bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing similarity measures with continuous and discrete protein models
Authors: Wallin Stefan , Farwer Jochen , Bastolla Ugo
Published: December 2002

There are many ways to define the distance between two protein structures, thus assessing their similarity. Here, we investigate and compare the properties of five different distance measures, including the standard root‐mean‐square deviation (cRMSD). The performance of these measures is studied from different perspectives with two different protein models, one continuous and the other discrete. Using the continuous model, we examine the correlation between energy and native distance, and the ability of the different measures to discriminate between the two possible topologies of a three‐helix bundle. Using the discrete model, we perform fits to real protein structures by minimizing different distance measures. The properties of the fitted structures are found to depend strongly on the distance measure used and the scale considered. We find that the cRMSD measure very effectively describes long‐range features but is less effective with short‐range features, and it correlates weakly with energy. A stronger correlation with energy and a better description of short‐range properties is obtained when we use measures based on intramolecular distances. Proteins 2003;50:144–157. © 2002 Wiley‐Liss, Inc.
Modeling repair events under intermittent failures and failures subject to unsuccessful repair
Authors: Hansen C. K. , Ascher H. E.
Published: December 2002

Intermittent failures are sometimes observed for a repairable system, such as an automobile. Such failures often lead to a series of unsuccessful repair attempts before the source of the failure has been identified and removed. Unsuccessful repair is also observed in cases where the failures are not intermittent. In order to model data involving repeated repair attempts related to the same failure, repair times cannot usually be assumed negligible and the model must be designed or modified to account for these. In this paper, we propose a modified version of the branching Poisson process model introduced by Lewis (1964). We discuss statistical inference procedures for this model and demonstrate these procedures using the service history of a new automobile. Copyright © 2002 John Wiley & Sons, Ltd.
The reliability analysis of balking and reneging in a repairable system with warm standbys
Authors: Ke Jau‐Chuan , Wang Kuo‐Hsiung
Published: December 2002

We study the reliability analysis of a repairable system with $m$ operating units, $w$ warm standby units and $R$ repairmen in which the balking and reneging of units are considered. It is assumed that failed units balk (refuse to join) with a constant probability ($1-b$) and renege (leave the queue after joining) according to a negative exponential distribution with parameter $r$. The failure times of the operating unit and of a standby unit are assumed to be exponentially distributed with parameters λ and α, respectively. The repair time distribution is also exponential. The repairable system is $K$ out of $m+w$, in which $K=1,2,\dots,m$. The reliability characteristics, such as the system reliability and the mean time to system failure (MTTF), in a repairable system are derived. Several cases are analysed graphically to study the effect of various parameters on the reliability and MTTF of the system. Copyright © 2002 John Wiley & Sons, Ltd.
Ant algorithm for single and multiobjective reliability optimization problems
Authors: Shelokar Prakash S. , Jayaraman V. K. , Kulkarni B. D.
Published: December 2002

The paper illustrates the application of the ant colony optimization algorithm to solve both continuous function and combinatorial optimization problems in reliability engineering. The ant algorithm is combined with the strength Pareto fitness assignment procedure to handle multiobjective problems. Further, a clustering procedure has been applied to prune the Pareto set and to maintain diversity. Benchmark case examples show the superiority of the ant algorithm to such problems. Copyright © 2002 John Wiley & Sons, Ltd.
Relationship between STS approach, scientific literacy, and achievement in biology
Authors: Mbajiorgu N. M. , Ali A.
Published: December 2002

This study set out to investigate the relationship between STS approach, scientific literacy (SL), and achievement in biology. A quasi‐experimental design of the nonequivalent group was employed. Four secondary schools, eight teachers, and 246 students from Nigeria were involved in the study. Two classes were randomly selected from each school and assigned to either the experimental or control group. Two instruments were used to collect data: an Achievement Test on Reproduction and Family Planning and a SL Scale. Results showed that there is no relationship between SL and achievement in biology. The split‐wise posttest regression showed a weak positive relationship between SL and achievement in biology for the experimental group and a no relationship for the control group. However, STS approach mediated between SL and achievement to effect a slightly stronger significant positive relationship. The slope of SL was greater when we controlled for instruction showing that the relationship between SL and achievement is not spurious when instruction is taken into account. We therefore conclude that STS approach might be affecting other variables in the science classroom that in turn affect achievement in the sciences. © 2002 Wiley Periodicals, Inc. Sci Ed 87:31–39, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10012
“Change is hard”: What science teachers are telling us about reform and teacher learning of innovative practices
Authors: Davis Kathleen S.
Published: December 2002

Over the last decade, significant efforts have been made to bring change to science classrooms. Educational researchers (Anderson, R. D., & Helms, J. V. (2001). Journal of Research in Science Teaching, 38(1), 3–16.) have pointed to the need to examine reform efforts systemically to understand the pathways and impediments to successful reform. This study provides a critical analysis of the implementation of an innovative science curriculum at a middle school site. In particular, the author explores the issues that surround teacher learning of new practices including the structures, policies, and practices that were in place within the reform context that supported or impeded teacher learning. Parallels are drawn between student and teacher learning and the importance of autonomy and decision‐making structures for both populations of learners. Findings presented include (1) how staff development with constructivist underpinnings facilitated teacher learning; (2) how regular and frequent opportunities for interactions with colleagues and outside support personnel contributed to teacher learning; (3) how the decline of such interactive forums and the continuation of old decision‐making structures restricted the development of teacher knowledge, expertise, and a common vision of the science program; and (4) how the process of field‐testing at this site limited the incorporation of teachers' prior knowledge and impacted teacher acquisition of new knowledge and skills. © 2002 Wiley Periodicals, Inc. Sci Ed 87:3–30, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.10037
Examining classroom interactions related to difference in students' science achievement
Authors: Zady Madelon F. , Portes Pedro R. , Dan Ochs V.
Published: December 2002

