bluuebunny/crossref_metadata_2025 huggingface dataset:
X‐ray diffraction and far‐UV CD studies of filaments formed by a leucine‐rich repeat peptide: structural similarity to the amyloid fibrils of prions and Alzheimer's disease β‐protein
Authors: Symmons Martyn F , Buchanan Sean G.St.C , Clarke David T , Jones Gareth , Gay Nicholas J
Published: July 2002

The development of neuro‐degenerative diseases often involves amyloidosis, that is the formation of polymeric fibrillar structures from normal cellular proteins or peptides. For example, in Alzheimer's disease, a 42 amino acid peptide processed from the amyloid precursor protein forms filaments with a β‐sheet structure. Because of this, the structure and dynamics of polymeric peptide filaments is of considerable interest. We showed previously that a 23 amino acid peptide constituting a single leucine‐rich repeat (LRRN) polymerises spontaneously in solution to form long filaments of a β‐sheet structure, a property similar to that of Alzheimer's β‐amyloid and prion peptides. Here we report that a variant of LRRN in which a highly conserved asparagine residue is replaced by aspartic acid does not form either filaments or β structure. By contrast, a variant which replaces this asparagine residue with glutamine forms filaments ultrastructurally indistinguishable from those of LRRN. Electron micrographs of LRRN filaments show that many consist of two interleaved strands which appear to have a ribbon‐like morphology. X‐ray diffraction patterns from oriented LRRN fibres reveal that they are composed of long β‐sheet arrays, with the interstrand hydrogen bonding parallel to the filament axis. This `cross‐β' structure is similar to that adopted by β‐amyloid and prion derived fibres. Taken together, these results indicate that the LRR filaments are stabilised by inter‐ or intra‐strand hydrogen bonded interactions comparable to the asparagine ladders of β‐helix proteins or the `glutamine zippers' of poly‐glutamine peptides. We propose that similar stabilising interactions may underlie a number of characterised predispositions to neuro‐degenerative diseases that are caused by mutations to amide residues. Our finding that amyloid‐like filaments can form from a peptide motif not at present correlated with degenerative disease suggests that a propensity for β‐filament formation is a common feature of protein sub‐domains.
High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria
Authors: Korshunov Sergey S. , Skulachev Vladimir P. , Starkov Anatoly A.
Published: July 2002

Formation of H2O2 has been studied in rat heart mitochondria, pretreated with H2O2 and aminotriazole to lower their antioxidant capacity. It is shown that the rate of H2O2 formation by mitochondria oxidizing 6 mM succinate is inhibited by a protonophorous uncoupler, ADP and phosphate, malonate, rotenone and myxothiazol, and is stimulated by antimycin A. The effect of ADP is abolished by carboxyatractylate and oligomycin. Addition of uncoupler after rotenone induces further inhibition of H2O2 production. Inhibition of H2O2 formation by uncoupler, malonate and ADP+Pi is shown to be proportional to the ΔΨ decrease by these compounds. A threshold ΔΨ value is found, above which a very strong increase in H2O2 production takes place. This threshold slightly exceeds the state 3 ΔΨ level. The data obtained are in line with the concept [Skulachev, V.P., Q. Rev. Biophys. 29 (1996), 169–202] that a high proton motive force in state 4 is potentially dangerous for the cell due to an increase in the probability of superoxide formation.
Lateral self‐assembly of E‐cadherin directed by cooperative calcium binding
Authors: Alattia Jean-René , Ames James B. , Porumb Tudor , Tong Kit I. , Heng Yew Meng , Ottensmeyer Peter , Kay Cyril M. , Ikura Mitsuhiko
Published: July 2002

We report the Ca2+ binding characteristics of recombinant Ecad12, a construct spanning the first two repeats of epithelial cadherin, and demonstrate the links between Ca2+ binding and dimer formation. Sedimentation equilibrium and dynamic light scattering experiments show that weak dimerization of Ecad12 occurs in the presence of 10 mM Ca2+ (K
P
d=0.17 mM), while no appreciable dimer formation was detected in the absence of Ca2+. Ca2+‐induced dimerization was also observed in electron microscopy images of Ecad12. We conclude from Ca2+ titration experiments monitored by tryptophan fluorescence and flow dialysis that dimerization does not affect the equilibrium binding constant for Ca2+. However, the value of the Hill coefficient for Ca2+ binding increases from 1.5 to 2.4 as the protein concentration increases, showing that dimer formation largely contributes to the cooperativity in Ca2+ binding. Based on these observations and previous crystallographic studies, we propose that calcium acts more likely as a geometrical aligner ensuring the proper assembly of cadherin molecules, rather than a simple adhesive.
Cloning and characterization of a novel human pH‐dependent organic cation transporter, OCTN1
Authors: Tamai Ikumi , Yabuuchi Hikaru , Nezu Jun-ichi , Sai Yoshimichi , Oku Asuka , Shimane Miyuki , Tsuji Akira
Published: July 2002

cDNA for a novel proton/organic cation transporter, OCTN1, was cloned from human fetal liver and its transport activity was investigated. OCTN1 encodes a 551‐amino acid protein with 11 transmembrane domains and one nucleotide binding site motif. It is strongly expressed in kidney, trachea, bone marrow and fetal liver and in several human cancer cell lines, but not in adult liver. When expressed in HEK293 cells, OCTN1 exhibited saturable and pH‐dependent [3H]tetraethyl ammonium uptake with higher activity at neutral and alkaline pH than at acidic pH. Furthermore, treatment with metabolic inhibitors reduced the uptake, which is consistent with the presence of the nucleotide binding site sequence motif. Although its subcellular localization and detailed functional characteristics are not clear at present, OCTN1 appears to be a novel proton antiporter that functions for active secretion of cationic compounds across the renal epithelial brush‐border membrane. It may play a role in the renal excretion of xenobiotics and their metabolites.
Isolation and characterization of the circulating form of human endostatin
Authors: Ständker Ludger , Schrader Michael , Kanse Sandip M , Jürgens Michael , Forssmann Wolf-Georg , Preissner Klaus T
Published: July 2002

