bluuebunny/crossref_metadata_2025 huggingface dataset:
Anisotropic effective interactions in a coarse‐grained tube picture of proteins
Authors: Banavar Jayanth R. , Maritan Amos , Seno Flavio
Published: October 2002

Recent studies have shown that a coarse‐grained description of a protein backbone represented as a tube of non‐zero thickness captures many of the common characteristics of small globular proteins. Here we argue that such a physical picture leads to a prediction of inherently anisotropic amino acid interactions. In order to test this prediction, we have carried out an extensive analysis of a data bank made up of 600 proteins with low sequence homology and covering many different three‐dimensional folds. This analysis, based on the study of the geometrical properties of the vectors joining next‐nearest neighbor Cα atoms along the chain, shows clearly that when amino acids are in contact, the distribution of their relative orientations is not random but exhibits peaks at specific angles whose values reflect, in general, the tubular nature of proteins and, more specifically, the nature of the secondary structure motifs, which are the building blocks of protein structures. Our results suggest that the incorporation of the relative orientation of amino acids in contact could play a vital role in simplified coarse‐grained schemes for determining effective interaction parameters for use in folding, threading, and docking. Proteins 2002;49:246–254. © 2002 Wiley‐Liss, Inc.
Development of novel pesticides based on phytoalexins: Part 2. Quantitative structure–activity relationships of 2‐heteroaryl‐4‐chromanone derivatives
Authors: Yang Guangfu , Jiang Xiaohua , Yang Huazheng
Published: October 2002

Phytoalexins are low‐molecular‐weight chemicals that immune systems of plants produce and accumulate in response to infections, especially those of fungal origin. Although their content is not high in plants, yet they have shown unique fungicidal activity and played an important role in the defence system of plants. In searching for novel environmentally benign fungicides with high activity, the structures of flavanone derivatives, one of the most important phytoalexins groups, have been modified via bioisosteric substitution and a series of 2‐heteroaryl‐4‐chromanones were designed and synthesized. They showed good fungicidal activities against rice blast disease, Pyricularia grisea (Sacc). Their IC50 values were tested in vitro and the relationship between structure and fungicidal activity was analyzed quantitatively using a Hansch–Fujita approach. The results showed that hydrophobicity was very important for fungicidal activity and there is apparently an optimum hydrophobic property for the molecules at a log Pow value of about 2.7. In addition, the results indicated that electronic effects played an important role in binding with the receptor and that the CO group was probably a electron‐accepting site. The quantitative structure–retention correlative equation of the title compounds was also established.

© 2002 Society of Chemical Industry
Automated structural assignment of derivatized complex N‐linked oligosaccharides from tandem mass spectra
Authors: Ethier Martin , Saba Julian A. , Ens Werner , Standing Kenneth G. , Perreault Hélène
Published: October 2002

Glycoprotein function is controlled by several biological factors, one of them being the structure of carbohydrate chains (glycans) attached to specific amino acids of the protein backbone. Changes in glycan structures have been shown to modify the secondary and tertiary conformation of glycoproteins, thus their function. Powerful analytical tools are available for the characterization of sugar structures, and recently mass spectrometry (MS) has been increasingly useful for this purpose. Manual interpretation of tandem mass spectrum is possible but tedious. Automated interpretation should speed the analysis and enhance the results obtained. A new computer program for automated interpretation of tandem MS spectra of complex N‐linked glycans oligosaccharides from mammals will be described. N‐Linked oligosaccharides standards were derivatized with 1‐phenyl‐3‐methyl‐5‐pyrazolone (PMP) and analyzed by matrix‐assisted laser desorption/ionization (MALDI)‐tandem MS. Simulated tandem mass spectra of other common glycans were also generated to test the algorithm. The MALDI‐MS/MS spectra featured resolved isotopic distributions for the [M + H]+ and fragment ions of oligosaccharides. These isotopic distributions complicated the automated analysis of the spectra and were removed to leave only monoisotopic peaks. An algorithm was written for this purpose, yielding simplified tandem mass spectra. Another algorithm is then used to determine the structure of the oligosaccharide. A score is then given to each structure, depending on agreement with experimental results. The program successfully assigned the true structure in 24 out of the 28 cases (86%) and the true structure was among the three top scoring structures in all cases. Copyright © 2002 John Wiley & Sons, Ltd.
Hippocampal expression of c‐fos is not essential for spatial learning
Authors: Zhang Jianhua , McQuade Jill M. Slane , Vorhees Charles V. , Xu Ming
Published: October 2002

The formation of long‐term memory is thought to involve underlying changes in synaptic strength. Many studies have focused on the mechanisms of spatial learning behavior in mammals that is critically dependent on the proper function of the hippocampus. Because of the enduring nature of long‐term memory, it is thought that gene expression is involved in this process. The immediate early gene (IEG) c‐fos encodes a transcription factor. The c‐Fos proteins form heterodimeric proteins with the c‐Jun family proteins and the resulting AP‐1 transcription complex plays a key role in coupling short‐term events elicited by stimuli received at the cell membrane to long‐term neuroplastic changes by regulating gene expression. c‐fos is induced in the hippocampus after spatial learning. Despite this knowledge, the precise role of c‐fos in memory formation and the underlying mechanisms remain unknown. To start investigating the role of c‐fos in learning and memory and underlying mechanisms, we evaluated spatial learning capabilities using mice carrying a hippocampal region‐specific mutation of c‐fos. We found that the c‐fos mutant mice exhibit normal spatial learning behaviors in both the Morris water maze and the Barnes maze tests compared to control mice. Our results suggest that hippocampal c‐fos expression is not essential for spatial learning. Synapse 46:91–99, 2002. © 2002 Wiley‐Liss, Inc.
Holocene Environmental Variability in Southern Greenland Inferred from Lake Sediments
Authors: Kaplan Michael R. , Wolfe Alexander P. , Miller Gifford H.
Published: October 2002

