bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Netrin-Mediated Axon Attraction by a Receptor Protein Tyrosine Phosphatase
Authors: Chang Chieh , Yu Timothy W. , Bargmann Cornelia I. , Tessier-Lavigne Marc
Published: July 2004

During axon guidance, the ventral guidance of the
Caenorhabditis elegans
anterior ventral microtubule axon is controlled by two cues, the UNC-6/netrin attractant recognized by the UNC-40/DCC receptor and the SLT-1/slit repellent recognized by the SAX-3/robo receptor. We show here that loss-of-function mutations in
clr-1
enhance netrin-dependent attraction, suppressing ventral guidance defects in
slt-1
mutants.
clr-1
encodes a transmembrane receptor protein tyrosine phosphatase (RPTP) that functions in AVM to inhibit signaling through the DCC family receptor UNC-40 and its effector, UNC-34/enabled. The known effects of other RPTPs in axon guidance could result from modulation of guidance receptors like UNC-40/DCC.
Messing with Common Sense
Authors: Solomon Miriam
Published: July 2004

Defending Science
--
Within Reason

Between Scientism and Cynicism. by Susan Haack. Prometheus Books, Amherst, NY, 2003. 411 pp. $28. ISBN 1-59102-117-0.

In an account written for both scientists and the public, the author explores issues of scientific evidence and method as well as the interdependence of science and society.
Evidence for Precipitation on Mars from Dendritic Valleys in the Valles Marineris Area
Authors: Mangold Nicolas , Quantin Cathy , Ansan Véronique , Delacourt Christophe , Allemand Pascal
Published: July 2004

Dendritic valleys on the plateau and canyons of the Valles Marineris region were identified from Thermal Emission Imaging System (THEMIS) images taken by Mars Odyssey. The geomorphic characteristics of these valleys, especially their high degree of branching, favor formation by atmospheric precipitation. The presence of inner channels and the maturity of the branched networks indicate sustained fluid flows over geologically long periods of time. These fluvial landforms occur within the Late Hesperian units (about 2.9 to 3.4 billion years old), when Mars was thought to have been cold. Our results suggest a period of warmer conditions conducive to hydrological activity.
Sites of Neocortical Reorganization Critical for Remote Spatial Memory
Authors: Maviel Thibault , Durkin Thomas P. , Menzaghi Frédérique , Bontempi Bruno
Published: July 2004

The hippocampus is crucial for spatial memory formation, yet it does not store long-lasting memories. By combining functional brain imaging and region-specific neuronal inactivation in mice, we identified prefrontal and anterior cingulate cortex as critical for storage and retrieval of remote spatial memories. Imaging of activity-dependent genes also revealed an involvement of parietal and retrosplenial cortices during consolidation of remote memory. Long-term memory storage within some of these neocortical regions was accompanied by structural changes including synaptogenesis and laminar reorganization, concomitant with a functional disengagement of the hippocampus and posterior cingulate cortices. Thus, consolidation of spatial memory requires a time-dependent hippocampal-cortical dialogue, ultimately enabling widespread cortical networks to mediate effortful recall and use of cortically stored remote memories independently.
Lack of a Fusion Requirement for Development of Bone Marrow-Derived Epithelia
Authors: Harris Robert G. , Herzog Erica L. , Bruscia Emanuela M. , Grove Joanna E. , Van Arnam John S. , Krause Diane S.
Published: July 2004

Analysis of developmental plasticity of bone marrow–derived cells (BMDCs) is complicated by the possibility of cell-cell fusion. Here we demonstrate that epithelial cells can develop from BMDCs without cell-cell fusion. We use the Cre/lox system together with β-galactosidase and enhanced green fluorescent protein expression in transgenic mice to identify epithelial cells in the lung, liver, and skin that develop from BMDCs without cell fusion.
Mass Spectrometric Imaging of Highly Curved Membranes During
Tetrahymena
Mating
Authors: Ostrowski Sara G. , Van Bell Craig T. , Winograd Nicholas , Ewing Andrew G.
Published: July 2004

Biological membrane fusion is crucial to numerous cellular events, including sexual reproduction and exocytosis. Here, mass spectrometry images demonstrate that the low-curvature lipid phosphatidylcholine is diminished in the membrane regions between fusing
Tetrahymena
, where a multitude of highly curved fusion pores exist. Additionally, mass spectra and principal component analysis indicate that the fusion region contains elevated amounts of 2-aminoethylphosphonolipid, a high-curvature lipid. This evidence suggests that biological fusion involves and might in fact be driven by a heterogeneous redistribution of lipids at the fusion site.
Putative Exopolysaccharide Synthesis Genes Influence
Pseudomonas aeruginosa
Biofilm Development
Authors: Matsukawa Masanori , Greenberg E. P.
Published: July 2004

An analysis of the
Pseudomonas aeruginosa
genomic sequence revealed three gene clusters, PA1381-1393, PA2231-2240, and PA3552-3558, in addition to the alginate biosynthesis gene cluster, which appeared to encode functions for exopolysaccharide (EPS) biosynthesis. Recent evidence indicates that alginate is not a significant component of the extracellular matrix in biofilms of the sequenced
P. aeruginosa
strain PAO1. We hypothesized that at least one of the three potential EPS gene clusters revealed by genomic sequencing is an important component of
P. aeruginosa
PAO1 biofilms. Thus, we constructed mutants with chromosomal insertions in PA1383, PA2231, and PA3552. The mutant with a PA2231 defect formed thin unstructured abnormal biofilms. The PA3552 mutant formed structured biofilms that appeared different from those formed by the parent, and the PA1383 mutant formed structured biofilms that were indistinguishable from those formed by the parent. Consistent with a previous report, we found that polysaccharides were one component of the extracellular matrix, which also contained DNA. We suggest that the genes that were inactivated in our PA2231 mutant are required for the production of an EPS, which, although it may be a minor constituent of the matrix, is critical for the formation of
P. aeruginosa
PAO1 biofilms.
Detachment Characteristics and Oxacillin Resistance of
Staphyloccocus aureus
Biofilm Emboli in an In Vitro Catheter Infection Model
Authors: Fux C. A. , Wilson S. , Stoodley P.
Published: July 2004

