bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti–interleukin‐6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled study
Authors: Straub Rainer H. , Härle Peter , Yamana Seizo , Matsuda Takemasa , Takasugi Kiyoshi , Kishimoto Tadamitsu , Nishimoto Norihiro
Published: May 2006

Objective

Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly evident in the increase in adrenal androgen levels during anti‐TNF therapy. This study investigated the influence on steroidogenesis of an interleukin‐6 (IL‐6)–neutralizing strategy using IL‐6 receptor monoclonal antibodies (referred to as MRA).

Methods

In a placebo‐controlled, double‐blind, randomized study over 12 weeks in 29 patients with RA being treated with prednisolone, 13 of whom received placebo and 16 of whom received 8 mg MRA/kg body weight, the effects of MRA on serum levels of adrenocorticotropic hormone (ACTH), cortisol, 17‐hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), androstenedione (ASD), estrone, and 17β‐estradiol, as well as their respective molar ratios, were determined.

Results

MRA therapy markedly improved clinical signs of inflammation (the erythrocyte sedimentation rate, swollen joint score, and Disease Activity Score in 28 joints). Serum levels of ACTH and cortisol and the molar ratio of cortisol to ACTH did not change. Although serum levels of DHEA and DHEAS remained stable during therapy, the DHEAS:DHEA molar ratio significantly decreased in treated patients (P = 0.048). Serum levels of ASD as well as the ASD:cortisol and ASD:17OHP molar ratios increased in MRA‐treated patients (minimum P < 0.004). Serum levels of estrone and 17β‐estradiol did not change. but the estrone:ASD molar ratio (an indicator of aromatization) decreased during 12 weeks of MRA treatment (P = 0.001).

Conclusion

Neutralization of IL‐6 increases secretion of biologically active adrenal androgens in relation to that of precursor hormones and estrogens. This is another important indication that proinflammatory cytokines interfere with adrenal androgen steroidogenesis in patients with RA.
Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor α in experimental arthritis
Authors: Khoury Maroun , Louis‐Plence Pascale , Escriou Virginie , Noel Danièle , Largeau Céline , Cantos Céline , Scherman Daniel , Jorgensen Christian , Apparailly Florence
Published: May 2006

Objective

Tumor necrosis factor α (TNFα) is among the most prominent cytokines in rheumatoid arthritis (RA) and is secreted mainly by macrophages. A direct method for restoring the immunologic balance in RA is use of small interfering RNA (siRNA) for silencing the TNFα transcript. The aim of this study was to determine the therapeutic effect of systemic administration of TNFα siRNA in an experimental model of RA, optimizing its delivery using new liposome formulations.

Methods

Murine macrophages were transfected with siRNA targeting TNFα, and expression was measured. The therapeutic effect in collagen‐induced arthritis (CIA) was assessed after intravenous delivery of TNFα siRNA. Delivery was optimized using a carrier DNA for complexation with the cationic liposome RPR209120/DOPE. Levels of TNFα and other cytokines were measured in sera and joint tissue–conditioned media. Biodistribution was determined using a fluorescent siRNA.

Results

In vitro, TNFα siRNA efficiently and specifically modulated the expression of TNFα at both the messenger RNA and protein levels. In vivo, complete cure of CIA was observed when TNFα siRNA was administered weekly, complexed with the liposome and combined with carrier DNA. Inhibition (50–70%) of articular and systemic TNFα secretion was detected in the siRNA‐injected groups, which correlated with a decrease in the levels of interleukin‐6 and monocyte chemotactic protein 1. The main organs targeted by siRNA were the liver and spleen; the addition of liposome RPR209120 and carrier DNA significantly increased organ uptake.

Conclusion

We demonstrated the efficiency of systemic delivery of siRNA designed to silence TNFα in CIA, using a liposome carrier system as a way to address the methodologic limitations in vivo.
Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: A randomized, placebo‐controlled trial
Authors: Langford Richard , McKenna Frank , Ratcliffe Stuart , Vojtassák Jozef , Richarz Ute
Published: May 2006

Objective

Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate‐to‐severe OA pain, in a placebo‐controlled study.

Methods

The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate‐to‐severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1‐week pretreatment run‐in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

Results

Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group.

Conclusion

TDF can reduce pain and improve function in patients with knee or hip OA.
Relationship of serum paraoxonase 1 activity and paraoxonase 1 genotype to risk of systemic lupus erythematosus
Authors: Tripi Laura M. , Manzi Susan , Chen Qi , Kenney Margaret , Shaw Penny , Kao Amy , Bontempo Franklin , Kammerer Candace , Kamboh M. Ilyas
Published: May 2006

Objective

Low serum paraoxonase 1 (PON1) activity determined with paraoxon as substrate has been found to be associated with coronary artery disease. This study was undertaken to examine the relationship of PON1 activity and genotype to risk of systemic lupus erythematosus (SLE).

Methods

The impact of 7 PON1 single‐nucleotide polymorphisms (SNPs) was analyzed in relation to PON1 activity, SLE risk, lupus nephritis, antiphospholipid antibody (aPL) positivity, and carotid vascular disease in 380 SLE patients (334 white, 46 black) and 497 controls (455 white, 42 black).

