bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic tools for quantitation by mass spectrometry
Authors: Lill Jennie
Published: June 2003

I.
Introduction
182

 II.
Relative Quantitation
184

A.  2‐D Gel Electrophoresis
184

B.  Metabolic Isotopic Labeling
185

    1.  15N
185

    2.  13C Enrichment and Depletion
185

    3.  Select Isotopic Amino Acid Incorporation
186

C.  Chemical Labeling
186

    1.  Labeling During Proteolysis: 18O Incorporation During Enzymatic Cleavage
186

    2.  Isotopic Tags—Isotope‐Codes Affinity Tag Reagents (ICAT)
187

    3.  Isotopic Tags—Acid‐Labile Isotope‐Coded Extractants (ALICE)
188

    4.  Lysine‐Specific Labeling
189

    5.  Phosphoserine‐ and Phosphothreonine‐Specific Labeling
189

    6.  N‐Terminus Labeling
189

        a.  Nicotinyl‐N‐hyxroxysuccinimide
189

        b.  Acylation
189

        c.  Amidination‐quantitation using enhanced signal tags (QUEST)
190

        d.  C‐terminusu labeling
190

D.  Differential Mass Mapping
190

III.
Absolute Quantitation
191

 IV.
Choice of Instrumentation
191

  V.
Overview, Discussion, and Future Directions
191

References

192

Techniques for the quantitation of proteins and peptides by mass spectrometry (MS) are reviewed. A range of labeling processes is discussed, including metabolic, enzymatic, and chemical labeling, and techniques that can be employed for comparative and absolute quantitation are presented. Advantages and drawbacks of the techniques are discussed, and suggestions for the appropriate uses of the methodologies are explained. Overall, the metabolic incorporation of isotopic labels provides the most accurate labeling strategy, and is most useful when an internal standard for comparative quantitation is needed. However, that technique is limited to research that uses cultured cells. © 2003 Wiley Periodicals, Inc., Mass Spec Rev 22:182–194, 2003; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/mas.10048
Quantitative high‐throughput analysis of drugs in biological matrices by mass spectrometry
Authors: Hopfgartner Gérard , Bourgogne Emmanuel
Published: June 2003

I.
Introduction
195

 II.
Automated Sample Preparation
197

A.  Sample Collection
197

B.  Sample Pooling
197

C.  Off‐Line Sample Preparation
199

D.  On‐Line Sample Preparation
200

    1.  Drirect Plasma Injection
201

     a.  Turbulent flow and large‐particle high‐flow separation
202

     b.  Restricted‐access media columns
203

    2.  Sample Pre‐Treatment
203

III.
Sample Analysis
203

A.  Separation Techniques
203

B.  Serial Approaches
204

    1.  Fast Chromatography
204

    2.  Monolithic HPLC Columns
204

    3.  Packed Column Supercritical Fluid Chromatography
205

C.  Parallel Approaches
205

 IV.
Detection
207

A.  Mass Analyzer
207

B.  Matrix Suppression
208

C.  Metabolite Interferences
209

  V.
Future Perspectives and Conclusions
209

Acknowledgments

210

References

210

To support pharmacokinetic and drug metabolism studies, LC–MS/MS plays more and more an essential role for the quantitation of drugs and their metabolites in biological matrices. With the new challenges encountered in drug discovery and drug development, new strategies are put in place to achieve high‐throughput analysis, using serial and parallel approaches. To speed‐up method development and validation, generic approaches with the direct injection of biological fluids is highly desirable. Column‐switching, using various packing materials for the extraction columns, is widely applied. Improvement of mass spectrometers performance, and in particular triple quadrupoles, also strongly influences sample preparation strategies, which remain a key element in the bioanalytical process. © 2003 Wiley Periodicals, Inc., Mass Spec Rev 22:195–214, 2003; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/mas.10050
The causes of mergers: tests based on the gains to acquiring firms' shareholders and the size of premia
Authors: Mueller Dennis C. , Sirower Mark L.
Published: June 2003

Despite the large number of event studies of mergers that have been undertaken, considerable disagreement still exists over whether mergers increase the value of the merging firms, and if so why. Most event studies measure the average returns to the acquired and acquiring companies' shareholders separately, and based on these averages conclude either that mergers increase wealth, or that they reduce it. From this the authors go on to claim support either for a hypothesis about how mergers increase efficiency, or for one that claims they do not. This paper develops a methodology that uses the distribution of gains and losses across the two samples of firms, and their relationship to one another to test four hypotheses about why mergers occur: (1) the market‐for‐corporate‐control hypothesis, (2) the synergy hypothesis, (3) the managerial discretion hypothesis, and (4) the hubris hypothesis. The hypotheses are tested with data for 168 mergers between large companies from 1978 through 1990. Considerable support is found for the managerial discretion and hubris hypotheses, and some support is found for the market‐for‐corporate‐control hypothesis. Little or no support is found for the hypothesis that mergers create synergies and that shareholders of both the acquiring and acquired firms share gains from these synergies. Copyright © 2003 John Wiley & Sons, Ltd.
The profitability‐risk tradeoff of just‐in‐time manufacturing technologies
Authors: Callen Jeffrey L. , Morel Mindy , Fader Chris
Published: June 2003