Sediments from Qipisarqo Lake provide a continuous Holocene paleoenvironmental record from southern Greenland. Following deglaciation and glacio-isostatic emergence of the basin from the sea ∼9100 cal yr B.P., proxies of lake paleoproductivity, including biogenic silica and organic matter, increased markedly until 6000 cal yr B.P. and thereafter remained stable over the ensuing warm three millennia. Subsequent decreases in these proxies, most dramatically between 3000 and 2000 cal yr B.P., show the lake's responses to initial Neoglacial cooling. Intervals of ameliorated limnological conditions occurred between 1300 and 900 and between 500 and 280 cal yr B.P., briefly interrupting the decreasing trend in productivity that culminated in the Little Ice Age. Increased lake productivity during the latter half of the 20th century, which reflects the limnological response to circum-arctic warming, still has not reached peak Holocene values. The Neoglacial climate of the last 2000 yr includes the most rapid high-amplitude environmental changes of the past nine millennia. The Norse thus migrated around the North Atlantic Ocean region in the most environmentally unstable period since deglaciation. Lacustrine sediment records provide a context with which to consider future environmental changes in the Labrador Sea region. In particular, any future warming will be superposed on a regional climate system that is currently exhibiting highly unstable behavior at submillennial timescales.
Induced folding of the U2AF35 RRM upon binding to U2AF65
Authors: Kellenberger Esther , Stier Gunter , Sattler Michael
Published: October 2002

The human essential splicing factor U2AF (U2 auxiliary factor) consists of 35 and 65 kDa subunits which form a highly stable heterodimer in solution. Copurification of the recombinant U2AF35 RNA recognition motif (U2AF35 RRM) and full‐length U2AF65 yields a soluble and functionally active minimal U2AF heterodimer. Recombinant U2AF35 RRM protein free and in complex with three different regions of U2AF65 was characterized by nuclear magnetic resonance spectroscopy. We found that the recombinant U2AF35 RRM is unstructured in solution but its tertiary structure is induced upon binding to U2AF65. This interaction is mediated by the N‐terminal proline‐rich region of U2AF65 and does not involve the U2AF65 RRMs.
RESONANCE STATES FROM POLES OF THE RELATIVISTIC S-MATRIX
Authors: KALDASS H. , BOHM A. , WICKRAMASEKARA S.
Published: October 2002

A state vector description for relativistic resonances is derived from the first order pole of the jth partial S-matrix at the invariant square mass value [Formula: see text] in the second sheet of the Riemann energy surface. To associate a ket, called Gamow vector, to the pole, we use the generalized eigenvectors of the four-velocity operators in place of the customary momentum eigenkets of Wigner, and we replace the conventional Hilbert space assumptions for the in- and out-scattering states with the new hypothesis that in- and out-states are described by two different Hardy spaces with complementary analyticity properties. The Gamow vectors have the following properties:

(i) They are simultaneous generalized eigenvectors of the four velocity operators with real eigenvalues and of the self-adjoint invariant mass operator M =(Pμ Pμ)1/2 with complex eigenvalue [Formula: see text].

(ii) They have a Breit–Wigner distribution in the invariant square mass variable [Formula: see text] and lead to an exactly exponential law for the decay rates and probabilities.
Formation of Ordered Mesoporous Carbon Material from a Silica Template by a One-Step Chemical Vapour Infiltration Process
Authors: Vix-Guterl Cathie , Boulard Séverine , Parmentier Julien , Werckmann Jacques , Patarin Joël
Published: October 2002

A well-ordered mesoporous carbon material has been prepared by a one-step chemical vapour infiltration process starting from a MCM-48 silica template.
Comparison of the enthalpic relaxation of poly(lactide–co‐glycolide) 50:50 nanospheres and raw polymer
Authors: Bailey N. A. , Sandor M. , Kreitz M. , Mathiowitz E.
Published: October 2002

The phenomenon of enthalpic relaxation was evaluated for poly(lactide‐co‐glycolide) (PLGA, 50:50), in terms of storage of nanospheres for use as a controlled drug delivery system. Samples were stored for different times and temperatures below the glass transition temperature (Tg). Relaxation occurred at a significant rate up to 15 degrees below the Tg of 39.2°C. The effect of polymer morphology was considered by comparing the relaxation kinetics of the raw polymer with that of nanospheres formed using a novel technique. The nanospheres were shown to have a larger change in heat capacity at the glass transition and a longer average relaxation time than that of the raw polymer, and the relationship between these two parameters was discussed. For both the raw polymer and the nanospheres, relaxation was found to occur at a significant rate at room temperature. The storage of this system at subambient temperatures was therefore deemed important for maintaining the physicochemical properties of the system. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1868–1872, 2002
Pure component recovery from polyamide 6/6 6 mixtures by selective dissolution and reprecipitation
Authors: Kartalis C. N. , Poulakis J. G. , Tsenoglou C. J. , Papaspyrides C. D.
Published: October 2002