Results

Compared with findings in controls, PON1 activity with paraoxon substrate was reduced both in white lupus patients (mean ± SEM 618.9 ± 24.0 units/liter versus 719.6 ± 24.6 units/liter; P = 0.007) and in black lupus patients (991.1 ± 82.7 units/liter versus 1,164.3 ± 101.4 units/liter; P = 0.2711). Low PON1 activity in SLE was not associated with the occurrence of aPL, carotid vascular disease, or the use of immunosuppressive drugs. In multiple regression analyses, the Q192R SNP was found to be independently associated with PON1 activity and explained 28% and 41% of the variation in PON1 activity in white patients and black patients, respectively. Stratification of the lupus sample by presence (n = 81) or absence (n = 247) of renal disease revealed significant associations with 3 promoter SNPs, with odds ratios of 3.82 (95% confidence interval [95% CI] 1.49–9.82, P = 0.005), 3.41 (95% CI 1.35–8.61, P = 0.009), and 2.17 (95% CI 1.01–4.68, P = 0.049).

Conclusion

To our knowledge, this is the first study to assess the role of PON1 activity in SLE risk in a large biracial sample from the US. Our data indicate that low PON1 activity determined with paraoxon substrate is independently associated with SLE and that certain PON1 SNPs are associated with lupus nephritis.
Noggin haploinsufficiency differentially affects tissue responses in destructive and remodeling arthritis
Authors: Lories Rik J. U. , Daans Melina , Derese Inge , Matthys Patrick , Kasran Ahmad , Tylzanowski Przemko , Ceuppens Jan L. , Luyten Frank P.
Published: May 2006

Objective

The balance between destruction and homeostatic or reparative responses determines the outcome of arthritis. Increasing evidence suggests a role for signaling pathways, essential for development and growth, in the maintenance of tissue homeostasis and attempts at repair. Inappropriate activation of such pathways may also have a role in disease progression. We undertook this study to determine the effect of shifting the balance in bone morphogenetic protein (BMP) signaling in different mouse models of arthritis.

Methods

Endogenous levels of noggin, a BMP antagonist, were reduced using heterozygous noggin+/LacZ mice in a model of inflammation‐driven destruction (methylated bovine serum albumin [mBSA]–induced monarthritis), a model of systemic autoimmune arthritis (collagen‐induced arthritis [CIA]), and a model of joint ankylosis (spontaneous arthritis in DBA/1 mice). In addition, we studied BMP inactivation by adenoviral noggin overexpression in destructive arthritis. Cartilage damage and activation of BMP signaling were studied by digital image analysis using Safranin O sulfated glycosaminoglycan staining and immunohistochemistry for phosphorylated Smads (Smads 1, 5, and 8), respectively.

Results

Noggin haploinsufficiency provided protection for articular cartilage against destruction in mBSA‐induced arthritis. Antagonist overexpression rendered cartilage more vulnerable in this model. Noggin gene transfer in knees affected by CIA also enhanced cartilage damage. Haploinsufficiency did not affect CIA, but noggin+/LacZ mice had an increased number of CD4‐positive cells with normal immune responses. In noggin+/LacZ DBA/1 mice with spontaneous arthritis, we observed delayed progression from cartilage to bone formation.

Conclusion

Tight spatiotemporal control of BMP signaling appears to be critical in the response of joint tissues in models of arthritis.
Increase in circulating endothelial precursors by atorvastatin in patients with systemic sclerosis
Authors: Kuwana Masataka , Kaburaki Junichi , Okazaki Yuka , Yasuoka Hidekata , Kawakami Yutaka , Ikeda Yasuo
Published: May 2006

Objective

To evaluate whether atorvastatin can increase bone marrow–derived circulating endothelial precursors (CEPs) and improve the vascular symptoms in patients with systemic sclerosis (SSc; scleroderma).

Methods

The study was designed as an open‐label, prospective study involving 14 patients with SSc who received 10 mg/day of atorvastatin for 12 weeks and were followed up for the subsequent 4 weeks. CEPs were quantified at weeks 0 (pretreatment), 4, 8, 12 (during treatment), and 16 (posttreatment) by cell sorting followed by 3‐color flow cytometry. Raynaud's phenomenon variables, global measures, and psychological scales as well as circulating angiogenic factors and endothelial activation/injury markers were serially assessed. The potential of CEPs to differentiate into mature endothelial cells was examined in cultures with angiogenic stimuli.

Results

None of the patients experienced an adverse event, but 1 dropped out because of an excessive decrease in serum total cholesterol. Atorvastatin treatment resulted in a 1.7‐ to 8.0‐fold increase in CEPs from baseline levels (P < 0.0001), but the numbers returned to within baseline levels at posttreatment. However, 8 patients (62%) experienced a gradual decrease in the number of CEPs, even while taking atorvastatin. Variables indicating the extent of Raynaud's phenomenon improved significantly, and up‐regulated levels of angiogenic factors and vascular endothelial activation/injury markers decreased significantly during atorvastatin treatment. These variables returned to within baseline levels after discontinuation of the drug. In contrast, atorvastatin failed to improve the in vitro maturation potential of CEPs.

