bluuebunny/crossref_metadata_2025 huggingface dataset:
Model reference adaptive iterative learning control for linear systems
Authors: Tayebi A.
Published: August 2006

In this paper, we propose a model reference adaptive control (MRAC) strategy for continuous‐time single‐input single‐output (SISO) linear time‐invariant (LTI) systems with unknown parameters, performing repetitive tasks. This is achieved through the introduction of a discrete‐type parametric adaptation law in the ‘iteration domain’, which is directly obtained from the continuous‐time parametric adaptation law used in standard MRAC schemes. In fact, at the first iteration, we apply a standard MRAC to the system under consideration, while for the subsequent iterations, the parameters are appropriately updated along the iteration‐axis, in order to enhance the tracking performance from iteration to iteration. This approach is referred to as the model reference adaptive iterative learning control (MRAILC). In the case of systems with relative degree one, we obtain a pointwise convergence of the tracking error to zero, over the whole finite time interval, when the number of iterations tends to infinity. In the general case, i.e. systems with arbitrary relative degree, we show that the tracking error converges to a prescribed small domain around zero, over the whole finite time interval, when the number of iterations tends to infinity. It is worth noting that this approach allows: (1) to extend existing MRAC schemes, in a straightforward manner, to repetitive systems; (2) to avoid the use of the output time derivatives, which are generally required in traditional iterative learning control (ILC) strategies dealing with systems with high relative degree; (3) to handle systems with multiple tracking objectives (i.e. the desired trajectory can be iteration‐varying). Finally, simulation results are carried out to support the theoretical development. Copyright © 2006 John Wiley & Sons, Ltd.
Dynamical adaptive synchronization
Authors: Efimov D. V.
Published: August 2006

The notions of dynamical synchronization and adaptive dynamical synchronization problems are introduced. The algorithm solving adaptive synchronization problem for a subclass of Lurie systems with exciting input is proposed. The performance and potentialities of proposed solutions are demonstrated by two examples related to formation control and self‐organization of swarm systems. Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis, Characterization, and Application of Mesoporous Silica Functionalized with Alkyl‐Hydroperoxides
Authors: Sasidharan M. , Kiyozumi Y. , Mal N. K. , Mizukami F.
Published: August 2006

A variety of alkyl hydroperoxides such as tert‐butyl‐, tert‐octyl‐, 1‐cyclopentyl‐, 1‐cyclohexyl‐, 3,4‐disubstituted‐1‐cyclohexyl‐, n‐propyl, and n‐undecyl‐hydroperoxides have been functionalized onto ordered mesoporous silica, SBA‐15, from the corresponding covalently anchored synthons. All the tert‐hydroperoxides are prepared by autoxidation using molecular O2 and an initiator, whereas other hydroperoxides are obtained by reaction with H2O2. For autoxidation, the use of a combination of an azoinitiator (AIBN) and N‐hydroxyphthalimide increased the hydroperoxide yield compared with using the azoinitiator alone. Synthons containing two or more tert‐ and sec‐hydrogens lead to higher peroxide yield compared to synthons with a single reactive site. Oxidation of Si–OH (silanol groups) with acidic H2O2 at low temperature produces Si–OOH. Reusability of these alkyl hydroperoxides is carried out by oxidation of alcohols obtained from the corresponding alkyl hydroperoxides using H2O2. Both the covalently anchored synthons and the resulting hydroperoxides are thoroughly characterized by powder X‐ray diffraction, 13C cross‐polarized magic angle spinning NMR, TG/DTA, Fourier transform IR spectroscopy, sorption, and surface area measurements. The quantification of the amount of alkyl hydroperoxide was carried out by iodometric titration using a thio solution. The hydroperoxides exhibit high activity for the epoxidation of styrene to styrene oxide and exhibit reasonably high efficiency for oxygen transfer.
Mesostructured Silica Chemically Doped with RuII as a Superior Optical Oxygen Sensor
Authors: Lei B. , Li B. , Zhang H. , Lu S. , Zheng Z. , Li W. , Wang Y.
Published: August 2006

Novel oxygen sensors consisting of a [Ru(bpy)2phen]2+ (bpy: 2,2′‐bipyridyl, phen: phenathroline) portion covalently grafted to a mesostructured silica‐based network are prepared in situ via a sol–gel approach with the help of cetyltrimethylammoniumbromide (CTAB) surfactant. 1,10‐Phenanthroline covalently grafted to 3‐(triethoxysilyl)propyl isocyanate is used as not only the sol–gel precursor but also as the second ligand of the Ru(bpy)2Cl2 · 2H2O complex to prepare the sol–gel‐derived mesostructured silicates for an oxygen sensor. For comparison purposes, the oxygen sensors in which [Ru(bpy)2phen]Cl2 is conventionally physically incorporated into the matrix are also prepared. Elemental analysis, NMR, Fourier transform IR, UV‐vis electronic absorption, luminescence‐intensity quenching Stern–Volmer plots, and excited‐state decay analysis are used to characterize the obtained oxygen sensors. These obtained bulk xerogels and spin‐coated thin films show that the homogeneity and the sensitivity of the covalently grafted samples are superior to those of the physically incorporated ones, and the highest sensitivity is obtained in the mesostructured bulk xerogel. This improvement in oxygen sensitivity is attributed to the increased diffusivity of oxygen in the uniform and nearly parallel porous structure of the Mobil Catalytic Material 41 mesostructured matrix, the enhanced homogeneity results from the covalently grafted propyl group in –Si–(CH2)3– that acts as the fundamental spacer which prevents interaction between the attached RuII complex and the silica matrix, and optimal dispersion in the mesopores during the sol–gel polycondensation. Furthermore, the greatly minimized leaching effect of the sensing molecules could be observed in the covalently grafted system. The covalent grafting strategy presented in this paper provides superior optical oxygen sensors with homogeneous distribution, improved sensitivity, and simplified calibration plots.
Highly Fluorinated Comb‐Shaped Copolymers as Proton Exchange Membranes (PEMs): Improving PEM Properties Through Rational Design
Authors: Norsten T. B. , Guiver M. D. , Murphy J. , Astill T. , Navessin T. , Holdcroft S. , Frankamp B. L. , Rotello V. M. , Ding J.
Published: August 2006