A selective dissolution/reprecipitation technique was applied for the effective recovery of Polyamide 6 (PA 6) and Polyamide 6 6 (PA 6 6) from their mixtures. The proposed process comprises mainly selective polyamide dissolution in an appropriate solvent at a specific temperature, reprecipitation of the polymer from the solution by addition of a nonsolvent, washing, and drying. A model mixture of virgin PA 6 and PA 6 6 pellets was initially tried, whereas in a following stage the selective dissolution technique was applied for the recovery of a PA‐copolymer layer from a three‐layered bottle end product also containing HDPE and EVA. End‐group analysis, dilute solution viscometry, and differential scanning calorimetry were used to assess the molecular weight preservation and crystallizability of the recycled polyamides. The recycled materials demonstrated excellent retention of the properties studied, although in the copolymer case, due to hydrolysis, a molecular weight decrease was detected, accompanied with a slight compositional shift, favoring the PA6 6 presence in the final product. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1924–1930, 2002
Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin
Authors: Shiotani Aya , Takami Masamichi , Itoh Kanami , Shibasaki Yoshinobu , Sasaki Takahisa
Published: October 2002

The differentiation and functions of osteoclasts (OCs) are regulated by osteoblast‐derived factors. Receptor activator of NFkB ligand (RANKL) is one of the key regulatory molecules in OC formation. Osteoprotegerin (OPG) is a novel secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis and binds to RANKL. We examined the biological actions of macrophage‐colony‐stimulating factor (M‐CSF), RANKL, and OPG on the differentiation of OCs isolated from cocultures of mouse osteoblastic cells and bone marrow cells. Preosteoclasts (pOCs) and OCs were characterized by their ultrastructure and the expression of OC markers such as tartrate‐resistant acid phosphatase (TRAP) and vacuolar‐type H+‐ATPase. pOCs formed without any additives expressed TRAP, but showed little resorptive activity on cocultured dentine slices. TRAP‐positive pOCs treated with M‐CSF began to fuse with each other, but lacked a ruffled border (RB) and showed almost no resorptive activity. pOCs treated with RANKL became TRAP‐positive multinucleated cells, which expressed intense vacuolar‐type H+‐ATPase along the RB membranes and exhibited prominent resorptive activity. Such effects of RANKL on pOCs were completely inhibited by the addition of OPG. OPG inhibited RB formation in mature OCs and reduced their resorptive activity, and also induced apoptosis of some OCs. These results suggest that 1) RANKL induces differentiation of functional OCs from pOCs, 2) M‐CSF induces macrophage‐like multinucleated cells, but not OCs, 3) OPG inhibits RB formation and resorptive activity in mature OCs, 4) OPG also induces apoptosis of OCs, and 5) RANKL and OPG are, therefore, important regulators of not only the terminal differentiation of OCs but also their resorptive function. Anat Rec 268:137–146, 2002. © 2002 Wiley‐Liss, Inc.
Cloning and expression of 32 kDa ferritin from Galleria mellonella
Authors: Kim Beom Su , Lee Chang Seok , Seol Ji Yeon , Yun Chi Young , Kim Hak R.
Published: October 2002

We have sequenced a cDNA clone encoding 32‐kDa ferritin subunit in the Wax Moth, Galleria mellonella. The 32‐kDa ferritin subunit cDNA was obtained from PCR using identical primer designed from highly conserved regions of insect ferritins. RACE PCR was used to obtain the complete protein coding sequence. The 32‐kDa ferritin subunit encoded a 232 amino acid polypeptide, containing a 19 leader peptide. The iron‐responsive element (IRE) sequence with a predicted stem‐loop structure was present in the 5′‐untranslated region of the wax moth 32‐kDa ferritin subunit mRNA. The 32‐kDa sequence alignment had 78 and 69% identity with Manduca sexta and Calpodes ethlius (G), respectively. The G. mellonella ferritin subunits showed minimal identity with each other (19%). The glycosylation site (Asn‐X‐Ser/Thr) was found in the 32‐kDa subunit but not in the 26‐kDa subunit. Northern blot analysis showed that the mRNA expression of the 32‐kDa ferritin was detected in the fat body and midgut. The fat body expression increased after 6 h and the mRNA in midgut dramatically increased about 3‐fold the expression level at 12 h after iron feeding. Western blot revealed that a protein level of the 32‐kDa subunit is abundant in midgut after 12 and 24 h iron feeding. Arch. Insect Biochem. Physiol. 51:80–90, 2002. © 2002 Wiley‐Liss, Inc.
Application of tube formula to distributional problems in multiway layouts
Authors: Kuriki Satoshi , Takemura Akimichi
Published: October 2002