Qualitative survey studies and a recent quantitative study by Callen et al. (2000) indicate that JIT manufacturing is more profitable than conventional non‐JIT manufacturing. This study tests the hypothesis that the excess profitability of JIT manufacturing just compensates for the additional operational risks of JIT technology relative to conventional manufacturing. An often‐suggested alternative hypothesis is that JIT manufacturing dominates conventional manufacturing in reducing costs and increasing revenues and that risk is not an issue. The multivariate results unambiguously reject the hypothesis that excess JIT profits are compensation for additional risk. We find that profitability is inversely related to risk, especially for JIT plants. We also find that the JIT plants in our sample are more profitable than non‐JIT plants even after adjusting for risk, consistent with the dominance argument. Copyright © 2003 John Wiley & Sons, Ltd.
Productive efficiency of English football teams—a data envelopment analysis approach
Authors: Haas Dieter J.
Published: June 2003

This paper investigates how close to their potential English Premier League Clubs play. Using a deterministic Data Envelopment Analysis Approach, the productive efficiency of 20 teams in the 2000/2001 season is measured and weaknesses of individual teams are disclosed. The sensitivity of results is analyzed with regard to different model specifications and variable combinations. Copyright © 2003 John Wiley & Sons, Ltd.
An economic analysis of Japanese distribution systems
Authors: Utaka Atsuo
Published: June 2003

We investigate Japanese distribution systems by using a successive monopoly model in which the dealer can increase demand for the commodity. We compare the Tatene system (TS) with the open price system (OPS), and show that in cases where the dealer's power of sales promotion is small (large), the total profits obtained through TS become larger (smaller) than those of the OPS. This result justifies the actual change from TS to OPS from an economic point of view. Copyright © 2003 John Wiley & Sons, Ltd.
Mast cells in the rat brain synthesize gonadotropin‐releasing hormone
Authors: Khalil Mona H. , Silverman Ann‐Judith , Silver Rae
Published: June 2003

Mast cells occur in the brain and their number changes with reproductive status. While it has been suggested that brain mast cells contain the mammalian hypothalamic form of gonadotropin‐releasing hormone (GnRH‐I), it is not known whether mast cells synthesize GnRH‐I de novo. In the present study, mast cells in the rat thalamus were immunoreactive to antisera generated against GnRH‐I and the GnRH‐I associated peptide (GAP); mast cell identity was confirmed by the presence of heparin, a molecule specific to mast cells, or serotonin. To test whether mast cells synthesize GnRH‐I mRNA, in situ hybridization was performed using a GnRH‐I cRNA probe, and the signal was identified as being within mast cells by the binding of avidin to heparin. GnRH‐I mRNA was also found, using RT‐PCR, in mast cells isolated from the peritoneal cavity. Given the function of GnRH‐I in the regulation of reproduction, changes in the population of brain GnRH‐I mast cells were investigated. While housing males with sexually receptive females for 2 h or 5 days resulted in a significant increase in the number of brain mast cells, the proportion of mast cells positive for GnRH‐I was similar to that in males housed with a familiar male. These findings represent the first report showing that mast cells synthesize GnRH‐I and that the mast cell increase seen in a reproductive context is the result of a parallel increase in GnRH‐I positive and non‐GnRH‐I positive mast cells. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 113–124, 2003
Vibration signals from the FT joint can induce phase transitions in both directions in motoneuron pools of the stick insect walking system
Authors: Bässler Ulrich , Sauer Arne E. , Büschges Ansgar
Published: June 2003

The influence of vibratory signals from the femoral chordotonal organ fCO on the activities of muscles and motoneurons in the three main leg joints of the stick insect leg, i.e., the thoraco–coxal (TC) joint, the coxa–trochanteral (CT) joint, and the femur–tibia (FT) joint, was investigated when the animal was in the active behavioral state. Vibration stimuli induced a switch in motor activity (phase transition), for example, in the FT joint motor activity switched from flexor tibiae to extensor tibiae or vice versa. Similarly, fCO vibration induced phase transitions in both directions between the motoneuron pools of the TC joint and the CT joint. There was no correlation between the directions of phase transition in different joints. Vibration stimuli presented during simultaneous fCO elongation terminated the reflex reversal motor pattern in the FT joint prematurely by activating extensor and inactivating flexor tibiae motoneurons. In legs with freely moving tibia, fCO vibration promoted phase transitions in tibial movement. Furthermore, ground vibration promoted stance–swing transitions as long as the leg was not close to its anterior extreme position during stepping. Our results provide evidence that, in the active behavioral state of the stick insect, vibration signals can access the rhythm generating or bistable networks of the three main leg joints and can promote phase transitions in motor activity in both directions. The results substantiate earlier findings on the modular structure of the single‐leg walking pattern generator and indicate a new mechanism of how sensory influence can contribute to the synchronization of phase transitions in adjacent leg joints independent of the walking direction. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 125–138, 2003
Role of calcineurin in activity‐dependent pattern formation in the dorsal lateral geniculate nucleus of the ferret
Authors: Leamey Catherine A. , Ho‐Pao Chrystal L. , Sur Mriganka
Published: June 2003

In the retinogeniculate pathway of the ferret, in addition to the separation of the inputs from the two eyes to form eye‐specific layers, there is also an anatomical segregation of the terminal arbors of on‐center retinal ganglion cells from the terminal arbors of off‐center retinal ganglion cell axons to form on/off sublaminae. Sublamination normally occurs during postnatal weeks 3–4 and requires the activity of retinal afferents, N‐methyl‐D‐aspartate receptors, nitric oxide synthase, and a target of nitric oxide, cyclic guanosine monophosphate. Calcineurin is a calcium/calmodulin dependent serine, threonine protein phosphatase suggested to mediate NMDA‐receptor dependent synaptic plasticity in the hippocampus. We have examined whether calcineurin plays a role during on/off sublamination in the dorsal lateral geniculate nucleus (dLGN) of the ferret. Immunohistochemistry showed that calcineurin expression is transiently up‐regulated in dLGN cells and neuropil during the period of on/off sublamination. A functional role for calcineurin during sublamination was investigated by blocking the enzyme locally via intracranial infusion of FK506. Treatment with FK506 during postnatal weeks 3–4 disrupted the appearance of sublaminae. These results suggest that calcineurin may play a role during this process of activity‐dependent pattern formation in the visual pathway. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 153–162, 2003
Fos‐like immunoreactivity in catecholaminergic brain nuclei after territorial behavior in free‐living song sparrows
Authors: Maney Donna L. , Ball Gregory F.
Published: June 2003