Conclusion

The results of this pilot study suggest that atorvastatin treatment can increase CEPs and may be effective in improving Raynaud's phenomenon, even in SSc patients who have CEP dysfunction intrinsically.
Abnormal microvascular response is localized to the digits in patients with systemic sclerosis
Authors: Murray A. K. , Moore T. L. , King T. A. , Herrick A. L.
Published: May 2006

Objective

To investigate the hypothesis that cutaneous microvascular perfusion of the dorsum of the hand (in response to local heating) and distal phalanx (in response to occlusion) is impaired in patients with systemic sclerosis (SSc) compared with healthy controls.

Methods

Twenty‐nine patients with SSc and 29 control subjects were recruited. Perfusion was monitored using novel dual‐wavelength laser Doppler imaging, allowing measurement of both smaller (capillaries) and larger (thermoregulatory) vessels. Postacclimatization, a baseline dorsum scan (red or green wavelength) was performed. A heating pad was placed on the dorsum (total stimulus time 6 minutes at 34–40°C), and following removal of the pad, baseline wavelength scans were performed until perfusion returned to baseline values. This was then repeated for the second wavelength. The maximum perfusion increase due to heating (PEAK1) and area under the perfusion–time curve (AUC) were determined. In addition, scans (both wavelengths) of the index finger were performed prior to and during 2 minutes of suprasystolic occlusion, and the response upon occlusion release was monitored with single‐point laser Doppler. The decrease in perfusion due to occlusion (from preocclusion baseline values) (%DECREASE) and the maximum increase (from baseline perfusion values under occlusion) in hyperemic perfusion upon removal of occlusion (PEAK/OCC) were calculated.

Results

PEAK1 and AUC values were not significantly different between patients and controls, as assessed with either wavelength. A significant difference between groups was found in the %DECREASE values with the green, but not the red, wavelength. A significant between‐group difference was also found in PEAK/OCC values, using both wavelengths.

Conclusion

This study suggests that SSc has no effect on microvascular perfusion in the dorsum of the hand, and that the abnormal microvascular response is localized to the digits, affecting both smaller and larger vessels.
Exposure to ELF magnetic and ELF‐modulated radiofrequency fields: The time course of physiological and cognitive effects observed in recent studies (2001–2005)
Authors: Cook C.M. , Saucier D.M. , Thomas A.W. , Prato F.S.
Published: May 2006

In 2002, we published a review of the cognitive and physiological effects of extremely low frequency magnetic fields (ELF MFs) and ELF‐modulated radiofrequency fields associated with mobile phones. Since the original preparation of that review, a significant number of studies have been published using techniques such as electroencephalography, event‐related potentials and positron emission tomography to investigate electromagnetic field effects upon human physiology and various measures of performance (cognitive, perceptual, behavioral). We review these recent studies, and when effects were observed, we reference the time course of observed effects (immediate or delayed). In our concluding remarks, we discuss a number of variables that are not often considered in human bioelectromagnetics studies, such as personality, individual differences and the specific laterality of ELF MF and mobile phone exposure over the brain. We also consider the sensitivity of various physiological assays and performance measures in the study of biological effects of electromagnetic fields. Bioelectromagnetics 27:613–627, 2006. © 2006 Wiley‐Liss, Inc.
Cover Picture: Detection of mRNA in Mammalian Cells with a Split Ribozyme Reporter (ChemBioChem 6/2006)
Authors: Hasegawa Sumitaka , Gowrishankar Gayatri , Rao Jianghong
Published: May 2006

The cover picture shows a split RNA reporter strategy for detecting target mRNA in mammalian cells. A tetrahymena group I intron ribozyme reporter is split into two halves, each of which carries a part of the coding sequence of the reporter mRNA, a fragment of the ribozyme, and an antisense sequence complementary to a target mRNA. Both halves bind with the target mRNA and are assembled into an active complex that trans‐splices and produces a complete reporter mRNA. The reporter mRNA is subsequently translated into the reporter enzyme, which can be detected by fluorogenic substrates. Further details can be found in the article by J. Rao et al. on p. 925 ff.
Stress reducing regulative effects of integrated mental training with self‐hypnosis on the secretion of dehydroepiandrosterone sulfate (DHEA‐S) and cortisol in plasma: a pilot study
Authors: Johansson Benny , Uneståhl Lars‐Eric
Published: May 2006

Early observations have shown that preventive educational efforts towards experience of stress entail advantages in terms of improved well‐being, health and performance. We examined the influence in healthy subjects of self‐hypnosis and mental training taught in group sessions, with individual training in between according to a standard protocol, and integrated in daily life and work for six months, on the alteration in plasma concentration of the stress hormone cortisol and the ‘anti ageing’ hormone dehydroepiandrosterone sulfate (DHEA‐S). DHEA‐S and cortisol were analysed in twelve healthy men and women, with six individuals randomly divided equally between experimental and control groups. In the experimental group DHEA‐S was significantly increased by 16% (P < 0.05), whereas plasma DHEA‐S in controls followed an expected age‐related decline. Cortisol was reduced by 12.3% (P < 0.05) in the experimental group, but remained unchanged in the control group. The ratio between plasma concentrations of DHEA‐S and cortisol that reflects stress‐related alteration in the adrenal secretion between androgens and glucocorticoids, increased significantly by 27.8% (P < 0.05) in the experimental group with a reduction of 8,2% in controls. The increase in plasma DHEA‐S under experimental conditions was equivalent to a range normally found in individuals 5 to 10 years younger. Copyright © 2006 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.
Triplet MLCT Photosensitization of the Ring‐Closing Reaction of Diarylethenes by Design and Synthesis of a Photochromic Rhenium(I) Complex of a Diarylethene‐Containing 1,10‐Phenanthroline Ligand
Authors: Ko Chi‐Chiu , Kwok Wai‐Ming , Yam Vivian Wing‐Wah , Phillips David Lee
Published: May 2006