A new class of comb‐shaped polymers for use as a proton conducting membrane is presented. The polymer is designed to combine the beneficial physical, chemical, and structural attributes of fluorinated Nafion‐like materials with higher‐temperature, polyaromatic‐based polymer backbones. The comb‐shaped polymer unites a rigid, polyaromatic, hydrophobic backbone with lengthy hydrophilic polymer side chains; this combination affords direct control over the polymer nanostructure within the membrane and results in distinct microphase separation between the opposing domains. The microphase separation serves to compartmentalize water into the hydrophilic polymer side chain domains, resulting in effective membrane water management and excellent proton conductivities.
The First Inert and Photostable Encapsulated Lanthanide(III) Complexes Based on Dendritic 9,10‐Diphenylanthracene Ligands: Synthesis, Strong Near‐Infrared Emission Enhancement, and Photophysical Studies
Authors: Baek N. S. , Kim Y. H. , Roh S.‐G. , Kwak B. K. , Kim H. K.
Published: August 2006

A series of inert and photostable encapsulated lanthanide(III) complexes—based on dendritic anthracene ligands—is shown for the first time to exhibit strong near‐IR emission bands via efficient energy transfer from the excited states of the peripheral antenna to the Ln3+ ions (Er3+, Yb3+, and Nd3+). A significant decrease in the fluorescence of the anthracene ligand is accompanied by a strong increase in the near‐IR emission of the Ln3+ ions. The near‐IR emission intensities of Ln3+ ions in the encapsulated Ln3+–dendrimer complexes are dramatically enhanced on increasing the generation number (n) of dendrons, owing to site‐isolation and light‐harvesting effects. Furthermore, a first attempt is made to distinguish between the site‐isolation and light‐harvesting effects in the present complexes. Photophysical studies indicate the sensitization of Ln3+ luminescence by energy transfer through the excited singlet state of the anthracene ligands, and the energy‐transfer efficiency between the dendritic anthracene ligands and the Ln3+ ion is evaluated to be in the range of 90 to 97 %. Their energy‐transfer efficiency is in good agreement with the result that the biexponential decays contain a radiative decay of anthracene units (< ca. 10 %) and an energy‐transfer component (> ca. 90 %) from the excited state of anthracene ligands to the Ln3+ ions. Time‐resolved luminescence spectra show monoexponential decays with a lifetime of 2 μs for the Er3+ ion 11 μs for the Yb3+ ion and 0.7 μs for the Nd3+ ion in thin films, and calculated intrinsic quantum yields of the Ln3+ ions are in the range of ca. 0.025 to 0.55 %.
Analysis of cake filtration data—A critical assessment of conventional filtration theory
Authors: Teoh Soo‐Khean , Tan R. B. H. , Tien Chi
Published: August 2006

Experimental results of constant‐pressure cake filtration of aqueous suspensions of four kinds of particles: CaCO3, Kaolin, Kromasil and TiO2 is presented. The data reported consist mainly of filtration performance results, that is, the cumulative filtrate volume and cake thickness as functions of time, which were obtained using a newly developed multifunction test cell. Based on these data, the medium resistance and the average cake specific resistance at various operating pressure were evaluated and corroborated with the results obtained from the compression‐permeability (C‐P) cell measurements. The filtration results were also compared with predictions from the solutions of the appropriate volume‐averaged equations of continuity using different pl − ps relationships. Generally speaking, with the appropriate pl − ps relationship, agreement between experiments and prediction was satisfactory. © 2006 American Institute of Chemical Engineers AIChE J, 2006
Variation in cortical bone histology within the human femur and its impact on estimating age at death
Authors: Chan Andrea H.W. , Crowder Christian M. , Rogers Tracy L.
Published: August 2006

Histological methods for the estimation of age at death using cortical bone are based on the evaluation of microstructural changes over time. Since histological analysis is a destructive method, most techniques attempt to limit the amount of cortical bone needed for analysis. Sample location, however, can have a significant effect on the accuracy of these methods. Furthermore, research demonstrates that both intersection and intrasection variation is present at the midshaft of the femur, which is the primary location for estimating age at death in humans. This research determines the extent of regional variation within the adult human femur and its effect on age estimation. Secondary osteon lamellae and Haversian canal ratio and cortical thickness were quantified. Thompson's All Males Left Femur regression equation was used to estimate age. Results show that significant regional variation occurs in the estimated ages derived from the posterior aspect of the femoral shaft and significant intrasection variation occurs in age estimates from the mid and mid‐distal cross‐sections. Thus, the inter and intrasection variation that occurs in bone remodeling within the femoral cortex has the potential to produce significant differences amongst age estimates taken from various femoral diaphyseal locations compared to the age estimated from the standard location used in Thompson's core method (1978). The results indicate that the use of this histological method is dependant on the ability to correctly identify the four anatomical locations, but the extracted core used for age estimation is not necessarily confined to the anterior midshaft. Am J Phys Anthropol, 2006. © 2006 Wiley‐Liss, Inc.
Assessment of coral reefs using herbivory/nutrient assays and indicator groups of benthic primary producers: a critical synthesis, proposed protocols, and critique of management strategies
Authors: Littler Mark M. , Littler Diane S.
Published: August 2006

