bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Response of Pipeline Free Spans Based on Beam Theory
Authors: Fyrileiv Olav , Mo̸rk Kim
Published: March 2009

One of the main risk factors for subsea pipelines exposed on the seabed is fatigue failure of free spans due to ocean current or wave loading. This paper describes how the structural response of a free span, as input to the fatigue analyses, can be assessed in a simple and still accurate way by using improved beam theory formulations. In connection with the release of the DNV Recommended Practice, DNV-RP-F105 “Free Spanning Pipelines”, the simplified structural response quantities have been improved compared to previous codes. The boundary condition coefficients for the beam theory formulations have been updated based an effective span length concept. This concept is partly based on theoretical studies and partly on a large number of FE analyses. The updated expressions are general and fit all types of soil and pipe dimensions for lower lateral and vertical vibration modes. The present paper focus on estimation of simplified response quantities such as lower natural frequencies and associated mode shapes. Hydrodynamical aspects of Vortex Induced Vibrations (VIV) are outside the scope of this paper.
Directional Spreading in Two-Peak Spectrum at the Norwegian Continental Shelf
Authors: Bitner-Gregersen Elzbieta M. , Hagen O̸istein
Published: March 2009

In practical applications, it is usually assumed that the wave spectrum is of a single mode form, and well modeled by a JONSWAP or Pierson-Moskowitz spectrum. This assumption is of a reasonable accuracy for severe sea states. However, moderated and low sea states are often of a combined nature, consisting of both wind-sea and swell and should be characterized by a double peak spectrum. The present paper discusses two-peak spectra observed in Norwegian waters, which are particularly affected by swell. The analysis is based on 5-year of directional data from Haltenbanken. A directional distribution for swell is suggested. Further, a procedure for including directional spreading in two-peak spectra is proposed. The method is illustrated for the two-peak Torsethaugen frequency spectrum (Torsethaugen, 1996), which is currently used by the Norwegian industry.
DQEM Analysis of In-Plane Vibration of Curved Beam Structures
Authors: Chen Chang-New
Published: March 2009

The development of differential quadrature element method (DQEM) in-plane vibration analysis model of arbitrarily curved nonprismatic beam structures was carried out. The DQEM uses the extended differential quadrature (EDQ) to discretize the differential eigenvalue equation defined on each element, the transition conditions defined on the inter-element boundary of two adjacent elements and the boundary conditions of the beam. Numerical results solved by the developed numerical algorithm are presented. The convergence of the developed DQEM analysis model is efficient. This numerical algorithm can be used to analyze the related offshore structures.
On the Occurrence of Strong Higher Harmonic Wave Forces and Induced Ringing Loads on Vertical Cylinders
Authors: Grue John , Huseby Morten
Published: March 2009

Experimental observations of a secondary load cycle in the force acting on a vertical cylinder exposed to long and steep waves are discussed. A complementary discussion of the occurrence of ringing of models of offshore structures is given. The height of the secondary load cycle is typically up to about 0.1–0.15 times the peak to peak force on the cylinder. The load cycle is observed for a nondimensional wavenumber kR in the range 0.1–0.33 and for a Froude number Fr = ωζm/gD exceeding about 0.4. Pronounced ringing occurs for the same parameter range. (k the wavenumber, R the cylinder radius, ω the wave frequency, ζm the maximal wave elevation, g the acceleration of gravity, D = 2R.)
Experimental Study and Prediction of Fatigue Crack Growth in Girth Welded Pipes
Authors: Zhang Yan H. , Maddox Stephen J. , Razmjoo G. Reza
Published: March 2009

Fracture mechanics fatigue crack growth analysis is widely used in the Engineering Critical Assessment of welded structures. An important requirement is an accurate solution for the stress intensity factor, K, for the particular type and geometry of crack under consideration. A case commonly encountered is the weld toe crack. A solution incorporating the stress intensity magnification factor, MK, to allow for the stress concentration effect of the welded joint, based on 2D FEA has been in use for many years. A new solution from 3D FEA has recently become available. However, in both cases, little has been done to validate the solutions against actual fatigue crack growth data. The results from a recent investigation of fatigue in large diameter (609mm OD × 20mm WT) girth-welded pipes provided an opportunity to do this. This paper presents a comparison of these crack growth data based on beachmarking information with predictions based on the 2D and 3D MK solutions. It was found that the 2D MK solution tended to over-estimate the crack growth rate, while the 3D solution provided better correlation between predicted and actual crack propagation behaviour. It is therefore recommended that the 3D MK solution should be used in the calculation of K for weld toe cracks.
On Remaining Fatigue Life Fracture Mechanics Analysis of Free-Spanning Pipelines Using Shell and Line-Spring Elements
Authors: Redaelli F. , Skallerud B. , Leira B. J.
Published: March 2009