Recently, fragments of extracellular proteins, including endostatin, were defined as a novel group of angiogenesis inhibitors. In this study, human plasma equivalent hemofiltrate was used as a source for the purification of high molecular weight peptides (10–20 kDa), and the isolation and identification of circulating human endostatin are described. The purification of this C‐terminal fragment of collagen α1(XVIII) was guided by MALDI‐MS and the exact molecular mass determined by ESI‐MS was found to be 18 494 Da. N‐terminal sequencing revealed the identity of this putative angiogenesis inhibitor and its close relation to mouse endostatin. The cysteine residues 1–3 and 2–4 in the molecule are linked by disulfide bridges. In vitro biological characterization of the native protein demonstrated no anti‐proliferative activity on different endothelial cell types. These data indicate that human endostatin, which is a putative angiogenesis inhibitor, is present in the circulation.
Substrate/propeptide‐derived endo‐epoxysuccinyl peptides as highly potent and selective cathepsin B inhibitors
Authors: Schaschke Norbert , Assfalg-Machleidt Irmgard , Machleidt Werner , Moroder Luis
Published: July 2002

Based on recent information about the anti‐substrate binding mode of the propeptide portion of procathepsin B and the well established substrate‐like binding of epoxysuccinyl‐dipeptide carboxylates to the S′ subsites of cathepsin B a new endo‐trans‐epoxysuccinyl peptide was synthesized that contains the dipeptide moiety Leu‐Pro‐OH for the P1′–P2′ substrate positions and the tripeptide moiety Leu‐Gly‐Gly‐OMe (sequence portion 46–48 of the propeptide) for the P2–P4 positions in anti‐substrate orientation. With an unequivocal (2S,3S) configuration this new trans‐epoxysuccinyl peptide derivative was found to inhibit cathepsin B with an apparent second‐order rate constant of 1 520 000 M−1 s−1 which represents so far the most potent inhibitor among E‐64‐derived compounds. Conversely, the (2R,3R) diastereomer exhibited a significantly lower inhibition potency. This observation fully agrees with our previous findings that inhibitor/enzyme interactions at the S subsites are favored by the (2S,3S) and reverse interactions at the S′ subsites by the (2R,3R) configuration of the trans‐epoxysuccinyl moiety.
Identification and characterization of a novel member of the dystrobrevin gene family
Authors: Puca Annibale Alessandro , Nigro Vincenzo , Piluso Giulio , Belsito Angela , Sampaolo Simone , Quaderi Nandita , Rossi Elena , Di Iorio Giuseppe , Ballabio Andrea , Franco Brunella
Published: July 2002

A new member of the dystrobrevin gene family was identified using a bioinformatics approach. Sequence analysis indicates that this gene, named DTN‐B, is highly homologous to the rabbit A0, the previously described dystrobrevin (DTN), Torpedo 87 kDa and to the C‐terminus of dystrophin. The coiled‐coil domain, shown to be the site of interaction between dystrobrevins and dystrophin, is highly conserved. Immunostaining studies indicate that DTN‐B and DTN expression is absent in affected muscle fibers from DMD patients and carriers.
Peptide binding consensus of the NHE‐RF‐PDZ1 domain matches the C‐terminal sequence of cystic fibrosis transmembrane conductance regulator (CFTR)
Authors: Wang Shusheng , Raab Ronald W , Schatz Peter J , Guggino William B , Li Min
Published: July 2002

The Na+‐H+ exchanger regulatory factor (NHE‐RF) is a cytoplasmic phosphoprotein that was first found to be involved in protein kinase A mediated regulation of ion transport. NHE‐RF contains two distinct protein interaction PDZ domains: NHE‐RF‐PDZ1 and NHE‐RF‐PDZ2. However, their binding partners are currently unknown. Because PDZ domains usually bind to specific short linear C‐terminal sequences, we have carried out affinity selection of random peptides for specific sequences that interact with the NHE‐RF PDZ domains and found that NHE‐RF‐PDZ1 is capable of binding to the CFTR C‐terminus. The specific and tight association suggests a potential regulatory role of NHE‐RF in cystic fibrosis transmembrane conductance regulator (CFTR) function.
Dipeptidyl peptidase IV (DP IV, CD26) is involved in regulation of DNA synthesis in human keratinocytes
Authors: Reinhold Dirk , Vetter Robert W , Mnich Kati , Bühling Frank , Lendeckel Uwe , Born Ilona , Faust Jürgen , Neubert Klaus , Gollnick Harald , Ansorge Siegfried
Published: July 2002