The catecholaminergic cell groups of the brainstem play an important role in the regulation of motivated behavior, including reproductive behavior. In songbirds, these cell groups project to telencephalic nuclei involved in singing and contain steroid hormone receptors, implicating them in the seasonal regulation of song. Whether these nuclei are involved in the activation of song on a short‐term, moment‐to‐moment basis is unknown. In this study, free‐living male song sparrows (Melospiza melodia) were subjected to simulated territorial intrusion (STI), which stimulates territorial singing. The resulting fos‐like immunoreactivity (FLI) was quantified in two HVc‐ and RA‐projecting catecholaminergic regions of the brainstem: the area ventralis of Tsai (AVT) and the midbrain central gray (GCt). Males subjected to STI showed more FLI in both of these regions than control males. In addition, FLI in both nuclei was correlated positively with the number of songs sung in response to STI. The number of flights directed at the intruder was correlated with FLI in AVT but not GCt. These results suggest a role for AVT and GCt, and thus possibly catecholamines, in the regulation of territorial behavior in songbirds. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 163–170, 2003
Selective involvement of the PI3K/PKB/bad pathway in retinal cell death
Authors: Campos Claudia B.L. , Bédard Pierre‐André , Linden Rafael
Published: June 2003

The phosphoinositide‐3‐kinase (PI3K)/protein kinase B (PKB)/Bad signal transduction pathway is engaged in the control of apoptosis in many different cell types, particularly through phosphorylation of the Bcl‐2 family protein Bad. We examined the involvement of this pathway in the control of programmed cell death in the retina of developing rats. PKB is constitutively phosphorylated in retinal tissue in vitro, whereas Bad was dephosphorylated both in Ser112 and Ser136. Cell death induced by either the PI3K inhibitor LY294002, or the general kinase inhibitor 2‐aminopurine, were followed by PKB dephosphorylation, but PKB was not modulated during cell death induced by the protein synthesis inhibitor anisomycin. Treatment of retinal tissue cultures with forskolin, which increases intracellular levels of cAMP, partially blocked apoptosis induced by both anisomycin and 2‐aminopurine, but not by LY294002, whereas forskolin invariably induced phosphorylation of Bad on both Ser112 and Ser136. The data suggest that Bad may be engaged in survival pathways in the immature retina, but pathways other than PI3K/PKB/Bad, and phosphorylation sites other than Ser112 and Ser136 in the Bad protein control cell survival in retinal tissue. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 171–177, 2003
Peripheral coding of bitter taste in Drosophila
Authors: Meunier Nicolas , Marion‐Poll Frédéric , Rospars Jean‐Pierre , Tanimura Teiichi
Published: June 2003

Taste receptors play a crucial role in detecting the presence of bitter compounds such as alkaloids, and help to prevent the ingestion of toxic food. In Drosophila, we show for the first time that several taste sensilla on the prothoracic legs detect bitter compounds both through the activation of specific taste neurons but also through inhibition of taste neurons activated by sugars and water. Each sensillum usually houses a cluster of four taste neurons classified according to their best stimulus (S for sugar, W for Water, L1 and L2 for salts). Using a new statistical approach based on the analysis of interspike intervals, we show that bitter compounds activate the L2 cell. Bitter‐activated L2 cells were excited with a latency of at least 50 ms. Their sensitivity to bitter compounds was different between sensilla, suggesting that specific receptors to bitter compounds are differentially expressed among L2 cells. When presented in mixtures, bitter compounds inhibited the responses of S and W, but not the L1 cell. The inhibition was effective even in sensilla where bitter compounds did not activate the L2 cell, indicating that bitter compounds directly interact with the S and W cells. Interestingly, this inhibition occurred with latencies similar to the excitation of bitter‐activated L2 cells. It suggests that the inhibition in the W and S cells shares similar transduction pathways with the excitation in the L2 cells. Combined with molecular approaches, the results presented here should provide a physiological basis to understand how bitter compounds are detected and discriminated. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 139–152, 2003
Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans
Authors: Tsalik Ephraim L. , Hobert Oliver
Published: June 2003

One approach to understanding behavior is to define the cellular components of neuronal circuits that control behavior. In the nematode Caenorhabditis elegans, neuronal circuits have been delineated based on patterns of synaptic connectivity derived from ultrastructural analysis. Individual cellular components of these anatomically defined circuits have previously been characterized on the sensory and motor neuron levels. In contrast, interneuron function has only been addressed to a limited extent. We describe here several classes of interneurons (AIY, AIZ, and RIB) that modulate locomotory behavior in C. elegans. Using mutant analysis as well as microsurgical mapping techniques, we found that the AIY neuron class serves to tonically modulate reversal frequency of animals in various sensory environments via the repression of the activity of a bistable switch composed of defined command interneurons. Furthermore, we show that the presentation of defined sensory modalities induces specific alterations in reversal behavior and that the AIY interneuron class mediates this alteration in locomotory behavior. We also found that the AIZ and RIB interneuron classes process odorsensory information in parallel to the AIY interneuron class. AIY, AIZ, and RIB are the first interneurons directly implicated in chemosensory signaling. Our neuronal mapping studies provide the framework for further genetic and functional dissections of neuronal circuits in C. elegans. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 178–197, 2003
Kinematic limit analysis modelling by a regularization approach and finite element method
Authors: Chaaba Ali , Bousshine Lahbib , De Saxce Gery
Published: June 2003