Rapid assessment protocols for determining and monitoring the status of any given coral reef are provided and include measuring: (a) standing stocks of functional indicator groups, (b) herbivore populations, (c) water‐column nutrient levels, (d) tissue C:N:P ratios, (e) algal physiological‐response assays, and (f) herbivory assays. These measurements can reveal quantitative tipping‐point levels beyond which resilience to undesirable phase shifts begins to become critically reduced. Universal tipping‐point approximations are reviewed for inorganic nutrients, and posited for the first time for herbivory.

The relative roles of top‐down and bottom‐up controls in determining benthic community structure and the health of coral reefs are especially important management concerns. This paper specifically addresses the top‐down effects of herbivory and bottom‐up effects of nutrient enrichment on critical indicator groups, i.e. reef‐building corals, crustose coralline algae, dense turf algae and frondose macroalgae.

A predominance of (a) massive corals and calcareous coralline algae relative to frondose macroalgae and algal turfs indicates a healthy spatially heterogeneous condition reflecting low nutrients and high herbivory. An abundance of (b) frondose macroalgae illustrates the least desirable condition of elevated nutrient levels and reduced herbivory, possibly reflecting pollution in concert with destructive herbivore fishing practices. High coverage of (c) coralline algae suggests healthy high herbivory levels, but problems with elevated nutrients that are inhibitory to some corals. Domination by (d) dense turf algae indicates desirably low nutrient levels, but an inadequate herbivory component.

The fast growth and turnover rates of fleshy algae compared to other reef organisms highlight their value as early warning indicators of reef degradation.

From a management perspective, levels of herbivory and nutrients rank among the most useful quantitative indicators of coral reef resilience; whereas, the degree of degradation and mortality are inferred from the above functional indicator groups of benthic primary producers.

Published in 2006 by John Wiley & Sons, Ltd.
Vancomycin Analogues Containing Monosaccharides Exhibit Improved Antibiotic Activity: A Combined One‐Pot Enzymatic Glycosylation and Chemical Diversification Strategy
Authors: Thayer Desiree A. , Wong Chi‐Huey
Published: August 2006

Many natural products contain carbohydrate moieties that contribute to their biological activity. Manipulation of the carbohydrate domain of natural products through multiple glycosylations to identify new derivatives with novel biological activities has been a difficult and impractical process. We report a practical one‐pot enzymatic approach with regeneration of cosubstrates to synthesize analogues of vancomycin that contain an N‐alkyl glucosamine, which exhibited marked improvement in antibiotic activity against a vancomycin‐resistant strain of Enterococcus.
A Brief Review on Software Developments for Group Sequential and Adaptive Designs
Authors: Wassmer Gernot , Vandemeulebroecke Marc
Published: August 2006

In this paper the currently available software we know for group sequential and adaptive designs is briefly reviewed. Stand‐alone packages as well as modules within software packages or programming languages exist. New software developments for adaptive designs enable the user to perform data dependent design adaptations while controlling the Type I error rate. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An Adaptive Hierarchical Test Procedure for Selecting Safe and Efficient Treatments
Authors: König Franz , Bauer Peter , Brannath Werner
Published: August 2006

We consider the situation where during a multiple treatment (dose) control comparison high doses are truncated because of lack of safety and low doses are truncated because of lack of efficacy, e.g., by decisions of a data safety monitoring committee in multiple interim looks. We investigate the properties of a hierarchical test procedure for the efficacy outcome in the set of doses carried on until the end of the trial, starting with the highest selected dose group to be compared with the placebo at the full level α. Left truncation, i.e., dropping doses in a sequence starting with the lowest dose, does not inflate the type I error rate. It is shown that right truncation does not inflate the type I error if efficacy and toxicity are positively related and dose selection is based on monotone functions of the safety data. A positive relation is given e.g. in the case where the efficacy and toxicity data are normally distributed with a positive pairwise correlation. A positive relation also applies if the probability for an adverse event is increasing with a normally distributed efficacy outcome. The properties of such truncation procedures are investigated by simulations. There is a conflict between achieving a small number of unsafely treated patients and a high power to detect safe and efficient doses. We also investigated a procedure to increase power where a reallocation of the sample size to the truncated treatments and the control remaining at the following stages is performed. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
How Practical are Adaptive Designs Likely to be for Confirmatory Trials?
Authors: Gould A. Lawrence
Published: August 2006

This is a discussion of the following papers appearing in this special issue on adaptive designs: ‘Confirmatory Seamless Phase II/III Clinical trials with Hypotheses Selection at Interim: General Concepts’ by Frank Bretz, Heinz Schmidli, Franz König, Amy Racine and Willi Maurer; and ‘Confirmatory Seamless Phase II/III Clinical Trials with Hypotheses Selection at Interim: Applications and Practical Considerations’ by Heinz Schmidli, Frank Bretz, Amy Racine and Willi Maurer. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Survival Endpoints and Adaptive Designs
Authors: Bauer Peter
Published: August 2006

