configuration. The environment supports distributed management and storage of information in a system-wide library, information management and storage that is machine oriented, not application oriented, and information storage structured as reusable components to enable reuse of information and know-how that is produced throughout the life cycle of machines.
CONTROL SYSTEM VERIFICATION BY EMULATION: AN APPLICATION TO OFF-LINE PRESS LINE THROUGHPUT RATE OPTIMIZATION
Authors: DANIELSSON FREDRIK , HANSBO ANITA
Published: September 2002

This study is part of a research project aims at off-line programming and verification of industrial control systems. In this paper, an off-line method for press line throughput rate optimization and control system verification is proposed, implemented and evaluated. The main tool is a virtual press station, developed by the first author, consisting of an emulated control system for a feeder/extractor robot which communicates with 3D-simulated production equipment. Moreover, several virtual press stations have been coupled and synchronized in a virtual press line. An important feature of the system is that the virtual robot controller is emulated, yielding an exact representation of the control logic and the possibility to run the entire system in virtual real time. The application considered is a sheet metal forming process where it is difficult to achieve maximum capacity utilization. There is much to gain if the control logic is improved and the throughput rate is increased. For this purpose, an automated robot motion optimization method is implemented and evaluated, using the virtual press line.
AN OBJECT ORIENTED MODEL FOR SCHEDULING IN AGILE MANUFACTURING
Authors: CELANO G. , COSTA A. , FICHERA S.
Published: September 2002

Agility represents a key factor in industry to handle the continuous market changes. Companies must re-organize their activities to be agile and competitive in such a dynamic environment. In particular, production planning and control tools are very important to optimize the manufacturing process responsiveness to sudden changes in customer demand. In this paper, an attempt has been made to develop an object-oriented software architecture that allows the optimal line organization to be determined once a set of parts to be produced has been ordered. An optimization module represented by a simulated annealing algorithm has been interfaced with an object oriented architecture to build up a framework that can be used to select both the optimal schedule, the buffer capacity and the speed of the conveyors in a very short time. The main characteristic of the proposed system is represented by its extremely high flexibility and reconfigurability with respect to the sudden changes in the customer orders that are reflected on the mix to be produced. A test case is provided to demonstrate the potential of using the proposed software architecture. A discussion on the obtained results is also developed to prove how the system is able to cope with lines characterized by different configurations of available resources.
INTEGRATED 3R AND VR TECHNOLOGIES FOR CREATIVE DESIGN AND MARKETING
Authors: YAO ALBERT W.-L. , KAO S. A. , LI D. Y.
Published: September 2002

Owing to stiff competition globally, the business operation of traditional industries, like the mould and die industry in Taiwan, urgently needs to be modernized. A wide spectrum of IT-tools and a variety of different computer-aided systems are currently available to provide best-in-class solutions for executing manufacturing and marketing tasks. Our aim in this project is to integrate the technologies of reverse engineering (RE), rapid prototyping (RP), rapid tooling (RT) and virtual reality (VR) for mould and die industries to effectively improve the performance of creative design, rapid manufacturing, training and marketing. The integration of RE/RP/RT technologies is known as 3R technology. From the reports, 3R technologies are capable of improving conceptual design quickly and effectively. With the improvement of computer and Internet technologies, the interaction of webbed VR has recently become an important business means to promote creative training and marketing. We call the integration of 3R and VR techniques 4R technology. This present methodology can help enterprises improve their capability for global competition.
PKM ANALYSIS AND DESIGN IN A VIRTUAL PROTOTYPING ENVIRONMENT
Authors: BIANCHI GIACOMO , FASSI IRENE , TOSATTI LORENZO MOLINARI
Published: September 2002

