bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic properties of APC‐decorated microtubules in living cells
Authors: Dayanandan Rejith , Butler Rachel , Gordon‐Weeks Phillip R. , Matus Andrew , Kaech Stefanie , Lovestone Simon , Anderton Brian H. , Gallo Jean‐Marc
Published: February 2003

The adenomatous polyposis coli (APC) tumour suppressor protein is a component of the Wnt signalling pathway in which it plays a major role in controlling nuclear accumulation of β‐catenin and hence in the modulation of β‐catenin‐regulated gene transcription. APC also associates with microtubules at the ends of cytoplasmic extensions in epithelial cells, a distribution that can be reproduced in COS cells ectopically expressing APC. To examine the effect of APC on microtubule properties, we monitored directly the behaviour of APC and of APC‐decorated microtubules by time‐lapse imaging of cytoplasmic extensions in live COS cells expressing APC tagged with a green fluorescent protein. On the proximal part of microtubules, APC was visualised as particulate material moving unidirectionally towards the plus end of microtubules. The distal parts of microtubules were uniformly decorated by APC and were animated by a motile behaviour in the form of aperiodic bending. This behaviour is likely to be the consequence of compression forces acting on microtubules encountering obstacles while elongating. The majority of APC‐decorated microtubules in transfected COS cells was sensitive to depolymerisation by nocodazole, but they contained detyrosinated and acetylated α‐tubulin, suggesting a reduction in the rate of subunit exchange at their growing end. Taken together, these results demonstrate that microtubule domains uniformly decorated by APC display dynamic and motile properties that may be significant for the postulated role of APC in targeting microtubules to specialised membrane sites. Cell Motil. Cytoskeleton 54:237–247, 2003. © 2003 Wiley‐Liss, Inc.
Smad3 mediates the TGF‐β‐induced contraction of type I collagen gels by mouse embryo fibroblasts
Authors: Liu Xiangde , Wen Fu‐Qiang , Kobayashi Tetsu , Abe Shinji , Fang Qiuhong , Piek Ester , Bottinger Erwin P. , Roberts Anita B. , Rennard Stephen I.
Published: February 2003

TGF‐β signals through TGF‐β receptors and Smad proteins. TGF‐β also augments fibroblast‐mediated collagen gel contraction, an in vitro model of connective tissue remodeling. To investigate the importance of Smad2 or Smad3 in this augmentation process, embryo‐derived fibroblasts from mice lacking expression of Smad2 or Smad3 genes were cast into native type I collagen gels. Fibroblast‐populated gels were then released into 0.2% FCS‐DMEM alone or with recombinant human TGF‐β1, β2, β3, or recombinant rat PDGF‐BB. Gel contraction was determined using an image analyzer. All three isoforms of TGF‐β significantly augmented contraction of collagen gels mediated by fibroblasts with genotypes of Smad2 knockout (S2KO), Smad2 wildtype (S2WT), and Smad3 wildtype (S3WT), but not Smad3 knockout (S3KO) mice. PDGF‐BB augmented collagen gel contraction by all fibroblast types. These results suggest that expression of Smad3 but not Smad2 may be critical in TGF‐β augmentation of fibroblast‐mediated collagen gel contraction. Thus, the Smad3 gene could be a target for blocking contraction of fibrotic tissue induced by TGF‐β. Cell Motil. Cytoskeleton 54:248–253, 2003. © 2003 Wiley‐Liss, Inc.
ALP and MLP distribution during myofibrillogenesis in cultured cardiomyocytes
Authors: Henderson James R. , Pomiès Pascal , Auffray Charles , Beckerle Mary C.
Published: February 2003

The Z‐line is a multifunctional macromolecular complex that anchors sarcomeric actin filaments, mediates interactions with intermediate filaments and costameres, and recruits signaling molecules. Antiparallel α‐actinin homodimers, present at Z‐lines, cross‐link overlapping actin filaments and also bind other cytoskeletal and signaling elements. Two LIM domain containing proteins, α‐actinin associated LIM protein (ALP) and muscle LIM protein (MLP), interact with α‐actinin, distribute in vivo to Z‐lines or costameres, respectively, and, when absent, are associated with heart disease. Here we describe the behavior of ALP and MLP during myofibrillogenesis in cultured embryonic chick cardiomyocytes. As myofibrils develop, ALP and MLP are observed in distinct distribution patterns in the cell. ALP is coincident with α‐actinin from the first stage of myofibrillogenesis and co‐distributes with α‐actinin to Z‐lines and intercalated discs in mature myofibrils. Interestingly, we also demonstrate using ALP‐GFP transfection experiments and an in vitro binding assay that the ALP‐α‐actinin binding interaction is not required to target ALP to the Z‐line. In contrast, MLP localization is not co‐incident with that of α‐actinin until late stages of myofibrillogenesis; however, it is present in premyofibrils and nascent myofibrils prior to the incorporation of other costameric components such as vinculin, vimentin, or desmin. Our observations support the view that ALP function is required specifically at actin anchorage sites. The subcellular distribution pattern of MLP during myofibrillogenesis suggests that it functions during differentiation prior to the establishment of costameres. Cell Motil. Cytoskeleton 54:254–265, 2003. © 2003 Wiley‐Liss, Inc.
Identification and characterisation of a novel human isoform of Arp2/3 complex subunit p16‐ARC/ARPC5. T.H. Millard, B. Behrendt, S. Launay, K. Fütterer, L.M. Machesky, Cell Motil.Cytoskeleton (2003) 54(1):81–90.
Authors: Millard Thomas H. , Behrendt Barbara , Launay Sophie , Fütterer Klaus , Machesky Laura M.
Published: February 2003

The original article to which this Erratum refers was published in Cell Motility and the Cytoskeleton 54(1) 81–90

Figure 1 was incorrectly printed in the article. The missing portions of the sequence are herein reprinted with the accompanying legend.