Recently, an integral geometric method called the tube method has been actively developed. The tube method gives us a powerful tool to tackle problems where conventional matrix theory such as the singular value decomposition cannot be applied. The aim of this paper is to survey several recent applications of the tube method to distributional problems in multiway layouts which are of practical importance but hardly handled by conventional methods. Null distributions of test statistics of the following three testing problems are discussed: (i) A test for interaction in three‐way layout based on the three‐way analogue of the largest singular value. (ii) Testing independence in ordered categorical data by maximizing row and column scores under order restriction. (iii) Detecting a change point in two‐way layout with ordinal factors. Copyright © 2002 John Wiley & Sons, Ltd.
Effect of dose and input rate on the brain penetration of BMS‐204352 following intravenous administration to rats
Authors: Krishna Rajesh , Palme Holly , Zeng Jianing , Srinivas Nuggehally
Published: October 2002

BMS‐204352 is a novel maxi‐K channel opener that is being developed for the treatment for stroke. The current study was designed to evaluate the plasma and brain pharmacokinetics of BMS‐204352 in rats, in particular, assessing the effect of dose and input rate on brain penetration of BMS‐204352. Rats (3 animals/group/time point) received a single intravenous dose of BMS‐204352 as 5 mg/kg bolus, 5 mg/kg 30 min infusion, 5 mg/kg 60 min infusion, and 10 mg/kg bolus dose, into the jugular vein. Terminal blood (for plasma) and brain samples were collected for up to 9 h post‐dose and samples were analyzed for the concentrations of intact BMS‐204352 using a validated liquid chromatographic tandem mass spectrometric method (LC/MS/MS). As dose increased from 5 to 10 mg/kg, both BMS‐204352 Cmax and AUC values increased in plasma and brain, somewhat greater in proportion to the increment in dose. Whereas the peak concentrations of BMS‐204352 were affected by infusion time, overall AUCs were comparable across the bolus and infusion groups. Terminal disposition (T‐half ranged from 1.6 to 2.7 h) of BMS‐204352 was unaltered as a function of input rate. BMS‐204352 crossed the blood–brain barrier with brain‐to‐plasma (B/P) ratios of approximately 7–11. Brain‐to‐plasma ratios appeared to be independent of dose and infusions produced somewhat higher brain penetration (B/P of ca. 11) as compared to bolus (B/P of ca. 7–8) dose. The decline of BMS‐204352 in the brain paralleled that of plasma independent of the input rate and dose. Copyright © 2002 John Wiley & Sons, Ltd.
Facilitating process control teaching and learning in a virtual laboratory environment
Authors: Murphy T. , Gomes V. G. , Romagnoli J. A.
Published: October 2002

The rapid pace of technological developments and the high cost of engineering equipment, pose several challenges to traditional modes of engineering education. Innovations in education are desirable. In particular, education on practical aspects of engineering and personnel training can be enhanced through the use of virtual laboratories. Such educative experiences allow a student to better understand the theoretical aspects of the discipline in addition to its integration with practical knowledge. In this work, the development, set‐up and application of a virtual twin heat exchanger plant is described. The philosophy and methodology of our approach is described, including the implementation details and our experience in using it. The effectiveness of the platform in educating students and in training industrial personnel is described. © 2002 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 79–87, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10011
Cross‐institutional assessment: Development and implementation of the On‐line Student Survey System
Authors: Hoare Raymond , Besterfield‐Sacre Mary , Ertman Dan , Gerchak Jessica , Johnson Troy , Shields Robert , Shuman Larry
Published: October 2002

As ABET has increased the need for routine student assessments, engineering faculty are faced with the problem of doing this in an efficient manner that minimizes the time required to conduct, tabulate, and analyze the requisite surveys. To meet this need, researchers at the University of Pittsburgh have developed the On‐line Student Survey System (OS3) to facilitate EC 2000 assessment and cross‐institutional benchmarking. OS3 allows multiple engineering schools to conduct customized, routine program evaluations using Web‐based surveys specifically designed to meet EC 2000 objectives. Since its inception, seven engineering schools have adopted OS3. This article provides an overview of the system, a des‐cription of its survey instruments, and an evaluation of the system. © 2002 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 88–97, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10013
The signaling adapter protein PINCH is up‐regulated in the stroma of common cancers, notably at invasive edges
Authors: Wang‐Rodriguez Jessica , Dreilinger Anna D. , Alsharabi Ghazwan M. , Rearden Ann
Published: October 2002

BACKGROUND

PINCH is an LIM (double zinc finger domain) protein that functions as an adapter at a key convergence point for integrin and growth factor signal transduction. Because no information is available regarding its expression in vivo in human tissues, this study evaluated the distribution and abundance of PINCH in patients with breast, prostate, lung, colon, and skin carcinomas.

METHODS

A polyclonal antibody was raised to a purified 6‐histidine PINCH fusion protein and used to evaluate 74 cases comprising 33 breast carcinomas (21 ductal carcinomas, 6 lobular carcinomas, 4 ductal carcinomas in situ, 2 lobular carcinomas in situ), 22 prostate carcinomas, 5 colon carcinomas, 6 lung carcinomas (3 adenocarcinomas and 3 squamous carcinomas), and 8 skin carcinomas (4 basal cell carcinomas and 4 squamous cell carcinomas) by immunoperoxidase histochemistry of formalin‐fixed, paraffin‐embedded tissues. Lysates of frozen tissue from the epithelium of two normal breasts and six breast carcinomas were evaluated by immunoblotting.