Kinematical approach by limit analysis is one of the fundamental methods used to predict the plastic limit state and it is applied successfully to deal with engineering problems in solid mechanics. The kinematical approach consists of minimizing the plastic dissipation power throughout the body, produced by plasticity, which involves functional with norm integrand. Besides, to derive the stress field within the body, one uses the inverse plastic law that is a subdifferential of the dissipation power. The complexity and possible singularity in the derivatives of functionals become a source of many numerical troubles. To overcome these encountered difficulties, we propose a solving algorithm by using a regularization procedure on the basis of the inf‐convolution operation. Some numerical applications by plane strain or axisymmetric finite element method are presented to illustrate the algorithm. Copyright © 2003 John Wiley & Sons, Ltd.
A frontal solver tuned for fully coupled non‐linear hygro‐thermo‐mechanical problems
Authors: Bianco Mauro , Bilardi Gianfranco , Pesavento Francesco , Pucci Geppino , Schrefler Bernhard A.
Published: June 2003

Solving fully coupled non‐linear hygro‐thermo‐mechanical problems relative to the behaviour of concrete at high temperatures using monolithic models is nowadays a very interesting and challenging computational problem. These models require an extensive use of computational resources, such as main memory and computational time, due to the great number of variables and the numerical characteristics of the coefficients of the linear systems involved. In this paper, a number of different variants of a frontal solver used within HITECOSP, an application developed within the BRITE Euram III ‘HITECO’ EU project, to solve multiphase porous media problems, are presented and evaluated with respect to their numerical accuracy and performance. When developing the variants, several optimization techniques have been adopted, such as data structure, cache and branches optimizations. Specifically, numerical accuracy has been evaluated using a modified componentwise backward error analysis. The main result of this work is a new solver which is both much faster and more accurate than the original one. Specifically, the code runs over five times faster and numerical errors are reduced by up to three orders of magnitude. Copyright © 2003 John Wiley & Sons, Ltd.
A Galerkin BEM for transient acoustic scattering by an absorbing obstacle
Authors: Ha‐Duong T. , Ludwig B. , Terrasse I.
Published: June 2003

This paper deals with the numerical resolution of the so‐called time‐domain boundary integral equations. The scattering problem by an absorbing obstacle serves as the model for this discussion. A new system of retarded potential boundary integral equations (RPBIE) is set up to solve the problem. Using an energy identity, we are able to prove the unconditional stability for standard conforming Galerkin approximation of the RPBIE. The actual space–time boundary elements are described in some detail, and their implementation has confirmed that stability in a wide range of situations and for large run times never reached before. Copyright © 2003 John Wiley & Sons, Ltd.
Three‐dimensional theory of elasticity for free vibration analysis of composite laminates via layerwise differential quadrature modelling
Authors: Zhang Jordan Z. , Ng T. Y. , Liew K. M.
Published: June 2003

In this paper, the free vibration analysis of simply‐supported and clamped composite laminates, especially thick laminates, is carried out. The three‐dimensional theory of elasticity is integrated into a layerwise model via differential quadrature discretization. All physical governing equations are satisfied, including the additional constraints of the characteristics of continuity and discontinuity of interfacial transverse and in‐plane strains and stresses along the interfaces of composite laminates. Effects of plate aspect and thickness ratios on the free vibration of these laminates are examined in detail. This study demonstrates the applicability, accuracy, and stability of the present methodology, for vibration analyses of composite structures of thick laminated constitution. Copyright © 2003 John Wiley & Sons, Ltd.
Anisotropic tetrahedral meshing via bubble packing and advancing front
Authors: Yamakawa Soji , Shimada Kenji
Published: June 2003

This paper presents a new computational method for anisotropic tetrahedral meshing. The method can control element anisotropy based on a specified 3×3 tensor field defined over a volumetric domain. Our method creates a tetrahedral mesh in two steps: (1) placing nodes at the centres of tightly packed ellipsoidal cells, called bubbles, in the domain, and (2) connecting the nodes by a modified advancing front followed by local transformation. The method creates a high‐quality anisotropic mesh that conforms well to a specified tensor field. Copyright © 2003 John Wiley & Sons, Ltd.
Topische Glucocorticoidtherapie: Bei Bronchialasthma und entzündlichen Dermatosen
Authors: Schäfer‐Korting Monika , Korting Hans Christian Günter
Published: July 2003

Aufgrund ihrer starken Wirksamkeit und der bei Beachtung der Therapierichtlinien guten Verträglichkeit sind topische Glucocorticoide bis heute zur Langzeitbehandlung des persistierenden Bronchialasthmas und zur Therapie akuter Exazerbationen des atopischen Ekzems sowie des Kontaktekzems unverzichtbar. Weitere Verbesserungen durch innovative Wirkstoffe und Trägersysteme sind zu erwarten.
Pharmazeutische Betreuung bei Langzeitmedikation: Zwischen Cortisonangst und ‐euphorie
Authors: Bertsche Thilo , Schulz Martin
Published: July 2003