The current study examines the cognitive supports that underlie achievement in science by using a cultural historical framework (L. S. Vygotsky (1934/1986), Thought and Language, MIT Press, Cambridge, MA.) and the activity setting (AS) construct (R. G. Tharp & R. Gallimore (1988), Rousing minds to life: Teaching, learning and schooling in social context, Cambridge University Press, Cambridge, MA.) with its five features: personnel, motivations, scripts, task demands, and beliefs. Observations were made of the classrooms of seventh‐grade science students, 32 of whom had participated in a prior achievement‐related parent–child interaction or home study (P. R. Portes, M. F. Zady, & R. M. Dunham (1998), Journal of Genetic Psychology, 159, 163–178). The results of a quantitative analysis of classroom interaction showed two features of the AS: personnel and scripts. The qualitative field analysis generated four emergent phenomena related to the features of the AS that appeared to influence student opportunity for conceptual development. The emergent phenomenon were science activities, the building of learning, meaning in lessons, and the conflict over control. Lastly, the results of the two‐part classroom study were compared to those of the home science AS of high and low achievers. Mismatches in the AS features in the science classroom may constrain the opportunity to learn. Educational implications are discussed. © 2002 Wiley Periodicals, Inc. Sci Ed 87:40–63, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/sce.1053
Shallow cylindrical tuned liquid damper for vibration control of high‐rise structures
Authors: Li S. J. , Li G. Q. , Tang J. , Li Q. S.
Published: December 2002

A new simplified model for the application of a shallow cylindrical tuned liquid damper (TLD) in structural vibration control is presented in this paper. The dynamic properties of a shallow liquid in cylindrical containers subjected to forced horizontal oscillation are analysed directly from the continuity and momentum equations of fluids. Following some practical assumptions, the nonlinear partial differential equations describing the wave movement of a shallow liquid in cylindrical containers is established and a numerical procedure for the solution of these equations is proposed using the finite element method. The formula for determining the control force provided by the shallow cylindrical TLD is presented and the effect of several parameters on the control efficiency of a shallow cylindrical TLD controlled structure under wind action is investigated. Copyright © 2002 John Wiley & Sons, Ltd.
Lymphotoxin‐β receptor mediates NEMO‐independent NF‐κB activation
Authors: Saitoh Tatsuya , Nakano Hiroyasu , Yamamoto Naoki , Yamaoka Shoji
Published: December 2002

Lymphotoxin‐β receptor (LTβR) is a member of the tumor necrosis factor receptor (TNFR) superfamily that activates nuclear factor‐κB (NF‐κB) through the IκB kinase (IKK) complex, the core of which is comprised of IKK1, IKK2 and NF‐κB essential modulator (NEMO). We demonstrate here that the LTβR signaling to NF‐κB activation does not necessarily require NEMO, which is essential for TNFR signaling. In the absence of NEMO, the p50 and RelB, but not RelA subunits of NF‐κB are found in the nuclear DNA binding complexes induced by the LTβR signaling. Our results thus disclose NEMO‐independent NF‐κB activation by LTβR.
HIV‐1 TAT‐mediated protein transduction and subcellular localization using novel expression vectors1
Authors: Yang Yonghui , Ma Jun , Song Zhiyin , Wu Mian
Published: December 2002

Several novel prokaryotic and eukaryotic expression vectors were constructed for protein transduction and subcellular localization. These vectors employed an N‐terminal stretch of 11 basic amino acid residues (47–57) from the human immunodeficiency virus type 1 (HIV‐1) TAT protein transduction domain (PTD) for protein translocation and cellular localization. The vectors also contained a six‐histidine (His6) tag at the N‐ or C‐terminus for convenient purification and detection, and a multiple cloning site for easy insertion of foreign genes. Some heterologous genes including HSV‐TK, Bcl‐rambo, Smac/DIABLO and GFP were fused in‐frame to TAT PTD and successfully overexpressed in Escherichia coli. The purified TAT‐GFP fusion protein was able to transduce into the mammalian cells and was found to locate mainly in the cytosol when exogenously added to the cell culture medium. However, using a transfection system, mammalian‐expressed TAT‐GFP predominantly displayed a nuclear localization and nucleolar accumulation in mammalian cell lines. This discrepancy implies that the exact subcellular localization of transduced protein may depend on cell type, the nature of imported proteins and delivery approach. Taken together, our results demonstrate that a TAT PTD length of 11 amino acids was sufficient to confer protein internalization and its subsequent cellular localization. These novel properties allow these vectors to be useful for studying protein transduction and nuclear import.
A nuclear protein tyrosine phosphatase activates p53 and induces caspase‐1‐dependent apoptosis
Authors: Gupta Sanjeev , Radha Vegesna , Sudhakar Ch , Swarup Ghanshyam
Published: December 2002

PTP‐S2/TC45 is a nuclear protein tyrosine phosphatase, which induces p53‐dependent apoptosis. Here we show that the p53 protein level increased in MCF‐7 cells in response to PTP‐S2 overexpression. PTP‐S2‐induced p53 protein was transcriptionally active and it could activate caspase‐1 gene expression from endogenous as well as ectopic promoter. Coexpression of an active site mutant of procaspase‐1 strongly inhibited PTP‐S2‐induced apoptosis. Mutant procaspase‐1 also inhibited apoptosis induced by p53 overexpression or doxorubicin treatment, which induce caspase‐1 gene expression. In contrast, apoptosis induced by staurosporine or cycloheximide, which do not increase caspase‐1 gene expression, was not affected by mutant procaspase‐1. These results suggest that caspase‐1 may be one of the mediators of p53‐dependent apoptosis in human cells.
Akt signaling mediates VEGF/VPF vascular permeability in vivo
Authors: Six Isabelle , Kureishi Yasuko , Luo Zhengyu , Walsh Kenneth
Published: December 2002

