bluuebunny/crossref_metadata_2025 huggingface dataset:
Anxiety and depression in an older research population and their impact on clinical outcomes in a randomised controlled trial
Authors: Allsup S J , Gosney M A
Published: December 2002

Introduction

Anxiety and depression are common in older people living in the community. The aim of the study was to investigate their impact on clinical outcomes during a randomised controlled trial investigating the cost benefits of influenza vaccination in fit and healthy, independent living 65–74 year olds.

Subjects and methods

A total of 729 people were recruited. Participants completed the hospital anxiety and depression scale (HADS) and EuroQol EQ-5D quality of life questionnaire immediately before receiving vaccination and every two months for the next six months after this. Side effects three days after vaccination and Barthel score at baseline were also recorded.

Results

At baseline the prevalence of “definite” anxiety in this sample (HADS score ≥11) was 4% and 1.2% of individuals had definite depression (HADS score ≥11). Individuals with anxiety or depression (HADS score ≥8) were more likely to complain of systemic side effects after vaccination and have a lower Barthel index score (p<0.001). Quality of life as measured by the EQ-5D visual analogue scale was reduced (p<0.001) at all time periods in those individuals with both anxiety and depression (HADS score ≥8 on both scales).

Conclusion

Although the prevalence of anxiety and depression in this sample was low, people with anxiety or depression were more likely to suffer from perceived side effects after influenza vaccine and have a lower Barthel and EQ-5D visual analogue score. In future studies the effect of anxiety and depression on older participants should be remembered and care taken to ensure that they do not affect results more than the intervention under study.
James Lind’s Treatise of the Scurvy (1753)
Authors: Bartholomew M
Published: December 2002

Lind is revered as the first doctor to conduct systematic clinical trials of potential cures for scurvy—trials in which oranges and lemons came out as decisive winners. The following paper argues that our modern understanding of scurvy and vitamin C has hindered our understanding of Lind’s own conception of his work and of the place within it of his clinical trials. Lind conceived of scurvy not as a disease of dietary deficiency, but of faulty digestion. In the full context of his Treatise of the Scurvy, and of his own medical practice, the seeming decisiveness of the trials fades, to be replaced by a sense of Lind’s bafflement at the nature of the disease to which he had devoted his career.
ROHLIN FLOWS ON THE CUNTZ ALGEBRA ${\mathcal O}_2$
Authors: KISHIMOTO AKITAKA
Published: December 2002

We prove that a quasi-free flow on [Formula: see text] has the Rohlin property if and only if the associated crossed product is purely infinite and simple and that the quasi-free flows on [Formula: see text] with the Rohlin property are cocycle conjugate with each other. The latter result also holds for any Cuntz algebra [Formula: see text] with m < ∞. We also give some remarks on Rohlin flows on a unital separable nuclear purely infinite simple C*-algebra.
ON THE VOLUME OF A LINE BUNDLE
Authors: BOUCKSOM SÉBASTIEN
Published: December 2002

Using the Calabi–Yau technique to solve Monge-Ampère equations, we translate a result of T. Fujita on approximate Zariski decompositions into an analytic setting and combine this to the holomorphic Morse inequalities in order to express the volume of a line bundle as the maximum of the mean curvatures of all the singular Hermitian metrics on it, with a way to pick an element at which the maximum is reached and satisfying a singular Monge–Ampère equation. This enables us to introduce the volume of any (1,1)-class on a compact Kähler manifold, and Fujita's theorem is then extended to this context.
SOBOLEV ESTIMATES OF SOLUTIONS OF THE $\bar{\partial}$-NEUMANN PROBLEM ON PARAMETERS
Authors: CHO SANGHYUN
Published: December 2002

Let [Formula: see text] be a smoothly bounded pseudoconvex complex manifold with a family of almost complex structures {ℒτ}τ ∈ I, 0 ∈ I. Assume that there is a smooth function λ which is strictly plurisubharmonic with respect to the structure ℒ0 in a neighborhood of bM. Then we prove the global regularity for [Formula: see text]-Neumann problem in Sobolev spaces both in space and parameter variables.
SOLUTIONS OF THE POLCHINSKI ERG EQUATION IN THE O(N) SCALAR MODEL
Authors: KUBYSHIN YU. A. , NEVES R. , POTTING R.
Published: December 2002

Solutions of the Polchinski exact renormalization group equation in the scalar O(N) theory are studied. Families of regular solutions are found and their relation with fixed points of the theory is established. Special attention is devoted to the limit N = ∞, where many properties can be analyzed analytically.
ON SOME PROPERTIES OF A MESON
Authors: BANERJEE S. N. , BHATTACHARYA A. , CHAKRABARTI B. , BANERJEE S.
Published: December 2002

The free energy analyzed in the framework of the quantum field theory in conjunction with the statistical model for a [Formula: see text] meson is found to undergo an expansion in the condensate wave function. The superconducting and fractal properties of the meson are found to originate from the branch-cut type of singularity in the wave function of the model in which the gauge symmetry breaking is manifest.
DIRAC MONOPOLES AND HAWKING RADIATION IN KOTTLER SPACETIME
Authors: BYTSENKO A. A. , GONCHAROV YU. P.
Published: December 2002

The natural extension of Schwarzschild metric to the case of nonzero cosmological constant Λ known as the Kottler metric is considered and it is discussed under what circumstances the given metric could describe the Schwarzschild black hole immersed in a medium with nonzero energy density. Under the latter situation such an object might carry topologically inequivalent configurations of various fields. The given possibility is analyzed for complex scalar field and it is shown that the mentioned configurations might be tied with natural presence of Dirac monopoles on black hole under consideration. In turn, this could markedly modify the Hawking radiation process.
INFLUENCE OF SUPERPOSITION OF COHERENT STATES OF LIGHT ON THE EVOLUTION OF THE FIELD ENTROPY AND ENTANGLEMENT IN THE INTENSITY-DEPENDENT JCM
Authors: OBADA A.-S. F. , HESSIAN H. A.
Published: December 2002

