bluuebunny/crossref_metadata_2025_split huggingface dataset:
E-Selectin Mediates Porphyromonas gingivalis Adherence to Human Endothelial Cells
Authors: Komatsu Toshinori , Nagano Keiji , Sugiura Shinsuke , Hagiwara Makoto , Tanigawa Naomi , Abiko Yuki , Yoshimura Fuminobu , Furuichi Yasushi , Matsushita Kenji 
Published: April 2012

ABSTRACTPorphyromonas gingivalis, a major periodontal pathogen, may contribute to atherogenesis and other inflammatory cardiovascular diseases. However, little is known about interactions betweenP. gingivalisand endothelial cells. E-selectin is a membrane protein on endothelial cells that initiates recruitment of leukocytes to inflamed tissue, and it may also play a role in pathogen attachment. In the present study, we examined the role of E-selectin inP. gingivalisadherence to endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) to induce E-selectin expression. Adherence ofP. gingivalisto HUVECs was measured by fluorescence microscopy. TNF-α increased adherence of wild-typeP. gingivalisto HUVECs. Antibodies to E-selectin and sialyl Lewis X suppressedP. gingivalisadherence to stimulated HUVECs.P. gingivalismutants lacking OmpA-like proteins Pgm6 and -7 had reduced adherence to stimulated HUVECs, but fimbria-deficient mutants were not affected. E-selectin-mediatedP. gingivalisadherence activated endothelial exocytosis. These results suggest that the interaction between host E-selectin and pathogen Pgm6/7 mediatesP. gingivalisadherence to endothelial cells and may trigger vascular inflammation.
Listeria monocytogenes Strain-Specific Impairment of the TetR Regulator Underlies the Drastic Increase in Cyclic di-AMP Secretion and Beta Interferon-Inducing Ability
Authors: Yamamoto Takeshi , Hara Hideki , Tsuchiya Kohsuke , Sakai Shunsuke , Fang Rendong , Matsuura Motohiro , Nomura Takamasa , Sato Fumihiko , Mitsuyama Masao , Kawamura Ikuo 
Published: April 2012

ABSTRACT

Among a number of laboratory strains of
Listeria monocytogenes
used in experimental infection, strain LO28 is highly capable of inducing robust beta interferon (IFN-β) production in infected macrophages. In this study, we investigated the molecular mechanism of the IFN-β-inducing ability of LO28 by comparing it with that of strain EGD, a low-IFN-β-inducing strain. It was found that LO28 secretes a large amount of IFN-β-inducing factor, which turned out to be cyclic di-AMP. The secretion of cyclic di-AMP was dependent on MdrT, a multidrug resistance transporter, and LO28 exhibited a very high level of
mdrT
expression. The introduction of a null mutation into
mdrT
abolished the ability of LO28 to induce IFN-β production. Examination of genes responsible for the regulation of
mdrT
expression revealed a spontaneous 188-bp deletion in
tetR
of LO28. By constructing recombinant strains of LO28 and EGD in which
tetR
from each strain was replaced, it was confirmed that the distinct ability of LO28 is attributable mostly to
tetR
mutation. We concluded that the strong IFN-β-inducing ability of LO28 is due to a genetic defect in
tetR
resulting in the overexpression of
mdrT
and a concomitant increase in the secretion of cyclic di-AMP through MdrT.
Loss of Meningococcal PilU Delays Microcolony Formation and Attenuates Virulence
In Vivo
Authors: Eriksson Jens , Eriksson Olaspers Sara , Jonsson Ann-Beth 
Published: April 2012

ABSTRACT

Neisseria meningitidis
is a major cause of sepsis and bacterial meningitis worldwide. This bacterium expresses type IV pili (Tfp), which mediate important virulence traits such as the formation of bacterial aggregates, host cell adhesion, twitching motility, and DNA uptake. The meningococcal PilT protein is a hexameric ATPase that mediates pilus retraction. The PilU protein is produced from the
pilT-pilU
operon and shares a high degree of homology with PilT. The function of PilT in Tfp biology has been studied extensively, whereas the role of PilU remains poorly understood. Here we show that
pilU
mutants have delayed microcolony formation on host epithelial cells compared to the wild type, indicating that bacterium-bacterium interactions are affected. In normal human serum, the
pilU
mutant survived at a higher rate than that for wild-type bacteria. However, in a murine model of disease, mice infected with the
pilT
mutant demonstrated significantly reduced bacterial blood counts and survived at a higher rate than that for mice infected with the wild type. Infection of mice with the
pilU
mutant resulted in a trend of lower bacteremia, and still a significant increase in survival, than that of the wild type. In conclusion, these data suggest that PilU promotes timely microcolony formation and that both PilU and PilT are required for full bacterial virulence.
Do pacifiers increase the risk of nosocomial diarrhoea? A cohort study
Authors: Sette Gabriela Cunha Schechtman , Mello Maria Júlia Gonçalves , Correia Jailson Barros , Sette Ioram Schechtman , Pontes da Silva Gisélia Alves , Soares de Lima Luciane 
Published: April 2012