Industrial adoption of PKMs may be eased by the availability of methodologies and integrated tools able to analyze in a short time PKMs of any architecture, providing the key data needed to design the machine. The proposed Virtual Prototyping Environment for PKM Analysis answers to these requirements, quickly estimating not only the reachable workspace, the Jacobian conditioning, but also the actuators' effort, internal loads in the mechanical structure and the effects of lumped structural compliances. A description of the developed VPE-PKM, based on a commercial Multi-body package, is given. Its effectiveness is shown, presenting results obtained by ITIA-CNR during the design of a 3 dof translational PKM for light deburring operations.
PRODUCT AND PROCESS DEVELOPMENT INTENSITY IN PROCESS INDUSTRY: A CONCEPTUAL AND EMPIRICAL ANALYSIS OF THE ALLOCATION OF COMPANY RESOURCES FOR THE DEVELOPMENT OF PROCESS TECHNOLOGY
Authors: LAGER THOMAS
Published: September 2002

In Process Industry, process development traditionally takes a large part of the company's total development efforts, but has nevertheless not received much attention in academic studies. As a part of a larger research project concerning process development in Process Industry, the allocation of company resources to R&D, and to process development in particular, has been investigated in an exploratory survey to R&D managers in European Process Industry (Mining & Mineral Industry, Food & Beverage Industry, Pulp & Paper Industry, Chemical Industry, Basic Metal Industry, and Other Process Industry). The results show that of the total resources for R&D, 40% was allocated to process development, and over 60% of the companies expected this figure to increase in the future. This figure not only shows the future importance of process development, but also indicates that the importance of product development in this group of companies is at present still rated higher than process development. The results from the study do not fit the most widely used theoretical models, and it is concluded that there is a need for better models with more explanatory power. The new concepts of product and process development intensity are introduced. The product and process development intensities can be looked upon as aggregated measures of individual development efforts by a company, and it is thus argued that they are of overall company strategic importance.
RESEARCH AND DEVELOPMENT IN RUSSIA AND ITS ROLE IN NATIONAL COMPETITIVENESS
Authors: OGLOBINA SVETLANA YURIEVNA , FARIA ANA PAULA , CABRAL-CARDOSO CARLOS
Published: September 2002

There is now a large body of literature showing that research and development (R&D) activities have a major impact in the economy, leading to increases in productivity, competitiveness and economic growth. Using the concept of national innovation system this paper is an attempt to understand the current status of Russian technological development and the role R&D might play in the transition from a command economy to a free-market economy. Despite the effects of a declining R&D workforce and continuing underfunding of R&D institutions, a considerable R&D potential is still in place. The major barriers for its effective contribution to economic and business recovery are discussed in detail. Some innovation and R&D policy implications at both central and regional levels are also drawn.
THE KEY TO SUCCESS IN INNOVATION PART I: THE ART OF INTERESSEMENT
Authors: AKRICH MADELEINE , CALLON MICHEL , LATOUR BRUNO , MONAGHAN ADRIAN
Published: September 2002

We all know of innovations which either made their creators a fortune or which led to their downfall. It is easy to retrospectively explain success as a stroke of genius or failure as a blatant mistake. Easy in retrospect…but what about innovation in the making? How does the innovator navigate the pitfalls which threaten him?
THE KEY TO SUCCESS IN INNOVATION PART II: THE ART OF CHOOSING GOOD SPOKESPERSONS
Authors: AKRICH MADELEINE , CALLON MICHEL , LATOUR BRUNO , MONAGHAN ADRIAN
Published: September 2002

"Solve the technical problems first", we often hear, "then we'll deal with the market". The real history of innovations does not generally follow this simple schema; it is made of adaptations, series of trial and error and countless negotiations between numerous social actors. A genuine combat from which conquerors who know how to choose good representatives emerge.
TOO MANY TOOLS? ON PROBLEM SOLVING IN NPD PROJECTS
Authors: BENDERS JOS , VERMEULEN PATRICK
Published: September 2002