We investigate the influence of superposition of coherent states of light on population inversion and the evolution of the field entropy for two-level atoms in the framework of the Jaynes–Cummings model. We compare the behavior of the system in the case of having a coherent superposition state and a statistical mixture of coherent states as an initial field. Our results show that the superposition of coherent states plays an important role in the evolution of the field entropy in the intensity-dependent Jaynes–Cummings model (JCM).
THEORY OF NO-FIELD QUANTUM HALL EFFECT BASED ON PHASE-CHARGE BOSON WAVE FUNCTION
Authors: SUGAHARA MASANORI , BOGOLUBOV NIKOLAI N.
Published: December 2002

The derivation of the non-magnetic Laughlin state and other macroscopic quantum states in the semi-localized 2D electron system in the network of circular molecular orbits is made by the study of zero-point plasma oscillation. In the imaginary time representation, the electric field is transformed to the vector potential. After the cancellation of the mean-field component of the inter-electron repulsive field with the ion-lattice field, the boson Hamiltonian with respect to the phase-charge fluctuation is obtained using a Chern–Simons gauge field. Based on the resultant boson wave function, the macroscopic quantum state in hole doping is found to lead to a superfluidity that is described by a coherent function when λΘ > λQ, and to the particle-number-definite state described by a Laughlin function when λQ > λΘ, where λΘ is the phase-coherence length and λQ is the incompressibility length.
WEAK-LOCALIZATION EFFECT IN SINGLE CRYSTAL TaN(001) FILMS
Authors: TIWARI ASHUTOSH , WANG H. , KUMAR D. , NARAYAN J.
Published: December 2002

We here report the manifestation of weak localization effects in the electrical resistivity of TaN (001) films grown on MgO (001) substrates by a pulsed laser deposition technique. These films were characterized by X-ray diffraction and Rutherford backscattering. High precision electrical resistivity measurements were performed on these films in the temperature range 12–300 K. A careful analysis of data showed these films to lie in the weakly localized regime with negative temperature coefficient of resistivity throughout the whole temperature range of study. A crossover from 2D localization at lower temperatures to 3D localization at higher temperatures was observed.
NEW LOCALIZED EXCITATIONS IN (2+1)-DIMENSIONAL INTEGRABLE SYSTEMS
Authors: LOU S.-Y. , TANG X.-Y. , QIAN X.-M. , CHEN C.-L. , LIN J. , ZHANG S.-L.
Published: December 2002

The new localized excitations of some (2+1)-dimensional integrable models obtained by the multi-linear variable separation approach (MLVSA) are reviewed. A universal formula with some arbitrary functions is obtained for some suitable physical quantities for various integrable models. By selecting the arbitrary functions appropriately, one may obtain abundant interesting localized excitations like the multi-dromions, lumps, ring solitons, breathers, instantons, peakons, compactons, foldons, chaotic and fractal patterns and so on. The localized excitations possess quite rich interaction behaviors.
ORDERING STRUCTURES IN A CHEMICALLY REACTING BINARY MIXTURE UNDER DRIVEN PARTICLES
Authors: REN CHUN-LAI , ZHU YUE-JIN , MA YU-QIANG
Published: December 2002

We investigate the pattern formation of a binary polymer mixture in the presence of chemical reaction A ⇌ B and with the inclusion of mobile particles under a modulated pinning potential. The presence of particles with a preferential attraction for one component of the mixture breaks the isotropy of the bulk phase-separating process and controls the orientational ordering of structures. On the other hand, the chemical reaction can change the relative volume of A and B components, leading to the formation of a wide variety of morphologies. We find that due to the competition among the chemical reaction, phase separation and externally-driven effect, some unusual ordering structures can be realized. The results may provide some important insights into designing novel ordering morphologies such as microporous structures and quantum dots.
DISCOVERING AND COMPOSING DISTRIBUTED ATOMIC AGENTS FOR IMAGERY AND GEOSPATIAL PROBLEM SOLVING
Authors: NOLAN JAMES J. , SOOD ARUN K. , SIMON ROBERT
Published: December 2002

This paper describes our approach to building a scalable, flexible agent-based architecture for imagery and geospatial processing. Central to this approach is the agent discovery and composition mechanism which scales to support networks with thousands of agents. The agent architecture implements over 100 imagery and geospatial processing agents based on the Java Advanced Imaging and OpenMap(TM) APIs. The agents are distributed over a Jini enabled network, and communicate with one another via JavaSpaces. We discuss our "atomic" approach in this paper: developing low-level processing agents that are used by application of specific agents. We discuss several concepts in this approach: agent lookup and discovery through traditional information retrieval techniques, the ability to rapidly prototype agents based on commercial software products, and a knowledge management approach that reuses prior processing approaches and results. We present results demonstrating the scalability of our agent discovery and composition mechanism to compare them with other traditional discovery mechanisms, and demonstrate how the discovery mechanism scales to support thousands of agents.
CHAOTIC ELECTROCONVECTION IN A LAYER OF DIELECTRIC LIQUID SUBJECTED TO UNIPOLAR INJECTION: MAXIMAL LYAPUNOV EXPONENTS
Authors: CASTELLANOS A. , PÉREZ A. T. , CHICÓN R.
Published: December 2002