VEGF is an endothelial cell cytokine that promotes angiogenesis and enhances microvascular permeability. Recently, it has been shown that the protein kinase Akt functions in a key intercellular signaling pathway downstream of VEGF. Here, we employed adenovirus‐mediated gene transfer in conjunction with the Miles assay in hairless albino guinea pigs to assess the role of Akt signaling in vascular permeability. VEGF‐induced vascular permeability was blocked by the transduction of a dominant negative mutant of Akt. Conversely, transduction of a constitutively active form of Akt promoted vascular permeability in a manner similar to VEGF protein administration. This Akt‐mediated increase in vascular permeability was inhibited by the eNOS inhibitor L‐NAME. These data show that Akt signaling is both necessary and sufficient for vascular permeability in an in vivo model.
Identification of a novel RNA silencing suppressor, NSs protein of Tomato spotted wilt virus
Authors: Takeda Atsushi , Sugiyama Kazuhiko , Nagano Hideaki , Mori Masashi , Kaido Masanori , Mise Kazuyuki , Tsuda Shinya , Okuno Tetsuro
Published: December 2002

RNA silencing or post‐transcriptional gene silencing (PTGS) in plants is known as a defense system against virus infection. Several plant viruses have been shown to encode an RNA silencing suppressor. Using a green fluorescent protein‐based transient suppression assay, we show that NSs protein of Tomato spotted wilt virus (TSWV) has RNA silencing suppressor activity. TSWV NSs protein suppressed sense transgene‐induced PTGS but did not suppress inverted repeat transgene‐induced PTGS. TSWV NSs protein is the first RNA silencing suppressor identified in negative‐strand RNA viruses.
A large number of novel Ergtoxin‐like genes and ERG K+‐channels blocking peptides from scorpions of the genus Centruroides
Authors: Corona Miguel , Gurrola Georgina B. , Merino Enrique , Cassulini Rita Restano , Valdez-Cruz Norma A. , Garcı́a Blanca , Ramı́rez-Domı́nguez Martha E. , Coronas Fredy I.V. , Zamudio Fernando Z. , Wanke Enzo , Possani Lourival D.
Published: December 2002

Twenty‐three novel sequences similar to Ergtoxin (ErgTx) were obtained by direct sequencing of peptides or deduced from gene cloned using cDNAs of venomous glands of Centruroides (C.) elegans, C. exilicauda, C. gracilis, C. limpidus limpidus, C. noxius and C. sculpturatus. These peptides have from 42 to 47 amino acid residues cross‐linked by four disulfide bridges. They share sequence similarities (60–98% compared with ErgTx1) and were shown to block ERG K+‐channels of F‐11 clone (N18TG‐2×rat DRG) cultured cells. An unrooted phylogenetic tree analysis of these peptides showed that they conform at least five different subfamilies, of which three are novel subfamilies.
Cyclin destruction in mitosis: a crucial task of Cdc20
Authors: Irniger Stefan
Published: December 2002

Proteolytic destruction of cyclins is a fundamental process for cell division. At the end of mitosis, degradation of mitotic cyclins results in the inactivation of cyclin‐dependent kinases. Cyclin proteolysis is triggered by the anaphase‐promoting complex/cyclosome (APC/C), a multi‐subunit complex which contains ubiquitin ligase activity. Recent data in yeast demonstrated that a partial degradation of the mitotic cyclin Clb2, mediated by APC/C and its activator protein Cdc20, is essential and sufficient for the mitotic exit. Remarkably, a complete inactivation of cyclin‐dependent kinases seems to be not essential. This review discusses recent novel insights into cyclin destruction and its implications for the mitotic exit.
Human HRD1 protects against ER stress‐induced apoptosis through ER‐associated degradation1
Authors: Kaneko Masayuki , Ishiguro Masataro , Niinuma Yoshifumi , Uesugi Mai , Nomura Yasuyuki
Published: December 2002

Stresses that impair the function of the endoplasmic reticulum (ER) lead to an accumulation of unfolded protein in the ER. Under these conditions, the expression of a variety of genes involved in preventing the accumulation of the unfolded proteins is induced. Yeast Hrd1p is an ER stress‐inducible ER membrane protein that acts as a ubiquitin ligase (E3) with a RING finger motif and plays a role in the ubiquitination of proteins in the ER. We report here the identification and characterization of a human homolog to yeast Hrd1p. The predicted structures are highly conserved from yeast to humans. Indeed, human HRD1 was localized to the ER and ubiquitinated its substrates. Furthermore, it was found that human HRD1 was up‐regulated by ER stress via IRE1 and ATF6, which are ER stress transducers. Interestingly, 293 cells stably expressing wild‐type HRD1, but not the C329S mutant, afforded resistance to ER stress‐induced apoptosis. These results suggest that the production of HRD1 is up‐regulated to protect against ER stress‐induced apoptosis by degrading unfolded proteins accumulated in the ER.
Mechanisms involved in interleukin‐15‐induced suppression of human neutrophil apoptosis: role of the anti‐apoptotic Mcl‐1 protein and several kinases including Janus kinase‐2, p38 mitogen‐activated protein kinase and extracellular signal‐regulated kinases‐1/2
Authors: Pelletier Martin , Ratthé Claude , Girard Denis
Published: December 2002