Complaints that new product development projects frequently encounter problems keep occurring, despite the availability of a considerable body of literature and a large and still increasing set of tools to guide such projects. Against the wider background of managerial problem-solving in general and NPD-literature more specifically, we present and analyse two NPD-projects within the same financial services firm. These show a marked contrast in success. The reasons for this difference are explored and conclusions are drawn about the usefulness of NPD-literature and tools.
On a sum analogous to Dedekind sum and its mean square value formula
Authors: Wenpeng Zhang
Published: September 2002

The main purpose of this paper is using the mean value
theorem of Dirichlet L‐functions to study the asymptotic property
of a sum analogous to Dedekind sum, and give an interesting mean
square value formula.
Subgroups of quasi‐HNN groups
Authors: Mahmood R. M. S. , Khanfar M. I.
Published: September 2002

We extend the structure theorem for the subgroups of the class of
HNN groups to a new class of groups called quasi‐HNN groups. The
main technique used is the subgroup theorem for groups acting on
trees with inversions.
Strict positive definiteness on spheres via disk polynomials
Authors: Menegatto V. A. , Peron A. P.
Published: September 2002

We characterize complex strictly positive definite functions on
spheres in two cases, the unit sphere of ℂq, q ≥ 3, and the unit sphere of the complex ℓ2. The results depend upon
the Fourier‐like expansion of the functions in terms of disk
polynomials and, among other things, they enlarge the classes of
strictly positive definite functions on real spheres studied in
many recent papers.
A note on operators of deletion and contraction for antichains
Authors: Matveev Andrey O.
Published: September 2002

The operators of deletion and contraction for clutters are
generalized to those for antichains of finite bounded posets. A
generalization of the result by Seymour (1976), describing the
relationship between the operators of deletion, contraction, and
the blocker map, is considered as a comparison in the lattice of
antichains of a poset.
On the relation between interior critical points of positivesolutions and parameters for a class of nonlinear boundary value problems
Authors: Afrouzi G. A. , Moghaddam M. Khaleghy
Published: September 2002

We consider the boundary value problem −u″(x) = λf(u(x)), x ∈ (0, 1); u′(0) = 0; u′(1) + αu(1) = 0, where α > 0, λ > 0 are parameters and f ∈ c2[0, ∞) such that f(0) < 0. In this paper, we study for the two cases ρ = 0 and ρ = θ (ρ is the value of the solution at x = 0 and θ is such that F(θ) = 0 where ) the relation between λ and the number of interior critical points of the nonnegative solutions of the above system.
An empirical Bayes derivation of best linear unbiased predictors
Authors: Karunamuni Rohana J.
Published: September 2002

Let (Y1, θ1), …, (Yn, θn) be independent real‐valued random vectors with Yi, given θi, is distributed according to a distribution depending only on θi for i = 1, …, n. In this paper, best linear unbiased predictors (BLUPs) of the θi′s are investigated. We show that BLUPs of θi′s do not exist in certain situations. Furthermore, we present a general empirical Bayes technique for deriving BLUPs.
Super and subsolutions for elliptic equations on all of ℝn
Authors: Afrouzi G. A. , Ghasemzadeh H.
Published: September 2002

By construction sub and supersolutions for the following
semilinear elliptic equation −△u(x) = λg(x)f(u(x)), x ∈ ℝn which arises in population genetics, we
derive some results about the theory of existence of solutions as
well as asymptotic properties of the solutions for every n and for the function g : ℝn → ℝ such that g is smooth and is negative at infinity.
A class of gap series with small growth in the unit disc
Authors: Sons L. R. , Ye Zhuan
Published: September 2002

Let β > 0 and let α be an integer which is at least
2. If f is an analytic function in the unit disc D which has power series representation
, limsupk→∞ (log+|ak|/logk) = α(1 + β), then the first author has proved that f is unbounded in every sector {z ∈ D : Φ − ϵ < argz < Φ + ϵ, for ϵ > 0}. A natural conjecture concerning these functions is that , where L(r) is the minimum of |f(z)| on |z| = r and M(r) is the maximum of |f(z)| on |z| = r. In this paper, investigations concerning this conjecture
are discussed. For example, we prove that and when ak = kα(1+β).
A new triple sum combinatorial identity
Authors: Sinyor Joseph , Tefera Akalu
Published: September 2002