The present paper addresses fatigue crack-growth for free-spanning pipelines. The main sources of cyclic stresses which cause the crack-growth are vortex-induced vibrations (VIV) of the pipeline in the cross-flow and in-line directions. In the presence of initial weld defects, such cyclic stresses may lead to leakage and sudden fracture. The crack-growth process is modelled using so-called line-spring elements. These are matched with shell elements which are applied for modelling the pipe itself. The crack-growth is simulated by performing several simulations with different crack sizes. The shape of the crack also allowed to vary during the growth (i.e a/c-ratio). The static equilibrium position of the pipeline for a specific free span is first established by the non-linear Finite Element program ABAQUS. The line-spring elements are matched to interface with the shell elements which represent the pipe outside the region where the crack is located. Based on such simulations, the stress intensity factors at the crack-tip are computed. These calculations are performed for several different crack-sizes. Finally, the remaining fatigue life is estimated by means of fracture mechanics in terms of analytical and semi-empirical approaches.
Geraniol Restores Antibiotic Activities against Multidrug-Resistant Isolates from Gram-Negative Species
Authors: Lorenzi Vannina , Muselli Alain , Bernardini Antoine François , Berti Liliane , Pagès Jean-Marie , Amaral Leonard , Bolla Jean-Michel
Published: March 2009

The essential oil of
Helichrysum italicum
significantly reduces the multidrug resistance of
Enterobacter aerogenes
,
Escherichia coli
,
Pseudomonas aeruginosa
, and
Acinetobacter baumannii
. Combinations of the two most active fractions of the essential oil with each other or with phenylalanine arginine β-naphthylamide yield synergistic activity. Geraniol, a component of one fraction, significantly increased the efficacy of β-lactams, quinolones, and chloramphenicol.
Characterization of Macrolide Efflux Pump
mef
Subclasses Detected in Clinical Isolates of
Streptococcus pyogenes
Isolated between 1999 and 2005
Authors: Blackman Northwood J. , Del Grosso M. , Cossins L. R. , Coley M. D. , Creti R. , Pantosti A. , Farrell D. J.
Published: March 2009

The macrolide efflux mechanism of resistance,
mef
, was characterized in community-acquired respiratory tract infections with
Streptococcus pyogenes.
Fifty-four (4.6%) M phenotype isolates were screen tested as negative for
mef
(A). Of these 54 isolates, 5 (0.4%), 27 (2.3%), and 1 (0.1%) were considered to be
mef
(I) positive, a novel mosaic variant of
mef
, or a novel subclass of
mef
, respectively. This study shows (i) the definitive presence of
mef
(E) in
S. pyogenes
and its global distribution, (ii) the presence of a mosaic variant of
mef
composed of
mef
(A) and
mef
(E), (iii) the previously undescribed presence of
mef
(I) in
S. pyogenes
, and (iv) the presence of a novel subclass of
mef
in
S. pyogenes
.
Reverse Transcriptase Inhibitors as Potential Colorectal Microbicides
Authors: Herrera Carolina , Cranage Martin , McGowan Ian , Anton Peter , Shattock Robin J.
Published: March 2009

We investigated whether reverse transcriptase (RT) inhibitors (RTI) can be combined to inhibit human immunodeficiency virus type 1 (HIV-1) infection of colorectal tissue ex vivo as part of a strategy to develop an effective rectal microbicide. The nucleotide RTI (NRTI) PMPA (tenofovir) and two nonnucleoside RTI (NNRTI), UC-781 and TMC120 (dapivirine), were evaluated. Each compound inhibited the replication of the HIV isolates tested in TZM-bl cells, peripheral blood mononuclear cells, and colorectal explants. Dual combinations of the three compounds, either NRTI-NNRTI or NNRTI-NNRTI combinations, were more active than any of the individual compounds in both cellular and tissue models. Combinations were key to inhibiting infection by NRTI- and NNRTI-resistant isolates in all models tested. Moreover, we found that the replication capacities of HIV-1 isolates in colorectal explants were affected by single point mutations in RT that confer resistance to RTI. These data demonstrate that colorectal explants can be used to screen compounds for potential efficacy as part of a combination microbicide and to determine the mucosal fitness of RTI-resistant isolates. These findings may have important implications for the rational design of effective rectal microbicides.
New Combinations of Mutations in VanD-Type Vancomycin-Resistant
Enterococcus faecium
,
Enterococcus faecalis
, and
Enterococcus avium
Strains
Authors: Depardieu F. , Foucault M.-L. , Bell J. , Dubouix A. , Guibert M. , Lavigne J.-P. , Levast M. , Courvalin P.
Published: March 2009

We studied the clinical isolates
Enterococcus faecium
NEF1, resistant to high levels of vancomycin (MIC, 512 μg/ml) and teicoplanin (MIC, 64 μg/ml);
Enterococcus faecium
BM4653 and BM4656 and
Enterococcus avium
BM4655, resistant to moderate levels of vancomycin (MIC, 32 μg/ml) and to low levels of teicoplanin (MIC, 4 μg/ml); and
Enterococcus faecalis
BM4654, moderately resistant to vancomycin (MIC, 16 μg/ml) but susceptible to teicoplanin (MIC, 0.5 μg/ml). The strains were distinct, were constitutively resistant via the synthesis of peptidoglycan precursors ending in
d
-alanyl-
d
-lactate, and harbored a chromosomal
vanD
gene cluster that was not transferable. New mutations were found in conserved domains of VanS
D
: at T
170
I near the phosphorylation site in NEF1, at V
67
A at the membrane surface in BM4653, at G
340
S in the G2 ATP-binding domain in BM4655, in the F domain in BM4656 (a 6-bp insertion), and in the G1 and G2 domains of BM4654 (three mutations). The mutations resulted in constitutivity, presumably through the loss of the phosphatase activity of the sensor. The chromosomal Ddl
d
-Ala:
d
-Ala ligase had an IS
19
copy in NEF1, a mutation in the serine (S
185
F) or near the arginine (T
289
P) involved in
d
-Ala1 binding in BM4653 or BM4655, respectively, and a mutation next to the lysine (P
180
S) involved in
d
-Ala2 binding in BM4654, leading to the production of an impaired enzyme. In BM4653