Es gibt zahlreiche Anwendungsgebiete für eine therapeutische Intervention mit Glucocorticoiden. Bei vielen dieser Krankheitsbilder ist zwischen einer lokalen und einer systemischen Therapie zu unterscheiden. Trotzdem dürfen diese beiden Therapiearten nicht isoliert voneinander betrachtet werden, sondern müssen mit ihren klinischen Vor‐ und Nachteilen gegeneinander abgewogen werden. Die Kenntnis der Häufigkeit und Ausprägung von Nebenwirkungen, in Abhängigkeit von Applikationsort und ‐art, ist zudem von besonderer Wichtigkeit. Auch die Unterschiede in der Behandlung von Kindern bzw. Erwachsenen sollten dem betreuenden Apotheker bekannt sein. Glucocorticoide können beispielsweise in der Behandlung des Asthma bronchiale maßgeblich die Krankheitsprogression verzögern und sehr wahrscheinlich die Letalität verringern. Durch die Pharmazeutische Betreuung trägt der Apotheker, der die Ängste und Probleme des Patienten durch eine gezielte Beratung ausräumt und damit die Compliance sicherstellt, damit ebenfalls maßgeblich zur Senkung der Morbidität und Mortalität bei. Bei der atopischen Dermatitis sind vor allem die profunden pharmazeutisch‐technologischen Kenntnisse und Erfahrungen des Apothekers gefragt. Mit Hilfe eines Neurodermitis‐Tagebuchs lassen sich gemeinsam mit Patient (Eltern) und Arzt eine optimale Basispflege sowie eine antiinflammatorische und juckreizstillende Therapie sicherstellen.
Glucocorticoide in der Nierentransplantation: Beispiel der soliden Organtransplantation
Authors: Hauser Ingeborg
Published: July 2003

Corticosteroide haben sich in den letzten 40 Jahren als Pharmaka zur Prophylaxe und vor allem Behandlung von Abstoßungsreaktionen bewährt. Je mehr man über deren Wirkmechanismus weiß, desto begründeter erscheint deren Anwendung nach solider Organtransplantation. Unbestritten ist der Einsatz von Corticosteroiden als primäre Abstoßungstherapie, da sie in ca. 50 % der Fälle erfolgreich ist. Zur Diskussion steht zu einer Zeit, in der wir über eine Vielfalt hochwirksamer Immunsuppressiva verfügen, ob Corticosteroide noch ihren Platz in der Initial‐ und Erhaltungstherapie nach Transplantation behaupten können. Der Grund für eine Zurückhaltung gegenüber Steroiden in der Dauertherapie sind sicher ihre vielfältigen Nebenwirkungen, die bleibende Schäden verursachen. Multizentrische prospektive Studien zur steroidfreien Erhaltungstherapie, die eine gleichwertige Effizienz gegenüber den steroidbeinhaltenden Regimen zeigen, stehen allerdings noch aus. Sie müssen sich bei den aktuell hervorragenden Transplantationsergebnissen unter Verwendung der steroidhaltigen Standardregime als ebenbürtig erweisen. Sicher sollte aber individuell für Patienten mit starken Steroidnebenwirkungen ein ebenso wirksames steroidfreies Regime gefunden werden. Eine spannende Frage der zukünftigen Transplantationsforschung bleibt die Rolle der Corticosteroide bei der Spenderkonditionierung und der Toleranzinduktion.
Ein Fett gegen Schmerzen
Authors: Holzgrabe Ulrike
Published: July 2003

Seit Jahrhunderten wissen wir, dass Marihuana gegen Schmerzen eingesetzt werden kann. Die Wirkung beruht auf dem Inhaltsstoff Δ9‐Tetrahydrocannabinol (THC), der an den Cannabinoid‐Rezeptor (CB‐1), einem heterotrimeren G‐Protein‐gekoppelten Rezeptor, bindet.
Zytostatika aus dem Meer
Authors: Holzgrabe Ulrike
Published: July 2003

Bodenbakterien aus der Gruppe der Actinomyceten sind seit langem Lieferanten für hoch wirksame Antibiotika. Dagegen sind Sekundärmetaboliten aus Actinomyceten des marinen Sediments noch eher selten.
SARS bereits besiegt?
Authors: Holzgrabe Ulrike
Published: July 2003

Die WHO meldete bis Ende Mai weltweit über 8000 Fälle des „schweren akuten Respiratorischen Syndroms”︁ SARS, davon der überwiegende Teil in China. Die sich schnell ausbreitende Epidemie hat Virologen aus 13 Laboratorien in 10 Ländern zusammengeführt, um möglichst schnell eine Lösung des Problems herbeizuführen. Eine Science‐Online‐Collection (Mai 2003) fasst die Ergebnisse seit Ausbruch der Krankheit am Beginn dieses Jahres zusammen.
Wie entsteht Bewusstsein?: Einfache Modelle der Selbstwahrnehmung
Authors: Schuster Heinz Georg
Published: June 2003

Was ist die funktionale Basis der Entstehung des Bewusstseins? Warum bringt dieses in der Evolution einen Vorteil? Diese Fragen werden anhand von drei Spielen untersucht, in denen die Spieler mathematisch modelliert sind. Im ersten Spiel lernt ein Spieler, seine Stellung in einer Hierarchie aus der Interaktion mit anderen zu erraten. Im zweiten Spiel macht ein Zuwachs des Gedächtnisses einen Spieler zum Gewinner: Das ermöglicht ihm einen Spiel entscheidenden Überblick über sein eigenes Verhalten und das seines Gegners. Im dritten Spiel müssen die Spieler die Farbe des Hutes auf dem eigenen Kopf aus der Reaktion des Gegners erraten. Hier ist die Fähigkeit von Vorteil, Inhalte aus dem Langzeit‐ und Kurzzeitgedächtnis im Geist abbilden und manipulieren zu können.
Farbige Schattensäume im Wasser: Spielwiese
Authors: Schlichting Hans Joachim
Published: June 2003

