bluuebunny/crossref_metadata_2025 huggingface dataset:
pH‐dependent photoautotrophic growth of specific photosystem II mutants lacking lumenal extrinsic polypeptides in Synechocystis PCC 6803
Authors: Eaton-Rye Julian J. , Shand Jackie A. , Nicoll William S.
Published: May 2003

The removal of either the PsbU or PsbV protein has been investigated in a cyanobacterial ΔPsbO strain and in mutants carrying deletions or substitutions in lumen‐exposed domains of CP47. These experiments have demonstrated a functional interaction between the PsbU protein and photosystem II (PSII) in the absence of the PsbO subunit. The control:ΔPsbO:ΔPsbU strain assembled PSII centers at pH 7.5 but did not evolve oxygen; however, photoautotrophic growth was restored at pH 10.0. In addition, several CP47 mutants, lacking extrinsic proteins, were obligate photoheterotrophs at pH 7.5 but photoautotrophic at pH 10.0, whereas other strains remained photoheterotrophs at alkaline pH.
Crystal structure of DsbDγ reveals the mechanism of redox potential shift and substrate specificity1
Authors: Kim Jae Hoon , Kim Seung Jun , Jeong Dae Gwin , Son Jeong Hee , Ryu Seong Eon
Published: May 2003

The Escherichia coli transmembrane protein DsbD transfers electrons from the cytoplasm to the periplasm through a cascade of thiol‐disulfide exchange reactions. In this process, the C‐terminal periplasmic domain of DsbD (DsbDγ) shuttles the reducing potential from the membrane domain (DsbDβ) to the N‐terminal periplasmic domain (DsbDα). The crystal structure of DsbDγ determined at 1.9 Å resolution reveals that the domain has a thioredoxin fold with an extended N‐terminal stretch. In comparison to thioredoxin, the DsbDγ structure exhibits the stabilized active site conformation and the extended active site α2 helix that explain the domain's substrate specificity and the redox potential shift, respectively. The hypothetical model of the DsbDγ:DsbDα complex based on the DsbDγ structure and previous structural studies indicates that the conserved hydrophobic residue in the C‐X‐X‐C motif of DsbDγ may be important in the specific recognition of DsbDα.
Post‐transcriptional regulation of gene expression by mitogen‐activated protein kinase p38
Authors: Clark Andrew R. , Dean Jonathan L.E. , Saklatvala Jeremy
Published: May 2003

The mitogen‐activated protein kinase p38 pathway was originally identified as a signalling cascade activated by pro‐inflammatory stimuli and cellular stresses, and playing a critical role in the translational regulation of pro‐inflammatory cytokine synthesis. In almost a decade since this discovery, a great deal has been learned about the role of the p38 pathway in the post‐transcriptional regulation of pro‐inflammatory gene expression. However, important questions remain to be answered concerning the specificity and mechanism or mechanisms of action of p38. This review describes recent progress and remaining puzzles in the field of post‐transcriptional regulation by p38.
Palmitoylation sites and processing of synaptotagmin I, the putative calcium sensor for neurosecretion
Authors: Heindel Ulrich , Schmidt Michael F.G , Veit Michael
Published: May 2003

Synaptotagmin I, the calcium sensor for neurotransmission, is palmitoylated. We have identified the palmitoylation sites as five cysteine residues located between the transmembrane and cytoplasmic regions. In contrast to wild‐type synaptotagmin, the non‐acylated mutant is not converted to the endoglycosidase‐H‐resistant form after expression in CV‐1 cells. This indicates a block in transport through the Golgi complex. However, when expressed in PC‐12 and RBL cells non‐acylated synaptotagmin is targeted to the plasma membrane and to secretory granules. No significant cleavage of [3H]palmitate from synaptotagmin was observed in pulse‐chase experiments. This indicates that the majority of fatty acids are structural rather than dynamic components.
MAP kinase‐mediated phosphoacetylation of histone H3 and inducible gene regulation
Authors: Clayton Alison L. , Mahadevan Louis C.
Published: May 2003

That signalling pathways, particularly the mitogen‐activated protein kinase cascades, elicit modification of chromatin proteins such as histone H3 by phosphorylation and/or acetylation concomitant with gene activation is now well established. The picture that is emerging is one of a complex and dynamic pattern of multiple modifications at the H3 tail. Here, we review the inducible gene systems where H3 modifications have been reported and re‐evaluate the controversy as to the kinase(s) that phosphorylates it as well as the proposed coupling between H3 phosphorylation and acetylation.
Extracellular proton alters the divalent cation binding affinity in a cyclic nucleotide‐gated channel pore
Authors: Rho Seong-Hwan , Park Chul-Seung
Published: May 2003

Extracellular protons in the range of 10−9 to 10−5 M effectively suppressed Na+ current (K
1/2=10−6.1) through the bovine retinal guanosine 3′,5′‐cyclic mononucleotide‐gated ion channel expressed in Xenopus oocytes. The reduction of channel current was mediated by a single glutamate residue (Glu363) within the pore‐forming region of the channel, also involved in extracellular divalent cation binding. Increasing the concentration of extracellular proton decreased the binding affinity of the extracellular divalent cation (e.g. Sr2+) and the large difference of binding affinity previously observed between the wild‐type and E363D mutant channel disappeared. These results indicate that the permeation characteristics of cyclic nucleotide‐gated ion channel can be altered by extracellular pH through a single acidic residue in the channel conduction pathway.
Prostaglandins prevent inducible nitric oxide synthase protein expression by inhibiting nuclear factor‐κB activation in J774 macrophages
Authors: D'Acquisto Fulvio , Sautebin Lidia , Iuvone Teresa , Di Rosa Massimo , Carnuccio Rosa
Published: May 2003