In the legend accompanying Figure 7, the residues referred to as "blue" appear in purple in the figure.
Framework for testing multi‐threaded Java programs
Authors: Edelstein Orit , Farchi Eitan , Goldin Evgeny , Nir Yarden , Ratsaby Gil , Ur Shmuel
Published: February 2003

Finding bugs due to race conditions in multi‐threaded programs is difficult, mainly because there are many possible interleavings, any of which may contain a fault. In this work we present a methodology for testing multi‐threaded programs which has minimal impact on the user and is likely to find interleaving bugs. Our method reruns existing tests in order to detect synchronization faults. We find that a single test executed a number of times in a controlled environment may be as effective in finding synchronization faults as many different tests. A great deal of resources are saved since tests are very expensive to write and maintain. We observe that simply rerunning tests, without ensuring in some way that the interleaving will change, yields almost no benefits. We implement the methodology in our test generation tool—ConTest. ConTest combines the replay algorithm, which is essential for debugging, with our interleaving test generation heuristics. ConTest also contains an instrumentation engine, a coverage analyzer, and a race detector (not finished yet) that enhance bug detection capabilities. The greatest advantage of ConTest, besides finding bugs of course, is its minimal effect on the user. When ConTest is combined into the test harness, the user may not even be aware that ConTest is being used. Copyright © 2003 John Wiley & Sons, Ltd.
High‐performance Java codes for computational fluid dynamics
Authors: Riley Christopher J. , Chatterjee Siddhartha , Biswas Rupak
Published: February 2003

The computational science community is reluctant to write large‐scale computationally‐intensive applications in Java due to concerns over Java's poor performance, despite the claimed software engineering advantages of its object‐oriented features. Naive Java implementations of numerical algorithms can perform poorly compared to corresponding Fortran or C implementations. To achieve high performance, Java applications must be designed with good performance as a primary goal. This paper presents the object‐oriented design and implementation of two real‐world applications from the field of computational fluid dynamics (CFD): a finite‐volume fluid flow solver (LAURA, from NASA Langley Research Center) and an unstructured mesh adaptation algorithm (2D_TAG, from NASA Ames Research Center). This work builds on our previous experience with the design of high‐performance numerical libraries in Java. We examine the performance of the applications using the currently available Java infrastructure and show that the Java version of the flow solver LAURA performs almost within a factor of 2 of the original procedural version. Our Java version of the mesh adaptation algorithm 2D_TAG performs within a factor of 1.5 of its original procedural version on certain platforms. Our results demonstrate that object‐oriented software design principles are not necessarily inimical to high performance. Copyright © 2003 John Wiley & Sons, Ltd.
Benchmarking Java against C and Fortran for scientific applications
Authors: Bull J. M. , Smith L. A. , Ball C. , Pottage L. , Freeman R.
Published: February 2003

Increasing interest is being shown in the use of Java for scientific applications. The Java Grande benchmark suite was designed with such applications primarily in mind. The perceived lack of performance of Java still deters many potential users, despite recent advances in just‐in‐time and adaptive compilers. There are, however, few benchmark results available comparing Java to more traditional languages such as C and Fortran. To address this issue, a subset of the Java Grande benchmarks has been re‐written in C and Fortran allowing direct performance comparisons between the three languages. The performance of a range of Java execution environments, C and Fortran compilers have been tested across a number of platforms using the suite. These demonstrate that on some platforms (notable Intel Pentium) the performance gap is now quite small. Copyright © 2003 John Wiley & Sons, Ltd.
Spar: a set of extensions to Java for scientific computation
Authors: van Reeuwijk C. , Kuijlman F. , Sips H. J.
Published: February 2003

We present a set of language extensions that improve the expressiveness and performance of Java for scientific computation. The language extensions allow the manipulation of multi‐dimensional arrays to be expressed more naturally, and to be implemented more efficiently. Furthermore, data‐parallel programming is supported, allowing efficient parallelization of a large class of operations on arrays. We also provide language extensions to construct specialized array representations, such as symmetric, block, and sparse matrices. These extensions are: tuples, parameterized types, array subscript overloading, and the inline modifier. These extensions are not only useful in the construction of special array representations, but are also useful in their own right. Finally, we add complex numbers as a primitive type to the language. We evaluate our language extensions using performance results. We also compare relevant code fragments of our extended language with standard Java implementations and language extensions proposed by others. Copyright © 2003 John Wiley & Sons, Ltd.
Run‐time optimizations for a Java DSM implementation
Authors: Veldema R. , Hofman R. F. H. , Bhoedjang R. A. F. , Bal H. E.
Published: February 2003

Jackal is a fine‐grained distributed shared memory implementation of the Java programming language. Jackal implements Java's memory model and allows multithreaded Java programs to run unmodified on distributed‐memory systems.