Über die Oberfläche eines trüben Gewässers hängende Zweige erzeugen im Wasser Schattensäulen, die von farbigen Rändern umgeben sind. Diese Farbsäume lassen sich durch Streuung des Lichts an Schwebeteilchen im Wasser erklären. Farbsäume um Schatten, die am Grund von klarem Wasser entstehen, gehen auf die Dispersion von Licht an der Grenzschicht von Luft und Wasser zurück.
Kaltes Leuchten erhellt die Vergangenheit: Lumineszenzdatierung
Authors: Wagner Günther A. , Greilich Steffen , Kadereit Annette
Published: June 2003

Die Lumineszenzmethode hat sich seit ihren Anfängen vor 50 Jahren zu einem wichtigen Datierungsverfahren für quarz‐ und feldspathaltige archäologische Fundstücke und quartärgeologische Ablagerungen entwickelt. Dabei werden Erhitzungs‐ oder Belichtungsereignisse datiert, bei denen das natürliche Lumineszenzsignal der Minerale zum letzten Mal gelöscht wurde. Der zeitliche Anwendungsbereich erstreckt sich bis zu Altern von hunderttausend Jahren. Neuere Entwicklungen ‐ insbesondere ortsaufgelöste Lumineszenzmessung im mikroskopischen Maßstab ‐ lassen nicht nur Fortschritte hinsichtlich der Altersgenauigkeit und des Altersbereichs erwarten, sondern eröffnen auch neue Anwendungsmöglichkeiten.
Durchstimmbare Dehnung in Platin
Authors: Weissmüller Jörg , Kramer Dominik , Viswanath Raghavan , Gleiter Herbert
Published: June 2003

Die Eigenschaften der kondensierten Materie sind durch die elektronische Bandstruktur bestimmt. Daher sind sie in Raumladungszonen an Oberflächen abhängig von der Ladungsdichte. Ein Team des Forschungszentrums Karlsruhe machte sich nun diesen Effekt zu Nutze und induzierte in metallischen Nanostrukturen durch eine elektrische Spannung reversible Änderungen der makroskopischen Eigenschaften [1].
Infrarotlicht für die Faseroptik
Authors: Drach Volker
Published: June 2003

Integrierte optoelektronische Komponenten sollen sowohl optische als auch elektronische Funktionen in einem Bauteil und auf der Basis des gleichen Materials ermöglichen. Mit dem technologisch etablierten Halbleitermaterial Galliumarsenid gelang dies kürzlich einer Forschergruppe um Janet Pan von der Yale‐Universität, New Haven, USA, indem sie einen für Faseroptiken geeigneten Infrarot‐Emitter herstellte [1].
Neue Teilchen am SLAC entdeckt
Authors: Ziegler Thomas
Published: June 2003

Die Teilchenphysik machte jüngst wieder von sich reden. Während der Beschleuniger am KEK in Japan neue Luminositätsrekorde brach, fand das Experiment Barbar am SLAC in Kalifornien ein neues subatomares Teilchen [1], das vermutlich aus zwei Quarks besteht. Die erstaunlich lange Lebenszeit und unerwartet geringe Masse können zur Zeit nicht mit konventionellen theoretischen Modellen erklärt werden.
Das Eiskalorimeter
Authors: Heering P.
Published: June 2003

Kalorimetrische Messungen gehören heute zum experimentellen Standardrepertoire im Bereich der Thermodynamik und der physikalischen Chemie. Das erste Gerät für derartige Messungen entwickelten Ende des 18. Jahrhunderts die französischen Wissenschaftler Antoine Laurent Lavoisier und Pierre Simon de Laplace.
Nicht‐triviale Aspekte im Pokerspiel
Authors: Loos Andreas
Published: June 2003

"Schach ist kein Spiel. Schach ist ein wohldefiniertes Problem für Rechner", fand er. Und mit Spielen kannte er sich aus: Sie waren eines seiner wichtigsten Forschungsfelder neben der Quantentheorie und der Meteorologie.
Kann man die Lichtausbreitung sehen?
Authors: Schlichting H.‐Joachim
Published: June 2003

Des Menschen Sinne sind trügerisch. Das wussten schon die Philosophen der Antike, denen physikalische Zusammenhänge noch fremd waren. Doch auch in der heutigen aufgeklärten Zeit ereignen sich noch Dinge, bei denen man seinen Augen nicht traut.
Reconstruction of ice complex remnants on the eastern Siberian arctic shelf
Authors: Gavrilov A. V. , Romanovskii N. N. , Romanovsky V. E. , Hubberten H.‐W. , Tumskoy V. E.
Published: July 2003