Various studies have shown that the membrane ectoenzyme dipeptidyl peptidase IV (DP IV, CD26), expressed on T, NK, and B cells in the human immune system, is involved in the regulation of DNA synthesis and cytokine production. Here, we clearly demonstrate that this enzyme is highly expressed also on human epidermal foreskin and split‐skin keratinocytes and that the specific DP IV inhibitors Lys[Z(NO2)]‐thiazolidide, Lys[Z(NO2)]‐pyrrolidide inhibit the enzymatic activity as well as the DNA synthesis of these cells. These data demonstrate that CD26 plays a role also in regulation of DNA synthesis of epidermal keratinocytes and that the enzymatic activity is required for mediating these effects.
Quercetin metabolites inhibit copper ion‐induced lipid peroxidation in rat plasma1
Authors: da Silva Edson L , Piskula Mariusz K , Yamamoto Norio , Moon Jae-Hak , Terao Junji
Published: July 2002

The oxidative susceptibility of plasma obtained from rats after intragastric administration of quercetin was studied to know whether or not quercetin acts as an in vivo antioxidant after metabolic conversion. Quercetin was raised in the rat blood plasma essentially as glucuronide and/or sulfate conjugates. The plasma obtained from rats after quercetin administration was more resistant against copper sulfate‐induced lipid peroxidation than the control plasma on the basis of the accumulation of cholesteryl ester hydroperoxides and the consumption of α‐tocopherol. The results strongly suggest that some conjugated metabolites of quercetin act as effective antioxidants when plasma is subject to metal ion‐induced lipid peroxidation.
Binding specificities and affinities of egf domains for ErbB receptors
Authors: Jones Jennifer T , Akita Robert W , Sliwkowski Mark X
Published: July 2002

ErbB receptor activation is a complex process and is dependent upon the type and number of receptors expressed on a given cell. Previous studies with defined combinations of ErbB receptors expressed in mammalian cells have helped elucidate specific biological responses for many of the recognized gene products that serve as ligands for these receptors. However, no study has examined the binding of these ligands in a defined experimental system. To address this issue, the relative binding affinities of the egf domains of eleven ErbB ligands were measured on six ErbB receptor combinations using a soluble receptor‐ligand binding format. The ErbB2/4 heterodimer was shown to bind all ligands tested with moderate to very high affinity. In contrast, ErbB3 showed much more restrictive ligand binding specificity and measurable binding was observed only with heregulin, neuregulin2β, epiregulin and the synthetic heregulin/egf chimera, biregulin. These studies also revealed that ErbB2 preferentially enhances ligand binding to ErbB3 or ErbB4 and to a lesser degree to ErbB1.
Native acridone synthases I and II from Ruta graveolens L. form homodimers
Authors: Lukačin Richard , Springob Karin , Urbanke Claus , Ernwein Claudia , Schröder Gudrun , Schröder Joachim , Matern Ulrich
Published: July 2002

Acridone synthase II cDNA was cloned from irradiated cell suspension cultures of Ruta graveolens L. and expressed in Escherichia coli. The translated polypeptide of M
r 42 681 revealed a high degree of similarity to heterologous chalcone and stilbene synthases (70–75%), and the sequence was 94% identical to that of acridone synthase I cloned previously from elicited Ruta cells. Highly active recombinant acridone synthases I and II were purified to apparent homogeneity by a four‐step purification protocol, and the affinities to N‐methylanthraniloyl‐CoA and malonyl‐CoA were determined. The molecular mass of acridone synthase II was estimated from size exclusion chromatography on a Fractogel EMD BioSEC (S) column at about 45 kDa, as compared to a mass of 44±3 kDa found for the acridone synthase I on Superdex 75. Nevertheless, the sedimentation analysis by ultracentrifugation revealed molecular masses of 81±4 kDa for both acridone synthases. It is proposed, therefore, that the acridone synthases of Ruta graveolens are typical homodimeric plant polyketide synthases.
Calcium release from InsP3‐sensitive internal stores initiates action potential in Chara
Authors: Biskup Bernhard , Gradmann Dietrich , Thiel Gerhard
Published: July 2002

Neomycin and U73122 are known to suppress inositol 1,4,5‐trisphosphate (InsP3) production by inhibition of phospholipase C. We studied the effects of these inhibitors on the excitatory currents, I
ex, in Chara corallina under voltage‐clamp conditions. Computer simulations of the experimental effects by a minimum model for the excitatory reaction pathway allow the assignment of the inhibitory effects to one specific reaction step, i.e. the release of Ca2+ from InsP3‐sensitive internal stores. In contrast, the inhibitory effect of La3+ on I
ex suggests inactivation of Cl− channels. Furthermore, ryanodine‐sensitive Ca2+ stores seem to be irrelevant for electrical excitation in Chara.
The N‐terminal 77 amino acids from tobacco N‐acetylglucosaminyltransferase I are sufficient to retain a reporter protein in the Golgi apparatus of Nicotiana benthamiana cells
Authors: Essl D , Dirnberger D , Gomord V , Strasser R , Faye L , Glössl J , Steinkellner H
Published: July 2002

In order to investigate sequences of tobacco N‐acetylglucosaminyltransferase I (GnTI), involved in targeting to and retention in the plant Golgi apparatus the cytoplasmic transmembrane stem (CTS) region of the enzyme was cloned in frame with the cDNA of the green fluorescent protein (gfp) and subsequently transiently expressed in Nicotiana benthamiana plants using a tobacco mosaic virus (TMV) based expression vector. Confocal laser scanning microscopy showed small fluorescent vesicular bodies in CTS‐gfp expressing cells, while gfp alone expressed in control plants was uniformly distributed in the cytoplasm. The CTS‐gfp fusion protein colocalised with immunolabelling observed by an antibody specific for the Golgi located plant Lewis a epitope. Furthermore, treatment with brefeldin A, a Golgi specific drug, resulted in the formation of large fluorescent vesiculated areas. These results strongly suggest a Golgi location for CTS‐gfp and as a consequence our findings reveal that the N‐terminal 77 amino acids of tobacco GnTI are sufficient to target to and to retain a reporter protein in the plant Golgi apparatus and that TMV based vectors are suitable vehicles for rapid delivery of recombinant proteins to the secretory pathway.
Oyster IKK‐like protein shares structural and functional properties with its mammalian homologues
Authors: Escoubas Jean-Michel , Briant Laurence , Montagnani Caroline , Hez Stephanie , Devaux Christian , Roch Philippe
Published: July 2002