This paper reviews the studies that have been carried out over the years to analyze the electroconvection of an insulating plane liquid layer subjected to unipolar charge injection from one of the electrodes. We consider in detail the motion near the onset of nonlinear instability that for brevity we call chaotic electroconvection. We also present some recent advances in the characterization of this chaotic motion. In particular, we have computed the maximal Lyapunov exponents for time series obtained from numerical simulation, for weak as well as strong injection regimes, and we discuss the relevance of these results for the characterization of this EHD chaos.
THE HOMOTOPY THEORY OF INVERSE SEMIGROUPS
Authors: LAWSON MARK V. , MATTHEWS JOSEPH , PORTER TIM
Published: December 2002

We show that abstract homotopy theory can be used to define a suitable notion of homotopy equivalence for inverse semigroups. As an application of our theory, we prove a theorem for inverse semigroup homomorphisms which is the exact counterpart of the well-known result in topology which states that every continuous function can be factorized into a homotopy equivalence followed by a fibration. We show that this factorization is isomorphic to the one constructed by Steinberg in his "Fibration Theorem", originally proved using a generalization of Tilson's derived category.
COMPUTATIONAL COMPLEXITY OF THE FINITE ALGEBRA MEMBERSHIP PROBLEM FOR VARIETIES
Authors: SZÉKELY ZOLTÁN
Published: December 2002

We exhibit finite algebras each generating a variety with NP-complete finite algebra membership problem. The smallest of these algebras is the flat graph algebra belonging to the tetrahedral graph, a graph of 6 vertices obtained by cutting and spreading out the surface of a tetrahedron on the plane. The sequence of graphs we use to build up our flat graph algebras is similar to the sequence exhibited by Wheeler in [36] , 1979, to describe the first order theory of k-colorable graphs. Graph algebras were introduced by Shallon in [34] , 1979, and investigated, among others, by Baker, McNulty and Werner in [2] , 1987. Flat algebras were constructed and used by McKenzie in [27] , 1996, to settle some open questions related to decidability, like Tarski's Finite Basis Problem. Flat graph algebras were also discussed by Willard in [37] , 1996, and Delić in [8] , 1998.
EQUATIONAL THEORIES GENERATED BY HYPERSUBSTITUTIONS OF TYPE (n)
Authors: DENECKE K. , KOPPITZ J. , NIWCZYK ST.
Published: December 2002

Hypersubstitutions map n-ary operation symbols to n-ary terms. Such mappings can be uniquely extended to mappings defined on the set of all terms. It turns out that the kernels of hypersubstitutions are fully invariant congruence relations on the (absolutely free) term algebra of the considered type. For an arbitrary type τ = (n), n ≥ 1, i.e. if one has only one n-ary operation symbol, we will describe all these congruence relations. The results will be applied to solve the hyperunification problem. Further we will give some generalizations to arbitrary types.
BUCKLING AND STRESS SOFTENING OF BEAM-COLUMNS UNDER COMPLEX THREE-DIMENSIONAL LOADING
Authors: LEVY R. , GAL E.
Published: December 2002

This paper is concerned with buckling and stress softening of beam-columns under axial compression, biaxial bending and torsion. Members with no warping whose cross sections vary along the axis in a uniform manner with respect to the principal directions are also considered. The basic four coupled differential equations governing the behavior of three-dimensional beam columns are reformulated to include varying cross sections. A 12 × 12 stiffness matrix is assembled by solving the equations 6 times (which is sufficient to describe 3D behavior) for a sequence of appropriate discontinuities using the finite difference method. Two sets of curves are then computed. One set displays interaction diagrams that highlight the stress softening of beam stiffnesses. The other set of curves displays the buckling compressive load of a rectangular cantilevered beam under a variety of tri-directional moments (two bending moments and one twisting moment).
ATOMISTIC CAPACITANCE OF A NANOTUBE ELECTROMECHANICAL DEVICE
Authors: ROTKIN SLAVA V. , SHRIVASTAVA VAISHALI , BULASHEVICH KIRILL A. , ALURU N. R.
Published: December 2002

An atomistic capacitance is derived for a single-wall carbon nanotube in a nano-electromechanical device. Multi-scale calculation is performed using a continuum model for the geometrical capacitance, and statistical and quantum mechanical approaches for the quantum capacitance of the nanotube. The geometrical part of the capacitance is studied in detail using full three-dimensional electrostatics. Results reported in this paper are useful for compact modeling of the electronic and electromechanical nanotube devices.
Skein modules of links in cylinders over surfaces
Authors: Lieberum Jens
Published: December 2002

We define the Conway skein module 𝒞 (M) of ordered based links in a 3‐manifold M. This module gives rise to 𝒞 (M)‐valued invariants of usual links in M. We determine a basis of the ℤ[z]‐module 𝒞 (Σ × [0, 1])/Tor (𝒞 (Σ × [0, 1])), where Σ is the real projective plane or a surface with boundary. For cylinders over the Möbius strip or the projective plane, we derive special properties of the Conway skein module, among them a refinement of a theorem of Hartley and Kawauchi about the Conway polynomial of strongly positive amphicheiral knots in S3. In addition, we determine the Homfly and Kauffman skein modules of Σ × [0, 1] where Σ is an oriented surface with boundary.
Acceleration of nonhyperbolic sequences of Mann
Authors: Graça Mário M.
Published: December 2002

Mann′s sequences are difficult to accelerate in the presence of a nonhyperbolic fixed point. New accelerators are constructed for Mann′s sequences which are useful even for other sets of very slowly convergent sequences.
On an nth‐order infinitesimal generator and time‐dependent operator differential equation with a strongly almost periodic solution
Authors: Rao Aribindi Satyanarayan
Published: December 2002