Synthesis of the diarylethene‐containing ligand L1 based on Suzuki cross‐coupling reaction between thienyl boronic acid and the dibromophenanthroline ligand is reported. On coordination to the rhenium(I) tricarbonyl complex system, the photochromism of L1 could be photosensitized and consequently extended from intraligand excitation at λ≤340 nm in the free ligand to metal‐to‐ligand charge‐transfer (MLCT) excitation at λ≤480 nm in the complex. The photochromic reactions were studied by 1H NMR, UV/Vis, and steady‐state emission spectroscopy. Photosensitization was further probed by ultrafast transient absorption and time‐resolved emission spectroscopy. The results provided direct evidence that the formation of the closed form by the MLCT‐sensitized photochromic process was derived from the 3MLCT excited state. This supports the photosensitization mechanism, which involves an intramolecular energy‐transfer process from the 3MLCT to the 3IL(L1) state that initiated the ring‐closure reaction. The photophysical and electrochemical properties of the complex were also investigated.
The Reaction Mechanism of a Complex Intercalation System: In Situ X‐ray Diffraction Studies of the Chemical and Electrochemical Lithium Intercalation in Cr4TiSe8
Authors: Behrens Malte , Kiebach Ragnar , Ophey Jannes , Riemenschneider Oliver , Bensch Wolfgang
Published: May 2006

The intercalation reaction between Cr4TiSe8and Li was investigated from a kinetic and an electrochemical perspective. The structural phase transition from monoclinic to trigonal symmetry was probed by in situ energy‐dispersive X‐ray diffraction (in situ EDXRD) for chemical intercalation with butyllithium (BuLi). A change in the kinetic mechanism was detected for the reaction at room temperature; this was interpreted in terms of a trend from phase boundary control to diffusion control. A single diffusion‐controlled mechanism is obeyed at 60 °C. The electrochemical measurements and the corresponding in situ X‐ray diffraction (in situ XRD) data revealed that the monoclinic host is intercalated up to the composition Lix≈0.1Cr4TiSe8before the characteristic phase transition starts. The monoclinic phase undergoes complex structural changes in the following two‐phase regime. Owing to the co‐existence of two phases, the cell potential is constant for 0.1<x<0.7 and 0.9<x<3.0. The subsequent intercalation into the trigonal phase leads to a pronounced increase in the cell volume of the trigonal phase that stops atx≈0.8. At this point, the complete reduction of TiIVgives rise to a voltage drop of the cell potential. XANES measurements revealed that the reduction of TiIVoccurs prior to the reduction of CrIII.
Helically Chiral Ferrocene Peptides Containing 1′‐Aminoferrocene‐1‐Carboxylic Acid Subunits as Turn Inducers
Authors: Barišić Lidija , Čakić Mojca , Mahmoud Khaled A. , Liu You‐nian , Kraatz Heinz‐Bernhard , Pritzkow Hans , Kirin Srećko I. , Metzler‐Nolte Nils , Rapić Vladimir
Published: May 2006

We present a detailed structural study of peptide derivatives of 1′‐aminoferrocene‐1‐carboxylic acid (ferrocene amino acid, Fca), one of the simplest organometallic amino acids. Fca was incorporated into di‐ to pentapeptides withD‐ andL‐alanine residues attached to either the carboxy or amino group, or to both. Crystallographic and spectroscopic studies (circular dicroism (CD), IR, and NMR) of about two dozen compounds were used to gain a detailed insight into their structures in the solid state as well as in solution. Four derivatives were characterized by single‐crystal X‐ray analysis, namely Boc‐Fca‐Ala‐OMe (16), Boc‐Fca‐D‐Ala‐OMe (17), Boc‐Fca‐β‐Ala‐OMe (18), and Boc‐Ala‐Fca‐Ala‐Ala‐OMe (21) (Boc=tert‐butyloxycarbamyl). CD spectroscopy is an extremely useful tool to elucidate the helical chirality of the metallocene core. Unlike in all other known ferrocene peptides, the helical chirality of the ferrocene is governed solely by the chirality of the amino acid attached to the N terminus of Fca. Depending on the degree of substitution of both cyclopentadiene (Cp) rings, different hydrogen‐bonding patterns are realized.1H NMR and IR spectroscopy, together with the results from X‐ray crystallography, give detailed information regarding not only the hydrogen‐bonding patterns of the compounds, but also the equilibria between different conformers in solution. Differences in chemical shifts of NH protons in dimethyl sulfoxide ([D6]DMSO) and CDCl3, that is, the variation ratio (vr), is used for the first time as a measure of the hydrogen‐bonding strength of individual CO⋅⋅⋅HN bonds in ferrocenoyl peptides. In dipeptides with one intramolecular hydrogen bond between the pendant chains, for example, in dipeptide16, an equilibrium between hydrogen‐bonded and open forms is observed, as testified by a vr value of around 0.5. Higher peptides, such as tetrapeptide21, are able to form two intramolecular hydrogen bonds stabilizing one single conformation in CDCl3solution (vr≈0). Due to the low barrier of Cp‐ring rotation, new and unnatural hydrogen‐bonding patterns are emerging. The systematic work described herein lays a solid foundation for the rational design of metallocene peptides with unusual structures and properties.
Amide‐Based Molecular Knots as Platforms for Fluorescent Switches
Authors: Passaniti Paolo , Ceroni Paola , Balzani Vincenzo , Lukin Oleg , Yoneva Albena , Vögtle Fritz
Published: May 2006

