bluuebunny/crossref_metadata_2025 huggingface dataset:
Tyrosine kinase inhibitors: From rational design to clinical trials
Authors: Traxler Peter , Bold Guido , Buchdunger Elisabeth , Caravatti Giorgio , Furet Pascal , Manley Paul , O'Reilly Terence , Wood Jeanette , Zimmermann Juerg
Published: August 2002

Protein kinases play a crucial role in signal transduction as well as in cellular proliferation, differentiation, and various regulatory mechanisms. The inhibition of growth related kinases, especially tyrosine kinases, might provide new therapies for diseases such as cancer. The progress made in the crystallization of protein kinases has confirmed that the ATP‐binding domain of tyrosine kinases is an attractive target for drug design. Three successful examples of drug design at Novartis using a tyrosine kinase as a molecular target are described. PKI166, a pyrrolo[2,3,‐d]pyrimidine derivative, is a dual inhibitor of both the EGFR and the ErbB2 kinases. The compound entered clinical trials in 1999, based on its favorable preclinical profile: potent inhibition of EGF‐mediated signalling in cells, in vivo antitumor activity in several EGFR overexpressing xenograft tumor models in nude mice, long‐lasting inhibition of EGF‐stimulated EGFR autophosphorylation in tumor tissue, good oral bioavailability in animals, and no prohibitive in vitro and in vivo toxicity findings. The anilino‐phthalazine derivative PTK787/ZK222584 (Phase I, co‐developed by Schering AG, Berlin) is a potent and selective inhibitor of both the KDR and Flt‐1 kinases with interesting anti‐angiogenic and pharmacokinetic properties (orally bioavailable). STI571 (Glivec™, Gleevec™), a phenylamino‐pyrimidine derivative, is a potent inhibitor of the Abl tyrosine kinase, which is present in 95% of patients with chronic myelogenous leukemia (CML). The compound specifically inhibits proliferation of v‐Abl and Bcr‐Abl expressing cells (including cells from CML patients) and shows anti‐tumor activity as a single agent in animal models at well‐tolerated doses. Pharmacologically relevant concentrations are achieved in the plasma of animals (oral administration). Promising data from phase I and II clinical trials in CML patients (98% haematological response rate in Phase I) support the fact that the STI571 represents a new treatment modality for CML. In addition, potent inhibition of the PDGFR and c‐Kit tyrosine kinases also indicates its possible clinical use in solid tumors. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 6, 499–512, 2001
Nasal columella reconstruction with a composite free flap from the root of auricular helix
Authors: Ozek Cuneyt , Gundogan Hakan , Bilkay Ufuk , Alper Mehmet , Cagdas Arman
Published: August 2002

Defects of the nasal columella result in significant cosmetic and functional deformities. Over the years, a variety of methods for nasal columella reconstruction have been described in the literature, as have the technical difficulties of reconstructing this subtle structure. Here, a successful reconstruction of a 3.0 × 2.0 cm‐wide nasal columella defect, with a chondrocutaneous microsurgical free flap from the root of the auricular helix, is presented. © 2002 Wiley‐Liss, Inc. MICROSURGERY 22:53–56 2002
Thermoelasticity with second sound—exponential stability in linear and non‐linear 1‐d
Authors: Racke Reinhard
Published: August 2002

We consider linear and non‐linear thermoelastic systems in one space dimension where thermal disturbances are modelled propagating as wave‐like pulses travelling at finite speed. This removal of the physical paradox of infinite propagation speed in the classical theory of thermoelasticity within Fourier's law is achieved using Cattaneo's law for heat conduction. For different boundary conditions, in particular for those arising in pulsed laser heating of solids, the exponential stability of the now purely, but slightly damped, hyperbolic linear system is proved. A comparison with classical hyperbolic–parabolic thermoelasticity is given. For Dirichlet type boundary conditions—rigidly clamped, constant temperature—the global existence of small, smooth solutions and the exponential stability are proved for a non‐linear system. Copyright © 2002 John Wiley & Sons, Ltd.
A new model to analyze the effects of noise in a real oscillator
Authors: Centurelli Francesco , Ercolani Alessandro , Tommasino Pasquale , Trifiletti Alessandro
Published: August 2002

A model to perform time‐domain simulations of noisy oscillators by means of linear time‐variant systems is presented. The proposed model has been implemented in an ODE simulation software, and the obtained power spectral density has been compared to the one obtained with the SpectreRF™ circuit simulator, denoting an error lower than 2 dB. © 2002 John Wiley & Sons, Inc. Microwave Opt Technol Lett 32: 305–307, 2002.
Resonance behavior of single U‐slot microstrip patch antenna
Authors: Bhalla R. , Shafai L.
Published: August 2002

Approximate equations for the operating frequencies of a single U‐slot microstrip patch antenna are presented based on the surface‐current distribution analysis on a microstrip patch. They are accurate within 5%. © 2002 John Wiley & Sons, Inc. Microwave Opt Technol Lett 32: 333–335, 2002.
The SiNxpassivation thickness effect on AlGaAs/InGaAs/GaAs pHEMT performance
Authors: Hongqin Li , Xiaowei Sun , Guanqun Xia
Published: August 2002

The silicon nitride passivation thickness has been investigated extensively for AlGaAs/InGaAs/GaAs pHEMT characteristics in this paper. The experimental results show that the cutoff frequency will drop as the passivation thickness increases for a pHEMT. The electronic performance of the pHEMT was affected severely when SiNxthickness was larger than 2000 Å. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 29: 81–84, 2001.
Design of ultra‐wideband multilayer slant linear polarizer using a genetic algorithm
Authors: Purushottam Y. , Prasad R. V. Hara , Misra V. C.
Published: August 2002