We investigated the effect of PGE2 and iloprost (a prostacyclin analogue) on inducible nitric oxide synthase (iNOS) protein expression and nuclear factor‐κB (NF‐κB) activation in lipopolysaccharide (LPS)‐stimulated J774 macrophages. Incubation of J774 cells with LPS (10 μg/ml) caused an increase of iNOS protein expression which was prevented in a concentration‐dependent fashion by PGE2 (0.1, 1, 10 μM) and iloprost (0.01, 0.1, 1 μM). Electrophoretic mobility shift assay indicated that both prostanoids blocked the activation of NF‐κB, a transcription factor necessary for NO synthase induction. PGE2 and iloprost also blocked disappearance of IκB‐α from cytosolic fraction and nuclear translocation of NF‐κB subunits p50 and p65. These results show for the first time that PGE2 and iloprost down‐regulate iNOS protein expression by inhibiting NF‐κB activation and suggest a negative feed‐back mechanism that may be important for limiting excessive or prolonged NO production in pathological events.
A phage‐based system to select multiple protein‐protein interactions simultaneously from combinatorial libraries
Authors: Rudert Fritz , Woltering Claudia , Frisch Christian , Rottenberger Christine , Ilag Leodevico L
Published: May 2003

Selectively infective phage (SIP) can be used to identify protein‐protein interactions. SIP was modified to facilitate the simultaneous selection of interacting protein pairs from large combinatorial libraries. An interference‐resistant phage was constructed which non‐covalently, but stably links the genetic information of an interacting pair, encoded separately on phage and phagemid vectors, by co‐packaging into hetero‐polyphages. In a model system, the interaction between a SIP‐selected peptide and the intracellular domain of the p75 neurotrophin receptor was detected in the presence of a 104‐fold excess of a non‐interacting control pair (jun leucine zipper and p75 intracellular domain) via SIP hetero‐polyphage transductants. To minimize the redundancy of transductants and to minimize possible ligand exchange generated in a solution‐based SIP screening, a filter‐based in situ infectivity screening was developed. The combination of the above techniques may provide a powerful system for rapid screening of very large sequence spaces.
Expression of lectin‐like oxidized low density lipoprotein receptor‐1 in human and murine macrophages: upregulated expression by TNF‐α
Authors: Moriwaki Hideaki , Kume Noriaki , Kataoka Hiroharu , Murase Takatoshi , Nishi Eiichiro , Sawamura Tatsuya , Masaki Tomoh , Kita Toru
Published: May 2003

Uptake of oxidized low density lipoprotein (Ox‐LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox‐LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin‐like Ox‐LDL receptor‐1 (LOX‐1), a novel Ox‐LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX‐1 can be induced after macrophage‐like differentiation in vitro in human peripheral blood monocytes and the related cell line THP‐1 cells. Furthermore, LOX‐1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF‐α. These results suggest that LOX‐1 in macrophages may play an important role in Ox‐LDL uptake and subsequent foam cell formation in this cell type.
Hypericin‐induced photosensitization of HeLa cells leads to apoptosis or necrosis
Authors: Vantieghem Annelies , Assefa Zerihun , Vandenabeele Peter , Declercq Wim , Courtois Stephane , Vandenheede Jackie R , Merlevede Wilfried , de Witte Peter , Agostinis Patrizia
Published: May 2003

Here we report that photoactivated hypericin can induce either apoptosis or necrosis in HeLa cells. Under apoptotic conditions the cleavage of poly(ADP‐ribose) polymerase (PARP) into the 85‐kDa product is blocked by the caspase inhibitors benzyloxycarbonyl‐Val‐Ala‐Asp‐fluoromethylketone (z‐VAD‐fmk) and benzyloxycarbonyl‐Asp‐Glu‐Val‐Asp‐fluoromethylketone (z‐DEVD‐fmk). Both inhibitors protect cells from apoptosis but cannot prevent hypericin‐induced necrosis. Conversely, HeLa cells overexpressing the viral cytokine response modifier A (CrmA), which inhibits caspase‐1 and ‐8, still undergo hypericin‐induced apoptosis and necrosis. Evidence is provided for the release of mitochondrial cytochrome c in the cytosol and for procaspase‐3 activation in the hypericin‐induced cell killing.
Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of α‐synuclein protein implicated in Parkinson's disease
Authors: El-Agnaf Omar M.A , Jakes Ross , Curran Martin D , Wallace Andrew
Published: May 2003

α‐Synuclein (α‐syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the α‐syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild‐type α‐syn, PD‐linked mutant α‐syn(Ala30Pro) and mutant α‐syn(Ala53Thr) proteins can self‐aggregate and form amyloid‐like filaments. The mutant α‐syn forms more β‐sheet and mature filaments than the wild‐type protein. These findings suggest that accumulation of α‐syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.
Effect of MI‐D, a new mesoionic compound, on energy‐linked functions of rat liver mitochondria
Authors: Cadena Silvia M.S.C , Carnieri Eva G.S , Echevarria Aurea , de Oliveira Maria Benigna M
Published: May 2003