A series of amide‐based molecular knots equipped selectively with fluorescent dansyl and/or pyrenesulfonyl moieties were synthesized from the readily available tris(allyloxy)knotane. UV/Vis absorption spectra, emission spectra, and the emission lifetimes of the fluorescent knotanes were investigated in chloroform at 298 K. The absorption spectra of the knotanes correspond to those of mixtures of their UV‐active constituents. The fluorescence quantum yields and lifetimes of the dansyl and pyrenesulfonyl moieties are partly quenched by the knotane platform. In the KN(Da)2(Py) species, the fluorescent excited state of the dansyl units (λmax=510 nm) lies at lower energy than the fluorescent excited state of the pyrenesulfonyl unit (λmax=385 nm), the emission of which is accordingly quenched with sensitization of the dansyl fluorescence. In the KN(Ao)2(Da), KN(Ao)(Da)2, and KN(Da)3 species, the addition of acids causes the protonation of their dansyl units with a consequent decrease in the intensity of the dansyl band at 510 nm and appearance of the emission band of the protonated dansyl unit (λmax=340 nm). Each dansyl unit of KN(Ao)(Da)2 and KN(Da)3 undergoes the independent protonation. In these incompletely protonated knotanes the fluorescence of the protonated dansyl units is partly quenched by nonprotonated ones. These processes can be quantitatively reversed upon addition of a base. In KN(Da)2(Py), an increase of the fluorescence of its pyrenesulfonyl group is observed when the dansyl groups are protonated. The results obtained show that the readily available and easily functionalizable amide‐knotanes can be used as an interesting scaffold to obtain fluorescent switches.
The long and short of it: Somite formation in mice
Authors: Gridley Thomas
Published: May 2006

A fundamental characteristic of the vertebrate body plan is its segmentation along the anterior–posterior axis. This segmental pattern is established during embryogenesis by the formation of somites, the transient epithelial blocks of cells that derive from the unsegmented presomitic mesoderm. Somite formation involves a molecular oscillator, termed the segmentation clock, in combination with gradients of signaling molecules such as fibroblast growth factor 8, WNT3A, and retinoic acid. Disruption of somitogenesis in humans can result in disorders such as spondylocostal dysostosis, which is characterized by vertebral malformations. This review summarizes recent findings concerning the role of Notch signaling in the segmentation clock, the complex regulatory network that governs somitogenesis, the genes that cause inherited spondylocostal dysostosis, and the mechanisms that regulate bilaterally symmetric somite formation. Developmental Dynamics 235:2330–2336, 2006. © 2006 Wiley‐Liss, Inc.
Uncovering the uncharacterized and unexpected: Unbiased phenotype‐driven screens in the mouse
Authors: Caspary Tamara , V. Anderson Kathryn
Published: May 2006

Phenotype‐based chemical mutagenesis screens for mouse mutations have undergone a transformation in the past five years from a potential approach to a practical tool. This change has been driven by the relative ease of identifying causative mutations now that the complete genome sequence is available. These unbiased screens make it possible to identify genes, gene functions and processes that are uniquely important to mammals. In addition, because chemical mutagenesis generally induces point mutations, these alleles often uncover previously unappreciated functions of known proteins. Here we provide examples of the success stories from forward genetic screens, emphasizing the examples that illustrate the discovery of mammalian‐specific processes that could not be discovered in other model organisms. As the efficiency of sequencing and mutation detection continues to improve, it is likely that forward genetic screens will provide an even more important part of the repertoire of mouse genetics in the future. Developmental Dynamics 235:2412–2423, 2006. © 2006 Wiley‐Liss, Inc.
Dynamic code reordering method for improvement of Java performance
Authors: Yamada Tetsuyasu , Tanaka Shinji , Shiraishi Satoshi , Koyanagi Keiichi
Published: May 2006