Interleukin‐15 (IL‐15) is a pro‐inflammatory cytokine known as a general inhibitor of apoptosis, which possesses potential therapeutic properties. Although IL‐15 was previously found to be a human neutrophil agonist, its mode of action remains unknown. Herein, we were interested in elucidating the mechanisms by which it delays neutrophil apoptosis. IL‐15 was found to induce tyrosine phosphorylation events and to prevent loss of the anti‐apoptotic Mcl‐1 protein expression. Using different signal transduction inhibitors, we found that Janus kinase (Jak)‐2, Jak‐3, p38 mitogen‐activated protein kinase (MAPK) and extracellular signal‐regulated kinase (ERK), but not G proteins, are involved in IL‐15‐induced suppression of apoptosis. Furthermore, we found that IL‐15 activates Jak‐2, p38 MAPK and ERK‐1/2, but, unlike granulocyte macrophage‐colony‐stimulating factor (GM‐CSF), it does not activate signal transducer and activator of transcription (STAT)‐5a/b. We conclude that IL‐15 delays neutrophil apoptosis via several pathways, and that Mcl‐1 and several kinases contribute to this. We also conclude that, unlike GM‐CSF, IL‐15 does not activate the Jak‐2/STAT‐5 pathway found to be important in neutrophil signaling.
Dynamic analysis of STAT6 signalling in living cells
Authors: Nelson Glyn , Wilde Geraint J.C , Spiller David G , Sullivan Elaine , Unitt John F , White Michael R.H
Published: December 2002

Functional activity of N‐ and C‐terminal fluorescent fusion proteins between STAT6 and EGFP was demonstrated through IL‐4‐dependent transcriptional activation and nuclear translocation. The N‐terminal (EGFP–STAT6) fusion protein appeared to be more active than the C‐terminal fusion. In HEK‐293 cells both fusion proteins formed fluorescent nuclear foci following IL‐4 stimulation, but in HeLa cells nuclear accumulation was homogeneous. Stimulation of the NF‐κB pathway through TNFα treatment, or expression of p65–EGFP fusion protein, repressed both basal STAT6‐dependent transcriptional activity and the extent of activation in response to IL‐4. This indicates a novel mechanism of inhibition of STAT6 signalling by NF‐κB activation.
Involvement of in vivo induced cheY‐4 gene of Vibrio cholerae in motility, early adherence to intestinal epithelial cells and regulation of virulence factors
Authors: Banerjee Rajat , Das Soumita , Mukhopadhyay Kanchan , Nag Sanjay , Chakrabortty Amit , Chaudhuri Keya
Published: December 2002

Using a global transcription profile approach cheY‐4 of Vibrio cholerae was identified as an in vivo induced gene. In the present study, duplication of the gene in the chromosome resulted in increased motility, increased chemotactic response towards isolated intestinal mucus layer and stronger adhesion to human intestinal epithelial cell line at an early phase of infection compared to wild type and a null mutant strain. In contrast to the cheY‐4 null mutant, duplication of cheY‐4 gene resulted in increased expression of ctxAB and tcpA, the two major virulence genes of V. cholerae.
Arginine metabolic pathways involved in the modulation of tumor‐induced angiogenesis by macrophages
Authors: Davel Lilia Elena , Jasnis Marı́a Adela , de la Torre Eulalia , Gotoh Tomomi , Diament Miriam , Magenta Gabriela , Sacerdote de Lustig E , Sales Marı́a Elena
Published: December 2002

Neovascularization, an essential step for tumor progression and metastasis development, can be modulated by the presence of macrophages (Mps) in the tumor microenvironment. The ability of Mps to regulate the angiogenicity of the LMM3 tumor cell line was studied. Peritoneal Mps from LMM3 tumor‐bearing mice (TMps) potentiate in vivo LMM3 angiogenicity. These results were confirmed by CD31 immunoblotting assays. The activity of TMps depended on nitric oxide synthase (NOS) and arginase (A) activity. By immunoblotting we evidenced that AI and AII isoforms were up‐regulated in TMps while the inducible and neuronal NOS isoforms were highly expressed in normal Mps. TMps might positively modulate tumor growth by stimulating angiogenic cascade mainly through polyamine synthesis.
Skeletal muscle mitochondrial free‐fatty‐acid content and membrane potential sensitivity in different thyroid states: involvement of uncoupling protein‐3 and adenine nucleotide translocase
Authors: Lombardi A , Silvestri E , Moreno M , De Lange P , Farina P , Goglia F , Lanni A
Published: December 2002

The effect of triiodothyronine (T3) on mitochondrial efficiency could be related to an increase in the concentrations of some proteins, such as uncoupling proteins (UCPs). Free fatty acids (FFA) seem to be a cofactor essential for the uncoupling activity of UCP3. In this paper, we report that the hypothyroidism–hyperthyroidism transition is accompanied by increases: (i) in the endogenous levels of mitochondrial FFA and (ii) in the sensitivity to FFA shown by the mitochondrial respiration rate and membrane potential, which correlated with the level of UCP3 protein. The level of the mRNA for adenine‐nucleotide translocase‐1 (ANT) was not affected by the thyroid state, while the ANT contribution to FFA‐induced changes in mitochondrial uncoupling was low in the hypothyroid and euthyroid states but became more relevant in the hyperthyroid state at the highest concentration of FFA.
The Impact of Spatial Clustering of Transport Infrastructure on Risk
Authors: Rosmuller Nils , van der Heijden Rob E C M
Published: December 2002