This is a discussion of the paper ‘Planning and analyzing adaptive group sequential survival trials’ by Gernot Wassmer, appearing in this special issue on adaptive designs. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Confirmatory Seamless Phase II/III Clinical Trials with Hypotheses Selection at Interim: Opportunities and Limitations
Authors: Jennison Christopher , Turnbull Bruce W.
Published: August 2006

This is a discussion of the following two papers in this special issue on adaptive designs: ‘Confirmatory seamless phase II/III clinical trials with hypotheses selection at interim: General concepts’ by Frank Bretz, Heinz Schmidli, Franz König, Amy Racine and Willi Maurer, and ‘Confirmatory seamless phase II/III clinical trials with hypotheses selection at interim: Applications and practical considerations’ by Heinz Schmidli, Frank Bretz, Amy Racine and Willi Maurer. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Adaptive vs. Group Sequential Self‐designing Trials
Authors: Mehrotra Devan V. , Fan Xiaoyin (Frank)
Published: August 2006

This is a discussion of the paper. ‘Repeated Confidence Intervals in Self‐Designing Clinical Trials and Switching between Non‐Inferiority and Superinferiority’ by Joachim Hartung and Guido Knapp, appearing in this special issue on adaptive designs. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Polarized infrared microspectroscopy of single spruce fibers: Hydrogen bonding in wood polymers
Authors: Schmidt Martin , Gierlinger Notburga , Schade Ulrich , Rogge Tilmann , Grunze Michael
Published: August 2006

We studied wood polymers in their native composite structure using mechanically isolated single spruce (Picea abies [L.] Karst.) fibers. Dichroic infrared spectra of fibers placed in a custom‐built microfluidic cuvette were acquired in air, in liquid (heavy) water, and in liquid dimethylacetamide using a novel combination of synchrotron‐based Fourier transform infrared microspectroscopy with polarization modulation. Differences were observed in the O–H stretching frequency region of the spruce spectra upon changing the ambient conditions. Analysis of these spectral variations provides information on hydrogen bonding, orientation, and accessibility of structural units of the wood polymers in the spruce cell walls. Our in situ approach contributes to a further understanding of the structural details of wood polymers in their native setting. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 546–555, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
An exclusion mechanism in ion exchange chromatography
Authors: Harinarayan C. , Mueller J. , Ljunglöf A. , Fahrner R. , Van Alstine J. , van Reis R.
Published: August 2006

Protein dynamic binding capacities on ion exchange resins are typically expected to decrease with increasing conductivity and decreasing protein charge. There are, however, conditions where capacity increases with increasing conductivity and decreasing protein charge. Capacity measurements on two different commercial ion exchange resins with three different monoclonal antibodies at various pH and conductivities exhibited two domains. In the first domain, the capacity unexpectedly increased with increasing conductivity and decreasing protein charge. The second domain exhibited traditional behavior. A mechanism to explain the first domain is postulated; proteins initially bind to the outer pore regions and electrostatically hinder subsequent protein transport. Such a mechanism is supported by protein capacity and confocal microscopy studies whose results suggest how knowledge of the two types of IEX behavior can be leveraged in optimizing resins and processes. © 2006 Wiley Periodicals, Inc.
Poly(lactic‐co‐glycolic acid) hollow fibre membranes for use as a tissue engineering scaffold
Authors: Ellis Marianne J. , Chaudhuri Julian B.
Published: August 2006

Mass transfer limitations of scaffolds are currently hindering the development of 3‐dimensional, clinically viable, tissue engineered constructs. We have developed a poly(lactide‐co‐glycolide) (PLGA) hollow fibre membrane scaffold that will provide support for cell culture, allow psuedovascularisation in vitro and provide channels for angiogenesis in vivo. We produced PDLLGA flat sheet membranes using 1, 4‐dioxane and 1‐methyl‐2‐pyrrolidinone (NMP) as solvents and water as the nonsolvent, and hollow fibre membranes, using NMP and water, by dry/wet‐ and wet‐spinning. The resulting fibres had an outer diameter of 700 μm and an inner diameter of 250 μm with 0.2–1.0 μm pores on the culture surface. It was shown that varying the air gap and temperature when spinning changed the morphology of the fibres. The introduction of a 50 mm air gap caused a dense skin of 5 μm thick to form, compared to a skin of 0.5 μm thick without an air gap. Spinning at 40°C produced fibres with a more open central section in the wall that contained more, larger macrovoids compared to fibres spun at 20°C. Culture of the immortalised osteogenic cell line 560pZIPv.neo (pZIP) was carried out on the PDLLGA flat sheets in static culture and in a PDLLGA hollow fibre bioreactor under counter‐current flow conditions. Attachment and proliferation was statistically similar to tissue culture polystyrene on the flat sheets and was also successful in the hollow fibre bioreactor. The PDLLGA hollow fibres are a promising scaffold to address the size limitations currently seen in tissue engineered constructs. Biotechnol. Bioeng. 2007;96: 177–187. © 2006 Wiley Periodicals, Inc.
Genetic inactivation of the APC gene contributes to the malignant progression of sporadic hepatocellular carcinoma: A case report
Authors: Katoh Hiroto , Shibata Tatsuhiro , Kokubu Akiko , Ojima Hidenori , Kosuge Tomoo , Kanai Yae , Hirohashi Setsuo
Published: August 2006