Catheter-related bloodstream infections due to
Staphylococcus aureus
are of increasing clinical importance. The pathophysiological steps leading to colonization and infection, however, are still incompletely defined. We observed growth and detachment of
S. aureus
biofilms in an in vitro catheter-infection model by using time-lapse microscopy. Biofilm emboli were characterized by their size and their susceptibility for oxacillin. Biofilm dispersal was found to be a dynamic process in which clumps of a wide range of diameters detach. Large detached clumps were highly tolerant to oxacillin compared with exponential-phase planktonic cultures. Interestingly, the degree of antibiotic tolerance in stationary-phase planktonic cultures was equal to that in the large clumps. The mechanical disruption of large clumps reduced the minimal bactericidal concentration (MBC) by more than 1,000 times. The MBC for whole biofilm effluent, consisting of particles with an average number of 20 bacteria was 3.5 times higher than the MBC for planktonic cultures. We conclude that the antibiotic resistance of detached biofilm particles depends on the embolus size and could be attributed to nutrient-limited stationary-phase physiology of cells within the clumps. We hypothesize that the detachment of multicellular clumps may explain the high rate of symptomatic metastatic infections seen with
S. aureus
.
Synthesis of the Heteropolysaccharide O Antigen ofEscherichia coliO52 Requires an ABC Transporter: Structural and Genetic Evidence
Authors: Feng Lu , Senchenkova Sof'ya N. , Yang Jinghua , Shashkov Alexander S. , Tao Jiang , Guo Hongjie , Cheng Jiansong , Ren Yi , Knirel Yuriy A. , Reeves Peter R. , Wang Lei
Published: July 2004

The structural and genetic organization of theEscherichia coliO52 O antigen was studied. As identified by sugar and methylation analysis and nuclear magnetic resonance spectroscopy, the O antigen ofE. coliO52 has a partially O-acetylated disaccharide repeating unit (O unit) containingd-fucofuranose and 6-deoxy-d-manno-heptopyranose, as well as a minor 6-deoxy-3-O-methylhexose (most likely, 3-O-methylfucose). The O-antigen gene cluster ofE. coliO52, which is located between thegalFandgndgenes, was found to contain putative genes for the synthesis of the O-antigen constituents, sugar transferase genes, and ABC-2 transporter genes. Further analysis confirmed that O52 employs an ATP-binding cassette (ABC) transporter-dependent pathway for translocation and polymerization of the O unit. This is the first report of an ABC transporter being involved in translocation of a heteropolysaccharide O antigen inE. coli. Genes specific forE. coliO52 were also identified.
Phenylphosphate Carboxylase: a New C-C Lyase Involved in Anaerobic Phenol Metabolism in
Thauera aromatica
Authors: Schühle Karola , Fuchs Georg
Published: July 2004

The anaerobic metabolism of phenol in the beta-proteobacterium
Thauera aromatica
proceeds via carboxylation to 4-hydroxybenzoate and is initiated by the ATP-dependent conversion of phenol to phenylphosphate. The subsequent
para
carboxylation of phenylphosphate to 4-hydroxybenzoate is catalyzed by phenylphosphate carboxylase, which was purified and studied. This enzyme consists of four proteins with molecular masses of 54, 53, 18, and 10 kDa, whose genes are located adjacent to each other in the phenol gene cluster which codes for phenol-induced proteins. Three of the subunits (54, 53, and 10 kDa) were sufficient to catalyze the exchange of
14
CO
2
and the carboxyl group of 4-hydroxybenzoate but not phenylphosphate carboxylation. Phenylphosphate carboxylation was restored when the 18-kDa subunit was added. The following reaction model is proposed. The
14
CO
2
exchange reaction catalyzed by the three subunits of the core enzyme requires the fully reversible release of CO
2
from 4-hydroxybenzoate with formation of a tightly enzyme-bound phenolate intermediate. Carboxylation of phenylphosphate requires in addition the 18-kDa subunit, which is thought to form the same enzyme-bound energized phenolate intermediate from phenylphosphate with virtually irreversible release of phosphate. The 54- and 53-kDa subunits show similarity to UbiD of
Escherichia coli
, which catalyzes the decarboxylation of a 4-hydroxybenzoate derivative in ubiquinone (
ubi
) biosynthesis. They also show similarity to components of various decarboxylases acting on aromatic carboxylic acids, such as 4-hydroxybenzoate or vanillate, whereas the 10-kDa subunit is unique. The 18-kDa subunit belongs to a hydratase/phosphatase protein family. Phenylphosphate carboxylase is a member of a new family of carboxylases/decarboxylases that act on phenolic compounds, use CO
2
as a substrate, do not contain biotin or thiamine diphosphate, require K
+
and a divalent metal cation (Mg
2+
or Mn
2+
) for activity, and are strongly inhibited by oxygen.
Mu-Like Prophage Strong Gyrase Site Sequences: Analysis of Properties Required for Promoting Efficient Mu DNA Replication
Authors: Oram Mark , Pato Martin L.
Published: July 2004