This paper focuses on Jackal's run‐time system, which implements a multiple‐writer, home‐based consistency protocol. Protocol actions are triggered by software access checks that Jackal's compiler inserts before object and array references. To reduce access‐check overhead, the compiler exploits source‐level information and performs extensive static analysis to optimize, lift, and remove access checks. We describe optimizations for Jackal's run‐time system, which mainly consists of discovering opportunities to dispense with flushing of cached data. We give performance results for different run‐time optimizations, and compare their impact with the impact of one compiler optimization. We find that our run‐time optimizations are necessary for good Jackal performance, but only in conjunction with the Jackal compiler optimizations described by Veldema et al. As a yardstick, we compare the performance of Java applications run on Jackal with the performance of equivalent applications that use a fast implementation of Java's Remote Method Invocation instead of shared memory. Copyright © 2003 John Wiley & Sons, Ltd.
CartaBlanca—a pure‐Java, component‐based systems simulation tool for coupled nonlinear physics on unstructured grids—an update
Authors: VanderHeyden W. B. , Dendy E. D. , Padial‐Collins N. T.
Published: February 2003

This paper describes a component‐based nonlinear physical system simulation prototyping package written entirely in Java using object‐oriented design. The package provides scientists and engineers with a ‘developer‐friendly’ software environment for large‐scale computational algorithm and physical model development. The software design centers on the Jacobian‐free Newton–Krylov solution method surrounding a finite‐volume treatment of conservation equations. This enables a clean component‐like implementation. We first provide motivation for the development of the software and then discuss software structure. The discussion includes a description of the use of Java's built‐in thread facility that enables parallel, shared‐memory computations on a wide variety of unstructured grids with triangular, quadrilateral, tetrahedral and hexahedral elements. We also discuss the use of Java's inheritance mechanism in the construction of a hierarchy of physics systems objects and linear and nonlinear solver objects that simplify development and foster software re‐use. We provide a brief review of the Jacobian‐free Newton–Krylov nonlinear system solution method and discuss how it fits into our design. Following this, we show results from example calculations and then discuss plans including the extension of the software to distributed‐memory computer systems. Copyright © 2003 John Wiley & Sons, Ltd.
Providing soft real‐time quality of service guarantees for Java threads
Authors: Pang James C. , Shoja Gholamali C. , Manning Eric G.
Published: February 2003

The Java platform has many characteristics that make it very desirable for integrated continuous media processing. Unfortunately, it lacks the necessary CPU resource management facilities to support quality of service (QoS) guarantees for soft real‐time multimedia tasks. In this paper, we present our new Java Virtual Machine, Q‐JVM, which brings CPU resource management to the Java platform. Q‐JVM is based on Sun's JVM version 1.1.5. It implements an enhanced version of the MTR‐LS algorithm in its thread scheduler. Combined with admission control that could be implemented in an application‐level resource manager, it is able to support QoS parameters such as fairness, bandwidth partitioning and delay bound guarantees, as well as the cumulative service guarantee. Our test results show that Q‐JVM is backward compatible with the standard JVM from Sun, has low scheduling overhead, and is able to provide QoS guarantees as specified. Copyright © 2003 John Wiley & Sons, Ltd.
CCJ: object‐based message passing and collective communication in Java
Authors: Nelisse Arnold , Maassen Jason , Kielmann Thilo , Bal Henri E.
Published: February 2003

CCJ is a communication library that adds MPI‐like message passing and collective operations to Java. Rather than trying to adhere to the precise MPI syntax, CCJ aims at a clean integration of communication into Java's object‐oriented framework. For example, CCJ uses thread groups to support Java's multithreading model and it allows any data structure (not just arrays) to be communicated. CCJ is implemented entirely in Java, on top of RMI, so it can be used with any Java virtual machine. The paper discusses three parallel Java applications that use collective communication. It compares the performance (on top of a Myrinet cluster) of CCJ, RMI and mpiJava versions of these applications and also compares their code complexity. A detailed performance comparison between CCJ and mpiJava is given using the Java Grande Forum MPJ benchmark suite. The results show that neither CCJ's object‐oriented design nor its implementation on top of RMI impose a performance penalty on applications compared to their mpiJava counterparts. The source of CCJ is available from our Web site http://www.cs.vu.nl/manta. Copyright © 2003 John Wiley & Sons, Ltd.
Supporting dynamic parallel object arrays
Authors: Lawlor Orion S. , Kalé Laxmikant V.
Published: February 2003

We present efficient support for generalized arrays of parallel data driven objects. Array elements are regular C++ objects, and are scattered across the parallel machine. An individual element is addressed by its ‘index’, which can be an arbitrary object rather than a simple integer. For example, an array index can be a series of numbers, supporting multidimensional sparse arrays; a bit vector, supporting collections of quadtree nodes; or a string. Methods can be invoked on any individual array element from any processor, and the elements can participate in reductions and broadcasts. Individual elements can be created or deleted dynamically at any time. Most importantly, the elements can migrate from processor to processor at any time. We discuss support for message delivery and collective operations in the face of such dynamic behavior. The migration capabilities of array elements have proven extremely useful, for example, in implementing flexible load balancing strategies and for exploiting workstation clusters adaptively. We present the design, an implementation, and performance results. Copyright © 2003 John Wiley & Sons, Ltd.
Platform independent dynamic Java virtual machine analysis: the Java Grande Forum benchmark suite
Authors: Gregg David , Power James , Waldron John
Published: February 2003

In this paper we present a platform independent analysis of the dynamic profiles of Java programs when executing on the Java Virtual Machine. The Java programs selected are taken from the Java Grande Forum benchmark suite and five different Java‐to‐bytecode compilers are analysed. The results presented describe the dynamic instruction usage frequencies, as well as the sizes of the local variable, parameter and operand stacks during execution on the JVM.