Although activated Wnt/β‐catenin pathway is considered to be one of the main driving forces of hepatocarcinogenesis, no somatic mutations of the adenomatous polyposis coli (APC) gene have been found in sporadic hepatocellular carcinoma (HCC) to date. Here we present a case of a sporadic nodule‐in‐nodule‐type HCC that provides the first evidence that biallelic genetic inactivation of the APC gene contributed to the development of the tumor. High‐density array‐based comparative genomic hybridization (aCGH) was performed to clarify genome‐wide chromosomal structural alteration profiles of both early and advanced components of this nodule‐in‐nodule HCC. aCGH analysis revealed a chromosomal loss of the APC gene locus only in the inner advanced component of this tumor. Direct sequencing of the remaining allele revealed a nonsense mutation at codon 682 in the Armadillo repeats, resulting in a truncated protein that lacked all of the β‐catenin‐binding motifs. Nonsense mutations at this location are rare among other types of cancer. In conclusion, combined with an immunohistochemical analysis of the β‐catenin protein, this case provides the first evidence that genetic inactivation of the APC gene can play a significant role in the progression of sporadic HCC, probably by activating the Wnt/β‐catenin pathway. © 2006 Wiley‐Liss, Inc.
Comprehensive assessment of DNA copy number alterations in human prostate cancers using Affymetrix 100K SNP mapping array
Authors: Liu Wennuan , Chang Baoli , Sauvageot Jurga , Dimitrov Latchezar , Gielzak Marta , Li Tao , Yan Guifang , Sun Jishan , Sun Jielin , Adams Tamara S. , Turner Aubrey R. , Kim Jin Woo , Meyers Deborah A. , Zheng Siqun Lilly , Isaacs William B. , Xu Jianfeng
Published: August 2006

Although multiple recurrent chromosomal alterations have been identified in prostate cancer cells, the specific genes driving the apparent selection of these changes remain largely unknown. In part, this uncertainty is due to the limited resolution of the techniques used to detect these alterations. In this study, we applied a high‐resolution genome‐wide method, Affymetrix 100K SNP mapping array, to screen for somatic DNA copy number (CN) alterations among 22 pairs of samples from primary prostate cancers and matched nonmalignant tissues. We detected 355 recurrent deletions and 223 recurrent gains, many of which were novel. As expected, the sizes of novel alterations tend to be smaller. Importantly, among tumors with increasing grade, Gleason sum 6, 7, and 8, we found a significant trend of larger number of alterations in the tumors with higher grade. Overall, gains are significantly more likely to occur within genes (74%) than are deletions (49%). However, when we looked at the most frequent CN alterations, defined as those in ≥4 subjects, we observed that both gains (85%) and deletions (57%) occur preferentially within genes. An example of a novel, recurrent alteration observed in this study was a deletion between the ERG and TMPRSS2 genes on chromosome 21, presumably related to the recently identified fusion transcripts from these two genes. Results from this study provide a basis for a systematic and comprehensive cataloging of CN alterations associated with grades of prostate cancer, and the subsequent identification of specific genes that associated with initiation and progression of the disease. This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/1045‐2257/suppmat. © 2006 Wiley‐Liss, Inc.
Microbial induction of CARD15 expression in intestinal epithelial cells via toll‐like receptor 5 triggers an antibacterial response loop
Authors: Begue B. , Dumant C. , Bambou J.C. , Beaulieu J.F. , Chamaillard M. , Hugot J.P. , Goulet O. , Schmitz J. , Philpott D.J. , Cerf‐Bensussan N. , Ruemmele F.M.
Published: August 2006

With the discovery of CARD15 as susceptibility gene for Crohn's disease (CD) a first link to a potential defect in the innate immune system was made. In this work we aimed to analyze enterocyte NOD2/CARD15 expression and regulation in response to bacterial motifs and the consequences of the most common CD‐specific CARD15 mutation on antibacterial responses of normal intestinal epithelial cells (IEC). Under normal conditions, IEC lines and ileal enterocytes did not express NOD2/CARD15 mRNA or protein, contrary to IEC derived from inflammatory CD sections. In vitro analyses revealed that the simple contact with non‐pathogenic commensal E. Coli K12 was sufficient to induced NOD2/CARD15 mRNA and protein in human IEC (HIEC). We identified bacterial flagellin interacting with TLR5 as major motif in this regulation of NOD2/CARD15. E. Coli mutants not expressing flagellin (ΔFliC) failed to induce CARD15. Similarly, in HIEC transfected with a plasmid encoding dominant negative TLR5, no CARD15 induction was observed after K12 contact. Isolated TLR2 or TLR4 stimulation had no or only a marginal effect on NOD2/CARD15 expression. NOD2/CARD15 negative HIEC were unresponsive to muramyl dipeptide (MDP), but once NOD2/CARD15 was induced, HIEC and Caco2 cells responded to intra or extracellular MDP presentation with the activation of the NFkB pathway. IEC transfected with the Crohn‐specific CARD15 mutant (F3020insC, FS) failed to activate NFkB after MDP‐challenge, in contrast to CARD15WT IEC. In response to MDP, IEC induced a massive antibacterial peptide (ABP) response, seen in the apical release of CCL20. This was completely abolished in IEC carrying CARD15FS. These data suggest a critical role of NOD2/CARD15 in the bacterial clearance of the intestinal epithelium while CD‐specific mutated NOD2/CARD15 causes an impaired epithelial barrier. J. Cell. Physiol. 209: 241–252, 2006. © 2006 Wiley‐Liss, Inc.
Transcriptional and proteolytic regulation of the insulin‐like growth factor‐I system of equine articular chondrocytes by recombinant equine interleukin‐1β
Authors: Porter Ryan M. , Akers R. Michael , Howard Rick D. , Forsten‐Williams Kimberly
Published: August 2006