In a Banach space, if u is a Stepanov almost periodic solution of a certain nth‐order infinitesimal generator and time‐dependent operator differential equation with a Stepanov almost periodic forcing function, then u, u′, …, u (n−2) are all strongly almost periodic and u (n−1) is weakly almost periodic.
A new proof of some identities of Bressoud
Authors: Chapman Robin
Published: December 2002

We provide a new proof of the following two identities due to
Bressoud: , , which can be considered as finite versions of the Rogers‐Ramanujan identities.
A note on the spectral operators of scalar type and semigroups of bounded linearoperators
Authors: Markin Marat V.
Published: December 2002

It is shown that, for the spectral operators of scalar type, the well‐known characterizations of the generation of C0‐ and analytic semigroups of bounded linear operators can be reformulated exclusively in terms of the spectrum of such operators, the conditions on the resolvent of the generator being automatically met and the corresponding semigroup being that of the exponentials of the operator.
On an abstract evolution equation with a spectral operator of scalar type
Authors: Markin Marat V.
Published: December 2002

It is shown that the weak solutions of the evolution equation y′(t) = Ay(t), t ∈ [0, T) (0 < T ≤ ∞), where A is a spectral operator of scalar type in a complex Banach space X, defined by Ball (1977), are given by the formula y(t) = e tAf, t ∈ [0, T), with the exponentials understood in the sense of the operational calculus for such operators and the set of the initial values, f′s, being ∩ 0≤t<TD(e tA), that is, the largest possible such a set in X.
Infinite two‐generator groups of class two and their non‐abelian tensor squares
Authors: Sarmin Nor Haniza
Published: December 2002

We classify all infinite 2‐generator groups of nilpotency class two and determine their non‐abelian tensor squares.
On the compatible weakly nonlocal Poisson brackets of hydrodynamic type
Authors: Maltsev Andrei Ya.
Published: December 2002

We consider the pairs of general weakly nonlocal Poisson brackets
of hydrodynamic type (Ferapontov brackets) and the corresponding integrable hierarchies. We show that, under the requirement of the nondegeneracy of the corresponding “first” pseudo‐Riemannian metric and also some nondegeneracy requirement for the nonlocal part, it is possible to introduce a “canonical” set of “integrable hierarchies” based on the Casimirs, momentum functional and some “canonical Hamiltonian functions.” We prove also that all the “higher” “positive” Hamiltonian operators and the “negative” symplectic forms have the weakly nonlocal form in this case. The same result is also true for “negative” Hamiltonian operators and “positive” symplectic structures in the case when both pseudo‐Riemannian metrics and are nondegenerate.
An entropic regularization method for solving systems of fuzzy linear inequalities
Authors: Liu F. B.
Published: December 2002

Solving systems of fuzzy linear inequalities could lead to the
solutions of fuzzy linear programs. It is shown that a system of
fuzzy linear inequalities can be converted to a regular min‐max
problem. An entropic regularization method is introduced for
solving such a problem. Some computational results are included.
The double bubble problem in spherical and hyperbolic space
Authors: Cotton Andrew , Freeman David
Published: December 2002

We prove that the standard double bubble is the least‐area way to
enclose and separate two regions of equal volume in ℍ3, and in S3 when the exterior is at least ten percent of S3.
Alzheimer Disease and Oxidative Stress
Authors: Perry George , Cash Adam D. , Smith Mark A.
Published: December 2002

Research in Alzheimer disease has recently demonstrated compelling evidence on the importance of oxidative processes in its pathogenesis. Cellular changes show that oxidative stress is an event that precedes the appearance of the hallmark pathologies of the disease, neurofibrillary tangles, and senile plaques. While it is still unclear what the initial source of the oxidative stress is in Alzheimer disease, it is likely that the process is highly dependent on redox‐active transition metals such as iron and
copper. Further investigation into the role that oxidative stress mechanisms seem to play in the pathogenesis of Alzheimer disease may lead to novel clinical interventions.
The Promise of Integrins as Effective Targets for Anticancer Agents
Authors: Rust William L. , Carper Stephen W. , Plopper George E.
Published: December 2002

This review will briefly describe integrin function, address why integrins are attractive targets for chemotherapeutic drug design, and discuss some ongoing studies aimed at inhibiting integrin activity. Integrins are cell surface heterodimeric receptors. They modulate many cellular processes including: growth, death (apoptosis), adhesion, migration, and invasion by
activating several signaling pathways. Many potential chemotherapeutic agents target integrins directly (eg, polypeptides, monoclonal antibodies, adenovirus vectors). These agents may be clinically useful in controlling the metastatic
spread of cancer.
Quantitative Trait Loci Associated with Foliar Trigonelline Accumulation in Glycine Max L
Authors: Cho Youngkoo , Njiti Victor N. , Chen Xinbo , Triwatayakorn Kanokporn , Kassem My Abdelmajid , Meksem Khalid , Lightfoot David A. , Wood Andrew J.
Published: December 2002

The objective of this study was to utilize a Glycine max RIL population to (1) evaluate foliar trigonelline (TRG) content in field‐grown soybean, (2) determine the heritability of TRG accumulation, and (3) identify DNA markers linked to quantitative trait loci (QTLs) conditioning variation in TRG accumulation. Frequency distributions of 70 recombinant inbred lines showed statistically no significant departure from normality (P > .05)
for TRG accumulation measured at pod development stage (R4). Six different molecular linkage groups (LGs) (B2, C2, D2, G, J, and K) were identified to be linked to QTLs for foliar TRG accumulation. Two unique microsatellite markers (SSR) on two different linkage groups identified QTL significantly associated with foliar TRG accumulation: a region on LG J (Satt285) (P = .0019,  R2 = 15.9%) and a second region on LG C2 (Satt079) (P = .0029,  R2 = 13.4%).
Vectorial Transcellular Calcium Transport in Intestine: Integration of Current Models
Authors: Larsson Dennis , Nemere Ilka
Published: December 2002