In our search for genes involved in oyster immunity we isolated a cDNA encoding a polypeptide closely related to the mammalian IκB kinase (IKK) family. IKK proteins play a central role in cell signaling by regulating nuclear factor‐κB (NF‐κB) activation. We report here the cloning of an oyster IKK‐like protein (oIKK) which possesses the characteristic organization of the mammalian IKK proteins, namely an amino‐terminal kinase domain followed by a leucine zipper region and a carboxyl‐terminal helix‐loop‐helix motif. When transfected into human cell lines, oIKK activated the expression of NF‐κB‐controlled reporter gene, whereas transfections with mutants of oIKK deleted within the kinase domain or within the helix‐loop‐helix motif respectively abolished and greatly reduced reporter gene activation. These results indicate that oIKK can replace the hIKK‐α in catalyzing NF‐κB nuclear translocation, and in triggering gene expression. Our results sustain the concept of an evolutionarily conserved signaling machinery in which IKK plays a major role.
Enzymatic synthesis of β‐lactam antibiotics using penicillin‐G acylase in frozen media
Authors: van Langen Luuk M. , de Vroom Erik , van Rantwijk Fred , Sheldon Roger
Published: July 2002

Penicillin‐G acylase (EC 3.5.1.11) fromEscherichia colicatalyzed the synthesis of various β‐lactam antibiotics in ice at −20°C with higher yields than obtained in solution at 20°C. The initial ratio between aminolysis and hydrolysis of the acyl‐enzyme complex in the synthesis of cephalexin increased from 1.3 at 20°C to 25 at −20°C. The effect on the other antibiotics studied was less, leading us to conclude that freezing of the reaction medium influences the hydrolysis of each nucleophile‐acyl‐enzyme complex to a different extent. Only free penicillin‐G acylase could perform transformations in frozen media: immobilized preparations showed a low, predominantly hydrolytic activity under these conditions.
Polypeptide release factor eRF1 from Tetrahymena thermophila: cDNA cloning, purification and complex formation with yeast eRF3
Authors: Karamyshev Andrew L. , Ito Koichi , Nakamura Yoshikazu
Published: July 2002

The first cDNA for the translational release factor eRF1 of ciliates was cloned from Tetrahymena thermophila. The coding frame contained one UAG and nine UAA codons that are reassigned for glutamine in Tetrahymena. The deduced protein sequence is 57% identical to human eRF1. The recombinant Tetrahymena eRF1 purified from a yeast expression system was able to bind to yeast eRF3 as do other yeast or mammalian eRF1s as a prerequisite step for protein termination. The recombinant Tetrahymena eRF1, nevertheless, failed to catalyze polypeptide termination in vitro with rat or Artemia ribosomes, at least in part, due to less efficient binding to the heterologous ribosomes. Stop codon specificity and phylogenetic significance of Tetrahymena eRF1 are discussed from the conservative protein feature.
Functional phage display of leech‐derived tryptase inhibitor (LDTI): construction of a library and selection of thrombin inhibitors
Authors: Tanaka Aparecida S. , Silva Melissa M. , Torquato Ricardo J.S. , Noguti Maria A.E. , Sampaio Claudio A.M. , Fritz Hans , Auerswald Ennes A.
Published: July 2002

The recombinant phage antibody system pCANTAB 5E has been used to display functionally active leech‐derived tryptase inhibitor (LDTI) on the tip of the filamentous M13 phage. A limited combinatorial library of 5.2×104 mutants was created with a synthetic LDTI gene, using a degenerated oligonucleotide and the pCANTAB 5E phagemid. The mutations were restricted to the P1–P4′ positions of the reactive site. Fusion phages and appropriate host strains containing the phagemids were selected after binding to thrombin and DNA sequencing. The variants LDTI‐2T (K8R, I9V, S10, K11W, P12A), LDTI‐5T (K8R, I9V, S10, K11S, P12L) and LDTI‐10T (K8R, I9L, S10, K11D, P12I) were produced with a Saccharomyces cerevisiae expression system. The new inhibitors, LDTI‐2T and ‐5T, prolong the blood clotting time, inhibit thrombin (K
i 302 nM and 28 nM) and trypsin (K
i 6.4 nM and 2.1 nM) but not factor Xa, plasma kallikrein or neutrophil elastase. The variant LDTI‐10T binds to thrombin but does not inhibit it. The relevant reactive site sequences of the thrombin inhibiting variants showed a strong preference for arginine in position P1 (K8R) and for valine in P1′ (I9V). The data indicate further that LDTI‐5T might be a model candidate for generation of active‐site directed thrombin inhibitors and that LDTI in general may be useful to generate specific inhibitors suitable for a better understanding of enzyme‐inhibitor interactions.
Functional analysis of rat renal organic anion transporter OAT‐K1: bidirectional methotrexate transport in apical membrane
Authors: Masuda Satohiro , Takeuchi Ayako , Saito Hideyuki , Hashimoto Yukiya , Inui Ken-ichi
Published: July 2002