DesignProspective cohort study.SettingTeaching paediatric hospital—Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Northeast Brazil.Participants378 of 536 infants admitted in paediatric wards from April to October 2009 were daily assessed during hospital stay until the first episode of nosocomial diarrhoea (ND), death or discharge. Infants with community-acquired diarrhoea, respiratory or haemodynamic instability and who stayed in hospital for <24 h were excluded.Primary and secondary outcome measuresIncidence and risk factors for ND and rates of pacifier faecal contamination.Results33 ND episodes occurred in 378 infants, with a cumulative incidence of 8.7% and density of 11.25/1000 patients-day. ND occurred in 8.2% (16/194) of pacifier users compared with 9.2% (17/184) in non-users (adjusted OR=0.88, 95% CI 0.43 to 1.80). In multivariate logistic regression analysis, duration of oxygen use (OR=1.61; 95% CI 1.18 to 2.20) and days of antimicrobial use (OR=1.62, 95% CI 1.34 to 1.94) were associated with higher risk of ND, whereas being breast fed (OR=0.40, 95% CI 0.17 to 0.93) and each day of hospital stay (OR=0.65, 95% CI 0.53 to 0.80) were protective factors. Faecal coliforms were isolated in 16% (27/169) of tested pacifiers, 77.8% of which had more than 100 000 CFU/ml. The probability of a child remaining free of an episode of diarrhoea up to the seventh day of hospitalisation in the ward was 91.2% (95% CI 87.7% to 94.9%). The log-rank test showed no statistical difference between pacifier users and non-users.ConclusionsND is a frequent healthcare-associated infection in paediatric wards, but the use of pacifiers during the stay in hospital does not seem to affect the incidence of ND in infants in many settings where the burden of diarrhoea is still high.
A practical solution to the client-LDNS mismatch problem
Authors: Huang Cheng , Batanov Ivan , Li Jin 
Published: April 2012

Internet services are often deployed in multiple (tens to hundreds) of geographically distributed data centers. They rely on Global Traffic Management (GTM) solutions to direct clients to the optimal data center based on a number of criteria like network performance, geographic location, availability, etc.
The GTM solutions, however, have a fundamental design limitation in their ability to accurately map clients to data centers - they use the IP address of the local DNS resolver (LDNS) used by a client as a proxy for the true client identity, which in some cases causes suboptimal performance. This issue is known as the client-LDNS mismatch problem. We argue that recent proposals to address the problem suffer from serious limitations. We then propose a simple new solution, named ``FQDN extension'', which can solve the client-LDNS mismatch problem completely. We build a prototype system and demonstrate the effectiveness of the proposed solution. Using JavaScript, the solution can be deployed immediately for some online services, such as Web search, without modifying either client or local resolver.
Identification of an Epigenetic Profile Classifier That Is Associated with Survival in Head and Neck Cancer
Authors: Poage Graham M. , Butler Rondi A. , Houseman E. Andrés , McClean Michael D. , Nelson Heather H. , Christensen Brock C. , Marsit Carmen J. , Kelsey Karl T. 
Published: April 2012