We prove a new triple sum combinatorial identity derived from rp(x, y, z) = (x+y−z)p − (xp + yp − zp), extending a previous result by Sinyor et al.
Notes on stability of the generalized gamma functional equation
Authors: Kim Gwang Hui , Xu Bing , Zhang Weinian
Published: September 2002

The Hyers‐Ulam stability in three senses is discussed by Kim
(2001) for the generalized gamma functional equation
g(x + p) = a(x)g(x) under some conditions which involve convergence
of complicated series. In this note, those conditions are
simplified to be checked easily and more interesting examples
other than the classical gamma functional equation are displayed.
On sectional and bisectional curvature of the H‐umbilical submanifolds
Authors: Ianus S. , Rizza G. B.
Published: September 2002

Let M be an H‐umbilical submanifold of an almost Hermitian
manifold . Some relations expressing the difference of
bisectional and of sectional curvatures of and of M
are obtained. The geometric notion of related bases for a pair of
oriented planes permits to write the second members in a
completely geometrical form. When the planes are not orthogonal,
more simple formulas are obtained. The paper ends with a remark,
concerning the vector field JH, and some special cases.
On the first power mean of L‐functions with the weight of general Kloosterman sums
Authors: Wenpeng Zhang
Published: September 2002

The main purpose of this paper is using the estimates for
character sums and the analytic method to study the first power mean of Dirichlet L‐functions with the weight of general Kloosterman sums, and give an interesting asymptotic formula.
Optimal Cusum schemes for monitoring variability
Authors: Poetrodjojo S. , Abdollahian M. A. , Debnath Narayan C.
Published: September 2002

Cumulative Sum (Cusum) Control Schemes are widely used in
industry for process and measurement control. Most Cusum
applications have been in monitoring shifts in the mean level of a
process rather than process variability. In this paper, we study
the use of Markov chain approach in calculating the
average run length (ARL) of a Cusum scheme when controlling
variability. Control statistics S and S2, where S is the
standard deviation of a normal process are used. The optimal
Cusum schemes to detect small and large increases in the
variability of a normal process are designed. The control
statistic S2 is then used to show that the Cusum scheme is
superior to the exponentially weighted moving average (EWMA) in
terms of its ability to quickly detect any large or small
increases in the variability of a normal process. It is also
shown that Cusum with control statistics sample variance (S2)
and sample standard deviation (S) perform uniformly better
than those with control statistic logS2. Fast initial response (FIR) Cusum properties are also presented.
Decay rates for solutions of a Timoshenko system with a memory condition at the boundary
Authors: Santos Mauro de Lima
Published: September 2002

We consider a Timoshenko system with memory condition at the
boundary and we study the asymptotic behavior of the
corresponding solutions. We prove that the energy decay with the
same rate of decay of the relaxation functions, that is, the
energy decays exponentially when the relaxation functions decays
exponentially and polynomially when the relaxation functions
decays polynomially.
On the location of the peaks of least‐energy solutions to semilinear Dirichlet problems with critical growth
Authors: Souto Marco A. S.
Published: September 2002

We study the location of the peaks of solution for the critical growth problem , u > 0 in Ω, u = 0 on ∂Ω, where Ω is a bounded domain; 2* = 2N/(N − 2), N ≥ 3, is the critical Sobolev exponent and f has a behavior like up, 1 < p < 2* − 1.
On three‐point boundary value problem with a weighted integral condition for a class of singular parabolic equations
Authors: Bouziani Abdelfatah
Published: September 2002