RESULTS

Immunostaining for PINCH was increased in the cytoplasm of fibroblastoid cells in areas of the tumor‐associated stroma in all carcinomatous tissues evaluated. The most intense stromal immunostaining for PINCH was noted at invasive edges, particularly in breast carcinomatous tissue. Immunoblotting of lysates from normal breast and breast carcinomatous tissue confirmed that PINCH protein expression was markedly increased in breast carcinomatous tissues.

CONCLUSIONS

PINCH is up‐regulated in tumor‐associated stromal cells, particularly at invasive edges, and may be a marker for stroma manifesting the ability to facilitate invasion. Because of this and because PINCH functions as a “molecular switch” in signal transduction, PINCH may be a new target for drug discovery aimed at the tumor‐associated stroma. Cancer 2002;95:1387–95. © 2002 American Cancer Society.

DOI 10.1002/cncr.10878
Developmental cell death in vivo: Rescue of neurons independently of changes at target tissues
Authors: Bunker Gillian L. , Nishi Rae
Published: October 2002

Programmed cell death is a prominent feature of neural development that is regulated by a variety of cell–cell interactions. We used the avian ciliary ganglion to dissect the relative contributions of target tissues vs. ganglionic inputs in regulating cell death. The two populations of the ciliary ganglion innervate different targets: choroid neurons innervate vasculature, whereas ciliary neurons innervate the iris and ciliary body. By counting after labeling all neurons with Islet‐1 and choroid neurons with anti‐somatostatin, we determined that α‐bungarotoxin (α‐btx) at 12.5 μg/day rescued only ciliary neurons, whereas 75 μg/day rescued both ciliary and choroid neurons. It is unlikely that α‐btx acted by blocking nerve transmission at both targets because the choroid vasculature lacked transcripts for α‐btx binding molecules. In addition, no inherent trophic activity could be ascribed to α‐btx, and survival could not be attributed to differences in total trophic activity of eyes from saline vs. α‐btx–treated embryos. In contrast, the α7 antagonist α‐methyllycaconitine (MLA) rescued ciliary neurons at 2.6 μg/day, whereas 26 μg/day rescued choroid neurons. Nerve terminals of ciliary neurons rescued with α‐btx were significantly larger; however, differences in nerve terminal size or branching of axons were not observed in ciliary neurons rescued with MLA or choroid neurons rescued by either MLA or α‐btx. Our results suggest that neuronal survival can be promoted independently of changes at the target tissues when orthograde signals acting by means of neuronal α7 nicotinic receptors are blocked. J. Comp. Neurol. 452:80–92, 2002. © 2002 Wiley‐Liss, Inc.
The use of negative penalty functions in constrained variational problems
Authors: Ilanko Sinniah
Published: October 2002

A major drawback of the penalty function method in solving constrained variational problems is the difficulty in choosing suitable penalty parameters that are large enough to effect a constraint but small enough to avoid computational problems. This problem stems from the fact that the appropriate penalty value is normally found by a trial and error process by gradually increasing the parameter until the results converge numerically. In this paper, it is shown that the constrained solution for the deflection of a beam is bounded by results from mathematical models using positive and negative penalty parameters. If this is true in general, any error due to the use of penalty functions in solving a variational problem may be determined and controlled by using positive and negative values for the penalty parameter. Copyright © 2002 John Wiley & Sons, Ltd.
Organizational emergence in networked collaboration
Authors: Hameri Ari‐Pekka , Puittinen Mikael , Syrjälahti Mikko
Published: October 2002

Research on complex adaptive systems has generated several conceptual parables to explain systems with emergent behaviour. One prominent use for terms such as self‐organization, evolutionary trajectories, co‐evolution and punctuated equilibrium has been in understanding human organizations. In such systems, emergent behaviour is demonstrated in novel structures, processes and spin‐offs that cannot be explained just by studying single components of the organization and the intelligence embedded in them. Instead of solely exploiting the qualitative explanatory power of the evolutionary concepts, this paper focuses also on quantitative methods to track emergent behaviour in a globally distributed, constantly fluctuating and highly networked project organization. The underlying case is that of CERN (CERN, the European Laboratory for Particle Physics, has its headquarters in Geneva. At present, its Member States are Austria, Belgium, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Netherlands, Norway, Poland, Portugal, the Slovak Republic, Spain, Sweden, Switzerland and the United Kingdom. Israel, the Russian Federation, Turkey, Yugoslavia (status suspended after the UN embargo, June 1992), the European Commission and UNESCO have observer status.) and its decade long accelerator project, which strongly relies on electronic communication and networking to achieve its major objectives due to be accomplished by the year 2006. By using time series and self‐organizing maps to analyse the global interaction among project groups and individuals the paper provides new insight to the understanding of emergent behaviour in human organizations. The key result of the study concerns the rigid deep structure of each case organization that seems to remain intact for the duration of the whole project. Copyright © 2002 John Wiley & Sons, Ltd.
Prospects for therapeutic vaccination with glatiramer acetate for neurodegenerative diseases such as Alzheimer's disease
Authors: Schwartz Michal , Kipnis Jonathan
Published: October 2002