In spite of decades of research, the exact subcellular pathway for calcium transport in intestine has not been elucidated. In this mini‐review, we present three models for vectorial movement of calcium across the cell: facilitated (cytoplasmic) diffusion, vesicular/lysosomal transport, and tunneling through the endoplasmic reticulum compartment. We conclude by offering one
way to integrate elements of these three models.
Playing Tag with HIF: The VHL Story
Authors: Leung Sherri K. , Ohh Michael
Published: December 2002

Inactivation of the von Hippel‐Lindau (VHL) tumour suppressor gene product pVHL is the cause of inherited VHL disease and is associated with sporadic kidney cancer. pVHL is found in a multiprotein complex with elongins B/C, Cul2, and Rbx1 forming an E3 ubiquitin ligase complex called VEC. This modular enzyme targets the α subunits of hypoxia‐inducible factor (HIF) for ubiquitin‐mediated destruction. Consequently, tumour cells lacking functional pVHL overproduce the products of HIF‐target genes such as vascular endothelial growth factor (VEGF), which promotes angiogenesis. This likely accounts for the hypervascular nature of VHL‐associated neoplasms. Although pVHL has been linked to the cell‐cycle, differentiation, and the regulation of extracellular matrix assembly, microenvironment pH, and tissue invasiveness, this review will focus on the recent insights into the molecular mechanisms governing the E3 ubiquitin ligase function of VEC.
Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients
Authors: Sbiti Aziza , El Kerch Fatiha , Sefiani Abdelaziz
Published: December 2002

Duchenne and Becker muscular dystrophy (DMD and BMD) are X‐linked diseases resulting from a defect in the dystrophin gene located on Xp21. DMD is the most frequent neuromuscular disease in humans (1/3500 male newborn). Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. We have analyzed DNA from 72 Moroccan patients with DMD/BMD using the multiplex polymerase chain reaction (PCR) to screen for exon deletions within the dystrophin gene, and to estimate the frequency of these abnormalities. We found dystrophin gene deletions in 37 cases. Therefore the frequency in Moroccan DMD/BMD patients is about 51.3%. All deletions were clustered in the two known hot‐spots regions, and in 81% of cases deletions were detected in the region from exon 43 to exon 52. These findings are comparable to those reported in other studies. It is important to note that in our population, we can first search for deletions of DMD gene in the most frequently deleted exons determined by this study. This may facilitate the molecular diagnosis of DMD and BMD in our country.
Randomly Amplified DNA Fingerprinting: A Culmination of DNA Marker Technologies Based on Arbitrarily‐Primed PCR Amplification
Authors: Waldron Julie , Peace Cameron P. , Searle Iain R. , Furtado Agnelo , Wade Nick , Findlay Ian , Graham Michael W. , Carroll Bernard J.
Published: December 2002

Arbitrarily‐primed DNA markers can be very useful for genetic fingerprinting and for facilitating positional cloning of genes. This class of technologies is particularly important for less studied species, for which genome sequence information is generally not known. The technologies include Randomly Amplified Polymorphic DNA (RAPD), DNA Amplification Fingerprinting (DAF), and Amplified Fragment Length Polymorphism (AFLP). We have modified the DAF protocol to produce a robust PCR‐based DNA marker technology called Randomly Amplified DNA Fingerprinting (RAF). While the protocol most closely resembles DAF, it is much more robust and sensitive because amplicons are labelled with either radioactive 33P or fluorescence in a 30‐cycle PCR, and then separated and detected
on large polyacrylamide sequencing gels. Highly reproducible RAF markers were readily amplified from either purified DNA or alkali‐treated intact leaf tissue. RAF markers typically display dominant inheritance. However, a small but significant portion of the RAF markers exhibit codominant inheritance and represent microsatellite loci. RAF compares favorably with AFLP for efficiency and reliability on many plant genomes, including the very large and complex genomes of sugarcane and wheat. While the two technologies detect about the
same number of markers per large polyacrylamide gel, advantages of RAF over AFLP include: (i) no requirement for enzymatic template preparation, (ii) one instead of two PCRs, and (iii) overall cost. RAF and AFLP were shown to differ in the selective basis of amplification of markers from genomes and could
therefore be used in complementary fashion for some genetic studies.
Perillyl Alcohol Inhibits Breast Cell Migration without Affecting Cell Adhesion
Authors: Wagner Johanna E. , Huff Janice L. , Rust William L. , Kingsley Karl , Plopper George E.
Published: December 2002

The monoterpene d‐limonene exhibits chemotherapeutic and chemopreventive potential in breast cancer patients. D‐limonene and its related compounds, perillyl alcohol and perillyl aldehyde, were chosen as candidate drugs for application in a screen for nontoxic inhibitors of cell migration. Using the nontumorigenic human breast cell line MCF‐10A, we delineated the toxicity as greatest for the perillyl aldehyde, intermediate for perillyl alcohol, and least for limonene. A noncytotoxic concentration of 0.5 mmol/L perillyl alcohol inhibited the migration, while the same concentration of limonene failed to do so. Adhesion of the MCF‐10A cell line and the human breast cancer cell line MDA‐MB 435 to fibronectin was unaffected by 1.5 mmol/L perillyl alcohol. 0.4 mmol/L perillyl alcohol inhibited the growth of MDA‐MB 435 cells. All migration‐inhibiting concentrations of perillyl alcohol for MDA‐MB 435 cells proved to be toxic. These results suggest that subtoxic doses of perillyl alcohol may have prophylactic potential in the treatment of breast cancer.
An asymptotic approach to inverse scattering problems on weakly nonlinear elastic rods
Authors: Kim Shinuk , Kreider Kevin L.
Published: December 2002