vanY
D

, a new insertion sequence, IS
Efa9
, belonging to the IS
3
family, resulted in the absence of
d
,
d
-carboxypeptidase activity. Strain BM4656 had a functional
d
-Ala:
d
-Ala ligase, associated with high levels of both VanX
D
and VanY
D
activities, and is the first example of a VanD-type strain with a functional Ddl enzyme. Study of these five clinical isolates, displaying various assortments of mutations, confirms that all VanD-type strains isolated so far have undergone mutations in the

vanS
D

or

vanR
D

gene, leading to constitutive resistance, but that the Ddl host ligase is not always impaired. Based on sequence differences, the
vanD
gene clusters could be assigned to two subtypes:
vanD-1
and
vanD-4
.
Genetic Organization of Transposase Regions Surrounding
bla
KPC
Carbapenemase Genes on Plasmids from
Klebsiella
Strains Isolated in a New York City Hospital
Authors: Gootz Thomas D. , Lescoe Mary Kay , Dib-Hajj Fadia , Dougherty Brian A. , He Wen , Della-Latta Phyllis , Huard Richard C.
Published: March 2009

Carbapenem-resistant
Klebsiella
strains carrying
Klebsiella pneumoniae
carbapenemases (KPC) are endemic to New York City and are spreading across the United States and internationally. Recent studies have indicated that the KPC structural gene is located on a 10-kb plasmid-borne element designated Tn
4401
. Fourteen
Klebsiella pneumoniae
strains and one
Klebsiella oxytoca
strain isolated at a New York City hospital in 2005 carrying either
bla
KPC-2
or
bla
KPC-3
were examined for isoforms of Tn
4401
. Ten of the
Klebsiella
strains contained a 100-bp deletion in Tn
4401
, corresponding to the Tn
4401
a isoform. The presence of this deletion adjacent to the upstream promoter region of
bla
KPC
in Tn
4401
a resulted in a different −35 promoter sequence of TGGAGA than that of CTGATT present in isoform Tn
4401
b. Complete sequencing of one plasmid carrying
bla
KPC
from each of three nonclonal isolates indicated the presence of genes encoding other types of antibiotic resistance determinants. The 70.6-kb plasmid from
K. pneumoniae
strain S9 carrying
bla
KPC-2
revealed two identical copies of Tn
4401
b inserted in an inverse fashion, but in this case, one of the elements disrupted a group II self-splicing intron. In
K. pneumoniae
strain S15, the Tn
4401
a element carrying
bla
KPC-2
was found on both a large 120-kb plasmid and a smaller 24-kb plasmid. Pulsed-field gel electrophoresis results indicate that the isolates studied represent a heterogeneous group composed of unrelated as well as closely related
Klebsiella
strains. Our results suggest that endemic KPC-positive
Klebsiella
strains constitute a generally nonclonal population comprised of various alleles of
bla
KPC
on several distinct plasmid genetic backgrounds. This study increases our understanding of the genetic composition of the evolving and expanding role of KPC-producing, healthcare-associated, gram-negative pathogens.
New Plasmid-Mediated Quinolone Resistance Gene,
qnrC
, Found in a Clinical Isolate of
Proteus mirabilis
Authors: Wang Minghua , Guo Qinglan , Xu Xiaogang , Wang Xiaoying , Ye Xinyu , Wu Shi , Hooper David C. , Wang Minggui
Published: March 2009

Since the discovery of
qnrA
in 1998, two additional
qnr
genes,
qnrB
and
qnrS
, have been described. These three plasmid-mediated genes contribute to quinolone resistance in gram-negative pathogens worldwide. A clinical strain of
Proteus mirabilis
was isolated from an outpatient with a urinary tract infection and was susceptible to most antimicrobials but resistant to ampicillin, sulfamethoxazole, and trimethoprim. Plasmid pHS10, harbored by this strain, was transferred to azide-resistant
Escherichia coli
J53 by conjugation. A transconjugant with pHS10 had low-level quinolone resistance but was negative by PCR for the known
qnr
genes,
aac(6′)-Ib-cr
and
qepA
. The ciprofloxacin MIC for the clinical strain and a J53/pHS10 transconjugant was 0.25 μg/ml, representing an increase of 32-fold relative to that for the recipient, J53. The plasmid was digested with HindIII, and a 4.4-kb DNA fragment containing the new gene was cloned into pUC18 and transformed into
E. coli
TOP10. Sequencing showed that the responsible 666-bp gene, designated
qnrC
, encoded a 221-amino-acid protein, QnrC, which shared 64%, 42%, 59%, and 43% amino acid identity with QnrA1, QnrB1, QnrS1, and QnrD, respectively. Upstream of
qnrC
there existed a new IS
3
family insertion sequence, IS
Pmi1
, which encoded a frameshifted transposase.
qnrC
could not be detected by PCR, however, in 2,020 strains of
Enterobacteriaceae
. A new quinolone resistance gene,
qnrC
, was thus characterized from plasmid pHS10 carried by a clinical isolate of
P
.
mirabilis
.
Statins as Potential Antimalarial Drugs: Low Relative Potency and Lack of Synergy with Conventional Antimalarial Drugs
Authors: Wong Rina P. M. , Davis Timothy M. E.
Published: March 2009