MI‐D (4‐phenyl‐5‐(4‐nitro‐cinnamoyl)‐1,3,4‐thiadiazolium‐2‐phenylamine chloride), a new mesoionic compound, depressed the phosphorylation efficiency of liver mitochondria as deduced from an accentuated decrease of the respiratory control coefficient and ADP/O ratio. Analysis of segments of the respiratory chain suggested that the MI‐D inhibition site is further on than complex I and between complexes II and III. The transmembrane electrical potential (Δψ) was collapsed dependent on MI‐D concentration. ATPase activity was dramatically increased by MI‐D in intact mitochondria, but inhibited in carbonylcyanide p‐trifluoromethoxyphenylhydrazone (FCCP)‐uncoupled mitochondria. These results suggest that MI‐D acts as an uncoupler agent, a property closely related to its structural characteristics.
Identification of the copper chaperone, CUC‐1, in Caenorhabditis elegans: tissue specific co‐expression with the copper transporting ATPase, CUA‐1
Authors: Wakabayashi Tokumitsu , Nakamura Norihiro , Sambongi Yoshihiro , Wada Yoh , Oka Toshihiko , Futai Masamitsu
Published: May 2003

A cDNA encoding a putative copper chaperone protein, CUC‐1, was cloned from Caenorhabditis elegans. CUC‐1 had the characteristic motifs of MTCXXC and KKTGK, and showed 49.3 and 39.1% sequence identity with yeast Atx1p and human HAH1, respectively. Expression of CUC‐1 cDNA complemented a null atx1 mutant, the yeast copper chaperone gene, thus demonstrating that CUC‐1 is a functional copper chaperone. Studies with transgenic worms indicated that cuc‐1 and cua‐1, which encodes the copper transporting ATPase, are expressed together in intestinal cells of adult and hypodermal cells in the larvae. cua‐1 was also expressed in pharyngeal muscle but cuc‐1 was not. These results suggest that CUC‐1 and CUA‐1 constitute a copper trafficking pathway similar to the yeast counterparts in intestinal and hypodermal cells, and CUA‐1 may have a different function in pharyngeal muscle.
Characterization of the wound‐induced metallocarboxypeptidase inhibitor from potato1
Authors: Villanueva Josep , Canals Francesc , Prat Salomé , Ludevid Dolors , Querol Enrique , Avilés Francesc X
Published: May 2003

A partial cDNA clone for the potato wound‐inducible metallocarboxypeptidase inhibitor (PCI) was isolated from a cDNA library constructed from mRNA of abscisic acid (ABA)‐treated potato leaves. The full 5′ region of the cDNA was obtained through a RACE‐PCR protocol. PCI mRNA encodes a precursor polypeptide which comprises a 29 residue N‐terminal signal peptide, a 27 residue N‐terminal pro‐region, the 39 residue mature PCI protein, and a 7 residue C‐terminal extension. Northern blot analysis demonstrates that the PCI gene is transcriptionally activated by wounding, and wound signaling can be induced by ABA and jasmonic acid. Subcellular localization of the protein was investigated by immunocytochemistry and electron microscopy, showing that PCI accumulates within the vacuole. A partial PCI precursor form, comprising the mature protein and the C‐terminal extension, has been expressed in Escherichia coli and characterized. Its inability to inhibit carboxypeptidases, and stability to carboxypeptidase digestion, suggest that the C‐terminal pro‐domain may have, besides a probable vacuolar sorting function, a role in modulation of the inhibitory activity of PCI.
Lack of effect of RPE65 removal on the enzymatic processing of all‐trans‐retinol into 11‐cis‐retinol in vitro
Authors: Choo Dong Won , Cheung Eric , Rando Robert R
Published: May 2003

RPE65 is a major membrane associated protein found in the vertebrate retinal pigment epithelium (RPE). Various studies have shown this protein to be essential for visual function, possibly at the level of the processing of retinoids. The pigment epithelium is the anatomical site in which the visual chromophore 11‐cis retinal is generated. The two critical RPE enzymes in the isomerization pathway are lecithin retinol acyl transferase (LRAT) and isomerohydrolase, which processes all‐trans‐retinyl esters into 11‐cis‐retinol. Both enzymes are membrane bound. It is shown here that RPE65 can be largely extracted (90–95%) from RPE membranes by 1 M KCl by itself, or with added detergent CHAPS. The almost quantitative extraction of RPE65 from RPE membranes has little or no effect on in vitro LRAT and isomerohydrolase activities in quantitative enzymatic assays using RPE membranes, suggesting that RPE65 may not have an important role to play in the enzymatic processing of all‐trans‐retinol into 11‐cis‐retinol in vitro.
The business value of quality management systems certification. Evidence from Australia and New Zealand
Authors: Terziovski Milé , Samson Danny , Dow Douglas
Published: May 2003

ISO 9000 certification is one of the most popular quality assurance systems in the world. Despite its overwhelming popularity, there is considerable confusion and frustration surrounding the role and business value of ISO 9000 certification. A review of the literature revealed a major gap in research in this area of quality/operations management. The purpose of this study is to test the strength of the relationship between ISO 9000 certification and organisational performance in the presence and absence of a total quality management (TQM) environment. Our analysis is primarily of a large random sample of manufacturing companies in Australia and New Zealand. The central finding is that ISO 9000 certification is not shown to have a significantly positive effect on organisational performance in the presence or absence of a TQM environment. This supports the view that on average ISO 9000 certification has little or no explanatory power of organisational performance.
Repair of patellar tendon injuries using a cell–collagen composite
Authors: Awad Hani A. , Boivin Gregory P. , Dressler Matthew R. , Smith Frost N. L. , Young Randell G. , Butler David L.
Published: May 2003