Elastic wave propagation in weakly nonlinear elastic rods is considered in the time domain. The method of wave splitting is employed to formulate a standard scattering problem, forming the mathematical basis for both direct and inverse problems. A quasi‐linear version of the Wendroff scheme (FDTD) is used to solve the direct problem. To solve the inverse problem, an asymptotic expansion is used for the wave field; this linearizes the order equations, allowing the use of standard numerical techniques. Analysis and numerical results are presented for three model inverse problems: (i) recovery of the nonlinear parameter in the stress‐strain relation for a homogeneous elastic rod, (ii) recovery of the cross‐sectional area for a homogeneous elastic rod, (iii) recovery of the elastic modulus for an inhomogeneous elastic rod.
Introduction to Grassmann manifolds and quantum computation
Authors: Fujii Kazuyuki
Published: December 2002

Geometrical aspects of quantum computing are reviewed elementarily for nonexperts and/or graduate students who are interested in both geometry and quantum computation. We show how to treat Grassmann manifolds which are very important examples of manifolds in mathematics and physics. Some of their applications to quantum computation and its efficiency problems are shown. An interesting current topic of holonomic quantum computation is also covered. Also, some related advanced topics are discussed.
High-dose cyclophosphamide with autologous lymphocyte–depleted peripheral blood stem cell (PBSC) support for treatment of refractory chronic autoimmune thrombocytopenia
Authors: Huhn Richard D. , Fogarty Patrick F. , Nakamura Ryotaro , Read Elizabeth J. , Leitman Susan F. , Rick Margaret E. , Kimball Janice , Greene Adeira , Hansmann Kristin , Gratwohl Alois , Young Neal , Barrett A. John , Dunbar Cynthia E.
Published: December 2002

Patients with refractory chronic autoimmune thrombocytopenia (AITP) have a significant risk of morbidity and mortality related to hemorrhage. High-dose (HD) cytotoxic therapy may produce remissions but entails risks related to myelosuppression. Hematopoietic stem cell support with lymphocyte-depleted grafts may accelerate hematologic recovery and concomitantly reduce repopulation by autoreactive immunocytes. Fourteen patients with chronic AITP, in whom multiple prior therapies including corticosteroids, splenectomy, intravenous immunoglobulin, and various cytotoxic or immunomodulatory regimens had failed, were treated with HD cyclophosphamide (50 mg/kg/d) and autologous granulocyte colony-stimulating factor (G-CSF)–mobilized leukocytes depleted of lymphocytes by immunomagnetic CD34+selection. There were no significant adverse events related to G-CSF, intravenous device insertion, or leukapheresis. Treatment-related complications included transient hemorrhagic cystitis (1 patient), vaginal bleeding (2 patients), gastrointestinal bleeding (1 patient), epistaxis (1 patient), and antibiotic-responsive febrile neutropenia (all patients). The mean time to absolute neutrophil count (ANC) more than 500/mm3 was 9 ± 0.6 days. Eight patients experienced antibiotic-responsive gram-positive bacteremia. A median of 2 platelet transfusions was required for stem cell mobilization, intravenous catheter insertion, and apheresis and a median of 9 platelet transfusions was required during hematopoietic recovery. Six patients obtained durable complete responses (platelet counts > 100 000/mm3 without other therapy) with maximum follow-up of 42 months. Two additional patients obtained durable partial responses (platelet counts significantly increased over baseline with reduced medication requirements and cessation of bleeding complications). This therapeutic approach is feasible for patients with severe chronic AITP, a substantial proportion of whom may obtain durable remissions. Larger controlled trials are recommended.
Broad-spectrum caspase inhibition paradoxically augments cell death in TNF-α–stimulated neutrophils
Authors: Liu Chien-Ying , Takemasa Akihiro , Liles W. Conrad , Goodman Richard B. , Jonas Mechthild , Rosen Henry , Chi Emil , Winn Robert K. , Harlan John M. , Chuang Peter I.
Published: December 2002

It is increasingly clear that there are caspase-dependent and -independent mechanisms for the execution of cell death and that the utilization of these mechanisms is stimulus- and cell type–dependent. Intriguingly, broad-spectrum caspase inhibition enhances death receptor agonist-induced cell death in a few transformed cell lines. Endogenously produced oxidants are causally linked to necroticlike cell death in these instances. We report here that broad-spectrum caspase inhibitors effectively attenuated apoptosis induced in human neutrophils by incubation with agonistic anti-Fas antibody or by coincubation with tumor necrosis factor-α (TNF-α) and cycloheximide ex vivo. In contrast, the same caspase inhibitors could augment cell death upon stimulation by TNF-α alone during the 6-hour time course examined. Caspase inhibitor–sensitized, TNF-α–stimulated, dying neutrophils exhibit apoptoticlike and necroticlike features. This occurred without apparent alteration in nuclear factor–κB (NF-κB) activation. Nevertheless, intracellular oxidant production was enhanced and sustained in caspase inhibitor-sensitized, TNF-α–stimulated neutrophils obtained from healthy subjects. However, despite reduced or absent intracellular oxidant production following TNF-α stimulation, cell death was also augmented in neutrophils isolated from patients with chronic granulomatous disease incubated with a caspase inhibitor and TNF-α. These results demonstrate that, in human neutrophils, TNF-α induces a caspase-independent but protein synthesis–dependent cell death signal. Furthermore, they suggest that TNF-α activates a caspase-dependent pathway that negatively regulates reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
Reversibility of CD34 expression on human hematopoietic stem cells that retain the capacity for secondary reconstitution
Authors: Dao Mo A. , Arevalo Jesusa , Nolta Jan A.
Published: December 2002