We deal with a three point boundary value problem for a class of
singular parabolic equations with a weighted integral condition
in place of one of standard boundary conditions. We will first
establish an a priori estimate in weighted spaces. Then, we prove
the existence, uniqueness, and continuous dependence of a strong
solution.
On an asymptotically linear elliptic Dirichlet problem
Authors: Zhang Zhitao , Li Shujie , Liu Shibo , Feng Weijie
Published: September 2002

Under very simple conditions, we prove the existence of one positive and one negative solution of an asymptotically linear elliptic boundary value problem. Even for the resonant case at infinity, we do not need to assume any more conditions to ensure the boundness of the (PS) sequence of the corresponding functional. Moreover, the proof is very simple.
Werner Syndrome
Authors: Chen Lishan , Oshima Junko
Published: September 2002

Werner syndrome is a premature aging disease caused by the
mutation in the WRN gene. The cloning and
characterization of the WRN gene and its product allows
investigators to study the disease and the human aging process at
molecular level. This review summarizes the recent progresses on
various aspects of the WRN research including functional
analysis of the protein, interactive cloning, complexes
formation, mouse models, and SNPs (single nucleotide
polymorphisms). These in depth investigations have greatly
advanced our understanding of the disease and elucidated future
research direction for Werner syndrome and the human aging
process.
Nucleotide Excision Repair, Genome Stability, and Human Disease: New Insight from Model Systems
Authors: Garfinkel David J. , Bailis Adam M.
Published: September 2002

Nucleotide excision repair (NER) is one of several DNA repair
pathways that are universal throughout phylogeny. NER has a broad
substrate specificity and is capable of removing several classes
of lesions to the DNA, including those that accumulate upon
exposure to UV radiation. The loss of this activity in
NER‐defective mutants gives rise to characteristic sensitivities
to UV that, in humans, is manifested as a greatly elevated
sensitivity to exposure to the sun. Xeroderma pigmentosum (XP),
Cockayne’s syndrome (CS), and trichothiodystrophy (TTD) are
three, rare, recessively inherited human diseases that are linked
to these defects. Interestingly, some of the symptoms in
afflicted individuals appear to be due to defects in
transcription, the result of the dual functionality of several
components of the NER apparatus as parts of transcription factor
IIH (TFIIH). Studies with several model systems have revealed
that the genetic and biochemical features of NER are
extraordinarily conserved in eukaryotes. One system that has been
studied very closely is the budding yeast Saccharomyces
cerevisiae. While many yeast NER mutants display the expected
increases in UV sensitivity and defective transcription, other
interesting phenotypes have also been observed. Elevated mutation
and recombination rates, as well as increased frequencies of
genome rearrangement by retrotransposon movement and
recombination between short genomic sequences have been
documented. The potential relevance of these novel phenotypes to
disease in humans is discussed.
Ku and the Stability of the Genome
Authors: Friedl Anna A.
Published: September 2002

Ku proteins are associated with a variety of cellular processes
such as repair of DNA‐double‐strand breaks, telomere maintenance
and retrotransposition. In recent years, we have learned a lot
about their cellular and molecular functions and it has turned
out that Ku‐dependent processes affect the stability of the
genome, both positively and negatively, in several ways. This
article gives an overview on the role of Ku in determining the
shape of the genome.
Answering the Call: Coping with DNA Damage at the Most Inopportune Time
Authors: Crowley David J. , Courcelle Justin
Published: September 2002

DNA damage incurred during the process of
chromosomal replication has a particularly high possibility of
resulting in mutagenesis or lethality for the cell. The SOS
response of Escherichia coli appears to be well adapted
for this particular situation and involves the coordinated
up‐regulation of genes whose products center upon the tasks of
maintaining the integrity of the replication fork when it
encounters DNA damage, delaying the replication process (a DNA
damage checkpoint), repairing the DNA lesions or allowing
replication to occur over these DNA lesions, and then restoring
processive replication before the SOS response itself is
turned off. Recent advances in the fields of genomics and
biochemistry has given a much more comprehensive picture of the
timing and coordination of events which allow cells to deal with
potentially lethal or mutagenic DNA lesions at the time of
chromosomal replication.
Recombinational DNA Repair in Cancer and Normal Cells: The Challenge of Functional Analysis
Authors: Willers Henning , Xia Fen , Powell Simon N.
Published: September 2002