Based on the analysis of seafloor topography together with historical, geological and palaeogeographical data obtained from published and archived sources, the position of former Ice Complex (IC) islands has been reconstructed. Within the Laptev Sea shelf and in the western part of the East Siberian Sea shelf, most of these islands have been destroyed by coastal thermal erosion and thermal abrasion during the last thousand years or so. The IC islands were the remnants of the ice‐rich syncryogenic freshwater terrestrial deposits (so called IC), which covered most of the arctic coastal plains and the emerged arctic shelf during the Late Pleistocene. At the present time, sandbanks exist at the places of former IC islands. These sandbanks are the subject of intense seafloor thermal abrasion. The approximate rates of seafloor thermal abrasion and the time of complete disappearance of these islands during the last thousand years have been estimated. The rate is different for different islands and for different time intervals. The most common values are between 0.02 and 0.3 m/year. Schematic maps of the former IC islands within the Laptev Sea and western part of the East Siberian Sea shelves have been compiled. Copyright © 2003 John Wiley & Sons, Ltd.
Lyapunov‐Krasovskii functionals for additional dynamics
Authors: Kharitonov Vladimir L. , Melchor‐Aguilar Daniel
Published: June 2003

A class of Lyapunov–Krasovskii functionals for the additional dynamics introduced by special transformation of time delay systems is given in the paper. Some basic properties of the functionals are also discussed. Copyright © 2003 John Wiley & Sons, Ltd.
An improved stability criterion for systems with distributed delays
Authors: Gu Keqin
Published: June 2003

This article improves the formulation of discretized Lyapunov functional method for systems with distributed delays. The main idea is to apply Jensen's inequality and variable elimination in matrix inequalities. The resulting stability criterion is much simpler. Experience in numerical calculation indicates that it generally converges to the analytical result as grid size decreases, and the speed of convergence is much faster than the previous method. The new formulation is also applicable to a wider class of systems. Copyright © 2003 John Wiley & Sons, Ltd.
Finite‐dimensional characterizations ofH∞control for linear systems with delays in input and output
Authors: Uchida K. , Ikeda K. , Azuma T. , Kojima A.
Published: June 2003

We formulateH∞control problems for linear systems with delays in input and output, and discuss possibility of finite‐dimensional characterizations of solutions. In the case when delay exists in control input and controlled output, first, we derive an output feedbackH∞control formula of the central solution type, which is given by using solutions of finite‐ and infinite‐dimensional Riccati matrix inequalities. Second, we show that, if the controlled output is chosen such that it satisfies the ‘prediction condition’, the solution to the infinite‐dimensional Riccati inequality can be calculated by solving a finite‐dimensional Riccati inequality. We provide a system theoretic interpretation for the prediction condition, and show that, if the prediction condition is satisfied, there is an equivalentH∞control problem for finite‐dimensional linear systems with no delay. Finally, the equivalence result is extended to the case when delay exists also in measurement output. Copyright © 2003 John Wiley & Sons, Ltd.
Adaptive identification of linear time‐delay systems
Authors: Orlov Y. , Belkoura L. , Richard J.P. , Dambrine M.
Published: June 2003

Synthesis of an adaptive parameter identifier is developed for linear dynamic systems with finitely many lumped delays in the state vector and control input. These systems are governed by linear functional differential equations with uncertain time‐invariant parameters and delays. The state of the system is assumed to be available for measurements. Constructive necessary and sufficient conditions for the system parameters and delays to be identifiable are provided. Once the parameter identifiability is guaranteed the simultaneous on‐line identification of the system parameters and delays is achieved by the adaptive identifier proposed. Theoretical results are supported by numerical simulation. Copyright © 2003 John Wiley & Sons, Ltd.
Bilateral teleoperation with communication delays
Authors: Niculescu Silviu‐Iulian , Taoutaou Damia , Lozano Rogelio
Published: June 2003

This paper focuses on the closed‐loop stability analysis of a teleoperation control scheme subject to time‐delays in the communication channel. The stability conditions derived using a frequency‐domain approach areanalyticaland easy to check.Delay‐independentas well as variousdelay‐intervalsstability cases are treated. The novelty of the approach lies in its simplicity for characterizing the stability regions in terms of the systems' parameters. Physical interpretations are included, and a simple example is presented. Copyright © 2003 John Wiley & Sons, Ltd.
Regional stabilization andH∞control of time‐delay systems with saturating actuators
Authors: Fridman E. , Pila A. , Shaked U.
Published: June 2003

A linear parameter varying approach is introduced for the design of a constant state‐feedback controller that locally stabilizes linear systems with state time‐varying delays and saturating actuators and achieves a prescribed performance level for all disturbances with uniformly bounded magnitudes. A polytopic representation is used to describe the saturation behaviour. Delay‐dependent sufficient conditions in terms of linear matrix inequalities (LMIs) are obtained for the existence of such a controller. An estimate is made of the domain of attraction for the disturbance‐free system. The conditions for the stabilizability andH∞performance of the system apply the Lyapunov–Krasovskii functional and the recent descriptor approach to the control of time‐delay systems, whereas the conditions for finding an ellipsoid that bounds the set of the states (in the Euclidean space) that are reachable from the origin in finite time are obtained via the Razumikhin approach. The resulting conditions are expressed in terms of linear matrix inequalities, with some tuning parameters, and they apply a different Lyapunov function to each of the vertex points that stem from the polytopic description of the saturation in the actuators. Copyright © 2003 John Wiley & Sons, Ltd.
Input‐output linearization with delay cancellation for nonlinear delay systems: the problem of the internal stability
Authors: Germani A. , Manes C. , Pepe P.
Published: June 2003