The cell surface protein CD34 is frequently used as a marker for positive selection of human hematopoietic stem/progenitor cells in research and in transplantation. However, populations of reconstituting human and murine stem cells that lack cell surface CD34 protein have been identified. In the current studies, we demonstrate that CD34 expression is reversible on human hematopoietic stem/progenitor cells. We identified and functionally characterized a population of human CD45+/CD34− cells that was recovered from the bone marrow of immunodeficient beige/nude/xid (bnx) mice 8 to 12 months after transplantation of highly purified human bone marrow–derived CD34+/CD38− stem/progenitor cells. The human CD45+ cells were devoid of CD34 protein and mRNA when isolated from the mice. However, significantly higher numbers of human colony-forming units and long-term culture-initiating cells per engrafted human CD45+ cell were recovered from the marrow of bnx mice than from the marrow of human stem cell–engrafted nonobese diabetic/severe combined immunodeficient mice, where 24% of the human graft maintained CD34 expression. In addition to their capacity for extensive in vitro generative capacity, the human CD45+/CD34− cells recovered from thebnx bone marrow were determined to have secondary reconstitution capacity and to produce CD34+ progeny following retransplantation. These studies demonstrate that the human CD34+ population can act as a reservoir for generation of CD34− cells. In the current studies we demonstrate that human CD34+/CD38− cells can generate CD45+/CD34− progeny in a long-term xenograft model and that those CD45+/CD34− cells can regenerate CD34+ progeny following secondary transplantation. Therefore, expression of CD34 can be reversible on reconstituting human hematopoietic stem cells.
T lymphocytes constitutively produce an interferonlike cytokine limitin characterized as a heat- and acid-stable and heparin-binding glycoprotein
Authors: Oritani Kenji , Hirota Seiichi , Nakagawa Taishirou , Takahashi Isao , Kawamoto Shin-ichiro , Yamada Masahide , Ishida Naoko , Kadoya Toshihiko , Tomiyama Yoshiaki , Kincade Paul W. , Matsuzawa Yuji
Published: December 2002

Several reports have described “multifunctional” eukaryotic mRNAs producing more than one protein through alternative translational initiation at multiple AUG codons. There are 2 such codons in the 5′ region of our recently cloned limitin gene where 2 open reading frames overlap by 34 nucleotides. The deduced protein translated from the first ATG contains 33 amino acids, lacks a signal peptide, and has no obvious effects on the transfected 293T cells. We found that the second ATG is more effective as a translational initiation site than the first ATG and yields a secreted protein of 182 amino acids with the same activity as products made with full-length limitin cDNA. Immunohistochemical and reverse transcription–polymerase chain reaction analysis revealed that the longer limitin protein is produced by mature T lymphocytes in spleen and thymus as well as by bronchial epithelial and salivary duct cells in healthy mice. Properties of recombinant limitin were determined, revealing it to be a serologically distinct, heat- and acid-stable, heparin-binding glycoprotein with the potential for dimerization. Although the longer limitin protein is structurally and characteristically related to type I interferons, its production is uniquely regulated by translation as well as transcription.
Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells
Authors: Sarfati Marika , Mateo Véronique , Baudet Sylvie , Rubio Manuel , Fernandez Christine , Davi Fréderic , Binet Jacques-Louis , Delic Jozo , Merle-Béral Hélène
Published: December 2002

Type 4 phosphodiesterase (PDE4) inhibitors reportedly induce apoptosis in chronic lymphocytic leukemia (CLL) cells. Following clinical improvement of one previously untreated CLL patient with sildenafil therapy, we evaluated the in vitro induction of apoptosis in CLL cells by 4 PDE5/6 inhibitors, including sildenafil, vardenafil, zaprinast, and methoxyquinazoline (MQZ). After 24 hours of culture, the various PDE inhibitors differed in their ability to induce apoptosis, with zaprinast displaying no killing effect. Normal B cells isolated from control donors were totally resistant to PDE-induced apoptosis. Vardenafil was 3 and 30 times more potent an inducer of apoptosis than sildenafil and MQZ, respectively. Both vardenafil and sildenafil failed to elevate adenosine 3′5′ cyclic monophosphate (cAMP) levels, largely excluding an inhibitory effect on cAMP-PDE3, -PDE4, and -PDE7. Vardenafil- or sildenafil-treated B-CLL cells displayed up to 30% intracellular active caspase 3. Drug-induced apoptosis was inhibited by the caspase inhibitor z-VAD.fmk, prevented by interleukin-4 (IL-4), and significantly reduced by stromal-derived factor1-α (SDF-1α). We conclude that vardenafil and sildenafil induce caspase-dependent apoptosis of B-CLL cells in vitro and thus might be considered in the treatment of CLL patients. However, further in vivo investigations should be warranted.
Mutations in the murine erythroid α-spectrin gene alter spectrin mRNA and protein levels and spectrin incorporation into the red blood cell membrane skeleton
Authors: Wandersee Nancy J. , Birkenmeier Connie S. , Bodine David M. , Mohandas Narla , Barker Jane E.
Published: December 2002