A major goal of current cancer research is to understand the
functional consequences of mutations in recombinational DNA
repair genes. The introduction of artificial recombination
substrates into living cells has evolved into a powerful tool to
perform functional analysis of DNA double strand break (DSB)
repair. Here, we review the principles and practice of current
plasmid assays with regard to the two major DSB repair pathways,
homologous recombination and nonhomologous end‐joining. A
spectrum of assay types is available to assess repair in a wide
variety of cell lines. However, several technical challenges
still need to be overcome. Understanding the alterations of DSB
repair in cancers will ultimately provide a rational basis for
drug design that may selectively sensitize tumor cells to
ionizing radiation and chemotherapy, thereby achieving
therapeutic gain.
XRCC2 is Required for the Formation of Rad51 Foci Induced by Ionizing Radiation and DNA Cross‐Linking Agent Mitomycin C
Authors: Liu Nan
Published: September 2002

XRCC2 protein shares weak amino acid sequence similarity with
Rad51, which is a central player in homologous recombinational
repair (HRR). Rad51 proteins assemble at the sites of HRR and form
visible nuclear foci in response to DNA damage. Xrcc2
hamster mutant irs1 cells are incapable of forming Rad51 foci
after ionizing irradiation or DNA cross‐linking agent mitomycin C
treatment, though the Rad51 protein level is normal in the
mutant. The defect can be corrected in an XRCC2
transformant. Time course study showed that the irs1 cells
primarily lacked the early response (2 hours after
irradiation) to form small Rad51 foci (type 1) and later response
(8 hours after irradiation) to form large foci (type 2).
These results suggested that XRCC2 is essential for the assembly
of the DNA damage‐induced Rad51 foci and that XRCC2 may play an
important role in the early stage of HRR.
Homologous Recombination and Its Role in Carcinogenesis
Authors: Bishop Alexander J. R. , Schiestl Robert H.
Published: September 2002

Cancer develops when cells no longer follow their normal pattern
of controlled growth. In the absence or disregard of such
regulation, resulting from changes in their genetic makeup, these
errant cells acquire a growth advantage, expanding into
precancerous clones. Over the last decade, many studies have
revealed the relevance of genomic mutation in this process, be it
by misreplication, environmental damage, or a deficiency in
repairing endogenous and exogenous damage. Here, we discuss
homologous recombination as another mechanism that can result in
a loss of heterozygosity or genetic rearrangements. Some of these
genetic alterations may play a primary role in carcinogenesis, but
they are more likely to be involved in secondary and subsequent
steps of carcinogenesis by which recessive oncogenic mutations are
revealed. Patients, whose cells display an increased frequency of
recombination, also have an elevated frequency of cancer, further
supporting the link between recombination and carcinogenesis.
Regulation of repair by the 26S proteasome
Authors: Sweder K. , Madura K.
Published: September 2002

Cellular processes such as transcription and DNA repair may be
regulated through diverse mechanisms, including RNA synthesis,
protein synthesis, posttranslational modification and protein
degradation. The 26S proteasome, which is responsible for
degrading a broad spectrum of proteins, has been shown to
interact with several nucleotide excision repair proteins,
including xeroderma pigmentosum B protein (XPB), Rad4, and Rad23.
Rad4 and Rad23 form a complex that binds preferentially to
UV‐damaged DNA. The 26S proteasome may regulate repair by
degrading DNA repair proteins after repair is completed or,
alternatively, the proteasome may act as a molecular chaperone to
promote disassembly of the repair complex. In either case, the
interaction between the proteasome and nucleotide excision repair
depends on proteins like Rad23 that bind ubiquitin‐conjugated
proteins and the proteasome. While the iteration between Rad4 and
Rad23 is well established, it will be interesting to determine
what other proteins are regulated in a Rad23‐dependent manner.
PML-RAR induces promyelocytic leukemias with high efficiency following retroviral gene transfer into purified murine hematopoietic progenitors
Authors: Minucci Saverio , Monestiroli Silvia , Giavara Sabrina , Ronzoni Simona , Marchesi Francesco , Insinga Alessandra , Diverio Daniela , Gasparini Patrizia , Capillo Manuela , Colombo Emanuela , Matteucci Cristian , Contegno Francesco , Lo-Coco Francesco , Scanziani Eugenio , Gobbi Alberto , Pelicci Pier Giuseppe
Published: September 2002