The bacteriophage Mu genome contains a centrally located strong gyrase site (SGS) that is required for efficient prophage replication. To aid in studying the unusual properties of the SGS, we sought other gyrase sites that might be able to substitute for the SGS in Mu replication. Five candidate sites were obtained by PCR from Mu-like prophage sequences present in
Escherichia coli
O157:H7 Sakai,
Haemophilus influenzae
Rd,
Salmonella enterica
serovar Typhi CT18, and two strains of
Neisseria meningitidis
. Each of the sites was used to replace the natural Mu SGS to form recombinant prophages, and the effects on Mu replication and host lysis were determined. The site from the
E. coli
prophage supported markedly enhanced replication and host lysis over that observed with a Mu derivative lacking the SGS, those from the
N. meningitidis
prophages allowed a small enhancement, and the sites from the
Haemophilus
and
Salmonella
prophages gave none. Each of the candidate sites was cleaved specifically by
E. coli
DNA gyrase both in vitro and in vivo. Supercoiling assays performed in vitro, with the five sites or the Mu SGS individually cloned into a pUC19 reporter plasmid, showed that the Mu SGS and the
E. coli
or
N. meningitidis
sequences allowed an enhancement of processive, gyrase-dependent supercoiling, whereas the
H. influenzae
or
Salmonella
serovar Typhi sequences did not. While consistent with a requirement for enhanced processivity of supercoiling for a site to function in Mu replication, these data suggest that other factors are also important. The relevance of these observations to an understanding of the function of the SGS is discussed.
Bacillus subtilis
YdiH Is a Direct Negative Regulator of the
cydABCD
Operon
Authors: Schau Matthew , Chen Yinghua , Hulett F. Marion
Published: July 2004

During aerobic respiration,
Bacillus subtilis
utilizes three terminal oxidases, cytochromes
aa
3
,
caa
3
, and
bd
. Cytochrome
bd
is encoded by the
cydABCD
operon. We report here the first identification of a regulator for the
cydABCD
operon, YdiH. While working with Δ
resDE
mutant strains, we identified colonies which contained suppressor mutations (
cmp
) which bypassed the requirement for ResD for all phenotypes not associated with cytochrome
aa
3
or
caa
3
. Mapping identified a class of Tn
10
insertions which were close to the
cmp
locus (Tn
10
-
2
) and a second class (Tn
10
-
1
) which was inserted in
cydD
, a gene which appears to be essential to the
cmp
phenotype. Sequencing of the
cmp
loci from four independent Δ
resDE cmp
isolates yielded four loss-of-function alleles of
ydiH
, a gene encoding a protein with homology to AT-rich DNA-binding proteins. Additionally, we determined that cytochrome
bd
was aberrantly expressed in the Δ
resDE cmp
background. Together these data led to the hypothesis that YdiH serves as a negative regulator of
cydABCD
expression, a hypothesis supported by both gel-shift and DNase I footprinting analyses. YdiH protected the
cydA
promoter region at three 22-bp repeats located in the long 5′ untranslated region (193 bp). Induction of the
cydABCD
operon in a Δ
resDE
background showed that expression of the terminal oxidase
bd
was responsible for the bypass phenotype observed in a Δ
resDE cmp
strain, indicating that cytochrome
bd
expression complemented the loss of cytochromes
aa
3
and
caa
3
in the Δ
resDE
strain.
P2 Growth Restriction on an
rpoC
Mutant Is Suppressed by Alleles of the
Rz1
Homolog
lysC
Authors: Markov Dmitry , Christie Gail E. , Sauer Brian , Calendar Richard , Park Taehyun , Young Ry , Severinov Konstantin
Published: July 2004

Escherichia coli
strain 397c carries a temperature-sensitive mutation,
rpoC397
, that removes the last 50 amino acids of the RNA polymerase β′ subunit and is nonpermissive for plating of bacteriophage P2. P2
gor
mutants productively infect 397c and define a new gene,
lysC
, encoded by a reading frame that extensively overlaps the P2 lysis accessory gene,
lysB
. The unusual location of
lysC
with respect to
lysB
is reminiscent of the
Rz/Rz1
lysis gene pair of phage λ. Indeed, coexpression of
lysB
and
lysC
complemented the growth defect of λ
Rz
/
Rz1
null mutants, indicating that the LysB/C pair is similar to Rz/Rz1 in both gene arrangement and function. Cells carrying the
rpoC397
mutation exhibited an early onset of P2-induced lysis, which was suppressed by the
gor
mutation in
lysC
. We propose that changes in host gene expression resulting from the
rpoC397
mutation result in changes in the composition of the bacterial cell wall, making the cell more susceptible to P2-mediated lysis and preventing accumulation of progeny phage sufficient for plaque formation.
Differences in Membrane Fluidity and Fatty Acid Composition between Phenotypic Variants of
Streptococcus pneumoniae
Authors: Aricha Barak , Fishov Itzhak , Cohen Zvi , Sikron Noga , Pesakhov Stella , Khozin-Goldberg Inna , Dagan Ron , Porat Nurith
Published: July 2004