Neurodegenerative diseases, whatever their primary causes, are characterized by certain common features, one of which is their self‐perpetuating nature. The ongoing progression of the disorder is due to the effects of destructive self‐compounds, whose presence in the tissues is an outcome of the early phase of the disease and which gradually destroy remaining functional neurons. Studies in our laboratory have led to the recent formulation of a novel concept of protective autoimmunity as the body's mechanism of defense against these destructive self‐compounds. This autoimmune response to central nervous system (CNS) insults is mediated by T‐cells and presumably operates by activating and regulating local microglia and infiltrating macrophages (inflammatory response) to carry out their function of clearing destructive material from the tissue at risk. We suggest that a well‐controlled autoimmunity counteracts and overcomes the destructive effects of the potentially harmful self‐compounds, at the cost of some loss of tissue. An additional risk to the individual is the induction of an autoimmune disease, which is likely to occur if the autoimmune response is malfunctioning. An optimal balance of the various factors will lead to an outcome of maximal benefit at minimal cost to the tissue. A procedure for safely boosting the autoimmune response, by vaccination with a weak self‐crossreactive antigen such as glatiramer acetate (also known as Cop‐1) was found to protect rats from glutamate toxicity, a major mediator of the spread of damage and a well‐known causative factor in neurodegenerative disorders. Cop‐1, when administered according to a different regimen, is an FDA‐approved drug for the treatment of multiple sclerosis. Different formulations of the same drug can therefore be used to treat two extreme manifestations of chronic degenerative diseases of the CNS. Drug Dev. Res. 56:143–149, 2002. © 2002 Wiley‐Liss, Inc.
Beta‐sheet breaker strategy for the treatment of Alzheimer's disease
Authors: Adessi Céline , Soto Claudio
Published: October 2002

Alzheimer's disease is a degenerative disorder of the brain for which there is no cure or effective treatment. Recent studies suggest that cerebral amyloid plaques play a central role in the pathogenesis of the disease. An attractive therapeutic strategy for Alzheimer's disease is to block the early steps of misfolding and aggregation of the soluble amyloid‐beta peptide. We have engineered synthetic β‐sheet breaker peptides to bind amyloid‐β peptide, stabilize the normal conformation, and destabilize the β‐sheet rich structure that leads to the formation of amyloid plaques. Results in vitro, in cell culture, and in vivo suggest that β‐sheet breaker peptide may be useful for blocking the process of cerebral amyloid deposition. Chemical modifications were introduced into the active peptides to improve their pharmacological properties. It remains to be proved that inhibition of the pathway leading to amyloid plaque deposition could be beneficial for the therapeutic treatment of Alzheimer's disease. Drug Dev. Res. 56:184–193, 2002. © 2002 Wiley‐Liss, Inc.
A model of equilibrium bed topography for meander bends with erodible banks
Authors: Darby Stephen E. , Delbono Ivana
Published: October 2002

Channel curvature produces secondary currents and a transverse sloping channel bed, along which the depth increases towards the outer bank. As a result deep pools tend to form adjacent to the outer bank, promoting bank collapse. The interaction of sediment grains with the primary and secondary flow and the transverse sloping bed also causes meanders to move different grain sizes in different proportions and directions, resulting in a consistent sorting pattern. Several models have been developed to describe this process, but they all have the potential to over‐predict pool depth because they cannot account for the influence of erodible banks. In reality, bank collapse might lead to the development of a wider, shallower cross‐section and any resulting flow depth discrepancy can bias associated predictions of flow, sediment transport, and grain‐size sorting. While bed topography, sediment transport and grain sorting in bends will partly be controlled by the sedimentary characteristics of the bank materials, the magnitude of this effect has not previously been explored. This paper reports the development of a model of flow, sediment transport, grain‐size sorting, and bed topography for river bends with erodible banks. The model is tested via intercomparison of predicted and observed bed topography in one low‐energy (5·3 W m−2 specific stream power) and one high‐energy (43·4 W m−2) study reach, namely the River South Esk in Scotland and Goodwin Creek in Mississippi, respectively. Model predictions of bed topography are found to be satisfactory, at least close to the apices of bends. Finally, the model is used in sensitivity analyses that provide insight into the influence of bank erodibility on equilibrium meander morphology and associated patterns of grain‐size sorting. The sensitivity of meander response to bank cohesion is found to increase as a function of the available stream power within the two study bends. Copyright © 2002 John Wiley & Sons, Ltd.
Temporal patterns of suspended sediment yield following moderate to extreme hydrological events recorded in varved lacustrine sediments
Authors: Lamoureux Scott
Published: October 2002

A 487‐year annually laminated (varved) sediment record from Nicolay Lake, Cornwall Island, in the Canadian High Arctic was evaluated to determine the impact that years with high sediment yields had on sediment yields in subsequent years. All of the 40 largest years showed evidence for increased sediment yield in the subsequent 10–30 years. The positive anomalies in lagging years were approximately scaled according to the size of the initiating year, although many intermediate years (25‐ to 100‐year recurrence) showed weak or variable responses. The smallest events considered (10‐ to 25‐year recurrence) showed a consistent, but low‐amplitude response. Additionally the 10‐year events revealed frequent negative sediment yield anomalies in the preceding decade. This behaviour was interpreted as a frequent sediment activation cycle initiated by the modest year, and leading to sediment yield hysteresis lasting 15–25 years. The largest years (greater than 50‐year recurrence) showed consistently above‐average sediment yields in the preceding decade, in part due to the frequent occurrence of moderate (Q10) years. It is hypothesized that temporary storage of sediment and previous initiation of erosion sites resulted in extraordinary sediment yields during intense summer rainfall events. This study demonstrates the potential use of varved lake sediment records to improve our understanding of long‐term sediment dynamics. These records present an opportunity to further develop and test sediment dynamic and routing models to gain insight into the interaction of time and space in fluvial and sediment delivery processes. Copyright © 2002 John Wiley & Sons, Ltd.
Highly accurate solutions of the bifurcation structure of mixed‐convection heat transfer using spectral method
Authors: Selmi M. , Nandakumar K.
Published: October 2002