In this letter, for the first time, a genetic algorithm is applied successfully for the design and optimization of a multilayer slant linear polarizer to cover a bandwidth of 1:18. In the algorithm, the fitness function is selected based on the return‐loss requirement. A minimum of 10 dB return loss in the specified bandwidth was achieved. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 30: 119–122, 2001.
Using equivalent currents to analyze antennas in complex environments
Authors: Las‐Heras F.
Published: August 2002

An efficient approach to analyze antennas in conducting environments is presented. It is based on the replacement of the antenna by sets of equivalent magnetic currents that become the sources of the impressed field over the conducting environment. The equivalent currents are calculated from the known near‐field pattern of the single antenna. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 31: 62–65, 2001.
Performance and efficiency of planar rectennas for short‐range wireless power transfer at 2.45 GHz
Authors: Heikkinen Jouko , Kivikoski Markku
Published: August 2002

The performance and efficiency of three planar rectennas, designed on three different PCB materials, have been evaluated at 2.45 GHz. A maximum RF‐to‐dc conversion circuit efficiency of 55% was achieved. An output dc voltage of 1 V was measured over a distance of 1 m from a rectenna having 7 dB antenna gain. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 31: 86–91, 2001.
Microstrip‐line‐fed printed shorted ring‐slot antennas for circular polarization
Authors: Chen Wen‐Shan , Huang Chien‐Chin , Wong Kin‐Lu
Published: August 2002

Designs of circularly polarized printed shorted annual and square ring‐slot antennas are proposed. Circular polarization (CP) radiation of the shorted ring‐slot antennas is achieved by selecting a proper length of the shorted section in the ring slot, which is about 3.9 and 8% of the mean circumference of annular and square ring slots, respectively, and feeding the ring slot using a microstrip line 90° to the shorted section. Prototypes of the proposed designs have been implemented. Experimental results show that good CP radiation performances are observed, and the 3 dB axial‐ratio CP bandwidths obtained for the annular and square ring‐slot antennas can reach about 8.4 and 8.1%, respectively. Details of the proposed CP designs and obtained experimental results are presented and discussed. © 2001 John Wiley & Sons, Inc. Microwave Opt Technol Lett 31: 137–140, 2001.
Pharmacokinetics of acyclovir in immunocompromized children with leukopenia and mucositis after chemotherapy: Can intravenous acyclovir be substituted by oral valacyclovir?
Authors: Eksborg Staffan , Pal Niklas , Kalin Mats , Palm Carina , Söderhäll Stefan
Published: August 2002

Background

The efficacy of oral acyclovir, a purine nucleoside analogue with activity against human herpes viruses, is limited as a result of its low bioavailability. Valacyclovir, the L‐valyl ester of acyclovir, has been developed as a pro‐drug to improve the bioavailability. The aim of the present study was to compare the pharmacokinetics of acyclovir after intravenous administration and after oral administration of vala cyclovir.

Procedure

The pharmacokinetics of acyclovir were studied in 18 children aged 1.4–18.1 years (median: 6.9 years; 9 females) after intravenous infusion (1 hr; median dose: 10.5 mg/kg). In 10 of the children the pharmacokinetics of acyclovir were also studied after oral administration of valacyclovir (median dose: 34.1 mg/kg). Quantification of acyclovir in serum was performed by reversed‐phase liquid chromatography with fluorometric detection. The pharmacokinetic analysis was performed by pharmacokinetic modelling.

Results

The serum concentration versus time curves of acyclovir were described by the two compartment model after intravenous administration and by the one compartment model with a zero‐ or first‐order absorption phase after oral administration of valacyclovir. The bioavailability of acyclovir after oral administration of valacyclovir was 45% (median value; 95% CI: 37–55%).

Conclusion

It is possible to substitute intravenous acyclovir therapy by oral valacyclovir therapy in children with leukopenia and mucositis after chemotherapy. This finding can at present not be fully implemented in clinical practice, since a commercial pharmaceutical formulation of valacyclovir aimed for children not able to swallow intact tablets is lacking. Crushed valacyclovir tablets have a very unpleasant taste, but can be administered to children through nasogastric tubes. Med. Pediatr. Oncol. 2002;38:240–246. © 2002 Wiley‐Liss, Inc.
Revised structures of Arillatanosides A–C from Polygala arillata
Authors: Teng Rongwei , Wu Zhijun , He Yineng , Wang Dezu , Yang Chongren
Published: August 2002

Arillatanosides A–C are three triterpenoid saponins from Polygala arillata Buch–Ham that have been reported previously, but with partially incorrect structures. Further investigation of their NMR data led to the conclusion that the terminal α‐L‐arabinopyranosyl unit originally proposed for Arillatanosides A–C (I–III) is actually a β‐D‐xylopyranosyl unit. Thus, the correct structures of Arillatanosides A–C are represented by 1–3. Complete NMR assignments of Arillatanosides A–C (1–3) and the related polygalasaponin XXXV (4) were achieved using modern 2D NMR techniques, such as DQF H–H COSY, HMQC, HMBC, TOCSY, 2D HMQC–TOCSY. Copyright © 2002 John Wiley & Sons, Ltd.
Coordination equilibrium in an Ln(III) macrocyclic chelate modulated by a reversible interaction with a weakly donor substituent
Authors: Dunand Frank A. , Aime Silvio , Geninatti Crich Simonetta , Giovenzana Giovanni B. , Merbach André E.
Published: August 2002