When the Java language is used in a large‐scale real‐time communications system, processing power presents a problem. The authors have been investigating an essential solution for this problem. This paper proposes a technique in which native code which has already been on‐line compiled by a JIT compiler is dynamically reordered, based on profiling data obtained in the Java execution environment. The realization procedure is clearly described. The technique is to place segments of compiled code with high execution frequency close to each other as a group in memory. In addition, codes with low execution frequency are allocated to another area, so that the codes with high frequencies are more compactly placed. By this measure, the instruction cache hit rate of the processor is greatly increased and the processing performance in a large‐scale program can be improved. The extent of performance improvement by applying the dynamic code reordering technique is evaluated, using applications with characteristics close to those of the real large‐scale real‐time communications program, and the effectiveness of the proposed method is demonstrated. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 89(11): 78–88, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20185
Performance analysis of Bluetooth system in the presence of microwave oven noises
Authors: Murakami Takahide , Matsumoto Yasushi , Fujii Katsumi , Sugiura Akira
Published: May 2006

Bluetooth is a short‐range wireless system using the 2.4‐GHz band, but has the problem of degradation of communication quality caused by the noise radiated by microwave ovens which share the same frequency band. In this paper, we theoretically and experimentally study the impact of microwave oven noise on Bluetooth. Time variations in the bit error rate with a fixed channel frequency are theoretically evaluated applying the time domain oven noise model represented by frequency and amplitude modulated wave to the theoretical equation of the bit error probability for frequency shift keying (FSK). The average bit error rate and the average packet error rate with the frequency hopping spread spectrum (FH‐SS) scheme are also evaluated. The results of theoretical study show that (1) microwave oven noise using an inverter power supply (inverter‐type) degrades average packet error rate more seriously than does a microwave oven not using an inverter power supply (transformer‐type), and that (2) FH‐SS is less effective in mitigating interference from inverter‐type oven noise compared with transformer‐type oven noise. Experiments are conducted using Bluetooth terminals. Error rates are measured using actual ovens and oven noise simulator based on the noise model. The effectiveness of the noise model applied in this paper in the evaluation of the Bluetooth transmission characteristics during microwave oven noise interference is demonstrated. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 89(11): 24–34, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20275
Relative speed‐based routing (RSR) for vehicle ad‐hoc networks
Authors: Yoshida Masashi , Arai Kunimitsu , Asami Shigeyuki , Miki Tetsuya
Published: May 2006

Vehicle ad‐hoc networks, which can be achieved by wireless connections between vehicles without using a special communication infrastructure, are attracting attention. A point to consider with respect to vehicle ad‐hoc networks is that dynamic changes in topology frequently occur. Unless a stable communications route with long life is constructed in intervehicle communications, the transmission of control packets generated when the communications route is disconnected will increase the overhead. In order to solve this problem, this paper proposes the RSR (relative speed‐based routing) routing protocol for vehicle ad‐hoc networks in which a stable communications route is constructed without using beacons or similar means. RSR is a routing protocol that uses the relative speed and the cumulative change of the distance to neighboring vehicles as the metric. The protocol is realized by including the relative speed and intervehicle distance information as elements in the route request packets used for reactive routing. RSR is compared by simulation to AODV, which is a typical reactive routing protocol, and FORP, which is a reactive routing protocol emphasizing stability. It is shown that RSR is better in terms of packet arrival ratio and stability. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 89(11): 1–11, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20293
Analysis of QCM gas sensor transient response by visualizing gas concentration
Authors: Tsujita Wataru , Nakamoto Takamichi , Ishida Hiroshi , Moriizumi Toyosaka
Published: May 2006

Gas‐source localization systems are required to quickly detect gas concentrations at various locations while moving. It is therefore necessary to design the system by taking account of the delay in the response and recovery of the gas sensor in the presence of variations in gas concentration. Also, in order to model the dynamic characteristics of the gas sensor in open air, it is essential to understand the delay in response and recovery of the gas sensor. To carry out a transient response analysis of such a gas sensor, it is necessary to know the gas concentration (changing in time) at the gas sensor. In the present study, in order to analyze the transient response of a QCM (quartz crystal microbalance) gas sensor, the gas concentration is visualized. A photodiode is placed close to the gas sensor and the intensity of scattered laser light is measured optically in order to know the concentration of the gas passing over the sensor. The sensor response and the intensity of scattered light are measured simultaneously and the sensor response is estimated from the visualized gas concentration by means of the models of a second‐order system and a neural network. When the measured results and the estimated results are compared, the model based on the neural network is found to estimate more accurately. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(6): 14–21, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10062
VCS‐IV: A real‐time vision system using a digital vision chip
Authors: Kagami Shingo , Komuro Takashi , Watanabe Yoshihiro , Ishikawa Masatoshi
Published: May 2006

A real‐time visual processing system based on a vision chip that aggregates per pixel digital processing circuitry is presented. The system supports the authors' latest vision chip and achieves high‐speed, high‐performance visual processing using an implementation that is small yet highly expandable and versatile. The main feature of the system is that the image capture function is programmable, with the operation of the internal pixel A–D conversion controlled from software at high time resolutions. The performance of the system is evaluated by application to basic visual processing and measurement systems, and examples of applications of the enhanced image capture function are presented. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(6): 34–43, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20269
Identifying errors in mathematical expressions using syntactic tree structures
Authors: Ikeda Koji , Nakamura Manabu , Otsuki Setsuko
Published: May 2006