Collagen gels were seeded with rabbit bone marrow‐derived mesenchymal stem cells (MSCs) and contracted onto sutures at initial cell densities of 1, 4, and 8 million cells/ml. These MSC–collagen composites were then implanted into full thickness, full length, central defects created in the patellar tendons of the animals providing the cells. These autologous repairs were compared to natural repair of identical defects on the contralateral side. Biomechanical, histological, and morphometric analyses were performed on both repair tissue types at 6, 12, and 26 weeks after surgery. Repair tissues containing the MSC–collagen composites showed significantly higher maximum stresses and moduli than natural repair tissues at 12 and 26 weeks postsurgery. However, no significant differences were observed in any dimensional or mechanical properties of the repair tissues across seeding densities at each evaluation time. By 26 weeks, the repairs grafted with MSC–collagen composites were one‐fourth of the maximum stress of the normal central portion of the patellar tendon with bone ends. The modulus and maximum stress of the repair tissues grafted with MSC–collagen composites increased at significantly faster rates than did natural repairs over time. Unexpectedly, 28% of the MSC–collagen grafted tendons formed bone in the regenerating repair site. Except for increased repair tissue volume, no significant differences in cellular organization or histological appearance were observed between the natural repairs and MSC–collagen grafted repairs. Overall, these results show that surgically implanting tissue engineered MSC–collagen composites significantly improves the biomechanical properties of tendon repair tissues, although greater MSC concentrations produced no additional significant histological or biomechanical improvement.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
The level of compressive load affects conclusions from statistical analyses to determine whether a lateral meniscal autograft restores tibial contact pressure to normal: A study in human cadaveric knees
Authors: Huang Arthur , Hull M. L. , Howell Stephen M.
Published: May 2003

This study addressed the question of whether the level of compressive load would affect the conclusions from statistical analyses aimed at determining how well a lateral meniscal autograft restores tibial contact (as indicated by the maximum contact pressure, mean pressure, and contact area) to that of the intact knee. If statistical analyses indicated that normal tibial contact was not restored with a higher, more physiologic load, then a secondary question was whether an autograft surgically implanted with bone plugs would improve tibial contact compared to that in a meniscectomized knee. Nine, fresh‐frozen human cadaveric knees were subjected to a low, non‐physiologic compressive load of 400 N and a higher, more physiologic compressive load of 1200 N under three conditions (lateral meniscus intact, lateral meniscus removed and reimplanted as an autograft, and lateral meniscus removed). Contact pressure on the lateral plateau was measured with pressure sensitive film at 0°, 15°, 30°, and 45° of flexion. At 400 N, p‐values from statistical analyses indicated that both the maximum and mean pressures with the autograft were comparable to those of the intact knee (p ≥ 0.685). However, at 1200 N, p‐values from statistical analyses indicated that both the maximum and mean pressures with the autograft were significantly greater than those of the intact knee (p ≤ 0.0001). Therefore studies designed to evaluate tibial contact pressure for a meniscal transplant should use a higher, more physiologic compressive load, because lower loads overestimate the transplant's effectiveness. Although none of the contact variables was restored to normal when the compressive load was increased to 1200 N, all of the contact variables were more normal than those of the meniscectomized knee. Thus, lateral meniscal allografts implanted using bone plugs can significantly improve contact pressure relative to a meniscectomized knee at the time of implantation.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Effect of compressive follower preload on the flexion–extension response of the human lumbar spine
Authors: Patwardhan Avinash G. , Havey Robert M. , Carandang Gerard , Simonds James , Voronov Leonard I. , Ghanayem Alexander J. , Meade Kevin P. , Gavin Thomas M. , Paxinos Odysseas
Published: May 2003

Traditional experimental methods are unable to study the kinematics of whole lumbar spine specimens under physiologic compressive preloads because the spine without active musculature buckles under just 120 N of vertical load. However, the lumbar spine can support a compressive load of physiologic magnitude (up to 1200 N) without collapsing if the load is applied along a follower load path. This study tested the hypothesis that the load–displacement response of the lumbar spine in flexion–extension is affected by the magnitude of the follower preload and the follower preload path. Twenty‐one fresh human cadaveric lumbar spines were tested in flexion–extension under increasing compressive follower preload applied along two distinctly different optimized preload paths. The first (neutral) preload path was considered optimum if the specimen underwent the least angular change in its lordosis when the full range of preload (0–1200 N) was applied in its neutral posture. The second (flexed) preload path was optimized for an intermediate specimen posture between neutral and full flexion. A twofold increase in flexion stiffness occurred around the neutral posture as the preload was increased from 0 to 1200 N. The preload magnitude (400 N and larger) significantly affected the range of motion (ROM), with a 25% decrease at 1200 N preload applied along the neutral path. When the preload was applied along a path optimized for an intermediate forward‐flexed posture, only a 15% decrease in ROM occurred at 1200 N. The results demonstrate that whole lumbar spine specimens can be subjected to compressive follower preloads of in vivo magnitudes while allowing physiologic mobility under flexion–extension moments. The optimized follower preload provides a method to simulate the resultant vector of the muscles that allow the spine to support physiologic compressive loads induced during flexion–extension activities.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro
Authors: Angele P. , Yoo J. U. , Smith C. , Mansour J. , Jepsen K. J. , Nerlich M. , Johnstone B.
Published: May 2003