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations resulting in fusion proteins of the retinoic acid receptor (RAR). Here, we report a novel murine model system for APL, based on the transduction of purified murine hematopoietic progenitors (lin−) using high-titer retroviral vectors encoding promyelocytic leukemia–RAR (PML-RAR), and the green fluorescent protein (GFP) as a marker. PML-RAR–expressing lin− cells were impaired in their ability to undergo terminal myeloid differentiation and showed increased proliferative potential in vitro. Inoculation of transduced lin− cells into syngeneic, irradiated mice resulted in the development of retinoic acid-sensitive promyelocytic leukemias at high frequency (> 80%) and short latency (approximately 4 months). Morphologic and immunophenotypic analysis revealed no gross abnormalities of the preleukemic bone marrows. However, hematopoietic progenitors from PML-RAR preleukemic mice showed a severe impairment in their ability to undergo myeloid differentiation in vitro. This result, together with the monoclonality or oligoclonality of the leukemic blasts, supports a “multiple-hit” model, where the fusion protein causes a “preleukemic” phase, and leukemia occurs after additional genetic lesions. This model system faithfully reproduces the main characteristics of human APL and represents a versatile tool for the in vitro and in vivo study of mechanisms of leukemogenesis and the design of protocols for differentiation treatment.
Mechanisms of CD47-induced caspase-independent cell death in normal and leukemic cells: link between phosphatidylserine exposure and cytoskeleton organization
Authors: Mateo Véronique , Brown Eric J. , Biron Guy , Rubio Manuel , Fischer Alain , Deist Françoise Le , Sarfati Marika
Published: September 2002

Dying cells, apoptotic or necrotic, are swiftly eliminated by professional phagocytes. We previously reported that CD47 engagement by CD47 mAb or thrombospondin induced caspase-independent cell death of chronic lymphocytic leukemic B cells (B-CLL). Here we show that human immature dendritic cells (iDCs) phagocytosed the CD47 mAb–killed leukemic cells in the absence of caspases 3, 7, 8, and 9 activation in the malignant lymphocytes. Yet the dead cells displayed the cytoplasmic features of apoptosis, including cell shrinkage, phosphatidylserine exposure, and decreased mitochondrial transmembrane potential (ΔΨm). CD47 mAb–induced cell death also occurred in normal resting and activated lymphocytes, with B-CLL cells demonstrating the highest susceptibility. Importantly, iDCs and CD34+ progenitors were resistant. Structure-function studies in cell lines transfected with various CD47 chimeras demonstrated that killing exclusively required the extracellular and transmembrane domains of the CD47 molecule. Cytochalasin D, an inhibitor of actin polymerization, and antimycin A, an inhibitor of mitochondrial electron transfer, completely suppressed CD47-induced phosphatidylserine exposure. Interestingly, CD47 ligation failed to induce cell death in mononuclear cells isolated from Wiskott-Aldrich syndrome (WAS) patients, suggesting the involvement of Cdc42/WAS protein (WASP) signaling pathway. We propose that CD47-induced caspase-independent cell death be mediated by cytoskeleton reorganization. This form of cell death may be relevant to maintenance of homeostasis and as such might be explored for the development of future therapeutic approaches in lymphoid malignancies.
Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell–induced apoptosis
Authors: Schneider E. Marion , Lorenz Ingrid , Müller-Rosenberger Michaela , Steinbach Gerald , Kron Martina , Janka-Schaub Gritta E.
Published: September 2002