When constructing a practical intelligent educational system, the system needs to have the ability to reconstruct a learner's answers complete with mistakes if it is to provide learning support adapted to the learner's response. This paper proposes the use of syntactic tree structures to identify a learner's errors as an effective and realistic method for implementing such functionality. Comparing a syntactic tree structure derived from a given mathematical expression using a DCG with that derived from a learner's answer using DCG, we are able to determine whether there is an error in the learner's response. In addition, by using the results of this error identification process we are able to provide adaptive support tailored to individual learners. © 2006 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 89(6): 55–62, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.20271
DNA fingerprinting of Vibrio cholerae and Aeromonas species by pulsed‐field minigel electrophoresis
Authors: Lopez‐Canovas Lilia , Bravo Laura , Herrera Jose , Riveron Ana Maria , Javer Elisa , Sanchez Axel , Fando Rafael , Noa Maria Dolores , Fernandez Anabel
Published: May 2006

DNA molecules of Vibrio cholerae and Aeromonas species were prepared by incubating immobilized cells for 4 and 2 h, respectively, with a nonenzymatic solution that contains chemical reagents only (NDSUPlus). This method gave results as reproducible as the enzymatic one that uses proteinase K, and rendered DNA molecules suitable for fingerprinting by mini‐CHEF electrophoresis. As rapid DNA separations at high electric field are achieved in mini‐CHEF chamber with low heat evolution, DNA restriction fragments were separated in 5 h at 10 V/cm in a single resolution window. Then, fragment separations in three resolution windows were done in 15 h. This time is shorter than the one needed by the large CHEF chamber for resolving fragments in a single resolution window. Three windows permitted to include larger numbers of restriction fragments in the calculation of isolate similarities. Both sample preparation and mini‐CHEF electrophoresis may represent an alternative for performing massive epidemiological studies of V. cholerae and Aeromonas species.
Dissection of mitochondrial superhaplogroup H using coding region SNPs
Authors: Brandstätter Anita , Salas Antonio , Niederstätter Harald , Gassner Christoph , Carracedo Angel , Parson Walther
Published: May 2006

Haplogroup H (hg H) includes about 40–50% of the West Eurasian mitochondrial DNA (mtDNA) samples investigated so far. In order to enhance discrimination within this haplogroup we selected 45 coding region SNPs that allow to ascribe samples to the main phylogenetic branches of super hg HV (that embraces hg H) and, in particular, to H sublineages with a much finer resolution than previous studies. SNP selection was carried out using the most up‐to‐date available literature on population and forensic genetics and extended by means of phylogenetic analysis of complete or coding region genomes (<430) and control region sequences. A meticulous inspection of the H phylogeny led us to the observation of various but uncharacterized subclades of hg H. The selected SNPs were amplified in two PCR‐multiplex reactions and subsequently targeted in three single‐base extension multiplex reactions. A total of 2214 West Eurasian samples were screened for hg H specific loci 2706 and 7028, of which 859 fell in hg H and were further subjected to subhaplogroup typing. We observed 35 different subhaplogroups in total, 33 of which were found at frequencies below 5%. This assay can be used as a prescreening tool in forensic casework for rapid discrimination between divergent lineages (very effective for high‐volume crime cases) or as discriminatory assay, when identical hg H haplotypes were obtained by control region sequencing.
Micellar electrokinetic chromatography of fluorescently labeled proteins on poly(dimethylsiloxane)‐based microchips
Authors: Roman Gregory T. , Carroll Susan , McDaniel Kevin , Culbertson Christopher T.
Published: May 2006

MEKC of standard proteins was investigated on PDMS microfluidic devices. Standard proteins were labeled with AlexaFluor® 488 carboxylic acid tetrafluorophenyl ester and filtered through a size‐exclusion column to remove any small peptides and unreacted label. High‐efficiency MEKC separations of these standard proteins were performed using a buffer consisting of 10 mM sodium tetraborate, 25 mM SDS, and 20% v/v ACN. A separation of BSA using this buffer in a 3.0 cm long channel generated a peak with a plate height of 0.38 μm in <20 s. Additional fast separations of myoglobin, α‐lactalbumin, lysozyme, and cytochrome c also yielded peaks with plate heights ranging from 0.54 to 0.72 μm. All proteins migrated with respect to their individual pIs. To improve the separations, we used a PDMS serpentine chip with tapered turns and a separation distance of 25 cm. The number of plates generated increased linearly with increasing separation distance on the extended separation channel chips; however, the resolution reached an asymptotic value after about 7 cm. This limited the peak capacity of the separation technique to 10–12.
Capillary electrophoresis method for determination ofD‐serine and its application for monitoring of serine racemase activity
Authors: Koval Dušan , Jirásková Jana , Stříšovský Kvido , Konvalinka Jan , Kašička Václav
Published: May 2006