The introduction of a squaric acid moiety at the secondary nitrogen center of DO3A [DO3A = 1,4,7‐tris(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane] yields the DO3ASQ ligand endowed with a potential octadenticity towards Ln(III) ions. On the basis of 17O NMR investigations on [Gd(DO3ASQ)(H2O)], 13C NMR observations on [Lu(DO3ASQ)(H2O)] and UV spectra of [Eu(DO3ASQ)(H2O)], it is suggested that [Ln(DO3ASQ)(H2O)] complexes are present in solution as a mixture of two isomers differing in the coordination number of the Ln(III) ion, being 8 and 9, respectively. Only in the latter isomer is the squaric moiety coordinated to the Ln(III) ion. Interestingly, the two isomers display different exchange rates of the coordinated water molecule. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling one‐ and two‐dimensional solid‐state NMR spectra
Authors: Massiot Dominique , Fayon Franck , Capron Mickael , King Ian , Le Calvé Stéphanie , Alonso Bruno , Durand Jean‐Olivier , Bujoli Bruno , Gan Zhehong , Hoatson Gina
Published: August 2002

With the description of more and more complex one‐ and two‐dimensional NMR experiments comes the need to develop methods to make a comprehensive interpretation of the various different experiments that can be carried out on the same sample or series of related samples. We present some examples of modelling one‐ and two‐dimensional solid‐state NMR spectra of I = ½ spin and quadrupolar nuclei, using laboratory‐developed software that is made available to the NMR community. Copyright © 2001 John Wiley & Sons, Ltd.
Progesterone induces activation in Octopus vulgaris spermatozoa
Authors: Tosti Elisabetta , Di Cosmo Anna , Cuomo Annunziata , Di Cristo Carlo , Gragnaniello Giovanni
Published: August 2002

The purpose of the present study was to determine whether Octopus vulgaris spermatozoa are activated by progesterone stimulation. Spermatozoa were collected from the spermatophores in the Needham's sac of the male (MS) and from the spermathecae of oviducal glands of the female (FS). We used transmission (TEM) and scanning (SEM) electron microscopy to study the morphology of untreated, Ca2+ ionophore A23187 and progesterone‐treated MS spermatozoa, and untreated FS spermatozoa. We showed that ionophore and progesterone stimulation of MS spermatozoa induce breakdown of the membranes overlapping the acrosomal region, exposing the spiralized acrosome. These modifications resemble the acrosome reaction observed in other species. FS stored in the spermathecae did not show the membranes covering the acrosomal region present in the MS spermatozoa. When ionophore and progesterone treatments were performed in Ca2+‐free artificial sea water, no changes were observed, suggesting the role of external calcium in modifying membrane morphology. Lectin studies showed a different fluorescence distribution and membrane arrangement of FS‐untreated spermatozoa with respect to the MS, suggesting that spermatozoa transferred in the female genital tract after mating, are stored in a pre‐activated state. The plasma membrane of the untreated MS and FS spermatozoa was labelled with Progesterone‐BSA‐FITC, indicating the presence of plasma membrane progesterone receptor. Taken together these data suggest that progesterone induces an acrosome‐ like reaction in MS spermatozoa similar to that induced by calcium elevation. In addition progesterone may play a role in the pre‐activation of spermatozoa stored in the female tract, further supporting the hypothesized parallelism between cephalopods and vertebrates. Mol. Reprod. Dev. 59:97–105, 2001. © 2001 Wiley‐Liss, Inc.
Identification of the cadherin subtypes present in the human peritoneum and endometriotic lesions: Potential role for P‐cadherin in the development of endometriosis
Authors: Chen George T.C. , Tai Chin‐Tao , Yeh Lian‐Shung , Yang Tung‐Chuan , Tsai Horng‐Der
Published: August 2002

Endometriosis is defined as endometrial tissue outside of the uterine cavity. The pathogenesis of this common disease remains poorly understood. However, the implantation and invasion of the viable cells from retrograde menstruation into the peritoneum is a widely accepted theory. To date, the mechanisms by which cell adhesion molecules mediate the development of human endometriosis remain unclear. Cadherins are a family of cell adhesion molecules that mediate cell–cell adhesion in a homophilic manner. In this study, the cadherins present in the peritoneum and endometriotic lesions were identified by RT‐PCR using degenerate primers. In addition, differences in the levels of the cadherin mRNA transcripts present in eutopic endometrium and endometriotic lesions of the same patients were then compared by semiquantitative RT‐PCR. Multiple cadherins were detected in the peritoneum and endometriotic lesions. Of these, P‐cadherin appears to be the predominant cadherin subtype present in the peritoneum. Similarly, P‐cadherin mRNA levels in endometriotic lesions were significantly greater than those observed in the corresponding eutopic endometrium. The expression of P‐cadherin in both the human peritoneum and endometriotic lesions suggests that this cell adhesion molecule may play a central role in the development of endometriosis by mediating endometrial‐peritoneal cell interactions in a homophilic manner. Mol. Reprod. Dev. 62: 289–294, 2002. © 2002 Wiley‐Liss, Inc.
Effects of cryopreservation of pronuclear‐stage rabbit zygotes on the morphological survival, blastocyst formation, and full‐term development after DNA microinjection
Authors: Hochi S. , Hirabayashi M. , Hirao M. , Kato M. , Kobayashi T. , Kimura K. , Hirasawa K. , Leibo S.P. , Ueda M.
Published: August 2002