The hypothesis has been formulated that spatial clustering of transport line infrastructures might generate higher risks in terms of higher probability of accidents and/or more severe consequences of accidents. The risk increase is assumed to be the result of interference between transport flows. No systematic research has been performed so far to test this hypothesis. This paper therefore presents the results of an empirical study on this subject based on accident data from the Netherlands. It is concluded that clustering of infrastructures has not caused a higher probability of accidents in the past. However, impacts of accidents in terms of the number of casualties are significantly more severe. This generates new discussions on the spatial planning of infrastructures on the one hand and the organisation of emergency response capabilities on the other.
The DAF-7 TGF-β signaling pathway regulates chemosensory receptor gene expression in C. elegans
Authors: Nolan Katherine M. , Sarafi-Reinach Trina R. , Horne Jennifer G. , Saffer Adam M. , Sengupta Piali
Published: December 2002

Regulation of chemoreceptor gene expression in response to environmental or developmental cues provides a mechanism by which animals can alter their sensory responses. Here we demonstrate a role for the daf-7 TGF-β pathway in the regulation of expression of a subset of chemoreceptor genes in Caenorhabditis elegans. We describe a novel role of this pathway in maintaining receptor gene expression in the adult and show that the DAF-4 type II TGF-β receptor functions cell-autonomously to modulate chemoreceptor expression. We also find that the alteration of receptor gene expression in the ASI chemosensory neurons by environmental signals, such as levels of a constitutively produced pheromone, may be mediated via a DAF-7-independent pathway. Receptor gene expression in the ASI and ASH sensory neurons appears to be regulated via distinct mechanisms. Our results suggest that the expression of individual chemoreceptor genes in C. elegans is subject to multiple modes of regulation, thereby ensuring that animals exhibit the responses most appropriate for their developmental stage and environmental conditions.
Trp-dependent auxin biosynthesis in Arabidopsis: involvement of cytochrome P450s CYP79B2 and CYP79B3
Authors: Zhao Yunde , Hull Anna K. , Gupta Neeru R. , Goss Kendrick A. , Alonso José , Ecker Joseph R. , Normanly Jennifer , Chory Joanne , Celenza John L.
Published: December 2002

The plant hormone auxin regulates many aspects of plant growth and development. Although several auxin biosynthetic pathways have been proposed, none of these pathways has been precisely defined at the molecular level. Here we provide in planta evidence that the twoArabidopsis cytochrome P450s, CYP79B2 and CYP79B3, which convert tryptophan (Trp) to indole-3-acetaldoxime (IAOx) in vitro, are critical enzymes in auxin biosynthesis in vivo. IAOx is thus implicated as an important intermediate in auxin biosynthesis. Plants overexpressing CYP79B2 contain elevated levels of free auxin and display auxin overproduction phenotypes. Conversely, cyp79B2 cyp79B3 double mutants have reduced levels of IAA and show growth defects consistent with partial auxin deficiency. Together with previous work on YUCCA, a flavin monooxygenase also implicated in IAOx production, and nitrilases that convert indole-3-acetonitrile to auxin, this work provides a framework for further dissecting auxin biosynthetic pathways and their regulation.
ELAV/Hu proteins inhibit p27 translation via an IRES element in the p27 5′UTR
Authors: Kullmann Michael , Göpfert Ulrich , Siewe Basile , Hengst Ludger
Published: December 2002

p27Kip1 restrains cell proliferation by binding to and inhibiting cyclin-dependent kinases. To investigate the mechanisms of p27 translational regulation, we isolated a complete p27 cDNA and identified an internal ribosomal entry site (IRES) located in its 5′UTR. The IRES allows for efficient p27 translation under conditions where cap-dependent translation is reduced. Searching for possible regulators of IRES activity we have identified the neuronal ELAV protein HuD as a specific binding factor of the p27 5′UTR. Increased expression of HuD or the ubiquitously expressed HuR protein specifically inhibits p27 translation and p27 IRES activity. Consistent with an inhibitory role of Hu proteins in p27 translation, siRNA mediated knockdown of HuR induced endogenous p27 protein levels as well as IRES-mediated reporter translation and leads to cell cycle arrest in G1.
Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis
Authors: Losada Ana , Hirano Michiko , Hirano Tatsuya
Published: December 2002

The establishment of metaphase chromosomes is an essential prerequisite of sister chromatid separation in anaphase. It involves the coordinated action of cohesin and condensin, protein complexes that mediate cohesion and condensation, respectively. In metazoans, most cohesin dissociates from chromatin at prophase, coincident with association of condensin. Whether loosening of cohesion at the onset of mitosis facilitates the compaction process, resolution of the sister chromatids, or both, remains unknown. We have found that the prophase release of cohesin is completely blocked when two mitotic kinases, aurora B and polo-like kinase (Plx1), are simultaneously depleted fromXenopus egg extracts. Condensin loading onto chromatin is not affected under this condition, and rod-shaped chromosomes are produced that show an apparently normal level of compaction. However, the resolution of sister chromatids within these chromosomes is severely compromised. This is not because of inhibition of topoisomerase II activity that is also required for the resolution process. We propose that aurora B and Plx1 cooperate to destabilize the sister chromatid linkage through distinct mechanisms that may involve phosphorylation of histone H3 and cohesin, respectively. More importantly, our results strongly suggest that cohesin release at the onset of mitosis is essential for sister chromatid resolution but not for condensin-mediated compaction.
Cognitive Procedural Learning in Patients With Fronto-Striatal Lesions
Authors: Schmidtke Klaus , Manner Hendrik , Kaufmann Robert , Schmolck Heike
Published: December 2002