These results, presenting a picture of the actual (rather than presumed) behaviour of the JVM, have implications both for the coverage aspects of the Java Grande benchmark suites, for the performance of the Java‐to‐bytecode compilers and for the design of the JVM. Copyright © 2003 John Wiley & Sons, Ltd.
Java Virtual Machine support for object serialization
Authors: Breg Fabian , Polychronopoulos Constantine D.
Published: February 2003

Distributed computing has become increasingly popular in the high‐performance community. Java's remote method invocation (RMI) provides a simple, yet powerful method for implementing parallel algorithms. The performance of RMI has been less than adequate, however, and object serialization is often identified as a major performance inhibitor. We believe that object serialization is best performed in the Java Virtual Machine (JVM), where information regarding object layout and hardware communication resources are readily available. We implement a subset of Java's object serialization protocol in native code, using the Java Native Interface (JNI) and JVM internals. Experiments show that our approach is up to eight times faster than Java's original object serialization protocol for array objects. Also, for linked data structures our approach obtains a moderate speedup and better scalability. Evaluation of our object serialization implementation in an RMI framework indicates that a higher throughput can be obtained. Parallel applications, written using RMI, obtain better speedups and scalability when this more efficient object serialization is used. Copyright © 2003 John Wiley & Sons, Ltd.
Sapphire: copying garbage collection without stopping the world
Authors: Hudson Richard L. , Moss J. Eliot B.
Published: February 2003

The growing use in concurrent systems of languages that require garbage collection (GC), such as Java, is raising practical interest in concurrent GC. Sapphire is a new algorithm for concurrent copying GC for Java. It stresses minimizing the amount of time any given application thread may need to block to support the collector. In particular, Sapphire is intended to work well in the presence of a large number of application threads, on small‐ to medium‐scale shared memory multiprocessors.

Sapphire extends previous concurrent copying algorithms, and is most closely related to replicating copying collection, a GC technique in which application threads observe and update primarily the old copies of objects. The key innovations of Sapphire are: (1) the ability to ‘flip’ one thread at a time (changing the thread's view from the old copies of objects to the new copies), as opposed to needing to stop all threads and flip them at the same time; (2) exploiting Java semantics and assuming any data races occur on volatile fields, to avoid a barrier on reads of non‐volatile fields; and (3) working in concert with virtually any underlying (non‐concurrent) copying collection algorithm. Copyright © 2003 John Wiley & Sons, Ltd.
Mitochondrial DNA studies of Native Americans: Conceptions and misconceptions of the population prehistory of the Americas
Authors: Eshleman Jason A. , Malhi Ripan S. , Smith David Glenn
Published: February 2003

A decade ago, the first reviews of the collective mitochondrial DNA (mtDNA) data from Native Americans concluded that the Americas were peopled through multiple migrations from different Asian populations beginning more than 30,000 years ago.1 These reports confirmed multiple‐wave hypotheses suggested earlier by other sources and rejected the dominant Clovis‐first archeological paradigm. Consequently, it appeared that molecular biology had made a significant contribution to the study of American prehistory. As Cann2 comments, the Americas held the greatest promise for genetics to help solve some of the mysteries of prehistoric populations. In particular, mtDNA appeared to offer real potential as a means of better understanding ancient population movements. A decade later, none of the early conclusions remain unequivocal. Nevertheless, in its maturity, the study of Native American mtDNA has produced a volume of reports that still illuminate the nature and timing of the first peopling and postcolonization population movements within the New World.
Potential flow around obstacles using the scaled boundary finite‐element method
Authors: Deeks Andrew J. , Cheng Liang
Published: February 2003

The scaled boundary finite‐element method is a novel semi‐analytical technique, combining the advantages of the finite element and the boundary element methods with unique properties of its own. The method works by weakening the governing differential equations in one co‐ordinate direction through the introduction of shape functions, then solving the weakened equations analytically in the other (radial) co‐ordinate direction. These co‐ordinate directions are defined by the geometry of the domain and a scaling centre. The method can be employed for both bounded and unbounded domains. This paper applies the method to problems of potential flow around streamlined and bluff obstacles in an infinite domain. The method is derived using a weighted residual approach and extended to include the necessary velocity boundary conditions at infinity. The ability of the method to model unbounded problems is demonstrated, together with its ability to model singular points in the near field in the case of bluff obstacles. Flow fields around circular and square cylinders are computed, graphically illustrating the accuracy of the technique, and two further practical examples are also presented. Comparisons are made with boundary element and finite difference solutions. Copyright © 2003 John Wiley & Sons, Ltd.
Neural networks for BEM analysis of steady viscous flows
Authors: Mai‐Duy Nam , Tran‐Cong Thanh
Published: February 2003