The objectives of this study were to examine the freezing sensitivity of pronuclear‐stage rabbit zygotes and to produce transgenic rabbits using the cryopreserved zygotes. Zygotes were cryopreserved either by one of two vitrification protocols or by one of the two conventional freezing protocols. The morphological survival rates of zygotes subjected to two‐step freezing in 1.5 M ethylene glycol and 0.1 M sucrose (74%) or to vitrification in 7.2 M ethylene glycol and 1.0 M sucrose (81%) were higher than those subjected to freezing in 1.5 M DMSO (46%) or to vitrification in a mixture of 2.0 M DMSO, 1.0 M acetamide, and 3.0 M propylene glycol (41%). But the in vitro development into blastocysts of zygotes cryopreserved by vitrification (17%) or to a lesser extent by freezing (52%) was impaired, when compared to that of fresh control zygotes (89%). Next, a fusion gene composed from bovine aS1‐casein promoter and a human GH structural gene (2.8 kb) was microinjected into the pronucleus of rabbit zygotes frozen–thawed in ethylene glycol and sucrose. Then, the presence of exogenous DNA in the genome of newborn offspring was determined by PCR. The post‐injection survival of frozen zygotes (97%) was the same as that of fresh control zygotes (96%). However, of 18 offspring derived from 414 frozen–thawed and DNA‐injected zygotes, no transgenic rabbits were produced. Of 52 offspring derived from 403 DNA‐injected fresh zygotes, 3 transgenic rabbits were found. Here we report the first rabbit offspring resulting from zygotes cryopreserved at the pronuclear‐stage, although the cryopreservation procedure employed must be improved if zygotes are to be used for systematic production of transgenic rabbits. Mol. Reprod. Dev. 60: 227–232, 2001. © 2001 Wiley‐Liss, Inc.
Characterization and potential function of a novel testis‐specific nucleoporin BS‐63
Authors: Cai Ying , Gao Ying , Sheng Qi , Miao Shiying , Cui Xiuyun , Wang Linfang , Zong Shudong , Koide Samuel S.
Published: August 2002

A 1933 bp cDNA fragment, coding a truncated testis‐specific novel nucleoporin, was isolated from a human testis λZAPII cDNA library, designated as BS‐63 and assigned GenBank accession number: U64675. By applying the methods of rapid amplification of cDNA ends (5′ RACE) and PCR, a full‐length BS‐63 cDNA composed of 5475 bp was obtained. BS‐63 cDNA contained an open reading frame consisting of 1765 codons and XFXFG or GLFG repetitive sequence motifs. These repetitive motifs are structural characteristic of nucleoporins. BS‐63 cDNA has high homology with Nup358/Ran BP2. A 1599 bp fragment, corresponding to the C‐terminus of BS‐63 cDNA, was prepared and expressed in E. coli BL21(DE3). The recombinant product was purified by affinity chromatography and SDS–PAGE and polyclonal antibodies raised. In rat testis section, the BS‐63 protein was localized at the sites of nuclear pores in spermatids by immuno‐gold transmission electron microscopy and on the nuclear membrane of Triton X‐treated sperm by colloidal silver immuno‐gold scanning electron microscopy. The recombinant BS‐63 protein can be phosphorylated in vitro with PKC and p34cdc2. A yeast two‐hybrid system was used to screen a mouse testis cDNA library to identify proteins capable of interacting with BS‐63. Using the 1.6 kb cDNA fragment as bait, the following interacting proteins were identified: Ran, transportin (karyopherin beta2), two proteins related to the nucleocytoplasmic transporter and aF10 protein. The latter protein is a putative transcriptor containing a cysteine‐rich N‐terminus, a LAP/PHD finger, a leucine zipper domain and a glutamine‐rich C‐terminus. Also it is highly expressed in murine testis and is located in the cell nucleus and cytoplasm. The interaction of BS‐63 with aF10 (696–1001aa) was validated by surface plasmon resonance and by affinity precipitation combined with Western blot. aF10 (696–1001aa) interacted in vitro with BS‐63 extracted from rat testis germ cells. It is hypothesized that BS‐63 is a testis‐specific nucleoporin and possibly acts as a docking site and a cotransporter of Ran and transportin. The complex performs the task of a carrier system in transporting aF10 into the nucleus of germ cells during spermiogenesis. Mol. Reprod. Dev. 61: 126–134, 2002. © 2002 Wiley‐Liss, Inc.
23Na MRI accurately measures fixed charge density in articular cartilage
Authors: Shapiro Erik M. , Borthakur Arijitt , Gougoutas Alexander , Reddy Ravinder
Published: August 2002

One of the initiating steps of osteoarthritis is the loss of proteoglycan (PG) molecules from the cartilage matrix. One method for assessing cartilage integrity, therefore, is to measure the PG content or fixed charge density (FCD) of cartilage. This report shows the feasibility of calculating FCD by 23Na MRI and introduces MRI protocols for human studies, in vivo. 23Na MRI was used to measure the sodium concentration inside bovine patellar cartilage. The sodium concentration was then converted to FCD (mM) by considering ideal Donnan equilibrium. These FCD measurements were compared to FCD measurements obtained through standard dimethylmethylene blue PG assays. There was a high correlation (slope = 0.89, r2 = 0.81) between the FCD measurements obtained by 23Na MRI and those obtained by the PG assays. These methods were then employed in quantifying the FCD of articular cartilage of human volunteers in vivo. Two imaging protocols were compared: one using a birdcage coil, the other using a transmit/receive surface coil. Both methodologies gave similar results, with the average sodium concentration of normal human patellar cartilage ranging from ∼240 to 260 mM. This corresponds to FCDs of –158 mM to –182 mM. Magn Reson Med 47:284–291, 2002. © 2002 Wiley‐Liss, Inc.
Direct in vivo measurement of human cerebral GABA concentration using MEGA‐editing at 7 Tesla
Authors: Terpstra Melissa , Ugurbil Kamil , Gruetter Rolf
Published: August 2002