In 65 patients with hemophagocytic lymphohistiocytosis (HLH), we found an as yet undescribed heterogeneity of defects in cellular cytotoxicity when assay conditions were modified by the incubation time, the presence of mitogen, or interleukin-2 (IL-2). The standard 4-hour natural killer (NK) test against K562 targets was negative in all patients. In patients deficient in type 1 (n = 21), type 2 (n = 5), and type 4 (n = 8) HLH, negative NK function could be reconstituted by mitogen, by IL-2, or by prolongation of the incubation time (16 hours), respectively. Most patients (n = 31) displayed the type 3 defect, defined by a lack of any cellular cytotoxicity independent of assay variations. The characteristic hypercytokinemia also concerned counterregulatory cytokines, such as proinflammatory interferon-γ (IFN-γ), simultaneously elevated with suppressive IL-10 in 38% of types 1–, 2–, and 4–deficient patients and in 71% of type 3–deficient patients. Elevated IFN-γ alone correlated with high liver enzymes, but sCD95-ligand and sCD25 did not—though these markers were expected to indicate the extent of histiocytic organ infiltration. Outcome analysis revealed more deaths in patients with type 3 deficiency (P = .017). Molecular defects were associated with homozygously mutated perforin only in 4 patients, but other type 3 patients expressed normal transcripts of effector molecules for target-cell apoptosis, including perforin and granzyme family members, as demonstrated by RNase protection analysis. Thus, target-cell recognition or differentiation defects are likely to explain this severe phenotype in HLH. Hyperactive phagocytes combined with NK defects may imply defects on the level of the antigen-presenting cell.
Mouse CD11c+ B220+ Gr1+plasmacytoid dendritic cells develop independently of the T-cell lineage
Authors: Ferrero Isabel , Held Werner , Wilson Anne , Tacchini-Cottier Fabienne , Radtke Freddy , MacDonald H. Robson
Published: September 2002

The developmental origin of dendritic cells (DCs) is controversial. In the mouse CD8α+ and CD8α− DC subsets are often considered to be of lymphoid and myeloid origin respectively, although evidence on this point is conflicting. Very recently a novel CD11c+ B220+ DC subset has been identified that appears to be the murine counterpart to interferon alpha (IFNα)–producing human plasmacytoid DCs (PDCs). We show here that CD11c+ B220+ mouse PDCs, like human PDCs, are present in the thymus and express T lineage markers such as CD8α and CD4. However, the intrathymic development of PDCs can be completely dissociated from immature T lineage cells in mixed chimeras established with bone marrow cells from mice deficient for either Notch-1 or T-cell factor 1, two independent mutations that severely block early T-cell development. Our data indicate that thymic PDCs do not arise from a bipotential T/DC precursor.
Skewed X-chromosome inactivation in monochorionic diamniotic twin sisters results in severe and mild hemophilia A
Authors: Valleix Sophie , Vinciguerra Christine , Lavergne Jean-Maurice , Leuer Marco , Delpech Marc , Negrier Claude
Published: September 2002

This study describes the genetic mechanisms responsible for the de novo occurrence of severe and mild hemophilia A in monozygotic twin females. Both twins were found to carry a previously known factor VIII mutation (Tyr16Cys) in the heterozygous state which most probably arose in the paternal germ line. Both twins showed concordant skewing of X inactivation toward the maternally derived normal X chromosome, the most severely affected twin exhibiting a higher percentage of inactivation of the normal X chromosome. The degree of skewing of X inactivation closely correlated with both the coagulation parameters and the clinical phenotype of the twins. Since these twins were monochorionic, such results suggest that the twinning event in this case has occurred after the onset of the X-inactivation period.