Renal organic anion transporter OAT‐K1 was stably transfected in MDCK cells and examined for its transport characteristics and membrane localization. OAT‐K1 mediated both uptake and efflux of methotrexate in the apical membranes. Immunoblotting showed that the apparent molecular mass of the expressed OAT‐K1 was 50 kDa, which was comparable to that found in the rat renal brush‐border membranes. The OAT‐K1‐mediated methotrexate transport was significantly inhibited in the presence of several organic anions such as folate and sulfobromophthalein. These findings suggest that OAT‐K1 mediates bidirectional methotrexate transport across the apical membranes, and may be involved in the renal handling of methotrexate.
LDL binds to surface‐expressed human T‐cadherin in transfected HEK293 cells and influences homophilic adhesive interactions
Authors: Resink Thérèse J. , Kuzmenko Yelena S. , Kern Frances , Stambolsky Dmitry , Bochkov Valery N. , Tkachuk Vsevolod A. , Erne Paul , Niermann Thomas
Published: July 2002

T‐cadherin (T‐cad) is an unusual glycosylphosphatidylinositol‐anchored member of the cadherin family of cell adhesion molecules. Binding of low density lipoproteins (LDLs) to T‐cad can be demonstrated on Western blots of smooth muscle cell lysates, membranes and purified proteins. Using HEK293 cells transfected with human T‐cad cDNA (T‐cad+), we have investigated the adhesion properties of expressed mature and precursor proteins and examined the postulate that LDL represents a physiologically relevant ligand for T‐cad. T‐cad+ exhibits an increased Ca2+‐dependent aggregation (vs. control) that was reduced by selective proteolytic cleavage of precursor T‐cad and abolished after either proteolytic or phosphatidylinositol‐specific phospholipase C (PI‐PLC) cleavage of both mature and precursor proteins, indicating that both proteins function in intercellular adhesion. T‐cad+ exhibited a significantly increased specific cell surface‐binding of [125I]‐LDL that was sensitive to PI‐PLC pre‐treatment of cells. Ca2+‐dependent intercellular adhesion of T‐cad+ was significantly inhibited by LDL. Our results support the suggestion that LDL is a physiologically relevant ligand for T‐cad.
Third‐trimester maternal serum β‐HCG level and umbilical blood flow in fetal growth retardation
Authors: Bartha J.L. , Comino‐Delgado R. , Arrabal J. , Escobar M.A.
Published: July 2002

Objective: To determine the relationship between maternal serum β‐HCG level and umbilical artery systolic/diastolic ratio in fetal growth retardation. Methods: Maternal serum β‐HCG was measured in 57 pregnant women in the third trimester, 31 with a fetal growth retardation and 26 with a normal growth. The systolic/diastolic ratio was measured in a midsection of the umbilical cord the same day of the biochemical determination. Results: The serum β‐HCG level was statistically significant higher in pregnant women with a fetal growth retardation associated with a high systolic/diastolic ratio (n = 9) (P < 0.001). There were no differences between the fetuses with a normal growth (n = 26) and those with an intrauterine growth retardation and a normal systolic/diastolic ratio (n = 22). There was a significant positive correlation between maternal serum β‐HCG level and umbilical artery systolic/diastolic ratio (P < 0.01). Conclusion: Fetal growth retardation due to Doppler‐defined vascular placental insufficiency is associated with a higher maternal serum β‐HCG level.
Arcs of integration: an international study of supply chain strategies
Authors: Frohlich Markham T. , Westbrook Roy
Published: July 2002

Though there is a wide acceptance of the strategic importance of integrating operations with suppliers and customers in supply chains, many questions remain unanswered about how best to characterize supply chain strategies. Is it more important to link with suppliers, customers, or both? Similarly, we know little about the connections between supplier and customer integration and improved operations performance. This paper investigated supplier and customer integration strategies in a global sample of 322 manufacturers. Scales were developed for measuring supply chain integration and five different strategies were identified in the sample. Each of these strategies is characterized by a different “arc of integration”, representing the direction (towards suppliers and/or customers) and degree of integration activity. There was consistent evidence that the widest degree of arc of integration with both suppliers and customers had the strongest association with performance improvement. The implications for our findings on future research and practice in the new millennium are considered.
The discipline of real cells
Authors: Hyer Nancy Lea , Brown Karen A
Published: July 2002

Cellular manufacturing (CM) has received strong endorsement as an innovation that enhances quality, throughput time, inventory turnover, workflow, space utilization, and flexibility [Nyman, L. (Ed.), 1992. Making Manufacturing Cells Work. Society of Manufacturing Engineers, Dearborn, MI.]. However, definitions of what truly is meant by the term ‘manufacturing cell’ vary somewhat among academics and to a large extent among practitioners [Shafer S.M., Meredith, J.M., Marsh, R.F., 1995. Omega 23(4), 361–376.]. These discrepancies can make it difficult to compare the results of studies focused on measuring the effectiveness of cells. It is our position that some of the confusion in the field derives from an assumption that a cell is simply a layout—nothing more—leaving room for numerous approaches to cell design and operation. Our goal in writing this paper is to suggest a more comprehensive perspective. Based on our ongoing field research and an exploration of the literature, we propose an underlying theory to describe the discipline necessary for effective cell operation. We differentiate real cells from other types of cells based on the presence of key linkages. In a real cell, work tasks and those who perform them are connected in terms of time, space and information. Of these linking mechanisms, which represent the core of the cell discipline, information appears to be the most significant determinant of effectiveness. Additionally, we emphasize that cell operators are central to the discipline, underscoring our position that a cell is more than an arrangement of equipment. Factors such as multi‐skilling, reduced set‐up times, small transfer batch size, and the presence of visual controls serve as enablers that strengthen the discipline, but are not fundamental to our theoretical definition. Configurations not adhering to the discipline of time, space, and information may be classified as latent or virtual cells, and may be expected to perform at levels less than those of real cells. Although our theory of cell discipline is grounded in observational study, its potential robustness will be confirmed most appropriately through carefully designed and executed field experiments.
Development, test reliability and validation of a classification for revision hip arthroplasty
Authors: Saleh Khaled J. , Holtzman Jeremy , Gafni Amiram , Saleh Lena , Jaroszynski Grzeogrz , Wong Paul , Woodgate Ian , Davis Aileen , Gross Allan E.
Published: July 2002