This paper presents a new neural network‐boundary integral approach for analysis of steady viscous fluid flows. Indirect radial basis function networks (IRBFNs) which perform better than element‐based methods for function interpolation, are introduced into the BEM scheme to represent the variations of velocity and traction along the boundary from the nodal values. In order to assess the effect of IRBFNs, the other features used in the present work remain the same as those used in the standard BEM. For example, Picard‐type scheme is utilized in the iterative procedure to deal with the non‐linear convective terms while the calculation of volume integrals and velocity gradients are based on the linear finite element‐based method. The proposed IRBFN‐BEM is verified on the driven cavity viscous flow problem and can achieve a moderate Reynolds number of 1400 using a relatively coarse uniform mesh. The results obtained such as the velocity profiles along the horizontal and vertical centrelines as well as the properties of the primary vortex are in very good agreement with the benchmark solution. Furthermore, the secondary vortices are also captured by the present method. Thus, it appears that an ability to represent the boundary solution accurately can significantly improve the overall solution accuracy of the BEM. Copyright © 2003 John Wiley & Sons, Ltd.
Numerical simulation of thermo‐solutal‐capillary migration of a dissolving drop in a cavity
Authors: Bassano Edmondo
Published: February 2003

In the present paper the thermo‐solutal‐capillary migration of a dissolving liquid drop, composed by a binary mixture having a miscibility gap, injected in a closed cavity with differentially heated end walls, is studied. The main goal of the analysis is to clarify if and how the drop migration is affected by the dissolution process. The numerical code is based on a finite volume formulation. A level‐set technique is used for describing the dynamics of the interface separating the different phases. A thermodynamic constraint fixes the concentration jump between the interface sides. This jump, together with that of the concentration normal derivatives, in turn defines the entity of the dissolution cross‐flow through the interface and the interface velocity relative to the fluid. Since the jump singularity of normal derivatives cannot be easily mollified, while retaining the necessary accuracy, a scheme for the species equation is elaborated that allows sharp jumps and has subcell resolution. Steady migration speeds are determined after the start‐up phase for different radii and temperature differences. The results will be used for the preparation of a sounding rocket space experiment. Copyright © 2003 John Wiley & Sons, Ltd.
Inter‐‐rater and test‐‐retest reliability of the Japanese version of the subjective deficit syndrome scale
Authors: Kokai M. , Inada T. , Ohara K. , Shimizu M. , Iwado H. , Morita Y.
Published: February 2003

The subjective deficit syndrome scale (SDSS) was established in 1990 by Jaeger et al. to assess systematically subjective experiences of schizophrenic patients. It was translated into Japanese in 1999 by this paper's second author (T.I.). In this study, the inter–rater reliability of this Japanese version (SDSS‐J) was examined. The subjects studied were 13 schizophrenic patients (male 6, female 7; respective average ages at study entry and disease onset: 41 and 25 years), who were being followed up at the outpatients' service of the Department of Neuropsychiatry, Hyogo College of Medicine. Four psychiatrists attended together, the systematic interview with each subject to rate the SDSS‐J and independently rated 19 items. The severity scales of the items assessed by these raters ranged from 0 to 4 for 12 items and from 0 to 3 for 7. The ANOVA ICC inter–rater reliability values for the 19 individual items ranged from 0.67 to 0.96. The ANOVA ICC test–retest reliability values achieved by two raters were also high overall, ranging from 0.72 to 1.00, except for one item (item 13) assessed by one rater. Our results suggest that the SDSS‐J is a potentially useful rating scale for evaluating subjective experiences of schizophrenic subjects. Copyright © 2002 John Wiley & Sons, Ltd.
Fluvoxamine as effective as clomipramine against symptoms of severe depression: results from a multicentre, double‐blind study
Authors: Zohar Joseph , Keegstra Harman , Barrelet Lucien
Published: February 2003

Background

Although selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants, their efficacy in severe depression remains to be further elucidated.

Method

A double‐blind, multicentre study was conducted in 86 severely depressed inpatients (≥ 25 on the 17‐item Hamilton depression rating scale [HAMD] total score) to compare the efficacy and safety of fluvoxamine with that of clomipramine. Following placebo run‐in, 86 patients were randomised to receive fluvoxamine or clomipramine (100–250 mg/day) for 8 weeks.

Results

Fluvoxamine and clomipramine both resulted in marked improvements; there were no statistically significant differences between them on the 17‐item HAMD total score, the clinical global impression severity of illness or global improvement items or the Montgomery–Åsberg depression rating scale, at any visit. At the end of the study, 71% in the fluvoxamine group and 69% in the clomipramine group were responders (≥ 50% decrease in 17‐item HAMD total score). However, fluvoxamine was better tolerated than clomipramine. Clomipramine was associated with a higher incidence of overall and treatment‐related adverse events. In addition, the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine (24% vs 11%).

Conclusion

Fluvoxamine and clomipramine are equally effective in severe depression, but fluvoxamine has a better safety and tolerability profile. Copyright © 2003 John Wiley & Sons, Ltd.
Coffee increases state anxiety in males but not in females
Authors: Botella Paloma , Parra Andrés
Published: February 2003

Coffee, reproducing the conditions under which caffeine is normally ingested, containing 3, 75, 150 or 300 mg of caffeine was given to healthy male and female volunteers. 25–30 min after drinking the beverage, they completed the Spanish version of the state‐trait anxiety inventory (STAI). The beverage increased state anxiety, in a dose‐dependent manner, in males but not in females. This could be due to a lesser sensitivity of females to coffee. Copyright © 2003 John Wiley & Sons, Ltd.
Seasonal variations in the binding of [3H]paroxetine to the platelet serotonin transporter sites in African–American cocaine‐dependent patients and healthy volunteers
Authors: Patkar Ashwin A. , Berrettini Wade H. , Lundy Allan , Murray Heather W. , Hill Kevin P. , Vergare Michael J. , Weinstein Stephen P.
Published: February 2003