Interleukin‐1 (IL‐1) and insulin‐like growth factor‐I (IGF‐I), which have opposing effects on matrix metabolism within articular cartilage, are thought to play prominent roles in the pathogenesis of osteoarthritis. To better understand the link between these anabolic (IGF‐I) and catabolic (IL‐1) stimuli, we examined exogenous IL‐1 regulation of the IGF‐I signaling system of articular chondrocytes (ACs). Equine ACs from non‐arthritic stifle joints were expanded in monolayer culture, encapsulated for 10 days in alginate beads, and stimulated as high‐density monolayers with recombinant equine IL‐1β (0, 1, 10 ng/ml) for 48 h. IL‐1β enhanced expression of IGF‐IR levels, as determined by both [125I]‐IGF‐I binding studies and Western blotting, while reducing the concentration of endogenous IGF‐I detected in conditioned media by radioimmunoassay. Western ligand blotting revealed that chondrocytes primarily secreted IGF binding proteins (IGFBPs) with molecular weights of 28–30 and 32–34 kDa, which were identified as IGFBPs 5 and 2, respectively, and that IL‐1β treatment diminished IGFBP‐2, the prominent homolog in conditioned media. Northern blot analysis suggested IL‐1β regulation of IGF‐I and, to some extent, IGF‐IR was mediated by transcription; however, the cytokine did not affect IGFBP‐2 expression. To test for evidence of proteolysis by matrix metalloproteinases (MMPs), additional cultures were co‐incubated with inhibitors for MMPs 2/9, 3, and 8. IGFBP‐2 suppression was partially reversed by gelatinase (MMP‐2/9) inhibition. In summary, these findings further delineate the role of IL‐1 as a key regulator of the IGF‐I system within articular cartilage, demonstrating that regulation occurs through both direct (transcriptional) and indirect (proteolytic) mechanisms. J. Cell. Physiol. 209: 542–550, 2006. © 2006 Wiley‐Liss, Inc.
PAK4 and αPIX determine podosome size and number in macrophages through localized actin regulation
Authors: Gringel Alexandra , Walz Daniel , Rosenberger Georg , Minden Audrey , Kutsche Kerstin , Kopp Petra , Linder Stefan
Published: August 2006

Podosomes are actin‐rich adhesion structures typical for monocytic cells and are implicated in migration and invasion. Major modes of podosome regulation include RhoGTPase signaling and actin regulatory pathways. However, it is not clearly understood how these signals induce highly localized changes in podosome formation and dynamics. Here, we show that the RhoGTPase effector PAK4, a member of the p21 associated kinase family, and its regulator αPIX (PAK‐interacting exchange factor), are central to podosome formation in primary human macrophages. Immunofluorescence, biochemical and microarray data indicate that PAK4 acts as physiological regulator of podosomes in this system. Accordingly, transfection of a specific shRNA, as well as expression of PAK4 truncation mutants, resulted in reduced numbers of podosomes per cell. Moreover, expression of kinase active or inactive PAK4 mutants enhanced or reduced the size of individual podosomes, respectively, indicating a modulatory influence of PAK4 kinase activity on podosome size. Similar to the results gained with PAK4, cellular/overexpressed PIX was shown to be closely associated with podosomes. Moreover, both overexpression of αPIX wt and a mutant lacking the SH3 domain led to coalescence of podosomes. In sum, we propose that PAK4 and αPIX can induce highly localized changes in actin dynamics and thereby regulate size and number of podosomes in primary human macrophages. J. Cell. Physiol. 209: 568–579, 2006. © 2006 Wiley‐Liss, Inc.
Proton spectroscopy provides accurate pathology on biopsy and in vivo
Authors: Mountford Carolyn , Lean Cynthia , Malycha Peter , Russell Peter
Published: August 2006

In the last 25 years, MR spectroscopy (MRS) has moved from being a basic research tool into routine clinical use. The spectroscopy method reports on those chemicals that are mobile on the MR time scale. Many of these chemicals reflect specific pathological processes but are complicated by the fact that many chemicals change at one time. There are currently two clinical applications for spectroscopy. The first is in the pathology laboratory, where it can be an adjunct to, and in some cases replacement, for difficult pathologies like Barrett's esophagus and follicular adenoma of the thyroid. The spectroscopy method on a breast biopsy can also report on prognostic indicators, including the potential for spread, from information present in the primary tumor alone. The second application for spectroscopy is in vivo to provide a preoperative diagnosis and this is now achievable for several organs including the prostate. The development of spectroscopy for clinical purposes has relied heavily on the serially‐sectioned histopathology to confirm the high accuracy of the method. The combination of in vivo MRI, in vivo MRS, and ex vivo MRS on biopsy samples offers a modality of very high accuracy for preoperative diagnosis and provision of prognostic information for human cancers. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Artifacts and pitfalls in diffusion MRI
Authors: Le Bihan Denis , Poupon Cyril , Amadon Alexis , Lethimonnier Franck
Published: August 2006

Although over the last 20 years diffusion MRI has become an established technique with a great impact on health care and neurosciences, like any other MRI technique it remains subject to artifacts and pitfalls. In addition to common MRI artifacts, there are specific problems that one may encounter when using MRI scanner gradient hardware for diffusion MRI, especially in terms of eddy currents and sensitivity to motion. In this article we review those artifacts and pitfalls on a qualitative basis, and introduce possible strategies that have been developed to mitigate or overcome them. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc.
Land use/cover change and landscape fragmentation analysis in the Bindura District, Zimbabwe
Authors: Kamusoko C. , Aniya M.
Published: August 2006