Previous studies on the role of prefronto-striatal loop systems for cognitive procedural learning (PL) brought inconsistent results. To examine whether the integrity of the dorsolateral prefrontal loop is indispensable for normal cognitive PL, we examined the acquisition of cognitive skills in 35 patients with focal prefrontal lesions, focal caudate lesions, and Huntington's Disease (HD), and compared it with a control group. To examine the potential role of the processing demands made by the cognitive tasks, a set of tasks was applied whose acquisition places demand either on reasoning and problem solving, or on the establishment of fast and repetitive processing routines. The Pursuit Rotor task was also studied with the aim to re-examine earlier findings of a functional segregation of motor and complex prefronto-striatal loops. Deficits of cognitive and motor PL were found to be limited to certain tasks and groups. PL of one task, which demanded rapid, repetitive processing of visuo-spatial stimuli, was impaired in all patient groups. PL of two problem-solving tasks was impaired in patients with focal and degenerative caudate lesions only. None of the groups was impaired at PL of Mirror Reading, another task demanding rapid and repetitive visuo-spatial processing, and none was impaired in a fifth task of language skill. Deficits of motor learning were only observed in patients in whom the motor loop was affected. These results suggest that the dorsolateral prefronto-striatal loop is involved in the establishment of cognitive processing routines. The comparison of patients with and without caudate lesions suggests that disconnection of this circuit is critical. However, the normal acquisition of two cognitive tasks even in this group indicates that the integrity of the dorsolateral prefrontal loop is not mandatory for normal cognitive PL. We discuss these dissociations with regard to the demand profiles of the applied tasks and the locations of the lesions.
Learning Directions of Objects Specified by Vision, Spatial Audition, or Auditory Spatial Language: Figure 1.
Authors: Klatzky Roberta L. , Lippa Yvonne , Loomis Jack M. , Golledge Reginald G.
Published: December 2002

The modality by which object azimuths (directions) are presented affects learning of multiple locations. In Experiment 1, participants learned sets of three and five object azimuths specified by a visual virtual environment, spatial audition (3D sound), or auditory spatial language. Five azimuths were learned faster when specified by spatial modalities (vision, audition) than by language. Experiment 2 equated the modalities for proprioceptive cues and eliminated spatial cues unique to vision (optic flow) and audition (differential binaural signals). There remained a learning disadvantage for spatial language. We attribute this result to the cost of indirect processing from words to spatial representations.
Philosophical pitfalls in cosmetic surgery: a case of rhinoplasty during adolescence
Authors: Hilhorst M T
Published: December 2002

In the process of deciding to undergo cosmetic surgery for aesthetic reasons, people may err in various ways. Adolescents in particular run the risk of making errors, and both parents and surgeons have special moral responsibilities to avoid disappointments. Parents should face a number of moral issues; if they fail to do so, surgeons have the moral if not legal responsibility, to raise these issues and take a moral stand. In this paper, a number of pitfalls are specified from a philosophical perspective. A request for surgery should not be granted if patients do not meet the standards required for stable decision making and a balanced judgment, and particularly in those cases where patients fail to understand the assumptions—in terms of human values—underlying the surgical intervention. Assessments of competence should go beyond formal conceptions of autonomy, and should, as will be shown, be made on an individual basis. Substantive questions of personal identity and identity formation, within the context of often rapid psychosocial development and emotional turmoil peculiar to adolescents, should be addressed. The key to the moral evaluation of this surgery therefore lies primarily in a patient’s life story.
Diseases are invisible
Authors: Fredriksen S
Published: December 2002

The success of modern medicine is closely related to its ability to transcend the human senses. Technological advances such as stethoscopes, microscopes, andxrays overstep the boundaries of human perception. They enable us to see what is invisible to the unaided senses. These technologies have brought about fundamental changes to medicine—for the most part for the better. But they have also caught us in a tragic trap. They have left us in an odd position where we can no longer trust our senses concerning the health status of our body. Sense transcending technologies have made us aware that we can have a serious disease without experiencing any symptoms at all. In order to benefit from these technologies, we have to live with inescapable side effects.
Does chaos theory have major implications for philosophy of medicine?
Authors: Holm S
Published: December 2002

In the literature it is sometimes claimed that chaos theory, non-linear dynamics, and the theory of fractals have major implications for philosophy of medicine, especially for our analysis of the concept of disease and the concept of causation. This paper gives a brief introduction to the concepts underlying chaos theory and non-linear dynamics. It is then shown that chaos theory has only very minimal implications for the analysis of the concept of disease and the concept of causation, mainly because the mathematics of chaotic processes entail that these processes are fully deterministic. The practical unpredictability of chaotic processes, caused by their extreme sensitivity to initial conditions, may raise practical problems in diagnosis, prognosis, and treatment, but it raises no major theoretical problems. The relation between chaos theory and the problem of free will is discussed, and it is shown that chaos theory may remove the problem of predictability of decisions, but does not solve the problem of free will. Chaos theory may thus be very important for our understanding of physiological processes, and specific disease entities, without having any major implications for philosophy of medicine.
Of pipes, persons, and patients
Authors: Sayers G M
Published: December 2002

Michel Foucault’s analysis of Magritte’s painting,Ceci N’est Pas Une Pipe, and the later work,Les Deux Mystéres, serves as a template, that is broadened to consider different representations of persons and patients. Kant’s noumenal person is contrasted with phenomenal persons, and the well individual is contrasted with the patient. Patients may be considered as the subject or object of illness, and both versions are “imprisoned” within a psychological and social context that curtails freedom, threatens continuity of existence, and may question the nature of their personhood.
Depressive illness delayed Hamlet’s revenge
Authors: Shaw A B
Published: December 2002