The in vitro sensitivity of
Plasmodium falciparum
to atorvastatin and rosuvastatin was assessed using chloroquine-sensitive and chloroquine-resistant strains. Although atorvastatin was more potent, it had weak activity (mean 50% inhibitory concentration of ≥17 μM) and an indifferent interaction with chloroquine and dihydroartemisinin. Bioassay of plasma from an atorvastatin-treated subject showed similar results.
Avian
Aspergillus fumigatus
Strains Resistant to both Itraconazole and Voriconazole
Authors: Beernaert L. A. , Pasmans F. , Van Waeyenberghe L. , Dorrestein G. M. , Verstappen F. , Vercammen F. , Haesebrouck F. , Martel A.
Published: March 2009

The in vitro susceptibilities of 59 avian
Aspergillus fumigatus
strains to amphotericin B, itraconazole, and voriconazole were determined using the standard microdilution broth method (CLSI M38-A2). Four isolates showed acquired resistance to itraconazole and voriconazole, harboring implications for the treatment of aspergillosis in both birds and humans.
Dynamics of Malaria Drug Resistance Patterns in the Amazon Basin Region following Changes in Peruvian National Treatment Policy for Uncomplicated Malaria
Authors: Bacon David J. , McCollum Andrea M. , Griffing Sean M. , Salas Carola , Soberon Valeria , Santolalla Meddly , Haley Ryan , Tsukayama Pablo , Lucas Carmen , Escalante Ananias A. , Udhayakumar Venkatachalam
Published: March 2009

Monitoring changes in the frequencies of drug-resistant and -sensitive genotypes can facilitate in vivo clinical trials to assess the efficacy of drugs before complete failure occurs. Peru changed its national treatment policy for uncomplicated malaria to artesunate (ART)-plus-mefloquine (MQ) combination therapy in the Amazon basin in 2001. We genotyped isolates collected in 1999 and isolates collected in 2006 to 2007 for mutations in the
Plasmodium falciparum
dihydrofolate reductase (Pf
dhfr
) and dihydropteroate synthase (Pf
dhps
) genes, multidrug resistance gene 1 (Pf
mdr-1
), the chloroquine (CQ) resistance transporter gene (Pf
crt
), and the Ca
2+
ATPase gene (Pf
ATP6
); these have been shown to be involved in resistance to sulfadoxine-pyrimethamine (SP), MQ, CQ, and possibly ART, respectively. Microsatellite haplotypes around the Pf
dhfr
, Pf
dhps
, Pf
crt
, and Pf
mdr-1
loci were also determined. There was a significant decline in the highly SP resistant Pf
dhfr
and Pf
dhps
genotypes from 1999 to 2006. In contrast, a CQ-resistant Pf
crt
genotype increased in frequency during the same period. Among five different Pf
mdr-1
allelic forms noted in 1999, two genotypes increased in frequency while one genotype decreased by 2006. We also noted previously undescribed polymorphisms in the Pf
ATP6
gene as well as an increase in the frequency of a deletion mutant during this period. In addition, microsatellite analysis revealed that the resistant Pf
dhfr
, Pf
dhps
, and Pf
crt
genotypes have each evolved from a single founder haplotype, while Pf
mdr-1
genotypes have evolved from at least two independent haplotypes. Importantly, this study demonstrates that the Peruvian triple mutant Pf
dhps
genotypes are very similar to those found in other parts of South America.
Involvement of SOCS3 in Regulation of CD11c
+
Dendritic Cell-Derived Osteoclastogenesis and Severe Alveolar Bone Loss
Authors: Zhang Xiaoxia , Alnaeeli Mawadda , Singh Bhagirath , Teng Yen-Tung A.
Published: March 2009

To investigate the role of suppressor of cytokine signaling (SOCS) molecules in periodontal immunity and RANKL-mediated dendritic cell (DC)-associated osteoclastogenesis, we analyzed SOCS expression profiles in CD4
+
T cells and the effect of SOCS3 expression in CD11c
+
DCs during periodontal inflammation-induced osteoclastogenesis and bone loss in nonobese diabetic (NOD) versus humanized NOD/SCID mice. Our results of ex vivo and in vitro analyses showed that (i) there is significantly higher SOCS3 expression associated with RANKL
+
T-cell-mediated bone loss in correlation with increased CD11c
+
DC-mediated osteoclastogenesis; (ii) the transfection of CD11c
+
DC using an adenoviral vector carrying a dominant negative SOCS3 gene significantly abrogates TRAP and bone-resorptive activity; and (iii) inflammation-induced TRAP expression, bone resorption, and SOCS3 activity are not associated with any detectable change in the expression levels of TRAF6 and mitogen-activated protein kinase signaling adaptors (i.e., Erk, Jnk, p38, and Akt) in RANKL
+
T cells. We conclude that SOCS3 plays a critical role in modulating cytokine signaling involved in RANKL-mediated DC-derived osteoclastogenesis during immune interactions with T cells and diabetes-associated severe inflammation-induced alveolar bone loss. Therefore, the development of SOCS3 inhibitors may have therapeutic potential as the target to halt inflammation-induced bone loss under pathological conditions in vivo.
Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor β Signaling in the Epithelium
Authors: Beisswenger Christoph , Lysenko Elena S. , Weiser Jeffrey N.
Published: March 2009