Spectral editing of the GABA spin system is hampered by coediting of macromolecule (MM) coherences. To reduce contamination arising from MMs in spectra edited for GABA, the highest field strength currently available for human experimentation (7 Tesla) and MEGA‐based editing were used. Despite judicious choice of experimental parameters, MM contamination was found to arise from field drifts. When the MM contribution was accounted for, [GABA] = 0.75 ± 0.14 μmol/g (mean ± SD, N = 16) relative to 8 μmol/g creatine (Cr), whereas without accounting for the MM signal [GABA*] = 0.88 ± 0.23 μmol/g (mean ± SD, N = 16). Incorporating the direct experimental assessment of MM contamination to the edited GABA signal substantially reduced the variance of the measurement, resulting in concentrations that were in excellent agreement with previous 13C labeling experiments. Magn Reson Med 47:1009–1012, 2002. © 2002 Wiley‐Liss, Inc.
17O relaxation time and NMR sensitivity of cerebral water and their field dependence
Authors: Zhu Xiao‐Hong , Merkle Hellmut , Kwag Jae‐Hwan , Ugurbil Kamil , Chen Wei
Published: August 2002

17O spin relaxation times and sensitivity of detection were measured for natural abundance H217O in the rat brain at 4.7 and 9.4 Tesla. The relaxation times were found to be magnetic field independent (T2 = 3.03 ± 0.08 ms, T = 1.79 ± 0.04 ms, and T1 = 4.47 ± 0.14 ms at 4.7T (N = 5); T2 = 3.03 ± 0.09 ms, T = 1.80 ± 0.06 ms, and T1 = 4.84 ± 0.18 ms at 9.4T (N = 5)), consistent with the concept that the dominant relaxation mechanism is the quadrupolar interaction for this nucleus. The 17O NMR sensitivity was more than fourfold higher at 9.4T than at 4.7T, for both the rat brain and a sodium chloride solution. With this sensitivity gain, it was possible to obtain localized 17O spectra with an excellent signal‐to‐noise ratio (SNR) within 15 s of data acquisition despite the relatively low gyromagnetic ratio of this nucleus. Such a 15‐s 2D 17O‐MRS imaging data set obtained for natural abundance H217O in the rat brain yielded an SNR greater than 40:1 for a ∼16μl voxel. This approach was employed to measure cerebral blood flow using a bolus injection of H217O via one internal carotid artery. These results demonstrate the ability of 17O‐MRS imaging to reliably map the H217O dynamics in the brain tissue, and its potential for determining tissue blood flow and oxygen consumption rate changes in vivo. Magn Reson Med 45:543–549, 2001. © 2001 Wiley‐Liss, Inc.
Coupling of neural activity and BOLD fMRI response: New insights by combination of fMRI and VEP experiments in transition from single events to continuous stimulation
Authors: Janz C. , Heinrich S.P. , Kornmayer J. , Bach M. , Hennig J.
Published: August 2002

Functional magnetic resonance imaging (fMRI) measures the correlation between the fMRI response and stimulus properties. A linear relationship between neural activity and fMRI response is commonly assumed. However, the response to repetitive stimulation cannot be explained by a simple superposition of single‐event responses. This might be due to neural adaptation or the hemodynamic changes underlying the fMRI BOLD response. To assess the influence of adaptation, the BOLD responses and visual evoked potentials (VEPs) to identical stimuli were recorded. To achieve different adaptation levels, 2‐s stimulus epochs alternated with different interstimulus intervals (ISI = 0.0, 0.4, 0.8, 2.0, and 12 s) were presented. Neural adaptation during the checkerboard reversal paradigm used for fMRI measurements is demonstrated. Even if the measured VEP amplitude is used as the weighting function for a linear model, the measured BOLD fMRI signal time‐course is not adequately predicted. Magn Reson Med 46:482–486, 2001. © 2001 Wiley‐Liss, Inc.
Creating a library of generalized Fourier sampling patterns for irregular 2D regions of support
Authors: Nagle S.K. , Levin D.N.
Published: August 2002

Multiple‐region MRI (mrMRI) represents a generalization of the Shannon sampling theorem to permit sparsek‐space sampling whenever the scanned object or its high‐contrast edges are confined to multiple known regions. Use of an optimal mrMRI sampling pattern produces an image with root‐mean‐squared (RMS) noise over the supporting regions equal to the RMS noise in a conventional Fourier image with the same total area of support. Analytical solutions for such sampling patterns have been described previously for all arrangements of two or three (noncollinear) supporting regions. This work describes a robust numerical method for creating a library of optimal and near‐optimal mrMRI sampling patterns for more complicated geometries. The average noise amplification over all sampling patterns in the demonstration library was only 4%, with 30% of the sampling patterns resulting in no noise amplification whatsoever. Magn Reson Med 46:624–627, 2001. © 2001 Wiley‐Liss, Inc.
Unifying linear prior‐information‐driven methods for accelerated image acquisition
Authors: Tsao Jeffrey , Behnia Babak , Webb Andrew G.
Published: August 2002