The objective of the study was to develop a valid and reliable classification system for failed hip arthroplasties. The study uses research principals derived from multi‐attribute utility theory and consensus group techniques. The development of the severity measure was done in two phases. Phase I of the study included: (a) questionnaire development, (b) submission of the questionnaire to the respondents, (c) data synthesis of the responses and item reduction, and (d) classification development and inter‐observer reliability testing. Phase II included: (a) resubmission of the instrument to the respondents for suggestions/feedback. (b) instrument revision by the co‐investigators based on the respondents' second feedback, and (c) inter‐observer reliability testing and intraoperative validity testing of the instrument. The questionnaires sought to capture expert opinion as to what clinical determinants obtained preoperatively (during patient interview, physical exam and review of plain radiographs – AP pelvis and hip lateral) that would in their clinical experience reveal intraoperative severity. There was an 80% (16/20) response rate from the outside experts invited to participate in the study. Based on item reduction and test‐retest analysis, a five‐grade radiographic classification for the acetabulum as well as the femur was developed. This system was then reviewed by 13 of the initial outside experts (16, 80%) who participated in the first round. Inter‐rater reliability testing of the final format of the classification revealed a weighted kappa statistic value of 0.88 between the two‐blinded raters (inter‐rater reliability) and 0.87 between the blinded raters and the reference standard (intraoperative validity). We conclude that the study developed a reliable and valid radiographic classification system for failed hip arthroplasty. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats
Authors: Meyer Ralph A. , Tsahakis Paul J. , Martin David F. , Banks David M. , Harrow Matt E. , Kiebzak Gary M.
Published: July 2002

The impact of age and ovariectomy on the healing of femoral fractures was studied in three groups of female rats at 8, 32 and 50 weeks of age at fracture. In the two older groups, the rats had been subjected to ovariectomy or sham surgery at random at 26 weeks of age. At fracture, all rats received unilateral intramedullary pinning of one femur and a middiaphyseal fracture. Rigidity and breaking load of the femora were evaluated at varying times up to 24 weeks after fracture induction by three‐point bending to failure. Bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry. In the youngest group, 8‐week‐old female rats regained normal femoral rigidity and breaking load by 4 weeks after fracture. They exceeded normal contralateral values by 8 weeks after fracture. In the middle group, at 32 weeks of age, fractures were induced, and the femora were harvested at 6 and 12 weeks after fracture. At 6 weeks after fracture there was partial restoration of rigidity and breaking load. At 12 weeks after fracture, only the sham‐operated rats had regained normal biomechanical values in their fractured femora, while the fractured femora of the ovariectomized rats remained significantly lower in both rigidity and breaking load. In contrast, for the oldest group of rats, 50 weeks old at fracture, neither sham‐operated nor ovariectomized rats regained normal rigidity or breaking load in their fractured femora within the 24 weeks in which they were studied. In all fractured bones, there was a significant increase in BMD over the contralateral intact femora due to the increased bone tissue and bone mineral in the fracture callus. Ovariectomy significantly reduced the BMD of the intact femora and also reduced the gain in BMD by the fractured femora. In conclusion, age and ovariectomy significantly impair the process of fracture healing in female rats as judged by measurements of rigidity and breaking load in three‐point bending and by accretion of mineral into the fracture callus. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Spontaneous embryonic motility: an enduring legacy
Authors: Bekoff Anne
Published: July 2002

This chapter addresses the influential contributions Viktor Hamburger has made to our understanding of embryonic motor behavior. With his classic review, published in 1963, Viktor Hamburger opened up the field of embryonic motor behavior, which had lain almost completely dormant for many years. He focused his observations and experimental studies on the spontaneously generated embryonic movements rather than on reflex responses. As a result, he and his colleagues firmly established the central generation of embryonic motility as a basic component of embryonic behavior in chicks. These studies were also extended to rat fetuses, showing that similar principles apply to mammalian fetuses. All of us who have followed after him owe Viktor Hamburger an enormous debt of gratitude for his pioneering work.
Involvement of P2 purinoceptors in the regulation ofdna synthesis in the neural retina of chick embryo
Authors: Sugioka Miho , Zhou Wen‐liang , Hofmann Hans‐dieter , Yamashita Masayuki
Published: July 2002