Colonization of the upper respiratory tract is an initial step that may lead to disease for many pathogens. To prevent compromise of the epithelial barrier, the host must monitor and tightly control bacterial levels on the mucosa. Here we show that innate immune functions of respiratory epithelial cells control colonization by
Streptococcus pneumoniae
and
Haemophilus influenzae
in a Toll-like receptor (TLR)-dependent manner. Activation of inflammatory pathways, including mitogen-activated protein kinase signaling, in respiratory epithelial cells was accompanied by the induction of the transforming growth factor β signaling cascade during early colonization. Thus, colonization resulted in upregulation of factors involved in a proinflammatory response (e.g., interleukin-6) as well as factors known to modulate the epithelial barrier (e.g., Snail-1). These in vivo data provided a link between inflammation control and maintenance of the mucosal barrier function during infection and emphasized the importance of TLR-dependent inflammatory responses of the respiratory epithelium.
Contribution of the
pst-phoU
Operon to Cell Adherence by Atypical Enteropathogenic
Escherichia coli
and Virulence of
Citrobacter rodentium
Authors: Cheng Catherine , Tennant Sharon M. , Azzopardi Kristy I. , Bennett-Wood Vicki , Hartland Elizabeth L. , Robins-Browne Roy M. , Tauschek Marija
Published: March 2009

Strains of enteropathogenic
Escherichia coli
(EPEC) generally employ the adhesins bundle-forming pili (Bfp) and intimin to colonize the intestine. Atypical EPEC strains possess intimin but are negative for Bfp and, yet, are able to cause disease. To identify alternative adhesins to Bfp in atypical EPEC, we constructed a transposon mutant library of atypical EPEC strain E128012 (serotype O114:H2) using Tn
phoA
. Six mutants that had lost the ability to adhere to HEp-2 cells were identified, and in all six mutants Tn
phoA
had inserted into the
pstSCAB-phoU
(Pst) operon. To determine if the Pst operon is required for adherence, we used site-directed mutagenesis to construct a
pstCA
mutant of E128012. The resultant mutant showed a reduced ability to adhere to HEp-2 cells and T84 intestinal epithelial cells, which was restored by trans-complementation with intact
pstCA
. To determine if
pst
contributes to bacterial colonization in vivo, a
pstCA
mutation was made in the EPEC-like murine pathogen,
Citrobacter rodentium
. C57BL/6 mice infected perorally with the
pstCA
mutant of
C. rodentium
excreted significantly lower numbers of
C. rodentium
than those given the wild-type strain. Moreover, colonic hyperplasia and diarrhea, which are features of infections with
C. rodentium
, were not observed in mice infected with the
pstCA
mutant but did occur in mice given the trans-complemented mutant. As mutations in
pst
genes generally lead to constitutive expression of the Pho regulon, our findings suggested that the Pho regulon may contribute to the reduced virulence of the
pstCA
mutants. To investigate this, we inactivated
phoB
in the
pstCA
mutants of EPEC E128012 and
C. rodentium
and found that the
phoB
mutation restored the adherent phenotype of both mutant strains. These results demonstrate that Pst contributes to the virulence of atypical EPEC and
C. rodentium
, probably by causing increased expression of an unidentified, Pho-regulated adhesin.
The Absence of Hck, Fgr, and Lyn Tyrosine Kinases Augments Lung Innate Immune Responses toPneumocystis murina
Authors: Nelson Michael P. , Metz Allison E. , Li Shaoguang , Lowell Clifford A. , Steele Chad
Published: March 2009

Src family tyrosine kinases (SFKs) phosphorylate immunotyrosine activation motifs in the cytoplasmic tail of multiple immunoreceptors, leading to the initiation of cellular effector functions, such as phagocytosis, reactive oxygen species production, and cytokine production. SFKs also play important roles in regulating these responses through the activation of immunotyrosine inhibitory motif-containing inhibitory receptors. As myeloid cells preferentially express the SFKs Hck, Fgr, and Lyn, we questioned the role of these kinases in innate immune responses toPneumocystis murina. Increased phosphorylation of Hck was readily detectable in alveolar macrophages after stimulation withP. murina. We further observed decreased phosphorylation of Lyn on its C-terminal inhibitory tyrosine inP. murina-stimulated alveolar macrophages, indicating that SFKs were activated in alveolar macrophages in response toP. murina. Mice deficient in Hck, Fgr, and Lyn exhibited augmented clearance 3 and 7 days after intratracheal administration ofP. murina, which correlated with elevated levels of interleukin 1β (IL-1β), IL-6, CXCL1/KC, CCL2/monocyte chemoattractant protein 1, and granulocyte colony-stimulating factor in lung homogenates and a dramatic increase in macrophage and neutrophil recruitment. AugmentedP. murinaclearance was also observed in Lyn−/−mice 3 days postchallenge, although the level was less than that observed in Hck−/−Fgr−/−Lyn−/−mice. A correlate to augmented clearance ofP. murinain Hck−/−Fgr−/−Lyn−/−mice was a greater ability of alveolar macrophages from these mice to killP. murinain vitro, suggesting that SFKs regulate the alveolar macrophage effector function againstP. murina. Mice deficient in paired immunoglobulin receptor B (PIR-B), an inhibitory receptor activated by SFKs, did not exhibit enhanced inflammatory responsiveness to or clearance ofP. murina. Our results suggest that SFKs regulate innate lung responses toP. murinain a PIR-B-independent manner.
Anaerobic Catabolism of Aromatic Compounds: a Genetic and Genomic View
Authors: Carmona Manuel , Zamarro María Teresa , Blázquez Blas , Durante-Rodríguez Gonzalo , Juárez Javier F. , Valderrama J. Andrés , Barragán María J. L. , García José Luis , Díaz Eduardo
Published: March 2009