In the ongoing quest for faster imaging and higher spatial resolution, several methods have been developed to speed up data acquisition by incorporating prior information about the object being imaged. This study shows that many of these methods can be integrated into a single common equation. The unified framework provides a conceptual link that facilitates comparison among these methods to reveal their strengths and weaknesses. By considering the limitations of existing methods, a new member in this class of methods was developed. The broad‐use linear acquisition speed‐up technique (BLAST) uses the estimated amount of change within the FOV as prior information. BLAST has the flexibility of incorporating a variable amount of prior information to avoid the misleading appearance of “phantom features,” which arise from overconstraining the reconstruction. Examples from dynamic imaging and MR thermometry are shown. Magn Reson Med 46:652–660, 2001. © 2001 Wiley‐Liss, Inc.
Mapping the velocity vector onto the spin vector: Two‐dimensional velocity‐selective spin excitation for MR flow imaging†
Authors: Wen Han
Published: August 2002

This article presents a two‐dimensional velocity‐selective spin excitation (2D‐VSP) method that enables quantitative imaging of motion in two directions in a single scan, without the need for image subtraction or combination. It is based on the idea of mapping a 2D velocity vector directly onto the transverse magnetization vector, such that the signal intensity reflects the speed of motion, while the signal phase represents the direction of motion. Experimental demonstration is presented in conjunction with an analysis of the accuracy of this method. VSP methods are often limited by inconsistent static signal suppression under variable shim and RF conditions. By using adiabatic RF pulses in a 2D‐VSP composite that possesses time‐reversal symmetry, consistent background suppression of 30‐fold or higher was demonstrated over experimental conditions of ±200 Hz off‐resonance and 30% RF field variation. Magn Reson Med 46:767–772, 2001. © 2001 Wiley‐Liss, Inc.
Electromyography of sternocleidomastoid muscle in ALS: A prospective study
Authors: Li Jun , Petajan Jack , Smith Gordon , Bromberg Mark
Published: August 2002

Needle electromyography (EMG) of the tongue is difficult to perform because of frequent uncontrollable movement. We chose the sternocleidomastoid (SCM) muscle as a possible alternative for assessing the involvement of the rostral neuraxis in amyotrophic lateral sclerosis (ALS). We prospectively studied 21 ALS patients during our initial diagnostic evaluation. EMG parameters that we recorded included the presence of abnormal spontaneous activity, pattern of motor unit potential recruitment, and configuration of motor unit action potentials. For the six patients with bulbar‐onset ALS, three had abnormalities in the SCM and three had abnormalities in the tongue. In contrast, for the 15 patients with limb‐onset ALS, 9 had abnormalities in the SCM, and only 3 had abnormalities in the tongue. Our results demonstrate the utility of needle EMG of the SCM in the evaluation of ALS. EMG of the SCM carries a similar sensitivity as the tongue in ALS patients with bulbar symptoms, but is more sensitive than the tongue in patients without bulbar symptoms. SCM innervation includes the rostral cervical cord and brainstem, and EMG abnormalities in this muscle support a diffuse involvement, which is unique to ALS. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000–000, 2002
Partial peripheral motor nerve lesions induce changes in the conduction properties of remaining intact motoneurons
Authors: Havton Leif A. , Hotson John R. , Kellerth Jan‐Olof
Published: August 2002

A partial injury or loss of peripheral motor axons is followed by compensatory sprouting of remaining intact motor axons in order to reinnervate muscle. Little is known, however, about the electrophysiologic properties proximally of these intact motoneurons and their axons following injury of neighboring motor axons. We studied the conduction properties of intact cat motor axons and motoneurons proximal to the site of a partial peripheral nerve section. Twelve weeks after the partial transection of the cat medial gastrocnemius motor nerve, there was a significant (7%) reduction in conduction velocity and a 13% prolongation in afterhyperpolarization half–decay time in the remaining intact motoneurons, compared with controls. Partial injury to motor nerves thus induces reactive electrophysiologic changes in the remaining intact motoneurons and their axons, perhaps associated with compensatory sprouting within partially denervated muscle. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 662–666, 2001
Distal sensory nerve conduction of the superficial peroneal nerve: New method and its clinical application
Authors: Oh Shin J. , Demirci Mehmet , Dajani Badr , Melo Aluisio C. , Claussen Gwen C.
Published: August 2002

The superficial peroneal nerve subserves sensation on the entire surface of the dorsum of the foot, except in small areas. All previously reported techniques for evaluating nerve conduction along this nerve tested a proximal portion of the nerve. We report a new method for evaluating sensory nerve conduction of the four branches of the distal superficial peroneal nerve. Two branches to the second and third toes of the medial dorsal cutaneous nerve and two branches to the fourth and fifth toes of the intermediate dorsal cutaneous nerve were studied orthodromically and antidromically in 37 feet of 21 normal volunteers using surface stimulating and recording electrodes and with a distance of 10 cm between the stimulating and recording electrodes. Maximum nerve conduction velocities (NCV) ranged from 41.8 to 46.9 m/s, and mean response amplitude ranged from 6.5 to 7.6 μV with the orthodromic technique. Values for NCV were almost identical when elicited by antidromic and orthodromic techniques, but response amplitudes were higher with the antidromic technique. Mean amplitudes of the distal superficial peroneal nerve were about 50% of the proximal superficial peroneal, and the conduction velocity in the distal superficial peroneal was slower than that in the proximal superficial peroneal nerve, by 8–14 m/s. In seven cases, distal superficial peroneal neuropathy was confirmed with this technique: two with proper digital neuropathy, two with medial dorsal cutaneous neuropathy, and three with intermediate dorsal cutaneous neuropathy. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 689–694, 2001
Quantitative assessment of cutaneous thermal and vibration sensation and thermal pain detection thresholds in healthy children and adolescents
Authors: Meier Petra M. , Berde Charles B. , DiCanzio James , Zurakowski David , Sethna Navil F.
Published: August 2002