Phase variation in the colonial opacity of
Streptococcus pneumoniae
has been implicated as a factor in the pathogenesis of pneumococcal disease. This study examined the relationship between membrane characteristics and colony morphology in a few selected opaque-transparent couples of
S. pneumoniae
strains carrying different capsular types. Membrane fluidity was determined on the basis of intermolecular excimerization of pyrene and fluorescence polarization of 1,6-diphenyl 1,3,5-hexatriene (DPH). A significant decrease, 16 to 26% (
P
≤ 0.05), in the excimerization rate constant of the opaque variants compared with that of the transparent variants was observed, indicating higher microviscosity of the membrane of bacterial cells in the opaque variants. Liposomes prepared from phospholipids of the opaque phenotype showed an even greater decrease, 27 to 38% (
P
≤ 0.05), in the pyrene excimerization rate constant compared with that of liposomes prepared from phospholipids of bacteria with the transparent phenotype. These findings agree with the results obtained with DPH fluorescence anisotropy, which showed a 9 to 21% increase (
P
≤ 0.001) in the opaque variants compared with the transparent variants. Membrane fatty acid composition, determined by gas chromatography, revealed that the two variants carry the same types of fatty acids but in different proportions. The trend of modification points to the presence of a lower degree of unsaturated fatty acids in the opaque variants compared with their transparent counterparts. The data presented here show a distinct correlation between phase variation and membrane fluidity in
S. pneumoniae
. The changes in membrane fluidity most probably stem from the observed differences in fatty acid composition.
Distribution, Genetic Diversity, and Variable Expression of the Gene Encoding Hyaluronate Lyase within theStreptococcus suisPopulation
Authors: King Samantha J. , Allen Andrew G. , Maskell Duncan J. , Dowson Christopher G. , Whatmore Adrian M.
Published: July 2004

AlthoughStreptococcus suisis an economically important pathogen of pigs and an occasional cause of zoonotic infections of humans knowledge of crucial virulence factors, and as a consequence targets for therapeutic or prophylactic intervention, remains limited. Here we describe a detailed study of the distribution, diversity, and in vitro expression of hyaluronate lyase, a protein implicated as a virulence factor of many mucosal pathogens. The gene encoding hyaluronate lyase,hyl, was present in all 309 bona fideS. suisisolates examined representing diverse serotypes, geographic sources, and clinical backgrounds. Examination of the genetic diversity ofhylby RFLP and sequence analysis indicated a pattern of diversity shared by many gram-positive surface proteins with a variable 5′ region encoding the most distal cell surface-exposed regions of the protein and a much more conserved 3′ region encoding domains more closely associated with the bacterial cell. Variation occurs by several mechanisms, including the accumulation of point mutations and deletion and insertion events, and there is clear evidence that genetic recombination has contributed to molecular variation in this gene. Despite the ubiquitous presence ofhyl, the corresponding enzyme activity was detected in fewer than 30% of the 309 isolates. In several cases this lack of activity correlates with the presence of mutations (either sequence duplications or point mutations) withinhylthat result in a truncated polypeptide. There is a striking absence of hyaluronate lyase activity in a large majority of isolates from classicS. suisinvasive disease, indicating that this protein is probably not a crucial virulence factor, although activity is present in significantly higher numbers of isolates associated with pneumonia.
Identification of a Broadly Active Phage Lytic Enzyme with Lethal Activity against Antibiotic-Resistant
Enterococcus faecalis
and
Enterococcus faecium
Authors: Yoong Pauline , Schuch Raymond , Nelson Daniel , Fischetti Vincent A.
Published: July 2004

Enterococcus faecalis
and
Enterococcus faecium
infections are increasingly difficult to treat due to high levels of resistance to antibiotics. PlyV12, a bacteriophage lytic enzyme, was isolated and shown to effectively kill both
E. faecalis
and
E. faecium
(including vancomycin-resistant strains), as well as other human pathogens. We propose its development and use as an alternative therapeutic tool.
Whole-Genome Expression Profiling of
Thermotoga maritima
in Response to Growth on Sugars in a Chemostat
Authors: Nguyen Tu N. , Ejaz Arvin D. , Brancieri Mark A. , Mikula Amy M. , Nelson Karen E. , Gill Steven R. , Noll Kenneth M.
Published: July 2004

To provide data necessary to study catabolite-linked transcriptional networks in
Thermotoga maritima
, we used full-genome DNA microarray analysis of global transcriptional responses to growth on glucose, lactose, and maltose in a chemostat. A much larger number of genes changed expression in cells grown on lactose than on maltose, each relative to genes expressed in cells grown on glucose. Genes encoding putative oligopeptide transporters were often coregulated with adjacent glycosidase-encoding genes. Genes encoding enzymes catalyzing NADH oxidation were up-regulated on both lactose and maltose. Genes involved in iron and sulfur metabolism were differentially expressed in response to lactose. These data help define the sets of coregulated genes and suggest possible functions for their encoded products.
GUT PRECURSORS IN SU(3)3-TYPE MODEL AND Ncolour>3
Authors: TRACAS N. D.
Published: July 2004

We investigate the SU (3)3 GUT model when signs of the model (precursors), due to low compactification scale, appear before the gauge couplings of the Standard Model get unified. The Kaluza–Klein state contribution seems to lead the gauge couplings to unification through a wide energy scale only in the case when the colour group is augmented to SU(4).
PRE-EQUILIBRIUM EMISSION IN DIFFERENTIAL CROSS-SECTION CALCULATIONS AND ANALYSIS OF EXPERIMENTAL DATA FOR 232Th
Authors: TEL E. , DEMİRKOL İ , ARASOĞLU A. , ŞARER B.
Published: July 2004