Much attention has been given to the influences of bioactive factors on mesenchymal progenitor cell differentiation and proliferation, but few studies have examined the effect of mechanical factors on these cells. This study examined the effects of cyclic hydrostatic pressure on human bone marrow‐derived mesenchymal progenitor cells undergoing chondrogenic differentiation. Aggregates of bone marrow‐derived mesenchymal progenitor cells were cultured in a defined chondrogenic medium and were subjected to cyclic hydrostatic pressure. Aggregates were loaded at various time points: single (day 1 or 3) or multiple (days 1–7). At 14 and 28 days, aggregates were harvested for histology, immunohistochemistry, and quantitative DNA and matrix macromolecule analysis. The aggregates loaded for a single day did not demonstrate significant changes in proteoglycan and collagen contents compared with the non‐loaded controls. In contrast, for the multi‐day loaded aggregates, statistically significant increases in proteoglycan and collagen contents were found on both day 14 and day 28. Aggregates loaded for seven days were larger and histological staining indicated a greater matrix/cell ratio. This study indicates that hydrostatic pressure enhances the cartilaginous matrix formation of mesenchymal progenitor cells differentiated in vitro, and suggests that mechanical forces may play an important role in cartilage repair and regeneration in vivo.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Mitogen‐activated protein (MAP) kinases mediate PMMA‐induction of osteoclasts
Authors: Abbas S. , Clohisy J. C. , Abu‐Amer Y.
Published: May 2003

Inflammatory osteolysis induced by implant‐derived wear debris is associated with infiltration of various cell‐types to the implant–bone interface leading to abundant secretion of pro‐inflammatory cytokines and activation of proteinases that together lead to propagation of the localized inflammatory response and periprosthetic bone erosion. Tumor necrosis factor family members are considered to be direct mediators of inflammation and osteolysis. These cytokines exert their osteoclastic effects via activation of the transcription factor NF‐κB and certain MAP kinases, including c‐Jun, Erks and p38, all known to be essential for the development of osteoclasts. We have recently documented that the osteoclastogenic cytokines TNF and RANKL play a pivotal role in the development of inflammatory osteolysis. We have also found that PMMA particles stimulate osteoclastogenesis, at least in part, by induction of RANKL, TNF, and by activation of the transcription factor NF‐κB. More importantly, our data indicate that inhibitors of the osteoclastogenic factors, TNF and RANKL abrogate particle‐induced osteoclastogenesis. In the current study, we investigated if PMMA particles activate MAP kinases, and the potential role of these kinases as mediators of osteolysis. Using kinase assays, we show that in osteoclast precursors, PMMA particles markedly and rapidly activate p38 and ERK MAP kinases. This activation was specific, evident by complete blockade with specific inhibitory compounds. Similarly, we show that PMMA particles activate the JNK pathway, which is known to be involved in inflammatory and osteoclastogenic events. We also show that p38 MAP kinase regulates PMMA‐activation of NF‐κB, thus providing a possible mechanism for particle action in osteoclast precursors. Finally, we provide evidence that specific inhibitors of MAP kinases are capable of inhibiting PMMA‐stimulated osteoclastogenesis. These data provide evidence that MAP kinases are potent mediators of particle‐induced osteoclastogenesis.
Antibiotics and the development of resistant microorganisms. Can homeopathy be an alternative?
Authors: Viksveen Petter
Published: May 2003

Antibiotic resistance is a global public health problem. Once confined primarily to hospitals it is now increasingly common in primary care. The prevalence of resistant bacteria is rising, and organisms resistant to almost all antibiotics have been identified. The main causes are indiscriminate prescribing and the use of antibiotics in animal feeds and other agricultural applications. Policies to restrict use of antibiotics have had limited success. Homeopathy may have a role to play in combating the development of antibiotic resistance. Clinical research suggests that homeopathy is effective in the treatment of upper respiratory tract infections in children, a frequent cause of inappropriate antibiotic prescribing. The EU recommends the use of homeopathy in organic animal husbandry, and it is used by significant numbers of farmers. At present there is little data on the effectiveness of homeopathy in this setting. Further research should be done.
Run-of-the-Mill Lunacy
Authors: ENCKE JEFFREY
Published: May 2003

In her 1980 interview with Charles Bukowski, Italian journalist Fernanda Pivano posed what seemed at first an innocuous question: “Why are you called Charles in the books and Hank in your private life?”
Intramammary pressure in the lactating sow in response to oxytocin and during natural milk ejections throughout lactation
Authors: Kent Jacqueline C , Kennaugh Linda M , Hartmann Peter E
Published: May 2003