Although seasonal fluctuations in several indices of serotonin function have been described, little is known about seasonality and serotonergic activity in substance abusers. We investigated whether there were seasonal differences in platelet serotonin transporter sites among cocaine dependent patients and controls. Platelet [3H]paroxetine binding, a measure of serotonin transporter sites, was assayed in 141 African–American cocaine‐dependent subjects and in 60 race matched healthy volunteers who served as the control group. Bmax (density of serotonin transporter) and Kd (affinity constant) values of [3H]paroxetine binding were compared during spring, summer, fall and winter. Consistent with our previous findings Bmax values were significantly lower in cocaine patients (639 ± 234) than in controls (906 ± 225) (t = 7.12, p < 0.001). Moreover, Bmax values showed a significant seasonal variation in controls with the highest values in summer and spring compared with fall and winter (F = 4.47, p < 0.01). However, there were no significant seasonal differences in Bmax values in cocaine patients. Kd values did not show any seasonal changes in either group. There were no effects of age or gender on seasonal variations in Bmax. The study demonstrates a seasonal effect on platelet serotonin uptake in healthy African–American volunteers. The lack of seasonal differences in transporter availability in cocaine patients indicates that the normal seasonal rhythm of serotonergic activity may be disturbed in cocaine abusers. Biological studies that employ platelet serotonin transporter sites as a marker of serotonin function should consider seasonal variations in these markers as a potential source of variance. Copyright © 2002 John Wiley & Sons, Ltd.
Early photoperiod history and short‐day responsiveness in siberian hamsters
Authors: Goldman Sharry L. , Goldman Bruce D.
Published: February 2003

Siberian hamsters exhibit seasonal, photoperiod influenced cycles of reproductive activity, body size, pelage characteristics, and thermoregulatory behavior. Laboratory populations generally exhibit inter‐individual variability in expression of photoperiod responsiveness, with a subset of individuals that fail to show the species typical responses to short photoperiod. This variability is partly explained by a genetic component, as it has been possible to increase the number of short‐day nonresponders by artificial selection. Responsiveness to short photoperiod is also substantially influenced by photoperiod history in this species; hamsters that have been raised under long (16L) or very long (18L) day lengths are less likely to exhibit winter‐type responses to short days as compared to hamsters raised under an intermediate (14L) day length. In the present experiment, we examined effects of age and early photoperiod history in a strain of Siberian hamsters that had been selected for short‐day nonresponsiveness. Hamsters transferred into short photoperiod on the day of birth were uniform in exhibiting winter‐type responses. However, hamsters raised until 25 days of age in either continuous illumination or in 16L exhibited variation in responsiveness when subsequently moved into short photoperiod. We conclude that virtually all hamsters of the short‐day nonresponsive strain are born responsive to short days. Subsequent development of resistance to potential short day effects is dependent on age and/or photoperiod history. J. Exp. Zool. 296A:38–45, 2003. © 2003 Wiley‐Liss, Inc.
Putative histidin‐rich proteins in the epidermis of lizards
Authors: Alibardi L. , Maurizii M.G. , Toni M. , Spisni E. , Taddei C.
Published: February 2003

In the stratum granulosum of mammalian epidermis, histidin‐rich proteins (filaggrins) determine keratin clumping and matrix formation into terminal keratinocytes of the stratum corneum. The nature of matrix, interkeratin proteins in the epidermis of nonmammalian vertebrates, and in particular in that of reptilian, mammalian progenitors are unknown. The present biochemical study is the first to address this problem. During a specific period of the renewal phase of the epidermis of lizards and during epidermal regeneration, keratohyalin‐like granules are formed, at which time they take up tritiated histidine. The latter also accumulate in cells of the alpha‐keratin layer (soft keratin). This pattern of histidine incorporation resembles that seen in keratohyalin granules of the stratum granulosum of mammalian epidermis. After injection of tritiated histidine, we have analysed the distribution of the radioactivity by histoautoradiography and electrophoretic gel autoradiography of epidermal proteins. Extraction and electrophoretic separation of interfilamentous matrix proteins from regenerating epidermis 3–48 hours post‐injection reveals the appearance of protein bands at 65–70, 55–58, 40–43, 30–33, 25–27, and 20–22 kDa. Much weaker bands were seen at 100, 140–160, and 200 kDa. A weak band at 20–22 kDa or no bands at all are seen in the normal epidermis in resting phase and in the dermis. In regenerating epidermis at 22 and 48 hours post‐injection, little variation in bands is detectable, but low molecular weight bands tend to increase slightly, suggesting metabolic turnover. Using anti‐filaggrin antibodies against rat, human, or mouse filaggrins, some cross‐reactivity was seen with more reactive bands at 40–42 and 33 kDa, but it was reduced or absent at 140, 95–100, 65–70, 50–55, and 25 kDa. This suggests that different intermediate degradative proteins of lizard epidermis may share some epitopes with mammalian filaggrins and are different from keratins with molecular weight ranging from 40 to 65–68 kDa. The immunocytochemical observation confirms that a weak filaggrin‐like immunoreactivity characterizes differentiating alpha‐keratogenic layers in normal and regenerating tail. A weak filaggrin labeling is discernable in small keratohyalin‐like granules but is absent from the larger granules and from mature keratinocytes. The present results indicate, for the first time, that histidine‐rich proteins are involved in the process of alpha‐keratinization in reptilian epidermis. The cationic, interkeratin matrix proteins implicated may be fundamentally similar in both theropsid‐derived and sauropsid amniotes. J. Exp. Zool. 296A:1–17, 2003. © 2003 Wiley‐Liss, Inc.
Entrainment of circadian locomotor activity rhythm of the nocturnal field mouse Mus booduga using daily injections of melatonin
Authors: Sharma Vijay Kumar , Chidambaram R.
Published: February 2003