In this study, neutron-emission spectra produced by (n,xn) reactions on nuclei 232 Th have been calculated. Angle-integrated cross-sections in neutron induced reactions on targets 232 Th have been calculated at the bombarding energies from 2 MeV to 18 MeV. We have investigated multiple pre-equilibrium matrix element constant from internal transition for 232 Th (n,xn) neutron emission spectra. In the calculations, the geometry dependent hybrid model and the cascade exciton model including the effects of pre-equilibrium have been used. Pre-equilibrium direct effects have been examined by using full exciton model. In addition, we have described how multiple pre-equilibrium emissions can be included in the Feshbach–Kerman–Koonin (FKK) fully quantum-mechanical theory. By analyzing (n,xn) reaction on 232 Th , with the incident energy from 2 MeV to 18 MeV, the importance of multiple pre-equilibrium emission can be seen clearly. All calculated results have been compared with experimental data. The obtained results have been discussed and compared with the available experimental data and found agreement with each other.
MODEL INDEPENDENT RESULTS FOR HEAVY QUARKONIUM
Authors: SOTO JOAN
Published: July 2004

We review a number of results for the spectrum and inclusive decays of heavy quarkonium systems which can be derived from QCD under well controlled approximations. They essentially follow from the hierarchy of scales in these systems, which can be efficiently exploited using non-relativistic effective field theories. In particular, we discuss under which conditions non-relativistic potential models emerge as effective theories of QCD.
TRAVELING SALESMAN PROBLEM OF SEGMENTS
Authors: XU JINHUI , LIN ZHIYONG , YANG YANG , BEREZNEY RONALD
Published: July 2004

In this paper, we present a polynomial time approximation scheme (PTAS) for a variant of the traveling salesman problem (called segment TSP) in which a traveling salesman tour is sought to traverse a set of n ∊-separated segments in two dimensional space. Our results are based on an interesting combinatorial result which bounds the total number of entry points in an optimal TSP tour and a generalization of Arora's technique5 for Euclidean TSP (of a set of points). The randomized version of our algorithm takes O(n2( log n)O(1/∊2)) time to compute a (1+∊)-approximation with probability ≥l/2, and can be derandomized with an additional factor of O(n2).
USING FUZZY TECHNIQUES TO MODEL STUDENTS IN WEB-BASED LEARNING ENVIRONMENTS
Authors: KOSBA ESSAM M. , DIMITROVA VANIA G. , BOYLE ROGER D.
Published: July 2004

The paper illustrates how fuzzy techniques can be applied to address problems experienced in widespread computing systems for distance learning. Many educational organizations use Web Course Management Systems (WCMS) to run distance courses. In such environments, facilitators often face difficulties in monitoring and understanding problems experienced by distance learners. An approach is proposed here where artificial advisors are built to offer distance-learning facilitators informed advice of what the problems/needs of individuals and groups may be, as well as to suggest appropriate actions when possible. We have developed the TADV (Teacher ADVisor) framework, which builds student, group, and class models based on the tracking information generated by WCMS, and uses these models to generate advice to the course instructors. This paper introduces TADV and describes the fuzzy approach used for extracting individual, group and class models. TADV is currently exemplified in a Discrete Mathematics course run at the Arab Academy for Science and Technology and Maritime Transport, Alexandria, Egypt.
EVALUATING THE INTELLIGENT FEATURES OF A WEB-BASED INTELLIGENT COMPUTER ASSISTED LANGUAGE LEARNING SYSTEM
Authors: TSIRIGA VICTORIA , VIRVOU MARIA
Published: July 2004

In this paper we present and discuss the results of the evaluation of an Intelligent Computer Assisted Language Learning (ICALL) system that operates over the Web. In particular, we aimed at evaluating the system along three dimensions: a) the effect of the intelligent features of the system on the learning outcome of students, b) the system's ability to provide individualized support to students that leads to more effective use of the system and c) the general usability and friendliness of the ICALL. To achieve this, we conducted an empirical study, where we compared the intelligent system with a non-intelligent version of it. The results of the study revealed that the students of the Web-based ICALL had gained more knowledge of the domain and had been able to interact with the system more effectively as compared to the students that had used the non-intelligent version of the system. However, the students of the intelligent version of the system found it more difficult and they needed more time to get acquainted with the system in comparison to the students of the non-intelligent system.
WARRANTY COST ANALYSIS: RENEWING WARRANTY WITH NON-ZERO REPAIR TIME
Authors: CHUKOVA S. , HAYAKAWA Y.
Published: July 2004

The main focus of this study is on the modeling of the warranty claims and evaluating the warranty expenses. The cost of each warranty claim depends on the repair time associated with the claim. Alternating renewal process is used to model the operating and repair times. The warranty costs over the warranty period under renewing free replacement policy are evaluated. Also, the expected warranty expenses over the life cycle of the product are studied. Numerical examples illustrate the ideas.
MEAN RESIDUAL LIFE AND OTHER PROPERTIES OF WEIBULL RELATED BATHTUB SHAPE FAILURE RATE DISTRIBUTIONS
Authors: LAI C. D. , ZHANG LINGYUN , XIE M.
Published: July 2004

The two-parameter Weibull distribution is widely used in reliability analysis. Because of its monotonic ageing behaviour, its applicability is hampered in certain reliability situations. Several generalizations and extensions of the Weibull model have been proposed in the literature to overcome this limitation but their properties have not yet been described in a unified manner. In this paper, graphical displays of the mean residual life curves of several families of Weibull related life distributions are given together with their corresponding failure rate functions. The relationship between these two functions are visibly demonstrated. We focus our attention on the Weibull related families that have bathtub or modified bathtub shape failure rates. Important reliability characteristics such as burn-in, change point and flatness of bathtub of these families are examined. Model selection and parameters estimation are also discussed.
ON LIFETIME ESTIMATION IN THE PRESENCE OF LENGTH-BIASED SAMPLING PLAN
Authors: AKMAN OLCAY
Published: July 2004