We developed a simple, non-invasive method to measure the intramammary pressure (IMP) response in sows during natural milk ejection and after i.v. injections of oxytocin. The teats of sows were cannulated and the amplitude and duration of IMP changes were measured via a pressure transducer linked to a computer. During natural milk ejections, the amplitude of the response was 5·5±1·8 kPa (mean±SD) and the duration of response at half the peak amplitude was 6·8±1·6 s. In response to oxytocin a threshold response occurred at 60 mIU oxytocin with no further change up to 200 mIU. The amplitude of the response to an i.v. dose of 60–200 mIU oxytocin (5·5±2·2 kPa) and duration (6·4±1·7 s) were similar to that during a natural milk ejection. The responses of two galactophorous ducts of a teat measured simultaneously were similar in peak amplitude and duration. When the responses of four glands of a sow were measured simultaneously, there was a lag time in the onset of the IMP peak from the anterior to the posterior glands, and an increase in the peak amplitude from anterior to posterior. Both during natural milk ejections and in response to oxytocin injections, there were significant differences in peak amplitude between sows. We also aimed to determine whether the pressure or duration of milk flow during natural milk ejections was limiting piglet growth rates. IMP of nine sows and the growth rates of their piglets were measured. Both the peak amplitude of IMP response and the growth rate of piglets increased over the course of lactation, but the relationship was not causal. We found that the growth rate of piglets did not depend on IMP amplitude or duration, but we suggest that it may depend on the frequency of suckling and/or the ability of piglets to withdraw milk while it is available.
Molecular characterization of the goat CSN1S101 allele
Authors: Cosenza Gianfranco , Illario Rosa , Rando Andrea , di Gregorio Paola , Masina Piero , Ramunno Luigi
Published: May 2003

Caseins (αs1, β, αs2, e κ) represent about 80% of the whole protein content of ruminant milk. Each of these proteins is encoded by single copy genes (CSN1S1, CSN2, CSN1S2 and CSN3, respectively) clustered on a ∼200-kb segment of chromosome 6 (Ferretti et al. 1990; Gallagher et al. 1994) in the order: CSN1S1, CSN2, CSN1S2 and CSN3 (Mercier & Vilotte, 1993). Furthermore, in cattle and goat CSN1S1 and CSN2 are convergently transcribed (Leroux & Martin, 1996; Rijnkles et al. 1997) and are only 20 and 12 kb apart, respectively.
The Swedish relief expedition to Antarctica 1903–04
Authors: Lewander Lisbeth
Published: May 2003

Swedish attempts in 1903–04 to rescue Otto Nordenskjöld's expedition to Antarctica are examined in the context of an international competition involving Sweden, Argentina, and France. The Swedish relief expedition, led by Captain Olof Gyldén, is viewed partly as a little-known expedition and partly for its potential as a major national event. The developments and progress of the Swedish and French expeditions are shown alongside those of the Argentine expedition, which ultimately was successful in its attempts to rescue Nordenskjöld. The Swedish relief expedition never produced a significant national collective memory, unlike several other unsuccessful rescue operations. Potential reasons for this are examined, including the role of internal conflicts among individuals both on the expedition and in Sweden, and the failure to make the expedition a national event. The different attempts to make the relief expedition a major nationalist effort included issues concerning choice of vessel, staff, and equipment; media accounts of competing relief expeditions in which Sweden's positive national features were contrasted with those of ‘others;’ and the views on the competition expressed by various participants.
Lone mothers, social exclusion and depression
Authors: TARGOSZ S. , BEBBINGTON P. , LEWIS G. , BRUGHA T. , JENKINS R. , FARRELL M. , MELTZER H.
Published: May 2003

Background. In this paper, data from the British National Survey of Psychiatric Morbidity are used to assess depressive disorders and markers of social disadvantage in women bringing up children on their own.

Method. The household component of the British National Surveys of Psychiatric Morbidity was based on a stratified random sample of >10000 subjects. This paper reports on 5281 women interviewed in person. Psychiatric symptoms and ICD-10 diagnoses were established by lay interviewers using the CIS-R. Results are presented in terms of depressive episode and mixed anxiety/depressive disorder. Housing tenure and access to a car were used as proxy measures of material status. The life event rate in the 6 months before interview was used to indicate overall exposure to stress, and subjects were asked in detail about perceived social support. Information was collected about various other sociodemographic attributes. Lone mothers were compared with supported mothers and with women not involved in care of children under 16.

Results. Lone mothers had prevalence rates of depressive episode of 7%, about three times higher than any other group. The milder condition, mixed anxiety/depression, was also increased in frequency. These increased rates of depressive conditions were no longer apparent after controlling for measures of social disadvantage, stress and isolation.

Conclusions. Lone mothers are increasing in numbers as marital stability declines. Their high rates of material disadvantage and of depressive disorder may have considerable implications for psychiatric and social policy.
To the Editor
Authors: BENTSEN HÅVARD
Published: May 2003

In the July 2002 issue of this journal, Pilling et al. published a meta-analysis of family intervention studies in schizophrenia.
Study of drift compression for heavy ion beams
Authors: QIN HONG , DAVIDSON RONALD C.
Published: May 2003

The longitudinal dynamics of drift compression and pulse shaping
for a space-charge-dominated heavy ion fusion beam is studied.
A nonperiodic quadrupole lattice is designed for a beam undergoing
drift compression, and an adiabatically matched solution is
found for the transverse envelope equations in the nonperiodic
lattice.
Repetitive induction voltage modulator for heavy ion fusion
Authors: HORIOKA K. , NAKAJIMA M. , WATANABE M. , HONDA M. , HOTTA E. , SHIHO M. , OGAWA M. , HASEGAWA J. , KISHIRO J. , TAKAYAMA K.
Published: May 2003