In this paper, we report the effects of daily injections of melatonin on the locomotor activity rhythm of the nocturnal field mouse Mus booduga. The locomotor activity rhythm of 45 animals was first monitored in constant darkness (DD) of the laboratory for about 15 days. The animals were then divided into three groups (experimental, vehicle‐treated control, and the nontreated control groups) and subjected to three different treatments. The animals from the experimental group (n=19) were administered daily a single subcutaneous (s.c.) injection of melatonin (1 mg/kg) for about 45 days. The vehicle treated controls (n=13) were administered daily injections of 50% dimethyl sulfoxide (DMSO) for about 45 days, and the nontreated controls (n=13) were handled similar to the other two groups without being administered injections. Following the treatments, the animals were maintained in DD for about 20 days, after which the experiments were terminated. A significantly larger percentage of animals from the experimental group either entrained or showed phase control to daily treatments, compared to the animals from the two control groups. These results suggest that externally administered melatonin can influence the phase of the circadian locomotor activity rhythm of M. booduga. The fact that none of the nontreated controls showed any sign of phase control to daily handling, clearly demonstrates that the entrainment or phase control in the melatonin treated group of animals is caused by melatonin alone and not due to handling. J. Exp. Zool. 296A:30–37, 2003. © 2003 Wiley‐Liss, Inc.
Reorganization of monoaminergic systems in the earthworm, Eisenia fetida, following brain extirpation
Authors: Csoknya Mária , Barna János , Hiripi László , Hámori József , Elekes Károly
Published: February 2003

The present study describes the major aspects of how monoaminergic (serotonin, dopamine) systems change in the course of regeneration of the brain in the earthworm (Eisenia fetida), investigated by immunocytochemistry, HPLC assay, and ligand binding. Following brain extirpation, the total regeneration time is about 80 days at 10°C. On the 3rd postoperative day serotonin, and on the 11th postoperative day tyrosine hydroxylase‐immunoreactive neurons can be observed in the wound tissue. Thereafter the number of the immunoreactive cells increases gradually, and by the 76th–80th postoperative days all serotonin‐ and tyrosine hydroxylase‐immunopositive neurons can be found in their final positions, similarly to those observed in the intact brain. Labeled neurons located in the dorsal part of the regenerated brain appear earlier than the cells in lateral and ventral positions. Both serotonin‐ and tyrosine hydroxylase‐immunoreactive neurons of the newly formed brain seem to originate from undifferentiated neuroblasts situated within and around the ventral ganglia and the pleura. Dopaminergic (tyrosine hydroxylase‐immunoreactive) elements may additionally derive from the proliferation of neurons localized in the subesophageal ganglion and the pharyngeal nerve plexus. Following brain extirpation, both serotonin and dopamine levels, assayed by HPLC, first increase in the subesophageal ganglion; by the 25th day of regeneration, the monoamine content decreases in it and increases in the brain. Hence it is suggested that monoamines are at least partly transported from this ganglion to the regenerating brain. At the same time, 3H‐LSD binding can be detected in the regenerating brain from the 3rd postoperative day, showing a continuous increase until the 80th postoperative day, suggesting a guiding role of postsynaptic elements in the monoaminergic reinnervation of the newly formed brain. J. Exp. Zool. 296A:18–29, 2003. © 2003 Wiley‐Liss, Inc.
Effects of androgens on sex differentiation of the urodele Pleurodeles waltl
Authors: Chardard D. , Kuntz S. , Chesnel A. , Flament S.
Published: February 2003

In nonmammalian vertebrates, steroids have been hypothesized to induce somatic sex differentiation, since manipulations of the steroidal environment of gonads have led to various degrees of sex reversal. Whereas the critical role of estrogens in ovarian differentiation is well documented, studies on androgens have produced a perplexing variety of results depending upon species variations and nature of androgens used. In this way, testosterone induces masculinization of females in some species but provokes paradoxical feminization of males in many other species such as the urodelan Pleurodeles waltl. In reptiles this phenomenon could be interpreted by conversion of exogenous testosterone to estradiol by aromatase. Treatments of Pleurodeles larvae with nonaromatizable androgens bring support to this hypothesis and suggest a role of androgens in sex differentiation. Dihydrotestosterone (DHT) could not induce the paradoxical feminization of ZZ larvae. In addition, DHT as well as 11β‐hydroxy‐androstenedione could drive a functional male differentiation of ZW larvae. Moreover, other 5α reduced androgens also induced sex reversal of female larvae. Yet, the 5α reductase inhibitor CGP 53133 and antiandrogens such as flutamide or cyproterone acetate did not exert any effect on male sex differentiation of ZZ larvae. Though the precise role of androgens is still unknown, especially for 11‐oxygenated androgens, our results suggest an implication in male sex differentiation. In this way, testosterone could play a pivotal role in being metabolized either into other androgens during testis differentiation or into estradiol during ovarian differentiation. J. Exp. Zool. 296A:46–55, 2003. © 2003 Wiley‐Liss, Inc.
Prolonged response to calling songs by the L3 auditory interneuron in female crickets (Acheta domesticus): Intracellular evaluation
Authors: Navia Benjamin , Stout John , Atkins Gordon
Published: February 2003