Quantitative sensory testing (QST) is a noninvasive, computer‐assisted method for assessing function in peripheral small and large sensory fibers. In order to use QST for clinical neurological assessment in children, it is necessary: (1) to determine whether children can reliably perform these tests and (2) to characterize normal ranges in healthy children. Values of cold sensation, warm sensation, cold pain, heat pain, and vibration sensation detection thresholds were determined in the hand and foot with the method of limits (MLI) and method of levels (MLE) in 101 healthy children aged 6–17 years using a commercially available device. Both MLI and MLE were well‐accepted by children, and there was good reproducibility between two sessions. The MLE takes longer to perform but produces lower thermal detection thresholds than the MLI. In the MLI, vibration and warm sensation showed higher thresholds in the foot than hand, whereas cold pain showed lower thresholds in the foot than hand. Based on these results, QST may be used to document and monitor the clinical course of sensory abnormalities in children with neurological disorders or neuropathic pain. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1339–1345, 2001
An accelerated algorithm for parameter identification in a hierarchical plasticity model accounting for material constraints
Authors: Simoni L. , Schrefler B. A.
Published: August 2002

The parameter identification procedure proposed in this paper is based on the solution of an inverse problem, which relies on the minimization of an error function of least‐squares type. The solution of the ensuing optimization problem, which is a constrained one owing to the presence of physical links between the optimization parameters, is performed by means of a particular technique of the feasible direction type, which is modified and improved when the problem turns to an unconstrained one. The algorithm is particularly efficient in the presence of hierarchical material models. The numerical properties of the proposed procedure are discussed and its behaviour is compared with usual optimization methods when applied to constrained and unconstrained problems. Copyright © 2001 John Wiley & Sons, Ltd.
On integration of a cyclic soil plasticity model
Authors: Manzari Majid T. , Prachathananukit Rung
Published: August 2002

Performance of three classes of explicit and implicit time‐stepping integrators is assessed for a cyclic plasticity constitutive model for sands. The model is representative of an important class of cyclic plasticity models for soils and includes both isotropic and nonlinear kinematic hardening. The implicit algorithm is based on the closest point projection method and the explicit algorithm follows a cutting‐plane integration procedure. A sub‐stepping technique was also implemented. The performance of these algorithms is assessed through a series of numerical simulations ranging from simulations of laboratory tests (such as triaxial and bi‐axial compression, direct shear, and cyclic triaxial tests) to the analysis of a typical boundary value problem of geotechnical earthquake engineering. These simulations show that the closest point projection algorithm remains stable and accurate for relatively large strain increments and for cases where the mean effective stress in a soil element reaches very small values leading to a liquefaction state. It is also shown that while the cutting plane (CP) and sub‐stepping (SS) algorithms provide high efficiency and good accuracy for small to medium size strain increments, their accuracy and efficiency deteriorate faster than the closest point projection method for large strain increments. The CP and SS algorithms also face convergence difficulties in the liquefaction analysis when the soil approaches very small mean effective stresses. Copyright © 2001 John Wiley & Sons, Ltd.
Implicit numerical integration for a kinematic hardening soil plasticity model
Authors: Rouainia M. , Muir Wood D.
Published: August 2002

Soil models based on kinematic hardening together with elements of bounding surface plasticity, provide a means of introducing some memory of recent history and stiffness variation in the predicted response of soils. Such models provide an improvement on simple elasto‐plastic models in describing soil behaviour under non‐monotonic loading. Routine use of such models requires robust numerical integration schemes. Explicit integration of highly non‐linear models requires extremely small steps in order to guarantee convergence. Here, a fully implicit scheme is presented for a simple kinematic hardening extension of the Cam clay soil model. The algorithm is based on the operator split methodology and the implicit Euler backward integration scheme is proposed to integrate the rate form of the constitutive relations. This algorithm maintains a quadratic rate of asymptotic convergence when used with a Newton–Raphson iterative procedure. Various strain‐driven axisymmetric triaxial paths are simulated in order to demonstrate the efficiency and good performance of the proposed algorithm. Copyright © 2001 John Wiley & Sons, Ltd.
Analysis of down times of jib cranes—A stochastic approach
Authors: Dharmadhikari Avinash , Deshmukh S.R.
Published: August 2002

In this paper a case study dealing with the maintenance problem of jib cranes is presented. A jib crane is viewed as a complex system whose performance is observed as a single realization over period of time. After pointing out limitations of existing stochastic models to analyze the observed realization a new family of bivariate stochastic processes is introduced. The data of jib crane is analyzed using new model and cross‐validated using part of the data set. It is noted that the new family of stochastic processes is useful to analyze bivariate data where one of the variables is finitely valued and the other is nonnegative and continuous. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 231–243, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10006
The multiplicative representation for multiple objectives optimization with an application for arms procurement
Authors: Brauers Willem K.
Published: August 2002