Activities of research and development on repetitive induction
voltage modulators in the Tokyo Institute of Technology–High
Energy Accelerator Research Organization group are presented
along with a discussion of the magnetic response of ferro-magnetic
materials to fast magnetization and a transient beam loading
in the modulators. The modulator is composed of independently
driven modules switched by field effect transistors. To make
waveform control, the induced voltages are stacked and synthesized
in the induction unit. A proof-of-principle experiment shows
that the module elements are successfully operated up to megahertz
levels with good reproducibility. For the evaluation of magnetic
core response, magnetic characteristics are investigated over
a wide range of parameters, and an empirical core loss scaling
is derived at minor-hysteresis loops. Using the prototype induction
module, we have also investigated the effect of beam loading.
Results indicate that the effect depends not only on the impedance
of the driving circuit but on nonlinearity of the magnetic-core
response. This means that the response of the induction modulator
depends on the time scale of domain motion and operating point
in the B-H plane of magnetic materials. Based on the progress
of the component technology in the induction accelerator and
database of magnetic materials, a system design has been developed.
Insight into the materials choice for inertial fusion energy
reactors considering radiation damage: Neutron irradiation
intensities and basic knowledge from multiscale modeling
Authors: PERLADO J.M. , DOMÍNGUEZ E. , LODI D. , MARIAN J. , SALVADOR M. , SANZ J. , GONZÁLEZ A.I. , CATURLA M.J. , DE LA RUBIA T. DÍAZ , WIRTH B.D. , COLOMBO L.
Published: May 2003

A review of structural materials choices under irradiation
in fusion environments is presented. Results on the neutron
source term and the intensities in the structural materials
as a function of pulse time, energy, and protection is given.
The role of multiscale modeling for understanding the basic
physics in irradiated materials is explained, and simulations
of metals under pulse irradiation and SiC are reported.
Image-to-space path planning for a SCARA manipulator with single color
camera
Authors: Reyes José F. , Chiang Luciano E.
Published: May 2003

This paper presents a methodology for image-to-space path planning of a SCARA manipulator with a single static color camera. The method proposes a two step algorithm for estimating object position on the image plane and then mapping into space to find required angular values of the manipulator joints. Tests were carried with a computational routine to estimate position on the image plane of a set of different fruits under natural light conditions. Finally the method was tested using a robotic arm and similarly structured objects. Hardware and software implementation of the present method is of low cost when compared to current commercial technology, and operational results are promising but dependent on environmental illumination control and camera calibration accuracy. The methodology is intended to be applied in the automatic classification of fruits.
Cost-oriented virtual reality and real-time control system architecture
Authors: Wollherr Dirk , Buss Martin
Published: May 2003

In this paper the use of inexpensive standard hardware and software is proposed in place of high-cost commercial solutions to set up real-time control experiments with a human in the control loop, including graphical and haptic virtual reality (VR). For this purpose a generic simulation environment for the implementation of control experiments using VR with haptic feedback and their evaluation, has been developed. As an example, setups of a car simulator with a human in the control loop and an inverted pendulum as an experiment for student laboratories are presented.
Proactive maintenance strategy for harbour crane operation improvement
Authors: Iung B. , Morel G. , Léger J.B.
Published: May 2003

Quay cranes are particular transportation devices for which operation's safety and CRAMP parameters (Cost, Reliability, Availability, Maintainability, and Productivity) should be fulfilled with regard to a harbor maintenance strategy. The maintenance process is first considered within a holistic modeling framework in order to cope with the current practices of treating strategic, operational and engineering maintenance issues independently without taking into account their interactions within
an entire Enterprise System. Proactive maintenance is then highlighted as a new model aiming to globally optimize the components operation parameters throughout three interacting prognosis, diagnosis and monitoring processes. Technical issues related to Intelligent Maintenance System are finally proposed in
order to support proactive maintenance operations at the enterprise field level and applied to quay cranes in a particular site within the frame of the European Eureka ‘Robcrane' project.
Book reviews
Authors: Andrew Alex M.
Published: May 2003

DESIGNING SOCIABLE ROBOTS, by Cynthia L. Breazeal, MIT Press,
Cambridge, Massachusetts, 2002, xviii + 263 pp., ISBN 0-262-02510-8, with CD-ROM (Hbk, £34.50).
Book reviews
Authors: Andrew Alex M.
Published: May 2003

INTELLIGENT INFORMATION SYSTEMS 2002: PROCEEDINGS OF THE IIS'2002 SYMPOSIUM,
SOPOT, POLAND, JUNE 3–6, 2002, edited by Mieczysław A. Kłopotek,
Sławomir T. Wierzchoń and Maciej Michalewicz, Physica-Verlag (A Springer-Verlag Company),
Heidelberg, 2002, x + 468 pp., ISBN 3-7908-1509-8, ISSN 1615-3871
(Pbk, £46.00). Advances in Soft Computing Series.
Book reviews
Authors: Andrew Alex M.
Published: May 2003

SPIKING NEURON MODELS: SINGLE NEURONS, POPULATIONS, PLASTICITY, by Wulfram Gerstner and Werner Kistler, Cambridge University Press, Cambridge, 2002, xiv + 479 pp., ISBN 0-521-89079-9 (Pbk, £24.95, also hardback, ISBN 0-521-81384-0 (£65.00).
Book reviews
Authors: Andrew Alex M.
Published: May 2003