Rapid land use/cover change and landscape fragmentation is occurring in many countries in central and southern Africa, as a result of colonial imbalances in land distribution, demographic pressure, agricultural expansion, government policies and environmental factors such as drought. This study analysed the dynamics of land use/cover and land degradation as revealed in landscape fragmentation in the Bindura District of Zimbabwe based on Landsat data for 1973 and 2000. A hybrid supervised/unsupervised classification approach coupled with GIS analyses was employed to generate land use/cover maps from which various class level landscape metrics were calculated using FRAGSTATS®, in order to analyse landscape fragmentation. The results show that agriculture, mixed rangeland, settlements, bareland and water increased, while woodland areas decreased. Consequently, the landscape became more highly fragmented as indicated by an increase in the patch number and a decrease in the mean patch size (MPS) of the woodland and mixed rangeland classes. This suggests that anthropogenic activities driven by agricultural expansion were the main causes of landscape fragmentation, leading to landscape degradation in the study area. Copyright © 2006 John Wiley & Sons, Ltd.
Reorganization of mouse sperm lipid rafts by capacitation
Authors: Thaler Catherine D. , Thomas Monzy , Ramalie Jenniffer R.
Published: August 2006

One of the hallmarks of mammalian sperm capacitation is the loss of cholesterol from the plasma membrane. Cholesterol has been associated with the formation of detergent insoluble membrane microdomains in many cell types, and sperm from several mammalian species have been shown to contain detergent‐resistant membranes (DRMs). The change in cholesterol composition of the sperm plasma membrane during capacitation raises the question of whether the contents of DRMs are altered during this process. In this study, we investigated changes in protein composition of DRMs isolated from uncapacitated or capacitated mouse sperm. TX‐100 insoluble membranes were fractionated by sucrose flotation gradient centrifugation and analyzed by Western and lectin blotting, and capacitation‐related differences in protein composition were identified. Following capacitation, the detergent insoluble fractions moved to lighter positions on the sucrose gradients, reflecting a global change in density or composition. We identified several individual proteins that either became enriched or depleted in DRM fractions following capacitation. These data suggest that the physiological changes in sperm motility, ability to penetrate the zona pellucida (ZP), ZP responsiveness, and other capacitation‐dependent changes, may be due in part to a functional reorganization of plasma membrane microdomains. Mol. Reprod. Dev. 73: 1541–1549, 2006. © 2006 Wiley‐Liss, Inc.
Efficient adenoviral‐mediated gene delivery into porcine mesenchymal stem cells
Authors: Bosch P. , Fouletier‐Dilling C. , Olmsted‐Davis E.A. , Davis A.R. , Stice S.L.
Published: August 2006

Mesenchymal stem cell (MSC) mediated gene therapy research has been conducted predominantly on rodents. Appropriate large animal models may provide additional safety and efficacy information prior to human clinical trials. The objectives of this study were: (a) to optimize adenoviral transduction efficiency of porcine bone marrow MSCs using a commercial polyamine‐based transfection reagent (GeneJammer, Stratagene, La Jolla, CA), and (b) to determine whether transduced MSCs retain the ability to differentiate into mesodermal lineages. Porcine MSCs (pMSCs) were infected under varying conditions, with replication‐defective adenoviral vectors carrying the GFP gene and GFP expression analyzed. Transduced cells were induced to differentiate in vitro into adipogenic, chondrogenic, and osteogenic lineages. We observed a 5.5‐fold increase in the percentage of GFP‐expressing pMSCs when adenovirus type 5 carrying the adenovirus type 35 fiber (Ad5F35eGFP) was used in conjunction with GeneJammer. Transduction of pMSCs at 10.3–13.8 MOI (1,500–2,000 vp/cell) in the presence of Gene Jammer yielded the highest percentage of GFP‐expressing cells (∼90%) without affecting cell viability. A similar positive effect was detected when pMSCs were infected with an Ad5eGFP vector. Presence of fetal bovine serum (FBS) during adenoviral transduction enhanced vector‐encoded transgene expression in both GeneJammer‐treated and control groups. pMSCs transduced with adenovirus vector in the presence of GeneJammer underwent lipogenic, chondrogenic, and osteogenic differentiation. Addition of GeneJammer during adenoviral infection of pMSCs can revert the poor transduction efficiency of pMSCs while retaining their pluripotent differentiation capacity. GeneJammer‐enhanced transduction will facilitate the use of adenoviral vectors in MSC‐mediated gene therapy models and therapies. Mol. Reprod. Dev. 73: 1393–1403, 2006. © 2006 Wiley‐Liss, Inc.
Complex relationship between changes in oxygenation status and changes in R: The case of insulin and NS‐398, two inhibitors of oxygen consumption
Authors: Jordan Bénédicte F. , Crokart Nathalie , Baudelet Christine , Cron Greg. O , Ansiaux Réginald , Gallez Bernard
Published: August 2006