Aromatic compounds belong to one of the most widely distributed classes of organic compounds in nature, and a significant number of xenobiotics belong to this family of compounds. Since many habitats containing large amounts of aromatic compounds are often anoxic, the anaerobic catabolism of aromatic compounds by microorganisms becomes crucial in biogeochemical cycles and in the sustainable development of the biosphere. The mineralization of aromatic compounds by facultative or obligate anaerobic bacteria can be coupled to anaerobic respiration with a variety of electron acceptors as well as to fermentation and anoxygenic photosynthesis. Since the redox potential of the electron-accepting system dictates the degradative strategy, there is wide biochemical diversity among anaerobic aromatic degraders. However, the genetic determinants of all these processes and the mechanisms involved in their regulation are much less studied. This review focuses on the recent findings that standard molecular biology approaches together with new high-throughput technologies (e.g., genome sequencing, transcriptomics, proteomics, and metagenomics) have provided regarding the genetics, regulation, ecophysiology, and evolution of anaerobic aromatic degradation pathways. These studies revealed that the anaerobic catabolism of aromatic compounds is more diverse and widespread than previously thought, and the complex metabolic and stress programs associated with the use of aromatic compounds under anaerobic conditions are starting to be unraveled. Anaerobic biotransformation processes based on unprecedented enzymes and pathways with novel metabolic capabilities, as well as the design of novel regulatory circuits and catabolic networks of great biotechnological potential in synthetic biology, are now feasible to approach.
Inhibition of Bacterial Ribosome Assembly: a Suitable Drug Target?
Authors: Maguire Bruce A.
Published: March 2009

The assembly of bacterial ribosomes is viewed with increasing interest as a potential target for new antibiotics. The in vivo synthesis and assembly of ribosomes are briefly reviewed here, highlighting the many ways in which assembly can be perturbed. The process is compared with the model in vitro process from which much of our knowledge is derived. The coordinate synthesis of the ribosomal components is essential for their ordered and efficient assembly; antibiotics interfere with this coordination and therefore affect assembly. It has also been claimed that the binding of antibiotics to nascent ribosomes prevents their assembly. These two contrasting models of antibiotic action are compared and evaluated. Finally, the suitability and tractability of assembly as a drug target are assessed.
Automatic metadata generation using associative networks
Authors: Rodriguez Marko A. , Bollen Johan , Sompel Herbert Van De
Published: March 2009

In spite of its tremendous value, metadata is generally sparse and incomplete, thereby hampering the effectiveness of digital information services. Many of the existing mechanisms for the automated creation of metadata rely primarily on content analysis which can be costly and inefficient. The automatic metadata generation system proposed in this article leverages resource relationships generated from existing metadata as a medium for propagation from metadata-rich to metadata-poor resources. Because of its independence from content analysis, it can be applied to a wide variety of resource media types and is shown to be computationally inexpensive. The proposed method operates through two distinct phases. Occurrence and cooccurrence algorithms first generate an associative network of repository resources leveraging existing repository metadata. Second, using the associative network as a substrate, metadata associated with metadata-rich resources is propagated to metadata-poor resources by means of a discrete-form spreading activation algorithm. This article discusses the general framework for building associative networks, an algorithm for disseminating metadata through such networks, and the results of an experiment and validation of the proposed method using a standard bibliographic dataset.
An adaptive threshold framework for event detection using HMM-based life profiles
Authors: Chen Chien Chin , Chen Meng Chang , Chen Ming-Syan
Published: March 2009

When an event occurs, it attracts attention of information sources to publish related documents along its lifespan. The task of event detection is to automatically identify events and their related documents from a document stream, which is a set of chronologically ordered documents collected from various information sources. Generally, each event has a distinct activeness development so that its status changes continuously during its lifespan. When an event is active, there are a lot of related documents from various information sources. In contrast when it is inactive, there are very few documents, but they are focused. Previous works on event detection did not consider the characteristics of the event's activeness, and used rigid thresholds for event detection. We propose a concept called life profile, modeled by a hidden Markov model, to model the activeness trends of events. In addition, a general event detection framework, LIPED, which utilizes the learned life profiles and the burst-and-diverse characteristic to adjust the event detection thresholds adaptively, can be incorporated into existing event detection methods. Based on the official TDT corpus and contest rules, the evaluation results show that existing detection methods that incorporate LIPED achieve better performance in the cost and F1 metrics, than without.
Information filtering and query indexing for an information retrieval model
Authors: Tryfonopoulos Christos , Koubarakis Manolis , Drougas Yannis
Published: March 2009

In the information filtering paradigm, clients subscribe to a server with continuous queries or profiles that express their information needs. Clients can also publish documents to servers. Whenever a document is published, the continuous queries satisfying this document are found and notifications are sent to appropriate clients. This article deals with the filtering problem that needs to be solved efficiently by each server: Given a database of continuous queries
db
and a document
d
, find all queries
q
∈
db
that match
d
. We present data structures and indexing algorithms that enable us to solve the filtering problem efficiently for large databases of queries expressed in the model
AWP
.
AWP
is based on named attributes with values of type text, and its query language includes Boolean and word proximity operators.
User language model for collaborative personalized search
Authors: Xue Gui-Rong , Han Jie , Yu Yong , Yang Qiang
Published: March 2009