This paper investigates the issue of the internal stability of nonlinear delay systems controlled with a feedback law that performs exact input–output, linearization and delay cancellation. In previous works the authors showed that, unlike with the case of systems without state delays, when the relative degree is equal to the number of state variables and the output is forced to be identically zero, delay systems still possess a non‐trivial internal state dynamics. Not only, in the same conditions delay systems are also characterized by a non‐trivial input dynamics. Obviously, both internal state and input dynamics should give bounded trajectories, otherwise the exact input–output linearization and delay cancellation technique cannot be applied. This paper studies the relationships between the internal state and input dynamics of a controlled nonlinear delay system. An interesting result is that a suitable stability assumption on the internal state dynamics ensures that, when the output is asymptotically driven to zero, both the state and control variables asymptotically decay to zero. Copyright © 2003 John Wiley & Sons, Ltd.
Persistent heterogeneity and sustainable innovation
Authors: Knott Anne Marie
Published: June 2003

One of the concerns with strategy as a field is that its goal (durable profits) appears at odds with that of microeconomics (homogeneous firms with zero profits). Thus even if we can find sources of durable profits, maybe we shouldn't—because doing so comes at the expense of social welfare. In this sense, strategy is an ‘economic bad.’ Probably the most vivid evidence of this tension is the fact that Porter's Competitive Strategy (1982) is Industrial Organization turned on its head—exploiting indications of anti‐competitive behavior to create prescriptions for durable profits. This study presents a parallax view in which the field of strategy is an economic good. In this view, heterogeneity stimulates innovation and economic growth. The underlying logic is that heterogeneity fuels diffusion; diffusion erodes leaders' shares; the loss of shares stimulates innovation, which in turn fuels new diffusion. I develop this view through a simple model of firms embedded in an industry, and then evaluate the model via simulation. The key issue for the model is whether there are steady states that sustain heterogeneity and innovation. Results indicate that heterogeneity persists in roughly half the industry conditions I examined. Furthermore innovation and growth are sustained under those conditions. What is comforting about the set of conditions is that they accommodate (and indeed require) all the things we hold dear: industrial policy, and strategic as well as routine behavior by firms. The new insights are as follows: (1) heterogeneity fuels growth (thus ‘strategy’ is an economic good, rather than anathema to allocative efficiency); (2) persistent heterogeneity is feasible even in the presence of spillovers (without isolating mechanisms); (3) but this heterogeneity (while persistent) requires managers to actively preserve the inherent value of their resource advantages—firms can't rest on their laurels; (4) policy prescriptions differ from those of prior innovation models. Copyright © 2003 John Wiley & Sons, Ltd.
The persistence of founder influence: management, ownership, and performance effects at initial public offering
Authors: Nelson Teresa
Published: June 2003

The purpose of this research is to apply a conceptual framework to questions of how, why, and when founders participate in the firms that they establish and to empirically test for the persistent influence of the founder on the firm after start‐up. A definition of the term ‘founder’ is proposed. Empirical tests compare firms with founder CEOs to those with nonfounder CEOs to determine whether governance and ownership relationships are distinguishable at initial public offering (IPO). In addition, investor reaction to founder‐led firms at IPO is tested. Results suggest that founder influence does persist in governance and ownership arrangements and that the stock market reaction to founder‐led firms is higher than for the comparison group, relative to accounting value. Copyright © 2003 John Wiley & Sons, Ltd.
Measuring organizational knowledge: a conceptual and methodological framework
Authors: Wilcox King Adelaide , Zeithaml Carl P.
Published: June 2003

Knowledge is fundamental to strategic success. Limited progress has been made, however, in measuring organizational knowledge. We employ research on resource‐based theory and organizational epistemology to suggest a perceptual approach to measuring knowledge. We present a research protocol to identify a domain of organizational knowledge resources within industries. Using a sample of organizations from the hospital and textile industries, we interviewed CEOs to identify the feasible set of knowledge resources. We presented this set to managers at those organizations to measure their perceptions of the value‐added of each knowledge resource for their organizations. The results demonstrate that the importance of knowledge resources varies by industry and organization, and calls to question efforts to generate an inventory of generic knowledge resources that is applicable across industries. Copyright © 2003 John Wiley & Sons, Ltd.
Diversification in context: a cross‐national and cross‐temporal extension
Authors: Mayer Michael , Whittington Richard
Published: June 2003

This research note examines the stability of diversification performance relationships in three countries (France, Germany and the United Kingdom), for two time periods (1982–84 and 1992–94). The aggregate findings, taking the three countries and two time periods together, support a general model favoring related‐constrained diversification. However, disaggregated analyses show sharp variations in different countries and time periods. The note concludes that although broad performance relationships can be found, these can be expressed very differently in particular contexts. We consider implications for further research. Copyright © 2003 John Wiley & Sons, Ltd.
Chief executive scanning emphases, environmental dynamism, and manufacturing firm performance
Authors: Garg Vinay K. , Walters Bruce A. , Priem Richard L.
Published: June 2003

Chief executives must allocate their scarce time for scanning efforts among relevant domains of their firms' external environment and their firms' internal circumstances. We argue that high‐performing CEOs vary their relative scanning emphases on different domains according to the level of dynamism they perceive in their external environments. The concepts of dominant logic and sector importance were used to develop predictions about which external domains and which internal domains should receive relatively more or less scanning emphasis in external environments that, overall, are more dynamic or more stable. A field survey of 105 single‐business manufacturing firms evaluated CEOs' scanning emphases and firm performance. Results indicated that, for dynamic external environments, relatively more CEO attention to the task sectors of the external environment and to innovation‐related internal functions was associated with high performance. In stable external environments, however, simultaneously increased scanning of the general sectors in the external environment and efficiency‐related internal functions produced higher performance. These relationships were strongest between relative scanning emphases among domains and sales growth. We discuss the implications of these results for researchers and practitioners. Copyright © 2003 John Wiley & Sons, Ltd.