If Hamlet had not delayed his revenge there would have been no play. Many explanations of the delay have been offered in the last four centuries. None is convincing. The interpretation which best fits the evidence best is that Hamlet was suffering from an acute depressive illness, with some obsessional features. He could not make a firm resolve to act. In Shakespeare’s time there was no concept of acute depressive illness, although melancholy was well known. Melancholy, however, would have been seen as a character defect. In the tragic model the hero brings himself and others to ruin because of a character defect. Thus, at the time, the play conformed to the tragic model. With today’s knowledge, it does not. This analysis adds to, but does not replace, other insights into the play.
Boron halide chelate compounds and their activity towards the demethylation of trimethylphosphate
Authors: Keizer Timothy S , De Pue Lauren J , Parkin Sean , Atwood David A
Published: December 2002

Salen(t-Bu)H2 (N,N'-ethylenebis(3,5-di-tert-butyl(2-hydroxy)benzylidenimine) and its derivatives were used to prepare boron compounds having the formula L(BCl2)2 (L = salen(t-Bu) (1), salpen(t-Bu) (2), salben(t-Bu) (3), salpten(t-Bu) (4), salhen(t-Bu) (5)). These are formed from the reaction of the corresponding L[B(OMe)2]2 with BCl3. In addition to being a new type of boron compound, they are also potential two-point Lewis acids. Indeed, they demonstrate Lewis acidic behavior in the dealkylation of trimethylphosphate. All of the compounds were characterized by mp, elemental analysis, 1H and 11B NMR, IR, MS, and in the case of 2 by X-ray crystallography.Key words: boron, salen, dealkylation.
The synthesis of [{n-Bu2Sn(S2N2)}2] and its use in the preparation of organometallic iridium sulfur nitrogen complexes
Authors: Aucott Stephen M , Slawin Alexandra MZ , Woollins J Derek
Published: December 2002

The addition of [n-Bu2SnCl2] to a solution of [S4N3][Cl] in liquid ammonia gave after extraction of the dry reaction mixture the new tin disulfur dinitrido compound [{n-Bu2Sn(S2N2)}2] (1). Reaction of [{n-Bu2Sn(S2N2)}2] (1) with the pentamethylcyclopentadienyl (Cp*) iridium derivatives [{IrCl(µ-Cl)(η5-C5Me5)}2] or [(η5-C5Me5)IrCl2(PPh3)] gave different products, which were dependent on the reactant ratios. A 1:1 reaction between 1 and [{IrCl(µ-Cl)(η5-C5Me5)}2] gave only [(η5-C5Me5)Ir(S2N2)] (2) in moderate yield; the same product in higher yield was obtained from a 2:1 reaction between 1 and [(η5-C5Me5)IrCl2(PPh3)]. Reaction of 1 and [(η5-C5Me5)2IrCl2(PPh3)] (1:1 molar ratio) in the presence of NH4[PF6] gave the unusual bimetallic species [(η5-C5Me5)IrCl(PPh3)(S2N2)Ir(η5-C5Me5)][PF6] (3). The X-ray crystal structures of 1, 2, and 3 are reported.Key words: liquid ammonia, tin sulfurnitrogen reagent, metathesis, sulfurnitrogen metallacycle, iridium complexes.
New hybrid inorganic-organic polymers containing cyclophosphazenes as pendant groups: Cyclophosphazene ligands containing hydrazone linkages and their conversion to polymers
Authors: Chandrasekhar Vadapalli , Krishnan Venkatasubbaiah , Athimoolam Arunachalampillai , Senthil Andavan Gurusamy Thangavelu
Published: December 2002

The reaction of the cyclotriphosphazene N3P3Cl5[O-C6H4-p-C6H4-p-CH=CH2] (2) with 10 equiv of N-methylhydrazine proceeds in a regio-specific manner to afford the multi-functional hydrazide N3P3[N(Me)NH2]5[O- C6H4-p-C6H4-p-CH=CH2] (3). Condensation of 3 with o-hydroxy benzaldehyde or pyridine-2-carboxaldehyde affords the corresponding hydrazones N3P3[N(Me)N=CH-C6H4-o-OH]5[O-C6H4-p-C6H4-p-CH=CH2] (4) and N3P3[N(Me)N=CH-C6H4N]5[O-C6H4-p-C6H4-p-CH=CH2] (5), respectively. These hydrazones can be homopolymerized to afford polymers 6 and 7 containing multi-site coordinating cyclophosphazenes as pendant groups.Key words: cyclophosphazene, hydrazone, pendant polymers, hybrid polymers, polymeric ligands.
Bisphosphine ligands containing two o-N,N-dimethylanilinyl substituents at each phosphorus atom
Authors: Jones Nathan D , Meessen Patric , Smith Martin B , Losehand Udo , Rettig Steven J , Patrick Brian O , James Brian R
Published: December 2002

The synthesis and complete characterization of the family of tetra(amine)bisphosphine ligands (o-NMe2C6H4)2P-(X)-P(o-NMe2C6H4)2, where X = CH2 (dmapm), (CH2)2 (dmape), and [Formula: see text] (dmapcp), are described. Crystal structure data are compared with known, analogous bisphosphines containing o-pyridyl or phenyl substituents in place of the o-dimethylanilinyl groups. Several short, intramolecular C-H···N distances in the anilinyl derivatives may represent the presence of weak hydrogen bonds. Key words: phosphine, amine, polydentate, hydrogen-bonding to N atoms.
Organophosphazenes. 25. The synthesis and electrochemistry of the dicobalt hexacarbonyl complexes of phenylethynylcyclophosphazenes
Authors: Bahadur Maneesh , Allen Christopher W , Geiger William E , Bridges Adam
Published: December 2002