In the presence of length-biasedness, a lifetime measure of interest may be estimated in two ways: (i) by modeling the data correctly using a length-biased distribution and using the resulting estimators in the original model as an adjustment, or (ii) by modeling the data correctly using a length-biased distribution, and obtaining the original lifetime measure of interest via a transformation, if one exists. Here we examine sufficiency in information context under transformations.
LEARNING AND IMITATION: TRANSITIONAL DYNAMICS IN VARIANTS OF THE BAM
Authors: HEYMANN D. , PERAZZO R. P. J. , SCHUSCHNY A. R.
Published: July 2004

We study the dynamics of self-organized systems when disturbed by shocks. For this purpose, we consider extensions of the "Bar Attendance Model" [1] (BAM), which provides a stylized setting for the analysis of the emergence of coordination in the behavior of a large collection of agents. We represent the learning process of the agents through genetic algorithms, which respond to global (publicly available) information. In addition, we allow the actions of agents to be influenced by local information, as expressed in the behavior and performance of neighboring individuals. In the context of the BAM, we show that, in the event of a shock, the imitation behavior may become widespread and generate a contagion cascade which mimics a collective panic. We use this framework to represent features of the dynamics of an actual bank run.
EMERGENCE OF ALLOMETRIC SCALING IN GENEALOGICAL TREES
Authors: CAMPOS PAULO R. A. , DE OLIVEIRA VIVIANE M. , MAIA LEONARDO P.
Published: July 2004

We investigate the emergence of power-law scalings in genealogical trees. Especially, we study the topological properties of genealogical trees both in the neutral evolution and the selective evolution. In all instances, we observe that the topologies of these trees are well described by a power-law scaling [Formula: see text], where Akis the number of nodes which are direct or indirect descendants of node k and Ck=∑jAjwhere the sum is taken over all nodes that contribute to Ak. This relation is well known in transportation networks as well as in metabolic networks, and it is referred to as allometric scaling. Furthermore, we observe a slight dependence of the scaling exponent η on the intensity of selection.
MULTISCALE COMPLEXITY/ENTROPY
Authors: BAR-YAM Y.
Published: July 2004

We discuss the role of scale dependence of entropy/complexity and its relationship to component interdependence. The complexity as a function of scale of observation is expressed in terms of subsystem entropies for a system having a description in terms of variables that have the same a priori scale. The sum of the complexity over all scales is the same for any system with the same number of underlying degrees of freedom (variables), even though the complexity at specific scales differs due to the organization/interdependence of these degrees of freedom. This reflects a tradeoff of complexity at different scales of observation. Calculation of this complexity for a simple frustrated system reveals that it is possible for the complexity to be negative. This is consistent with the possibility that observations of a system that include some errors may actually cause, on average, negative knowledge, i.e. incorrect expectations.
BEHAVIORAL FOUNDATIONS AND EQUILIBRIUM NOTIONS FOR SOCIAL NETWORK FORMATION PROCESSES
Authors: CARAYOL NICOLAS , ROUX PASCALE
Published: July 2004

This paper develops a framework for studying social network formation. Partly built upon a formalism used in theoretical economics, the network formation process we introduce is locally driven by agents who maximize a given individual payoff function. We examine two simple models and observe the limiting distributions of stochastically stable networks. We find that these networks share some of the features observed for social networks. In particular, we find critical values of the parameters for which the selected networks exhibit small world properties.
AN INVESTIGATION OF THE PHASE TRANSITIONS OF A FAMILY OF PROBABILISTIC AUTOMATA
Authors: MÜHLENBEIN HEINZ , AUS DER FÜNTEN THOMAS
Published: July 2004

We investigate a family of totalistic probabilistic cellular automata (PCA) which depend on three parameters. For the uniform random neighborhood and for the symmetric 1D PCA the exact stationary distribution is computed for all finite n. This result is used to evaluate approximations (uni-variate and bi-variate marginals). It is proven that the uni-variate approximation (also called mean-field) is exact for the uniform random neighborhood PCA. The exact results and the approximations are used to investigate phase transitions. We compare the results of two order parameters, the uni-variate marginal and the normalized entropy. Sometimes different transitions are indicated by the Ehrenfest classification scheme. This result shows the limitations of using just one or two order parameters for detecting and classifying major transitions of the stationary distribution. Furthermore, finite size scaling is investigated. We show that extrapolations to n=∞ from numerical calculations of finite n can be misleading in difficult parameter regions. Here, exact analytical estimates are necessary.
EXPECTING THE UNEXPECTED: DISRUPTIVE TECHNOLOGICAL CHANGE PROCESSES AND THE ELECTRIC VEHICLE
Authors: DYERSON ROMANO , PILKINGTON ALAN
Published: July 2004

Here we explore the role of possible disruptive technologies in the US automobile sector and the reaction of established firms to that threat. More specifically, US regulators have signalled a shift towards zero emission vehicles; threatening the hegemony of the high emission car built using conventional technology. This presents an opportunity to study the effect of regulation in shaping knowledge flows, an area somewhat neglected by innovation studies especially with regard to meeting environmental concerns. To do so, we use patent citations to explore knowledge flows in the development of the electric vehicle. Our analysis suggests that the strategic responses of the US incumbent firms have displayed a sophisticated short and long-term reaction.
t-INNOVATION: USING INFORMATION AND COMMUNICATION TECHNOLOGY TO ACHIEVE STRATEGIC INNOVATION
Authors: ANDERSON JAMIE , MARKIDES CONSTANTINOS
Published: July 2004