Insulin and NS‐398 have been reported to inhibit oxygen consumption in experimental tumor models, thereby increasing oxygenation and radiosensitization. The aim of this work was to use MRI to study changes in murine FSaII tumor hemodynamics after administration of those oxygen consumption inhibitors. A multiple‐echo gradient‐echo (GRE) MRI sequence (4.7 T) was used to map changes in three factors: the GRE signal (at TE = 20 ms), the parameter S0 (theoretical signal at TE = 0 ms), and the relaxation rate R. Perfusion maps were obtained by dynamic contrast‐enhanced (DCE) MRI. Insulin caused a significant decrease in the tumor blood oxygen level‐dependent (BOLD) signal over time. factor This was likely the result of decreased blood flow, since both S0 and the percentage of perfused tumor decreased as well. Tumor R did not change significantly in response to the treatments, which is surprising considering that other non‐MRI techniques (electron paramagnetic resonance (EPR) oximetry and fiber‐optic probes) have shown that tumor oxygenation increases after treatment. This suggests that metabolic changes associated with vasoactive challenges may have an unpredictable influence on blood saturation and R. In conclusion, this study further emphasizes the fact that changes in BOLD signal and R in tumors do not depend uniquely on changes in oxygenation status. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Do carbamates cause polyneuropathy?
Authors: Lotti Marcello , Moretto Angelo
Published: August 2006

Carbamates are reversible inhibitors of acetylcholinesterase, and some also inhibit neuropathy target esterase (NTE), the target in organophosphate‐induced delayed polyneuropathy. However, based on mechanistic considerations, these carbamates were thought to be unable to initiate polyneuropathy. Consequently, clinical reports of polyneuropathy associated with carbamate exposures have been disregarded. We discuss three cases of polyneuropathy that occurred after severe poisoning by methylcarbamates. In addition, high repeated doses of phenyl N‐methyl N‐benzylcarbamate caused nearly 100% NTE inhibition and polyneuropathy in the hen model. These data suggest the need to reconsider the long‐standing tenet that carbamates cannot cause polyneuropathy. Alternatively, a preexisting subclinical neuropathy in these individuals may have been amplified by carbamates, as observed in animal models. We suggest that individuals with underlying neuropathy (e.g., diabetics) who are poisoned by carbamates should be followed closely. In addition, procedures for the current risk assessment of carbamate pesticides may need to be reconsidered. Muscle Nerve, 2006
Late appearance of dropped head syndrome after radiotherapy for Hodgkin's disease
Authors: Rowin Julie , Cheng Grace , Lewis Steven L. , Meriggioli Matthew N.
Published: August 2006

We present three cases of dropped head syndrome that occurred as a complication of mantle field (i.e., lymph nodes of the neck, axillae, and mediastinum) or whole‐body radiation therapy for Hodgkin's disease. These cases are characterized by a late onset (2–27 years after radiation treatment), fibrosis, and contraction of the anterior cervical muscles, and atrophy of the posterior neck and shoulder girdle. This report adds to the increasing literature about the late neurological complications of radiation therapy and describes a previously unrecognized cause of dropped head syndrome. Muscle Nerve, 2006
Kinesthesia: The role of muscle receptors
Authors: Proske Uwe
Published: August 2006

The kinesthetic sense, the sense of position and movement of our limbs, has been the subject of speculation for more than 400 years. The present‐day view is that it is signaled principally by muscle spindles, with a subsidiary role played by skin and joint receptors. The problem with muscle spindles as position sensors is that they are able to generate impulses in response to muscle length changes as well as from fusimotor activity. The central nervous system must be able to distinguish between activity from the two sources. Recent observations on position sense after fatigue and during load‐bearing suggest that an additional source of kinesthetic information comes from a centrally generated sensation, the sense of effort. This has consequences for kinesthesia in the presence of the force of gravity. A contribution from central feedback mechanisms to the sense of effort is relevant to certain clinical conditions. Muscle Nerve, 2006
The long‐term effects of perinatal glucocorticoid exposure on the host defence system of the respiratory tract
Authors: Theogaraj E , John CD , Dewar A , Buckingham JC , Smith SF
Published: August 2006

Glucocorticoids are used to mature the fetal lung at times of threatened premature delivery. These drugs modify leukocyte profiles when administered in adulthood, but their effects on the mature host defence system following administration during the perinatal period are incompletely understood. In this study, the long‐term effects of perinatal dexamethasone exposure on rodent host defence cells in the pulmonary airspaces, the perivascular compartment of the lung, and the blood were investigated. Rats were treated prenatally (gestational days 16–19) or neonatally (postnatal days 1–7) by inclusion of dexamethasone in the mothers' drinking water (1 µg/ml). The pups were then allowed to develop to adulthood (P60‐80), at which time respiratory tissues were collected for light and electron microscopy and bronchoalveolar lavage (BAL), and blood for cell count and fluorescent activated cell‐sorting (FACS) analysis. Prenatal treatment had no effect on any parameter examined. Following neonatal dexamethasone exposure, light microscopy of the lung tissue revealed a significant reduction in the number of cells in the perivascular space in both the central and the peripheral regions of the adult lung, but no differences in the number of cells in the airspaces. Neonatal dexamethasone exposure was also characterized by a significant reduction in the total number of white cells in the peripheral blood in adulthood and in particular, the number of lymphocytes relative to neutrophils was significantly reduced at maturity in these animals. The results show that neonatal, but not prenatal, dexamethasone exposure significantly alters the distribution of host defence cells in the blood and lung at maturity compared with control animals. The early neonatal period is characterized by the stress hyporesponsive period in the rat, when endogenous glucocorticoid levels are very low. Therefore, exogenous glucocorticoids administered during this time are likely to have marked ‘programming’ effects on glucocorticoid‐sensitive tissues. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.