This paper is concerned with producing highly accurate solution and bifurcation structure using the pseudo‐spectral method for the two‐dimensional pressure‐driven flow through a horizontal duct of a square cross‐section that is heated by a uniform flux in the axial direction with a uniform temperature on the periphery. Two approaches are presented. In one approach, the streamwise vorticity, streamwise momentum and energy equations are solved for the stream function, axial velocity, and temperature. In the second approach, the streamwise vorticity and a combination of the energy and momentum equations are solved for stream function and temperature only. While the second approach solves less number of equations than the first approach, a grid sensitivity analysis has shown no distinct advantage of one method over the other. The overall solution structure composed of two symmetric and four asymmetric branches in the range of Grashof number (Gr) of 0–2 × 106 for a Prandtl number (Pr) of 0.73 has been computed using the first approach. The computed structure is comparable to that found by Nandakumar and Weinitschke (1991) using a finite difference scheme for Grashof numbers in the range of 0–1×106. The stability properties of some solution branches; however, are different. In particular, the two‐cell structure of the isolated symmetric branch that has been found to be unstable by the study of Nandakumar and Weinitschke is found to be stable by the current study. Copyright © 2002 John Wiley & Sons, Ltd.
Numerical study of flows of complex fluids between eccentric cylinders using transformation functions
Authors: Radu Grecov Dana , Clermont Jean‐Robert
Published: October 2002

In this paper, we investigate fluid flows between eccentric cylinders by means of two stream‐tube analyses. The first method considers a one‐to‐one global transformation function that allows the physical domain to be transformed into a mapped domain, used as computational domain, that involves concentric streamlines. The second approach uses local transformations and domain decomposition techniques to deal with mixed flow regimes. Both formulations are particularly adapted for handling time‐dependent constitutive equations, since particle‐tracking problems are avoided. Mass conservation is verified in both formulations and the relevant numerical procedure can be carried out using simple meshes built on the mapped streamlines. Fluids obeying anelastic and viscoelastic constitutive equations are considered in the calculations. The numerical results are consistent with those in the literature for the flow rates tested. Application of the method to the K‐BKZ memory‐integral constitutive equation highlights significant differences between the model predictions and those provided by more simple rheological models. Copyright © 2002 John Wiley & Sons, Ltd.
Homocysteine in neuropsychiatric disorders of the elderly
Authors: Reutens Sharon , Sachdev Perminder
Published: October 2002

Objective

There is increasing interest in homocysteine as a risk factor for neuropsychiatric disorders such as stroke, dementia, depression and Parkinson's disease. This article reviews the current literature on the relationship between homocysteine and these disorders to ascertain if any clinical recommendations can be made.

Method

A MEDLINE and EMBASE search was made for English language publications between 1966 and 2002 using the search terms ‘Homocysteine’ and ‘Stroke’, ‘Dementia’, ‘Vascular Dementia’, ‘Alzheimer's dementia’, ‘Cognition disorders or cognitive decline or memory disorders’, ‘Depression or depressive disorders’ or ‘Parkinson's disease’. In addition, individual articles were hand searched for relevant references.

Results

Cross‐sectional studies consistently suggest that elevated homocysteine increases the risk of stroke, and may also increase the risk of leukoariosis, vascular dementia (VaD), cognitive impairment and Alzheimer's disease (AD). Longitudinal studies of homocysteine as a risk factor are few and inconsistently supportive of these associations. No intervention trials to determine the effect of lowering homocysteine levels have yet been published. The pathological mechanisms for homocysteine‐mediated disease await complete elucidation. Mild hyperhomocysteinemia is common in the elderly population, and folate supplementation can decrease homocysteine levels.

Conclusion

The epidemiological evidence for homocysteine as a risk factor for neuropsychiatric disease is an emerging area of great interest. Screening the population for hyperhomocysteinemia cannot be recommended at this stage, but individuals at increased risk of cerebrovascular disease or cognitive impairment should be investigated and treated for elevated homocysteine levels. Copyright © 2002 John Wiley & Sons, Ltd.
Changing assumptions about who can learn
Authors: Campbell, George
Published: October 2002

When students at any level fail to learn, we don't ask, “What are we doing wrong?” or “Should we attempt a different pedagogical approach or a different motivational strategy?” We simply deduce that they are not smart enough.
Understanding and optimizing multisource feedback
Authors: Atwater Leanne E. , Waldman David A. , Brett Joan F.
Published: October 2002

This article integrates the most recent research results on the topic of multisource feedback with what
researchers have learned over the years about performance feedback in general. We believe that this review and set
of recommendations represent the state of the art at this time. We provide practitioners with new ideas about how
to continue to improve the multisource feedback process in their organizations. We also suggest ideas for feedback
providers and facilitators about how to maximize the success of the feedback process. Additionally, we provide
“food for thought” for researchers concerning ideas for future research. © 2002 Wiley
Periodicals, Inc.
In the trenches at the talent wars: competitive interaction for scarce human resources
Authors: Gardner Timothy M.
Published: October 2002