Traditional personalized search approaches rely solely on individual profiles to construct a user model. They are often confronted by two major problems: data sparseness and cold-start for new individuals. Data sparseness refers to the fact that most users only visit a small portion of Web pages and hence a very sparse user-term relationship matrix is generated, while cold-start for new individuals means that the system cannot conduct any personalization without previous browsing history. Recently, community-based approaches were proposed to use the group's social behaviors as a supplement to personalization. However, these approaches only consider the commonality of a group of users and still cannot satisfy the diverse information needs of different users. In this article, we present a new approach, called collaborative personalized search. It considers not only the commonality factor among users for defining group user profiles and global user profiles, but also the specialties of individuals. Then, a statistical user language model is proposed to integrate the individual model, group user model and global user model together. In this way, the probability that a user will like a Web page is calculated through a two-step smoothing mechanism. First, a global user model is used to smooth the probability of unseen terms in the individual profiles and provide aggregated behavior of global users. Then, in order to precisely describe individual interests by looking at the behaviors of similar users, users are clustered into groups and group-user models are constructed. The group-user models are integrated into an overall model through a cluster-based language model. The behaviors of the group users can be utilized to enhance the performance of personalized search. This model can alleviate the two aforementioned problems and provide a more effective personalized search than previous approaches. Large-scale experimental evaluations are conducted to show that the proposed approach substantially improves the relevance of a search over several competitive methods.
The Effect of Voice Output on AAC-Supported Conversations of Persons with Alzheimer’s Disease
Authors: Fried-Oken Melanie , Rowland Charity , Baker Glory , Dixon Mayling , Mills Carolyn , Schultz Darlene , Oken Barry
Published: March 2009

The purpose of this study was to determine whether the presence or absence of digitized 1--2-word voice output on a direct selection, customized Augmentative and Alternative Communication (AAC) device would affect the impoverished conversations of persons with dementia. Thirty adults with moderate Alzheimer’s disease participated in two personally relevant conversations with an AAC device. For twelve of the participants the AAC device included voice output. The AAC device was the Flexiboard
TM
containing sixteen messages needed to discuss a favorite autobiographical topic chosen by the participant and his/her family caregivers. Ten-minute conversations were videotaped in participants’ residences and analyzed for four conversational measures related to the participants’ communicative behavior. Results show that AAC devices with digitized voice output depress conversational performance and distract participants with moderate Alzheimer’s disease as compared to similar devices without voice output. There were significantly more 1-word utterances and fewer total utterances when AAC devices included voice output, and the rate of topic elaborations/initiations was significantly lower when voice output was present. Discussion about the novelty of voice output for this population of elders and the need to train elders to use this technology is provided.
User Interaction with Word Prediction
Authors: Trnka Keith , McCaw John , Yarrington Debra , McCoy Kathleen F. , Pennington Christopher
Published: March 2009

Word prediction systems can reduce the number of keystrokes required to form a message in a letter-based AAC system. It has been questioned, however, whether such savings translate into an enhanced communication rate due to the additional overhead (e.g., shifting of focus and repeated scanning of a prediction list) required in using such a system. Our hypothesis is that word prediction has high potential for enhancing AAC communication rate, but the amount is dependent in a complex way on the accuracy of the predictions. Due to significant user interface variations in AAC systems and the potential bias of prior word prediction experience on existing devices, this hypothesis is difficult to verify. We present a study of two different word prediction methods compared against letter-by-letter entry at simulated AAC communication rates. We find that word prediction systems can in fact speed communication rate (an advanced system gave a 58.6% improvement), and that a more accurate word prediction system can raise the communication rate higher than is explained by the additional accuracy of the system alone due to better utilization (93.6% utilization for advanced versus 78.2% for basic).
Estradiol upregulates the expression of oxytocin receptor in colon in rats
Authors: Feng Mei , Qin Junfang , Wang Chao , Ye Yanfang , Wang Shuanglian , Xie Dongping , Wang Paulus S. , Liu Chuanyong
Published: March 2009

The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E2). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E2 (4–100 μg/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E2 was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E2 increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.
MEK/ERK inhibitor U0126 affects in vitro and in vivo growth of embryonal rhabdomyosarcoma
Authors: Marampon Francesco , Bossi Gianluca , Ciccarelli Carmela , Di Rocco Agnese , Sacchi Ada , Pestell Richard G. , Zani Bianca M.
Published: March 2009

We reported previously that the disruption of c-Myc through mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibition blocks the expression of the transformed phenotype in the embryonal rhabdomyosarcoma (ERMS) cell line (RD), thereby inducing myogenic differentiation in vitro. In this article, we investigate whether MEK/ERK inhibition, by the MEK/ERK inhibitor U0126, affects c-Myc protein level and growth of RMS tumor in an in vivo xenograft model. U0126 significantly reduced RMS tumor growth in RD cell line-xenotransplanted mice. Immunobiochemical and immunohistochemical analysis showed (a) phospho-active ERK levels were reduced by U0126 therapy and unaltered in normal tissues, (b) phospho-Myc and c-Myc was reduced commensurate with phospho-ERK inhibition, and (c) reduction in Ki-67 and endothelial (CD31) marker expression. These results indicate that MEK/ERK inhibition affects growth and angiogenic signals in tumor. The RD-M1 cultured xenograft tumor-derived cell line and the ERMS cell line TE671 responded to U0126 by arresting growth, down-regulating c-Myc, and initiating myogenesis. All these results suggest a tight correlation of MEK/ERK inhibition with c-Myc down-regulation and arrest of tumor growth. Thus, MEK inhibitors may be investigated for a signal transduction-based targeting of the c-Myc as a therapeutic strategy in ERMS. [Mol Cancer Ther 2009;8(3):543–51]
Predictors of Cerebral Arteriopathy in Children With Arterial Ischemic Stroke
Authors: Amlie-Lefond Catherine , Bernard Timothy J. , Sébire Guillaume , Friedman Neil R. , Heyer Geoffrey L. , Lerner Norma B. , deVeber Gabrielle , Fullerton Heather J.
Published: March 2009