The syntheses of the dicobalt hexacarbonyl complexes, N3P3F6-n(C[Formula: see text]CPhCo2(CO)6)n (n = 1 (3), n = 2 (4)), is reported. The introduction of the organometallic fragment allows for simplification of the NMR spectra and separation of the isomers of the disubstituted (4) derivatives. Electrochemical studies show that 3 undergoes a reversible one-electron reduction. At 233 K, the geminal isomer of 4 undergoes two separate reversible one-electron reductions. The ESR spectra of the radical anions of 3 and 4 have been obtained and show the absence of delocalization of unpaired spin density from the organometallic cluster to the phosphazene.Key words: cyclophosphazenes, cobaltalkyne clusters, electrochemistry, ESR.
Synthesis of a PennPhosruthenium(II) complex: The first crystal structure of a PennPhos-metal complex
Authors: Akotsi Okwado M , McDonald Robert , Bergens Steven H
Published: December 2002

The chiral bis(phosphine) ligand P,P'-1,2-phenylenebis[(1R,2S,4R,5S)-2,5-dimethyl-7-phosphabicyclo [2.2.1]heptane], [(R,S,R,S)-Me-PennPhos] (1) reacts with trans-RuCl2(NBD)Py2 (NBD = norbornadiene, Py = pyridine) (2) in CH2Cl2 at 45°C to form two diastereomers of the triply chloride bridged cation [{(1)RuPy}2(µ-Cl)3)][Cl] (3) in the ratio 1:3. The isomers were studied by NMR spectroscopy and separated by crystallization from CD2Cl2hexanes mixture. The major diastereomer is one of the anti-diastereomers and contains face-sharing bioctahedral diruthenium (Ru(II, II)) molecules with a RuRu distance of 3.289 Å. This diastereomer crystallizes in the monoclinic space group C2 (No. 5) with the cell dimensions a(Å) = 28.102(2), b(Å) = 20.5344(15), c(Å) = 12.7692(10), β(°) = 95.7411(16), V(Å3) = 7331.6(9), and Z = 4. The Me-PennPhos ligand adopts an unexpected bent, non-C2 symmetric conformation upon coordination to ruthenium.Key words: PennPhos crystal structure, diruthenium complexes, triply bridged complexes, bisphosphine ruthenium complexes.
SiCl4ethanol as a trimerization agent for organometallics: convenient syntheses of the symmetrically substituted arenes 1,3,5-C6H3R3 where R = (C5H4)Mn(CO)3 and (C5H4)Fe(C5H5)
Authors: Gupta Hari K , Reginato Nada , Ogini Francis O , Brydges Stacey , McGlinchey Michael J
Published: December 2002

Trimerization of acetylferrocene and of (acetylcyclopentadienyl)tricarbonyl-manganese proceeds efficiently in the presence of ethanol and tetrachlorosilane. The resulting 1,3,5-trisubstituted benzenes have been characterized by X-ray crystallography and compared with the structure of (1,3,5-triphenylbenzene)tris(tricarbonylchromium). The efficacy of EtOHSiCl4 as a combined reagent for the trimerization of polycyclic ketones is also discussed. Finally, the synthesis and structure of [CpMn(CO)2]2(µ-C=CHPr), derived from the reaction of cymantrene with butyllithium and phenylacetyl chloride at room temperature, is described.Key words: ketone, condensation, cyclization, organometallics, arenes.
A LATTICE BOLTZMANN MODEL FOR THE SHALLOW WATER EQUATIONS WITH TURBULENCE MODELING
Authors: ZHOU J. G.
Published: December 2002

A lattice Boltzmann model for the shallow water equations with turbulence modeling (LABSWETM) is developed. The flow turbulence is efficiently and naturally taken into account by incorporating the standard subgrid-scale stress model into the lattice Boltzmann equation in a consistent manner with the lattice gas dynamics. The model is applied to solve two flow problems and is verified by comparing numerical predictions with analytical solutions and available experimental data. The results show that the LABSWETM is able to provide basic features of flow turbulence and produce good predictions for turbulent shallow water flows.
EQUILIBRIUM, EVOLUTIONARY STABILITY AND GRADIENT DYNAMICS
Authors: FLÅM SJUR DIDRIK
Published: December 2002

Considered here are equilibria, notably those that solve noncooperative games. Focus is on connections between evolutionary stability, concavity and monotonicity. It is shown that evolutionary stable points are local attractors under gradient dynamics. Such dynamics, while reflecting search for individual improvement, can incorporate myopia, imperfect knowledge and bounded rationality/competence.
ASSESSING THE ANTICOMPETITIVE EFFECT OF MERGERS FOR MARKET POWER
Authors: FAULI-OLLER RAMON
Published: December 2002

In a symmetric setting with constant marginal costs, the welfare loss from mergers depends on the aggregate response of non-participating firms. This response in turn depends on the degree of concavity of the demand. As the degree of concavity of demand is not observable, we obtain conditions that guarantee that the premerger elasticity of demand can be used for antitrust purposes.
Improving Drug Supply Chain Security
Authors: Kannarkat Joseph T. , Denham Michael W. , Sarpatwari Ameet
Published: January 2024

This Viewpoint discusses the importance of the Drug Supply Chain Security Act and the need for pharmaceutical supply chain safeguards.