HUMANS AND AUTOMATION: SYSTEM DESIGN AND RESEARCH ISSUES, by Thomas B. Sheridan, Wiley, in cooperation with the Human Factors and Ergonomics
Society, Santa Barbara, California, 2002, pp. xii, 264. ISBN 0-471-23428-1. Wiley Series in System Engineering and Management HFES Issues in Human Factors and Ergonomics Series, Vol. 3 (Hardback, £37.50).
14. SOCIAL CHANGE AND LANGUAGE SHIFT: SOUTH AFRICA
Authors: Kamwangamalu Nkonko M.
Published: May 2003

Studies of social change and language maintenance and shift have tended to focus on minority immigrant languages (e.g., Fishman, 1991; Gal, 1979; Milroy, 2001; Stoessel, 2002). Very little is known about language shift from a demographically dominant language to a minority but economically dominant one (e.g., Bowerman, 2000; de Klerk, 2000; Kamwangamalu, 2001, 2002a,b, & in press; Reagan, 2001). This chapter contributes to such research by looking at the current language shift from majority African languages such as Sotho, Xhosa, and Zulu to English in South Africa. In particular, it examines to what extent the sociopolitical changes that have taken place in South Africa (i.e., the demise of apartheid and its attendant structures) have impacted everyday linguistic interaction and have contributed to language shift from the indigenous African languages to English, especially in urban Black communities. It argues that a number of factors, among them the economic value and international status of English, the perceived lower status of the indigenous African languages, the legacy of apartheid-based Bantu education, the new multilingual language policy, the linguistic behaviors of language policy makers, etc., interact in complex ways to accelerate language shift in urban Black communities. In conclusion, the chapter explores ways in which the observed language shift can be curbed to prevent what Skutnabb-Kangas (2000) has termed “linguistic genocide,” particularly in a country that has a well-documented history of this phenomenon (Lanham, 1978; Prabhakaran, 1998).
Neural Network-Based Geometry Classification for Navigation Satellite Selection
Authors: Jwo Dah-Jing , Lai Chien-Cheng
Published: May 2003

The neural networks (NN)-based geometry classification for good or acceptable navigation satellite subset selection is presented. The approach is based on classifying the values of satellite Geometry Dilution of Precision (GDOP) utilizing the classification-type NNs. Unlike some of the NNs that approximate the function, such as the back-propagation neural network (BPNN), the NNs here are employed as classifiers. Although BPNN can also be employed as a classifier, it takes a long training time. Two other methods that feature a fast learning speed will be implemented, including Optimal Interpolative (OI) Net and Probabilistic Neural Network (PNN). Simulation results from these three neural networks are presented. The classification performance and computational expense of neural network-based GDOP classification are explored.
A Trend Analysis of Air Traffic Occurrences in the UK Airspace
Authors: Majumdar Arnab , Ochieng Washington
Published: May 2003

The volume of air traffic has increased considerably in the United Kingdom in recent decades and with further predicted increases, there is concern that safety is not compromised. In the UK, the number of occurrences is a key safety performance indicator. An occurrence can be thought of as a failure in the chain of operations in the air traffic system. Some of these occurrences result in a loss of separation between aircraft, varying from a slight loss of separation posing no danger of collision to a very serious loss with a significant risk of collision, known as an airprox. However, in the UK this definition is extended to include controller overload that does not necessarily involve a loss of separation. This paper analyses recent occurrence trends in the UK airspace attributed to air traffic control during the period 1998 to 2000 using data from the Civil Aviation Authority and the United Kingdom Airprox Board. The results indicate a decline in the rate of occurrences over the period 1990–1999 due to safety aids on board aircraft and in control rooms. Furthermore, the different conditions under which airproxes occur have been explored and observations made on duration and causes of controller overloads.
A New Approach to Sequential Tidal Prediction
Authors: El-Rabbany Ahmed , El-Diasty Mohamed
Published: May 2003

Accurate tide prediction is required for safe marine navigation in shallow waters as well as for other marine operations. Traditionally, tide prediction was carried out using the harmonic method, which is based on the identification of the harmonic tidal constituents existing in the tidal record. Unfortunately, however, unless long tidal records are available at the tide gauges, some important tidal constituents may not be identified. This, in turn, deteriorates the accuracy of the tidal prediction. More recently, a sequential least-squares prediction method capable of using relatively short tidal records was developed. This method allows for the modifications and corrections of the original solution of the tidal constituents when new observations and parameters are included. Although it reduces the computation time significantly compared to the batch harmonic method, this method exhibits large residuals particularly when very short tidal records are used. To overcome the limitations of the sequential least-squares method, a neural network-based model is developed for sequentially predicting the tidal heights using tide data series collected at various tide gauges. A modular, three-layer feedforward neural network trained using the back-propagation algorithm is used for this purpose. Tide data from three tide gauges are used to validate the model. A comparison is made between the developed neural network model and the sequential least squares method for tidal prediction. It is shown that the accuracy level of the tidal prediction has improved by a factor of 5 when using the neural network model.
Sabinevon Fischer on the Barcelona pavilion plus two other reviews
Authors: von Fischer Sabine , Hill Richard
Published: May 2003

The building that for many incorporates the essence of twentieth-century Modern architecture existed for only six months. Critics have called the Barcelona Pavilion a myth, an icon, an image. In this book, Josep Quetglas claims that it is a stage where the performance can only be described by ‘emptiness and the future’. And although what is true for theatre might not apply to architecture, the dramatic dynamics inherent in modern theatre's concern that the stage set should never repeat the text of the play do help explain the varied and contradictory interpretations of the Barcelona Pavilion.