Serine racemase (SR) is an enzyme responsible for the biosynthesis ofD‐serine, the coagonist of theN‐methyl‐D‐aspartate receptor, in the brain. Therefore, it has been suggested as a possible therapeutic target for the treatment of various neurodegenerative diseases. To develop a potent inhibitor of SR, a simple, sensitive, fast, and robust assay is needed. In this paper, a new CE method for the determination ofD‐serine is described. Serine enantiomers are resolved in the form ofo‐phthaldialdehyde (OPA)/2‐mercaptoethanol (2‐ME) derivatives in an alkaline BGE composed of 50 mM sodium tetraborate, pH 9.7, and containing 40 mM 2‐hydroxypropyl‐γ‐CD as a chiral selector. The problem of time‐limited stability of OPA/2‐ME derivatives has been overcome by employing in‐capillary derivatization of the sample,i.e., the derivatization reaction was carried out directly in the separation capillary in the first phase of the CE run. UV‐absorption detection at 230 nm allowed concentration detection limit of 3 μM. Baseline resolution ofD‐ andL‐serine derivatives was achieved in less than 10 min. This fact, together with the simple sample pretreatment, allowed application of the method to medium‐throughput monitoring of SR activity, such as the screening of potential SR inhibitors. A good agreement was achieved between the developed CE method and the previously established HPLC method for determination of the inhibition constant,Ki, of a new SR inhibitor,L‐erythro‐3‐hydroxyaspartate.
Retracted and replaced: a flow‐condition‐based interpolation finite element procedure for triangular grids
Authors: Kohno Haruhiko , Bathe Klaus‐Jürgen
Published: May 2006

The following article from the International Journal for Numerical Methods in Fluids ‘A flow‐condition‐based interpolation finite element procedure for triangular grids’ by Haruhiko Kohno and Klaus‐Jürgen Bathe published online on 3 August 2005 in Wiley InterScience (www.interscience.wiley.com) and in print on 10 October 2005 in the
International Journal for Numerical Methods in Fluids Volume 49 Issue 8 pp. 849–875 has been retracted and replaced by agreement between the authors, the journal editors and John Wiley & Sons, Ltd. The article has been retracted due to printing errors which have been corrected in the replacement article.(DOI: 10.1002/fld.1246)
Nanotechnology occupational and environmental health and safety: Education and research needs for an emerging interdisciplinary field of study
Authors: Genaidy Ash , Karwowski Waldemar
Published: May 2006

Commercialization of nanotechnology (NT) has the potential to affect the health and safety of the industrial workforce and the general public. The main objective of this position paper is to present an education and research framework for the emerging interdisciplinary field of NT occupational and environmental health and safety. The specific aims of this program are to (a) establish evidence‐based guidelines for the protection/promotion of individual health and safety along the life cycle of nano‐based products in light of the best available scientific information, technologies, and best practices; (b) present and address issues of importance to individual health and safety in nanomanufacturing enterprises in different industry sectors, environment, and public consumer health (civilian and military); (c) provide a forum for idea exchange and research agenda on the use of NT in prevention/treatment of specific occupational/environmental diseases; and (d) disseminate the latest research findings on NT and occupational and public health, and nano‐health technologies for occupational diseases. © 2006 Wiley Periodicals, Inc. Hum Factors Man 16: 247–253, 2006.
Factors influencing implementation of occupational safety and health management systems by enterprises in Poland
Authors: Podgórski Daniel
Published: May 2006

Implementing legal regulations in occupational safety and health (OSH) as well as other actions aimed at improving working conditions in industry in many countries run in parallel with promoting nonobligatory OSH management systems (OSH MS). To define a scientific basis for working out a set of guidelines for promoting OSH MS, a survey was conducted in 40 companies. This research aimed to identify motivational factors for decisions to introduce OSH MS. Four groups of professionals who participated in the decision‐making process related to implementing OSH MS were interviewed: (a) the most senior managers of the enterprise, (b) representatives of top management for implementation and maintenance of OSH MS, (c) safety and health managers, and (d) workers' safety representatives. The results indicate the need for: (1) improving the efficiency of programs promoting implementation of OSH MS; (2) considering the role of economic incentives in promoting these systems; (3) developing and promoting training packages related to OSH management, adjusted particularly to the needs of employees and their representatives to increase their involvement in OSH activities; and (4) modifying legal solutions establishing a system of differentiated premium rates for social insurance against occupational accidents and diseases. © 2006 Wiley Periodicals, Inc. Hum Factors Man 16: 255–267, 2006.
Changing the internal health and safety organization through organizational learning and change management
Authors: Hasle Peter , Jensen Per Langaa
Published: May 2006

Research from several countries indicates that the internal health and safety organization is marginalized in most companies, and it is difficult for the professionals to secure a proper role in health and safety on the companies' present agenda. The goal of a Danish project involving a network of 11 companies was to search for a solution to this problem. The health and safety managers and safety representatives played the role of “change agents” for local projects aiming to develop the health and safety organization. The study showed that 3 of the 11 companies proved to be able to implement successful changes; 5 were partially successful; 3 were nonperformers. The more successful outcomes seem to depend on the abilities of change agents to handle a complex and unpredictable project. Based on these case studies, it has been possible to deduce some strategies change agents must follow to fulfill such a process. Such strategies require the ability to be able to identify opportunities for change, establish a sustainable problem definition, and build coalitions. An amoeba model is suggested as a metaphor for this type of development project. © 2006 Wiley Periodicals, Inc. Hum Factors Man 16: 269–284, 2006.