The activation of P2 purinoceptors induces Ca2 mobilization in the earlyembryonic chick neural retina. This purinergic Ca2 response declines parallel with thedecrease in mitotic activity during retinal development. To investigate the role of P2purinoceptors in the regulation of retinal cell proliferation, we studied the effects of the P2purinoceptor antagonists suramin and pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS), and of the agonist ATP on DNA synthesis in retinal organcultures from embryonic day 3 (E3) chick. Suramin inhibited [3H]‐thymidineincorporation in a dose‐dependent manner (IC50 : ∼70 μM). PPADS alsoreduced [3H]‐thymidine incorporation with maximum inhibition of 46% at 100 μM. Exogenous ATP enhanced [3H]‐thymidine incorporation in adose‐dependent manner to maximally 200% of control (EC50 : ∼70 μM). Indissociated retinal cultures from E7 chick, both antagonists showed similar inhibitory effects on [3H]‐thymidine incorporation without affecting cell viability. In line with theseobservations, the presence of extracellular ATP was demonstrated both in vitro and in vivo. In the medium of E3 retinal organ cultures, the concentration of ATP increased25‐fold within 1 h of incubation and this concentration was kept for at least 24 h. In the chickamniotic fluid, the ATP concentration was nearly 3 μM at E3 and declined to 0.15 μM at E7. The results indicate that P2 purinoceptors activated by autocrine or paracrinerelease of ATP are involved in the regulation of DNA synthesis in the neural retina at earlyembryonic stages.
The role of serotonin in depression and anxiety
Authors: Deakin JFW
Published: July 2002

The different coping responses to three types of aversive events - future threats, acute events and chronic stress — may be modulated by 5HT projections. Dysfunction in these coping mechanisms could cause, respectively: generalised anxiety disorder, panic, and depression. This theory proposes that dorsal raphe nucleus projections to 5HT2 and 5HT1D receptors mediate anticipatory anxiety and normally motivate avoidance of threats. The brain aversion system may be held in check by dorsal raphe nucleus 5HT projections to mediate behavioural inhibition during anticipatory anxiety. Proximal aversive stimuli such as pain and asphyxia elicit the fight-flight reflex mediated by the amygdala-hypothalamic-periaqueductal grey brain aversion system. Panic attacks may thus be due to spontaneous activation of this system. Median raphe projections to 5HT1A receptors have been implicated in adaptation to chronic stress-resilence. There is good evidence that 5HT1A function breaks down in depression and causes the depressed state. Experimental tests of this theory suggest that viewing anxiety, panic, and depression as dysfunctions in neurochemically and anatomically specific coping systems is heuristically useful.
Mapping the Trap‐State Landscape in 2D Metal‐Halide Perovskites Using Transient Photoluminescence Microscopy
Authors: Seitz Michael , Meléndez Marc , Alcázar‐Cano Nerea , Congreve Daniel N. , Delgado‐Buscalioni Rafael , Prins Ferry
Published: February 2021

Transient microscopy is of vital importance in understanding the dynamics of optical excited states in optoelectronic materials, as it allows for a direct visualization of the movement of energy carriers in space and time. Important information on trap‐state dynamics can be obtained using this technique, typically observed as a slow‐down of energy transport as carriers are trapped at defect sites. To date, however, studies of the trap‐state dynamics have been mostly limited to phenomenological descriptions of the early time‐dynamics. Here, it is shown how long‐acquisitiontime transient photoluminescence microscopy can be used to provide a detailed map of the trapstate landscape in 2D perovskites, in particular when used in combination with transient spectroscopy. An anomalous evolution of the studied exciton distribution is observed, which cannot be explained with existing models for trap limited exciton transport that only account for a single trap type. Instead, using a continuous diffusion model and performing Brownian dynamics simulations, it is shown that this behavior can be explained by accounting for a distinct distribution of traps in this material. These results highlight the value of transient microscopy as a complementary tool to more common transient spectroscopy techniques in the characterization of excited state dynamics in semiconductors.
Adults with Cerebral Palsy Require Ongoing Neurologic Care: A Systematic Review
Authors: Smith Sarah E. , Gannotti Mary , Hurvitz Edward A. , Jensen Frances E. , Krach Linda E. , Kruer Michael C. , Msall Michael E. , Noritz Garey , Rajan Deepa S. , Aravamuthan Bhooma R.
Published: February 2021

Cerebral palsy (CP) neurologic care and research efforts typically focus on children. However, most people with CP are adults. Adults with CP are at increased risk of new neurologic conditions, such as stroke and myelopathy, that require ongoing neurologic surveillance to distinguish them from baseline motor impairments. Neurologic factors could also contribute to the motor function decline, chronic pain, and chronic fatigue that are commonly experienced by adults with CP. Based on a systematic literature review, we suggest (1) guidelines for neurologic surveillance and neurologist referral and (2) clinical research questions regarding the evolving neurologic risks for adults with CP. ANN NEUROL 2021;89:860–871
Recent trends in the chromatographic analysis of volatile flavor and fragrance compounds: Annual review 2020
Authors: Louw Stefan
Published: February 2021

The chromatographic analysis of volatile flavor and fragrance compounds is performed routinely in several industries and in many fields of scientific research. Typical applications include food‐, environmental‐, essential oil‐ and cosmetics analysis. Even though the analysis of flavors and fragrances have become increasingly standardized during the past decade, there are still a large variety of techniques that can be used for their extraction, chemical analysis, and sensory analysis. Moreover, there are certain less commonly used techniques that are now being used with increased frequency and that are showing the potential of being used as alternatives to the existing standard techniques. In this annual review, the techniques that were most commonly used in 2020 for the investigation of these volatile compounds are discussed. In addition, a number of emerging trends are discussed, notably the use of solvent assisted flavor evaporation (SAFE) for extraction, GC ion mobility spectrometry (IMS) for volatile compound analysis and electronic senses, that is, E‐noses and E‐tongues, for sensory analysis. Miscellaneous hyphenated techniques, advances in stationary phase chemistry and a number of interesting applications are also highlighted.
Vorgespannte Trockenfugen für modulare Brücken unter zyklischer Belastung
Authors: Schaarschmidt David , Flederer Holger
Published: February 2021