The L3 auditory interneuron in female Acheta domesticus, produces two different responses to the male calling song: an immediate response and a prolonged response. The prolonged response exhibited spiking activity and a correlated prolonged depolarization, both of which are clearly seen in intracellular recordings. The morphology revealed by intracellular staining was clearly the L3 neuron. The amplitude of the prolonged depolarization associated with the prolonged response increased with increases in sound intensity, resulting in increased spiking rates. Both depolarization and sound presentation increased the spiking rate and the slope of pre‐potentials (thus leading to spiking threshold more quickly). Injecting hyperpolarizing current had the expected opposite effect. The effects of positive current injection and sound presentation were additive, resulting in spiking rates that were approximately double the rates in response to sound alone. Short postsynaptic potentials (PSPs), whose duration ranged from 15–60 ms, which may lead to action potentials were also observed in all recordings and summated with the prolonged depolarization, increasing the probability of spiking. J. Exp. Zool. 296A:63–71, 2003. © 2003 Wiley‐Liss, Inc.
Synthesis of 15N‐, 13C‐, and 2H‐labeled methanandamide analogs
Authors: Yao Fen‐Mei , Palmer Sonya L. , Khanolkar Atmaram D. , Tian Xiaoyu , Guo Jianxin , Makriyannis Alexandros
Published: February 2003

Four isotopically labeled, metabolically stable analogs of arachidony‐lethanolamide (anandamide), an endogenous cannabinoid ligand, were synthesized via a five‐step reaction sequence starting from arachidonic acid. These stable methanandamide derivatives will serve as probes for studying the conformational properties of anandamide in model membrane systems using solid‐state NMR spectroscopy. The synthetic methods described can be applied to the preparations of other anandamide analogs with isotopic labeling in different positions of the molecule, which could be utilized in biochemical and pharmacological experiments. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of N, N‐diethyl‐4‐[phenyl‐(piperidin‐4‐ylidene)methyl]‐[carboxy‐14C]benzamide, a potent δ opioid receptor agonist
Authors: Gawell Lars
Published: February 2003

The synthesis of carbon‐14 labelled N,N‐diethyl‐4‐[phenyl‐(piperidin‐4‐ylidene)methyl]‐benzamide is described. The radioisotope is introduced via an aryllithium reaction with 14CO2 to form the labelled acid, which is subsequently transformed into the amide. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of 3H and 14C labeled (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐indol‐2‐one, maxipost™. An agent for post‐stroke neuroprotection
Authors: Dischino Douglas D. , Gribkoff Valentin K. , Hewawasam Piyasena , Luke George M. , Rinehart J. Kent , Spears Tony L. , Starrett John E.
Published: February 2003

The syntheses of tritium labeled (S)‐3‐(5‐chloro‐2‐[OC3H3]methoxyphenyl‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐1H‐indol‐2‐one, and carbon‐14 (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐[2,3‐14C2] indol‐2‐one are reported. The 3H‐labeled compound was prepared in a two‐step synthesis from C3H3I. The final product was purified via chiral HPLC to yield the desired enantiomer in a 4% radiochemical yield and a specific activity of 60 Ci/mmol. The 14C‐labeled compound was prepared in a four‐step synthesis from diethyl [carboxylate‐14C1,2] oxalate. The final product was purified via chiral HPLC to yield the desired enantiomer in a 20% radiochemical yield and a specific activity of 28.4 μCi/mg. Copyright © 2002 John Wiley & Sons, Ltd.
Synthesis of carbon‐14 labeled (R)‐3‐fluoro‐4‐(2′‐(5′′, 6′′, 7′′, 8′′‐tetrahydro‐5′′, 5′′, 8′′, 8′′‐tetramethyl‐2′′‐naphthyl)‐[2′‐hydroxy‐14C])[carbonyl‐14C]acetamidobenzoic acid
Authors: Dischino Douglas D. , Lee Che‐Wah , Belema Makonen , Zusi Christopher
Published: February 2003

Carbon‐14 labeled (R)‐3‐fluoro‐4‐(2′‐(5′′, 6′′, 7′′, 8′′‐tetrahydro‐5′′, 5′′, 8′′, 8′′‐tetramethyl‐2′′‐naphthyl)‐[2′‐hydroxy‐14C])[carbonyl‐14C]acetamidobenzoic acid, 1, was prepared in a six step radioactive synthesis from diethyl [carboxylate‐14C1,2] oxalate. The penultimate compound was purified by chiral HPLC, which following deprotection yielded 1 in an overall radiochemical yield of 6.8%. The specific activity of the final product was found to be 24.5 µCi/mg with a radiochemical purity of > 99% as determined by HPLC. Derivatization of 1 via trimethylsilyl diazomethane to the corresponding methyl ester 9, followed by chiral HPLC analysis, demonstrated that 1 had an optical purity of > 99% ee. Copyright © 2002 John Wiley & Sons, Ltd.