Over the past few years, numerous industries have been disrupted by the arrival of "strategic innovators" — companies that attack the established competitors using radical new strategies and guerrilla tactics. In this article, we explore how strategic innovators utilize Information and Communication Technology (ICT) to successfully implement their radical strategies. We argue that proactively using ICT in a strategic (rather than operational) way to achieve architectural innovation and to quickly scale-up an innovative business design are keys to success. We highlight our arguments using detailed examples of several successful strategic innovators.
Oxalate inhibits renal proximal tubule cell proliferation via oxidative stress, p38 MAPK/JNK, and cPLA2 signaling pathways
Authors: Han Ho Jae , Lim Min Jin , Lee Yun Jung
Published: July 2004

Exposure of renal proximal tubule cells to oxalate may play an important role in cell proliferation, but the signaling pathways involved in this effect have not been elucidated. Thus the present study was performed to examine the effect of oxalate on 3H-labeled thymidine incorporation and its related signal pathway in primary cultured rabbit renal proximal tubule cells (PTCs). The effects of oxalate on [3H]thymidine incorporation, lactate dehydrogenase (LDH) release, Trypan blue exclusion, H2O2 release, activation of mitogen-activated protein kinases (MAPKs), and 3H-labeled arachidonic acid (AA) release were examined in primary cultured renal PTCs. Oxalate inhibited [3H]thymidine incorporation in a time- and dose-dependent manner. However, its analogs did not affect [3H]thymidine incorporation. Oxalate (1 mM) significantly increased H2O2 release, which was blocked by N-acetyl-l-cysteine (NAC) and catalase (antioxidants). Oxalate significantly increased p38 MAPK and stress-activated protein kinase (SAPK)/c-Jun NH2-terminal kinase (JNK) activity, not p44/42 MAPK. Oxalate stimulated [3H]AA release and translocation of cytosolic phospholipase A2 (cPLA2) from the cytosolic fraction to the membrane fraction. Indeed, oxalate significantly increased prostaglandin E2 (PGE2) production compared with control. Oxalate-induced inhibition of [3H]thymidine incorporation and increase of [3H]AA release were prevented by antioxidants (NAC), a p38 MAPK inhibitor (SB-203580), a SAPK/JNK inhibitor (SP-600125), or PLA2 inhibitors [mepacrine and arachidonyl trifluoromethyl ketone (AACOCF3)], but not by a p44/42 MAPK inhibitor (PD-98059). These findings suggest that oxalate inhibits renal PTC proliferation via oxidative stress, p38 MAPK/JNK, and cPLA2 signaling pathways.
Cardiac contractile dysfunction in J2N-k cardiomyopathic hamsters is associated with impaired SR function and regulation
Authors: Babick Andrea P. , Cantor Elliott J. F. , Babick John T. , Takeda Nobuakira , Dhalla Naranjan S. , Netticadan Thomas
Published: July 2004

Although dilated cardiomyopathy (DCM) is known to result in cardiac contractile dysfunction, the underlying mechanisms are unclear. The sarcoplasmic reticulum (SR) is the main regulator of intracellular Ca2+ required for cardiac contraction and relaxation. We therefore hypothesized that abnormalities in both SR function and regulation will contribute to cardiac contractile dysfunction of the J2N-k cardiomyopathic hamster, an appropriate model of DCM. Echocardiographic assessment indicated contractile dysfunction, because the ejection fraction, fractional shortening, cardiac output, and heart rate were all significantly reduced in J2N-k hamsters compared with controls. Depressed cardiac function was associated with decreased cardiac SR Ca2+ uptake in the cardiomyopathic hamsters. Reduced SR Ca2+ uptake could be further linked to a decrease in the expression of the SR Ca2+-ATPase and cAMP-dependent protein kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16. Depressed PLB phosphorylation was paralleled with a reduction in the activity of SR-associated PKA, as well as an elevation in protein phosphatase activity in J2N-k hamster. The results of this study suggest that an alteration in SR function and its regulation contribute to cardiac contractile dysfunction in the J2N-k cardiomyopathic hamster.
Primary granule release from human neutrophils is potentiated by soluble fibrinogen through a mechanism depending on multiple intracellular signaling pathways
Authors: Tuluc Florin , Garcia Analia , Bredetean Ovidiu , Meshki John , Kunapuli Satya P.
Published: July 2004

N-Formyl-methionyl-leucyl-phenylalanine (fMLP) is a potent activator of neutrophil degranulation. The intracellular signaling mechanisms involved in the potentiating effect of fibrinogen on fMLP-induced primary granule release from human neutrophils were investigated. Fibrinogen caused a significant leftward shift of the concentration-response curve of fMLP-induced elastase release. An antibody against Mac-1 (CD11b/CD18) prevented the potentiating effect of fibrinogen, suggesting that soluble fibrinogen potentiates fMLP-induced degranulating effect by a mechanism mediated by the integrin Mac-1. Fibrinogen enhanced fMLP-induced tyrosine phosphorylation in human neutrophils and markedly enhanced the phosphorylation of mitogen-activated protein kinases (MAPK) caused by fMLP. However, U0126, an inhibitor of p44/42 MAPK activation, or SB-203580, an inhibitor of p38 MAPK, did not alter the effect of fibrinogen on fMLP-induced elastase release. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) kinase inhibitor, and genistein, a nonspecific tyrosine kinase inhibitor, strongly inhibited fMLP-induced elastase release both in the presence and in the absence of fibrinogen. An Akt/PKB inhibitor failed to alter the potentiating effect of fibrinogen, suggesting that the effect of fibrinogen is mediated by Akt-independent pathways. Gö6976, an inhibitor of classical PKC isoforms, caused a significant inhibition of fMLP-induced elastase release in the presence or absence of fibrinogen, while nonselective inhibitors of PKC, Ro 31-8220, GF-109203X, and staurosporine, caused potentiation of fMLP-induced elastase release. We conclude that fibrinogen potentiation of primary granule release induced by fMLP is mediated by the integrin CD11b/CD18 through pathways dependent on PI3K and tyrosine kinases, but other regulatory mechanisms may be also involved.
Aging exacerbates negative remodeling and impairs endothelial regeneration after balloon injury
Authors: Torella Daniele , Leosco Dario , Indolfi Ciro , Curcio Antonio , Coppola Carmela , Ellison Georgina M. , Russo Viviana G. , Torella Michele , Volti Giovanni Li , Rengo Franco , Chiariello Massimo
Published: July 2004