A number of indicators suggest that the social norms that once deterred labor market competitors from hiring or
“poaching” each others' employees are breaking down. This study explores the competitive
interaction that results when one firm attempts to hire employees from a competing firm (known as “talent
raiding”). Results suggest that attributes of the raiding firm, the targeted firm, and targeted human
capital will affect how a targeted firm responds to a talent raid. The study suggests a number of tactics raiding
firms can use to avoid retaliation and suggests tactics targeted firms can use to repel would‐be talent
raiders. © 2002 Wiley Periodicals, Inc.
Anti‐epidermal growth factor receptor‐antibody therapy for treatment of breast cancer
Authors: Solbach Christine , Roller Marc , Ahr Andre , Loibl Sibylle , Nicoletti Maria , Stegmueller Manfred , Kreysch Hans‐Georg , Knecht Rainald , Kaufmann Manfred
Published: October 2002

Recent studies demonstrated that tumors overexpressing the epidermal growth factor receptor (EGF‐R, erbB‐1) are associated with poor clinical outcome. This led to the development of a variety of monoclonal antibodies targeting the extracellular domain of this receptor tyrosine kinase. The aim of our study was the evaluation of anti‐EGF‐R antibody EMD 55900 therapy for treatment of breast cancer. On the basis of 299 tumor specimens derived from breast cancer patients, we investigated EGF‐R expression and generated a collective of primary xenotransplants in athymic nude mice. The animals received therapy in 2 treatment schedules to investigate the therapeutic response in early stages of tumor formation as well as on well established tumors. Using 6 different tumors with EGF‐R expression levels between 10–300 fmol/mg total protein, we found a therapeutic effect when the EGF‐R expression of the tumors was at least 40 fMol/mg. On the basis of these experimental data and our EGF‐R expression analysis of breast cancer specimens, we conclude that up to 15% of breast cancer patients could benefit from this monotherapy with EMD 55900. © 2002 Wiley‐Liss, Inc.
Biostability of electrically conductive polyester fabrics: An in vitro study
Authors: Jiang Xiaoping , Tessier Dominic , Dao Lê H. , Zhang Ze
Published: October 2002

The biostability of a series of polypyrrole (PPy)‐coated polyester fabrics was investigated in an in vitro model. PPy‐coated sample fabrics were incubated in saline at 37°C for 1 and 2 weeks. After each period of incubation, the surface electrical resistivity of the sample fabrics was measured to monitor the changes caused by the incubation. Redoping was then performed by immersing the sample fabrics in a 1N HCl solution at room temperature for 30 min, which was followed by another measurement of the surface resistivity. The surface morphology of the sample fabrics was observed by scanning electron microscopy. The surface chemical composition of the fabrics and the oxidation of nitrogen in PPy were measured with X‐ray photoelectron spectroscopy. The surface electrical resistivity of the PPy‐coated fabrics was found to increase with the progress of incubation, which was mainly caused by dedoping and uptake of oxygen. This increase was nonlinear and accelerated with time. The surface resistivity of most of the samples was retained in the range of 103–104 Ω/square after 1 week of incubation, which was considered suitable for short‐term electrical stimulation applications. Physical deterioration represented by the cracking and delamination of the PPy coating was occasionally observed on the sample fabrics showing the most significant increase of resistivity. Further improvement of the stability of conductivity is highly desirable. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 507–513, 2002
Virological and immunological effects of salvage therapy following treatment interruption and a shift in HIV‐1 resistance genotype
Authors: Izopet Jacques , Souyris Corinne , Sandres‐Sauné Karine , Puissant Bénédicte , Obadia Martine , Pasquier Christophe , Puel Jacqueline , Blancher Antoine , Massip Patrice
Published: October 2002

The circulating human immunodeficiency virus type 1 (HIV‐1) population of patients in whom many prior therapy regimens have failed often undergo a shift from a drug‐resistant virus to a wild‐type virus following interruption of treatment. This study analyses the virological and immunological effects of salvage therapy following treatment interruption and a shift from a drug‐resistance genotype. Twenty‐one HIV‐1 infected patients who had genotype reversion by population‐based sequencing after 3 months of treatment interruption were given a new salvage regimen consisting of 3–5 drugs selected according to their treatment history. Seven (33%) of 21 patients who had fewer than 200 HIV‐1 RNA copies/ml until month 12 were defined as virological responders. Four patients were transient responders and 10 were nonresponders. The virological responders were more frequently CDC group A and had higher CD4 + T lymphocyte counts at the time of treatment resumption. The peripheral blood T CD4 + and T CD8 + lymphocyte populations of the patients declined significantly during treatment interruption. Only virological responders showed significant increases in their CD4 + T lymphocyte count 12 months after treatment resumption and these counts rapidly returned to pre‐interruption baseline values in most of these patients. Treatment interruption could be useful for optimising salvage therapy for patients previously given many failing regimens. However, controlled trials are needed to assess the clinical benefit of this strategy. J. Med. Virol. 68:305–310, 2002. © 2002 Wiley‐Liss, Inc.