Background—

Cerebral arteriopathies, including an idiopathic focal cerebral arteriopathy of childhood (FCA), are common in children with arterial ischemic stroke and strongly predictive of recurrence. To better understand these lesions, we measured predictors of arteriopathy within a large international series of children with arterial ischemic stroke.

Methods and Results—

Between January 2003 and July 2007, 30 centers within the International Pediatric Stroke Study enrolled 667 children (age, 29 days to 19 years) with arterial ischemic stroke and abstracted clinical and radiographic data. Cerebral arteriopathy and its subtypes were defined using published definitions; FCA was defined as cerebral arterial stenosis not attributed to specific diagnoses such as moyamoya, arterial dissection, vasculitis, or postvaricella angiopathy. We used multivariate logistic regression techniques to determine predictors of arteriopathy and FCA among those subjects who received vascular imaging. Of 667 subjects, 525 had known vascular imaging results, and 53% of those (n=277) had an arteriopathy. The most common arteriopathies were FCA (n=69, 25%), moyamoya (n=61, 22%), and arterial dissection (n=56, 20%). Predictors of arteriopathy include early school age (5 to 9 years), recent upper respiratory infections, and sickle cell disease, whereas prior cardiac disease and sepsis reduced the risk of arteriopathy. The only predictor of FCA was recent upper respiratory infection.

Conclusions—

Arteriopathy is prevalent among children with arterial ischemic stroke, particularly those presenting in early school age, and those with a history of sickle cell disease. Recent upper respiratory infection predicted cerebral arteriopathy and FCA in particular, suggesting a possible role for infection in the pathogenesis of these lesions.
Short Telomeres and Prognosis of Hypertension in a Chinese Population
Authors: Yang Zhiwei , Huang Xin , Jiang Hong , Zhang Yanrong , Liu Hongxia , Qin Chuan , Eisner Gilbert M. , Jose Pedro , Rudolph Lenhard , Ju Zhenyu
Published: March 2009

Aging is a major risk factor for hypertension and cardiovascular disease. Accumulating evidence suggests that telomere length is a marker for biological aging of the cardiovascular system. Telomere length is determined by genetic and environmental factors. Studies in different racial populations are required to determine the prognostic value of telomere length in hypertension and cardiovascular diseases. The main objective of this study was to investigate the association between leukocyte telomere length and the risk and prognosis of hypertension in a Chinese population. The relative telomere length of leukocytes was determined by a quantitative PCR-based method in 767 subjects: 379 healthy controls and 388 hypertensive patients, ages 30 to 80 years. The median telomere length ratio, 0.57 (interquartile range: 0.48 to 0.72), was shorter in hypertensive than in healthy normotensive subjects (0.67; interquartile range: 0.53 to 0.93;
P
<0.001). After 5 years of follow-up, subjects with shorter telomeres were at a higher risk of developing coronary artery disease than individuals with longer telomeres (odds ratio: 3.315; 95% CI: 1.662 to 6.609;
P
<0.001). Multivariate analysis showed that short telomere length and hypertension were independent risk factors for developing coronary artery disease. Our data suggest that mean leukocyte telomere length is a potential predictor of coronary artery disease and support the hypothesis that differences in biological aging can contribute to the risk and variability of developing hypertension and cardiovascular diseases.
Alcohol Use, Abuse, and Treatment in People of African Descent
Authors: Sutherland Marcia E. , Ericson Rayna
Published: March 2009

The use and abuse of alcohol is prevalent in many nations across the globe, but few studies have examined within-group differences found in people of African descent in the United States, in Africa, and in the Caribbean. A review of current research about alcohol use, abuse, and treatment in people of African descent is presented, including information about risk factors and contributors to alcohol use. Examples of education and prevention interventions are also described. Finally, conclusions based on the review of the research literature as well as recommendations for future research are explained.
Story Writing
Authors: Lane Kathleen Lynne , Graham Steve , Harris Karen R. , Little M. Annette , Sandmel Karin , Brindle Mary
Published: March 2009

The effects of a secondary academic intervention implemented within the context of a three-tiered, positive behavior support model were examined in this study. Second-grade students with limited writing skills who also had either externalizing or internalizing behavior patterns were identified for participation using schoolwide data. Students learned how to plan and write stories using the self-regulated strategy development model. Results of two multiple-probe designs, one for students with externalizing behaviors (three females, four males) and a second for students with internalizing behaviors (two females, four males), revealed lasting increases in story elements as well as improvements in story quality and length. Teachers and students rated the intervention favorably, with most reporting that the intervention exceeded their initial expectations. Limitations and directions for future research are presented.