Many older patients, because of their high prevalence of coronary artery disease, are candidates for percutaneous coronary interventions (PCI), but the effects of vascular aging on restenosis after PCI are not yet well understood. Balloon injury to the right carotid artery was performed in adult and old rats. Vascular smooth muscle cell (VSMC) proliferation, apoptotic cell death, together with Akt induction, telomerase activity, p27kip1, and endothelial nitric oxide synthase (eNOS) expression was assessed in isolated arteries. Neointima hyperplasia and vascular remodeling along with endothelial cell regeneration were also measured after balloon injury. Arteries isolated from old rats exhibited a significant reduction of VSMC proliferation and an increase in apoptotic death after balloon injury when compared with adult rats. In the vascular wall of adult rats, balloon dilation induced Akt phosphorylation, and this was barely present in old rats. In arteries from old rats, Akt-modulated cell cycle check points like telomerase activity and p27kip1 expression were decreased and increased, respectively, compared with adults. After balloon injury, old rats showed a significant reduction of neointima formation and an increased vascular negative remodeling compared with adults. These results were coupled by a marked delay in endothelial regeneration in aged rats, partially mediated by a decreased eNOS expression and phosphorylation. Interestingly, chronic administration of l-arginine prevented negative remodeling and improved reendothelialization after balloon injury in aged animals. A decreased neointimal proliferation, an impaired endothelial regeneration, and an increase in vascular remodeling after balloon injury were observed in aged animals. The molecular mechanisms underlying these responses seem to be a reduced Akt and eNOS activity.
Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of δ-opioid receptor
Authors: Okubo Shinji , Tanabe Yujirou , Takeda Kenji , Kitayama Michihiko , Kanemitsu Seiyu , Kukreja Rakesh C. , Takekoshi Noboru
Published: July 2004

We examined whether ischemic preconditioning (IPC) attenuates ischemia-reperfusion injury, in part, by decreasing apoptosis and whether the δ-opioid receptor (DOR) plays a pivotal role in the regulation of apoptosis. Rabbits were subjected to 30-min coronary artery occlusion (CAO) and 180 min of reperfusion. IPC was elicited with four cycles of 5-min ischemia and 10-min reperfusion before CAO. Morphine (0.3 mg/kg iv) was given 15 min before CAO. Naloxone (Nal; 10 mg/kg iv) and naltrindole (Nti; 10 mg/kg iv), the respective nonselective and selective DOR antagonists were given 10 min before either morphine or IPC. Infarct size (%risk area) was reduced from 46 ± 3.8 in control to 11.6 ± 1.0 in IPC and 19.5 ± 3.8 in the morphine group (means ± SE; P < 0.001 vs. control). Nal blocked the protective effects of IPC and morphine, as shown by the increase in infarct size to 38.6 ± 7.2 and 44.5 ± 1.8, respectively. Similarly, Nti blocked IPC and morphine-induced protection. The percentage of apoptotic cells (revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) decreased in IPC (3.6 ± 1.9) and morphine groups (5.2 ± 1.2) compared with control group (12.4 ± 1.6; P < 0.001). Nti pretreatment increased apoptotic cells 11.2 ± 2.2% in IPC and 12.1 ± 0.8% in morphine groups. Nal failed to block inhibition of apoptosis in the IPC group (% of cells: 5.7 ± 1.3 vs. 3.6 ± 1.9 in IPC alone; P > 0.05). These results were also confirmed by nucleosomal DNA laddering pattern. We conclude that IPC reduces lethal injury, in part, by decreasing apoptosis after ischemia-reperfusion and activation of the DOR may play a crucial role in IPC or morphine-induced myocardial protection.
Estimates for the norms of solutions of difference systems with several delays
Authors: Medina Rigoberto
Published: July 2004

We derive explicit stability conditions for time‐dependent
difference equations with several delays in Cn (the set of
n complex vectors) and estimates for the size of the solutions.
The growth rates obtained here are not necessarily decay rates.
Novel Marine Compounds: Anticancer or Genotoxic?
Authors: Arif Jamal M. , Al-Hazzani Amal A. , Kunhi Muhammed , Al-Khodairy Fahad
Published: July 2004

In the past several decades, marine organisms have generously
gifted to the pharmaceutical industries numerous naturally
bioactive compounds with antiviral, antibacterial,
antimalarial, anti‐inflammatory, antioxidant, and anticancer
potentials. But till date only few anticancer drugs (cytarabine,
vidarabine) have been commercially developed from marine
compounds while several others are currently in different
clinical trials. Majority of these compounds were tested in the
tumor xenograft models, however, lack of anticancer potential
data in the chemical‐ and/or oncogene‐induced pre‐initiation
animal carcinogenesis models might have cost some of the marine
anticancer compounds an early exit from the clinical trials. This
review critically discusses importance of preclinical
evaluation, failure of human clinical trials with certain
potential anticancer agents, the screening tests used, and choice
of biomarkers.