Multiple Objectives Optimization is much seen in combination with linear functions and even with linear programming, together with an adding of the objectives by using weights. With distance functions, normalization instead of weights is used. It is also possible that together with an additive direct influence of the objectives on the utility function a mutual utility of the objectives exists under the form of a multiplicative representation. A critical comment is brought on some representations of this kind. A full‐multiplicative form may offer other opportunities, which will be discussed at length in an effort to exclude weights and normalization. This theoretical approach is followed by an application for arms procurement. © 2002 Wiley Periodicals, Inc. Naval Research Logistics 49: 327–340, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/nav.10014
Sequential and systematic sampling plans for the Markov‐dependent production process
Authors: P. Vellaisamy  , Sankar S.
Published: August 2002

Acceptance sampling plans are used to assess the quality of an ongoing production process, in addition to the lot acceptance. In this paper, we consider sampling inspection plans for monitoring the Markov‐dependent production process. We construct sequential plans that satisfy the usual probability requirements at acceptable quality level and rejectable quality level and, in addition, possess the minimum average sample number under semicurtailed inspection. As these plans result in large sample sizes, especially when the serial correlation is high, we suggest new plans called “systematic sampling plans.” The minimum average sample number systematic plans that satisfy the probability requirements are constructed. Our algorithm uses some simple recurrence relations to compute the required acceptance probabilities. The optimal systematic plans require much smaller sample sizes and acceptance numbers, compared to the sequential plans. However, they need larger production runs to make a decision. Tables for choosing appropriate sequential and systematic plans are provided. The problem of selecting the best systematic sampling plan is also addressed. The operating characteristic curves of some of the sequential and the systematic plans are compared, and are observed to be almost identical. © 2001 John Wiley & Sons, Inc. Naval Research Logistics 48: 451–467, 2001
A single‐period inventory placement problem for a serial supply chain
Authors: Chung Chia‐Shin , Flynn James , Stalinski Piotr
Published: August 2002

This article addresses the inventory placement problem in a serial supply chain facing a stochastic demand for a single planning period. All customer demand is served from stage 1, where the product is stored in its final form. If the demand exceeds the supply at stage 1, then stage 1 is resupplied from stocks held at the upstream stages 2 through N, where the product may be stored in finished form or as raw materials or subassemblies. All stocking decisions are made before the demand occurs. The demand is nonnegative and continuous with a known probability distribution, and the purchasing, holding, shipping, processing, and shortage costs are proportional. There are no fixed costs. All unsatisfied demand is lost. The objective is to select the stock quantities that should be placed different stages so as to maximize the expected profit. Under reasonable cost assumptions, this leads to a convex constrained optimization problem. We characterize the properties of the optimal solution and propose an effective algorithm for its computation. For the case of normal demands, the calculations can be done on a spreadsheet. © 2001 John Wiley & Sons, Inc. Naval Research Logistics 48:506–517, 2001
Investigation of the initial dip in fMRI at 7 Tesla
Authors: Yacoub Essa , Shmuel Amir , Pfeuffer Josef , Van De Moortele Pierre‐Francois , Adriany Gregor , Ugurbil Kamil , Hu Xiaoping
Published: August 2002

In agreement with optical imaging studies, previous fMRI studies have reported an initial decrease (i.e. the initial dip) in the BOLD response, which is believed to arise from an increase in oxygen consumption and to be mostly microvascular. To date, experimental studies of the initial dip in humans have been performed at fields up to 4 T, with relatively low spatial resolution. Because the sensitivity to microvascular contribution is increased at high magnetic fields, the present study investigated the initial dip at 7 T. In addition, to reduce the partial volume effect, the study is conducted at a high spatial resolution. The initial dip was detected in all subjects studied and was found to reside mostly in the gray matter. The relative amplitude of the early response was found to be 0.6, higher than that at 4 T (0.3) and 1.5 T (0.11). In addition, based on the assumption that the initial dip is a result of increased oxygen utilization, the fractional change in oxygen utilization was estimated to be 40% of that of the fractional change in cerebral blood flow. These results are in agreement with the notion that the initial dip arises from an increase in oxygen consumption. Copyright © 2001 John Wiley & Sons, Ltd.

Abbreviations used:

CBF

cerebral blood flow

CMRO2

cerebral metabolic rate of oxygen

OVS

outer volume suppression

PVE

partial volume effect
Diffusion‐weighted in vivo localized proton MR spectroscopy of human cerebral ischemia and tumor
Authors: Harada Masafumi , Uno Masaaki , Hong Fang , Hisaoka Sonoka , Nishitani Hiromu , Matsuda Tsuyoshi
Published: August 2002

The apparent diffusion coefficients (ADCs) of water and brain metabolites were determined by proton MR spectroscopy on a clinical MR scanner for healthy volunteers and for pathological changes in cases of acute cerebral infarction and brain tumor. The ADCs of N‐acetyl aspartate (NAA) and creatines in tissue involved in acute infarction were decreased compared to normal control values, while in tumors they showed increased values. Since NAA is a neuronal marker, these findings suggest that neuronal cell viscosity changes according to the pathological status of the tissue. The lactate ADC was significantly larger than the values for other major metabolites in cases of ischemia and tumor, suggesting that lactate is present in a different compartment. These results indicate that metabolite diffusion data can be used to reveal changes in the intracellular environment depending on the pathological status. Copyright © 2002 John Wiley & Sons, Ltd.