Tetramers of α- and β-spectrin heterodimers, linked by intermediary proteins to transmembrane proteins, stabilize the red blood cell cytoskeleton. Deficiencies of either α- or β-spectrin can result in severe hereditary spherocytosis (HS) or hereditary elliptocytosis (HE) in mice and humans. Four mouse mutations,sph, sphDem,sph2BC, and sphJ, affect the erythroid α-spectrin gene, Spna1, on chromosome 1 and cause severe HS and HE. Here we describe the molecular alterations in α-spectrin and their consequences insph2BC/sph2BC andsphJ/sphJerythrocytes. A splicing mutation, sph2BC initiates the skipping of exon 41 and premature protein termination before the site required for dimerization of α-spectrin with β-spectrin. A nonsense mutation in exon 52, sphJ eliminates the COOH-terminal 13 amino acids. Both defects result in instability of the red cell membrane and loss of membrane surface area. Insph2BC/sph2BC, barely perceptible levels of messenger RNA and consequent decreased synthesis of α-spectrin protein are primarily responsible for the resultant hemolysis. By contrast, sphJ/sphJmice synthesize the truncated α-spectrin in which the 13-terminal amino acids are deleted at higher levels than normal, but they cannot retain this mutant protein in the cytoskeleton. ThesphJdeletion is near the 4.1/actin-binding region at the junctional complex providing new evidence that this 13-amino acid segment at the COOH-terminus of α-spectrin is crucial to the stability of the junctional complex.
Rapamycin-induced G1 arrest in cycling B-CLL cells is associated with reduced expression of cyclin D3, cyclin E, cyclin A, and survivin
Authors: Decker Thomas , Hipp Susanne , Ringshausen Ingo , Bogner Christian , Oelsner Madlene , Schneller Folker , Peschel Christian
Published: December 2002

In B-cell chronic lymphocytic leukemia (B-CLL), malignant cells seem to be arrested in the G0/early G1phase of the cell cycle, and defective apoptosis might be involved in disease progression. However, increasing evidence exists that B-CLL is more than a disease consisting of slowly accumulating resting B cells: a proliferating pool of cells has been described in lymph nodes and bone marrow and might feed the accumulating pool in the blood. Rapamycin has been reported to inhibit cell cycle progression in a variety of cell types, including human B cells, and has shown activity against a broad range of human tumor cell lines. Therefore, we investigated the ability of rapamycin to block cell cycle progression in proliferating B-CLL cells. We have recently demonstrated that stimulation with CpG-oligonucleotides and interleukin-2 provides a valuable model for studying cell cycle regulation in malignant B cells. In our present study, we demonstrated that rapamycin induced cell cycle arrest in proliferating B-CLL cells and inhibited phosphorylation of p70s6 kinase (p70s6k). In contrast to previous reports on nonmalignant B cells, the expression of the cell cycle inhibitor p27 was not changed in rapamycin-treated leukemic cells. Treatment with rapamycin prevented retinoblastoma protein (RB) phosphorylation in B-CLL cells without affecting the expression of cyclin D2, but cyclin D3 was no longer detectable in rapamycin-treated B-CLL cells. In addition, rapamycin treatment inhibited cyclin-dependent kinase 2 activity by preventing up-regulation of cyclin E and cyclin A. Interestingly, survivin, which is expressed in the proliferation centers of B-CLL patients in vivo, is not up-regulated in rapamycin-treated cells. Therefore, rapamycin interferes with the expression of many critical molecules for cell cycle regulation in cycling B-CLL cells. We conclude from our study that rapamycin might be an attractive substance for therapy for B-CLL patients by inducing a G1 arrest in proliferating tumor cells.
Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571)
Authors: Scheuring Urban J. , Pfeifer Heike , Wassmann Barbara , Brück Patrick , Atta Johannes , Petershofen Eduard K. , Gehrke Brigitte , Gschaidmeier Harald , Hoelzer Dieter , Ottmann Oliver G.
Published: December 2002

The Abl kinase inhibitor imatinib mesylate (STI571) has significant and rapid antileukemic activity in Philadelphia chromosome/Bcr-Abl–positive acute lymphoblastic leukemia (Ph+ ALL) but such activity is usually of short duration except for a small proportion of patients. To determine the prognostic significance of early Bcr-Abl levels and changes in peripheral blood (PB) and bone marrow (BM), serial samples of 56 patients with relapsed or refractory Ph+ ALL treated in phase 2 trials of imatinib were analyzed by quantitative polymerase chain reaction (PCR). Imatinib induced a complete hematologic response (CHR) or complete marrow response (marrow-CR) in 40 patients (good responders) and a partial (n = 2) or no (n = 14) remission in the remaining patients (poor responders). Compared with baseline, the median Bcr-Abl/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios decreased significantly in PB by 2.65, 2.64, and 3.11 log steps after 2 weeks, 4 weeks, and at the time of best response, respectively. In BM, the decline of median Bcr-Abl/GAPDH was 0.75, 1.37, and 2.78 logs, respectively. Thus, Bcr-Abl levels decreased more rapidly in PB than in BM (median time to best level 31 vs 39 days). Low Bcr-Abl/GAPDH ratios below 10−4 in PB and below 10−2 in BM after 2 weeks were significantly associated with good responses after 4 weeks. Moreover, Bcr-Abl levels (< 10−2) in BM of good responders after 4 weeks discriminated between 2 groups of patients with significantly different median time to progression (139 vs 22 days). The data show that Bcr-Abl levels in PB and BM after 2 weeks of imatinib treatment and in BM after 4 weeks have predictive relevance and may guide the application of additional therapies.