Modulares Bauen mit Betonfertigteilen gewinnt in den letzten Jahren verstärkt an Bedeutung. Aktuelle Entwicklungen in Praxis und Forschung untersuchen das Fügen der einzelnen Module völlig ohne Ortbeton, Vergussmörtel, Klebung oder Schubnocken. Eine Möglichkeit zur Kraftübertragung bietet das Aktivieren der Oberflächenreibung mittels Vorspannung. Während die Schertragfähigkeit maßgeblich vom Haftreibungsbeiwert abhängt, ist die Biegetragfähigkeit an die Dekompression der Trockenfuge gebunden. Aus statischer Sicht ist die wirklichkeitsnahe Beurteilung der Oberflächentopographie essentiell. In der DIN EN 1992‐1‐1 wird diese in vier Stufen von sehr glatt bis verzahnt eingeteilt, wodurch die Vielzahl an unterschiedlichen Oberflächenqualitäten nur grob abgebildet wird. Darüber hinaus ist die uneingeschränkte Übertragbarkeit des Coulombschen Reibungsgesetzes auf den Beton, vor allem bei höheren Druckspannungen in der Fuge, zu überprüfen. Zwei nennenswerte Anwendungsfelder des modularen Bauens stellen Brückenbauwerke und Windenergieanlagen dar. Beide Bauwerksgruppen unterliegen vorwiegend nichtruhenden Belastungen, welche ermüdungsrelevante Beanspruchungen im Kontaktbereich hervorrufen. Um dauerhafte, ermüdungsresistente und sichere Bauwerke zu errichten, müssen die maßgeblichen Beanspruchungscharakteristika sowie deren Auswirkungen auf die Kontaktoberfläche und die Betonmatrix identifiziert und untersucht werden.
Predicting 2‐year all‐cause mortality after contemporary PCI: Updating the logistic clinical SYNTAX score
Authors: Chichareon Ply , van Klaveren David , Modolo Rodrigo , Kogame Norihiro , Takahashi Kuniaki , Chang Chun‐Chin , Tomaniak Mariusz , Yuan Jinqing , Xie Lihua , Song Ying , Qiao Shubin , Yang Yuejin , Guan Changdong , Zurakowski Aleksander , van Geuns Robert‐Jan , Sabate Manel , Ong Paul J. , Wykrzykowska Joanna J. , Piek Jan J. , Garg Scot , Hamm Christian , Steg Gabriel , Vranckx Pascal , Valgimigli Marco , Windecker Stephan , Juni Peter , Onuma Yoshinobu , Steyerberg Ewout , Xu Bo , Serruys Patrick W.
Published: February 2021

Aims

We aimed to update the logistic clinical SYNTAX score to predict 2 year all‐cause mortality after contemporary percutaneous coronary intervention (PCI).

Methods and results

We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital.

Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2 year all‐cause mortality and included into the new model.

The c‐indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72–0.76), 0.75 (95% CI 0.73–0.77), and 0.78 (95% CI 0.76–0.80), respectively. The c‐index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67–0.77) compared to the refitted original model (0.69; 95% CI 0.64–0.74). The models overestimated the observed 2 year all‐cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population.

Conclusions

The new model of the logistic clinical SYNTAX score better predicts 2 year all‐cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI.
Shape Selectivity of a Metallo Cavitand Host Allows Separation of n‐Alkanes from Isooctane
Authors: Wan Yun‐Hui , Rahman Faiz‐Ur , Rebek Julius , Yu Yang
Published: February 2021

Main observation and conclusion

The use of a metallo cavitand for the selective sequestration of n‐alkanes from their mixtures with isooctane is described. Competition experiments and NMR spectroscopy are used to show the preference of a water‐soluble cavitand host for guests that are hydrophobic and have narrow or flat shapes. The host showed selectivity for trans 1,4‐dimethylcyclohexane over the cis‐isomers. The separations of n‐alkanes from isooctane by gas/liquid adsorption and a liquid/liquid extraction are detailed.
Positional Electronic Effects in Iminopyridine‐N‐oxide Nickel Catalyzed Ethylene Polymerization†
Authors: Chi Mingjun , Chen Ao , Pang Wenmin , Tan Chen , Chen Changle
Published: February 2021

Main observation and conclusion

A series of dibenzhydryl‐based iminopyridine‐N‐oxide ligands bearing a range of electron‐donating or ‐withdrawing substituents (OMe, H, and NO2) and corresponding nickel pre‐catalysts are prepared and characterized. The substituents are installed at different positions on the ligand structure, including 4‐position of the pyridine‐N‐oxide moiety (position X) and 4‐position of the aniline moiety (position Y). These nickel pre‐catalysts are highly active in ethylene polymerization with the addition of very little amount of aluminum cocatalysts, leading to the formation of polyethylenes with molecular weights of well above one million. Electron‐donating substituents make the catalysts sensitive to polymerization temperature. In contrast, the catalysts bearing electron‐withdrawing NO2 substituents show relatively steady performances at different temperatures. Most importantly, we demonstrate that different substituents and different positions both play important roles in determining the properties of nickel catalysts. This provides an alternative strategy for the future design of high‐performance polymerization catalyst.