Abstract
Panels of prognostic biomarkers selected using candidate approaches often do not validate in independent populations, so additional strategies are needed to identify reliable classifiers. In this study, we used an array-based approach to measure DNA methylation and applied a novel method for grouping CpG dinucleotides according to well-characterized genomic sequence features. A hypermethylation profile among 13 CpG loci, characterized by polycomb group target genes, mammalian interspersed repeats, and transcription factor–binding sites (PcG/MIR/TFBS), was associated with reduced survival (HR, 3.98; P = 0.001) in patients with head and neck squamous cell carcinoma. This association was driven by CpGs associated with the TAP1 and ALDH3A1 genes, findings that were validated in an independent patient group (HR, 2.86; P = 0.04). Together, the data not only elucidate new potential targets for therapeutic intervention in head and neck cancer but also may aid in the identification of poor prognosis patients who may require more aggressive treatment regimens. Cancer Res; 72(11); 2728–37. ©2012 AACR.
The CDK4/6 Inhibitor PD0332991 Reverses Epithelial Dysplasia Associated with Abnormal Activation of the Cyclin-CDK-Rb Pathway
Authors: Cabrera M. Carla , Díaz-Cruz Edgar S. , Kallakury Bhaskar V.S. , Pishvaian Michael J. , Grubbs Clinton J. , Muccio Donald D. , Furth Priscilla A. 
Published: April 2012

Abstract
Loss of normal growth control is a hallmark of cancer progression. Therefore, understanding the early mechanisms of normal growth regulation and the changes that occur during preneoplasia may provide insights of both diagnostic and therapeutic importance. Models of dysplasia that help elucidate the mechanisms responsible for disease progression are useful in highlighting potential targets for prevention. An important strategy in cancer prevention treatment programs is to reduce hyperplasia and dysplasia. This study identified abnormal upregulation of cell cycle–related proteins cyclin D1, cyclin-dependent kinase (CDK)4, CDK6, and phosphorylated retinoblastoma protein (pRb) as mechanisms responsible for maintenance of hyperplasia and dysplasia following downregulation of the initiating viral oncoprotein Simian virus 40 (SV40) T antigen. Significantly, p53 was not required for successful reversal of hyperplasia and dysplasia. Ligand-induced activation of retinoid X receptor and PPARγ agonists attenuated cyclin D1 and CDK6 but not CDK4 or phosphorylated pRb upregulation with limited reversal of hyperplasia and dysplasia. PD0332991, an orally available CDK4/6 inhibitor, was able to prevent upregulation of cyclin D1 and CDK6 as well as CDK4 and phosphorylated pRb and this correlated with a more profound reversal of hyperplasia and dysplasia. In summary, the study distinguished CDK4 and phosphorylated pRb as targets for chemoprevention regimens targeting reversal of hyperplasia and dysplasia. Cancer Prev Res; 5(6); 810–21. ©2012 AACR.
Cell Therapy Limits Myofibroblast Differentiation and Structural Cardiac Remodeling
Authors: Fedak Paul W.M. , Bai Liping , Turnbull Jeannine , Ngu Janet , Narine Kishan , Duff Henry J. 
Published: April 2012

Background—
Experimental cell therapy attenuates maladaptive cardiac remodeling and improves heart function. Paracrine mechanisms have been proposed. The effect of cell therapy on post infarction cardiac fibroblast and extracellular matrix (ECM) regulation was examined.

Methods and Results—
Vascular smooth muscle cells (VSMC) were injected into the border zone of subacute infarcted syngeneic Fischer rat hearts and compared with medium-injected controls. Twelve weeks post injection, cell-treated hearts showed preserved ECM content and attenuated structural chamber remodeling. Myofibroblast activation (α-smooth muscle actin expression) was decreased significantly, while basic fibroblast growth factor (bFGF) expression, a known inhibitor of transforming growth factor β-1–induced fibroblast differentiation, was increased. Matrix metalloproteinase-2 expression and activation by gelatin zymography was unchanged between groups, while its endogenous inhibitor, tissue inhibitors of matrix metalloproteinase (TIMP)-2, showed both increased expression and enhanced inhibitory capacity in cell-treated hearts. To define paracrine mechanisms, in vitro effects of VSMC conditioned media on myofibroblast activation were assessed by 3-D collagen gel contraction assay. VSMC conditioned media significantly inhibited collagen contraction, while a specific bFGF inhibitor abolished this paracrine response. TIMP-2 induced collagen contraction, but the effect was suppressed in the presence of bFGF.

Conclusions—
Extracellular matrix dysregulation post myocardial infarction is improved by cell therapy. These data suggest that cell transplantation attenuates myofibroblast activation and subsequent maladaptive structural chamber remodeling through paracrine mechanisms involving bFGF and TIMP-2.
Long-Term (>10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly-
l
-Lactic Acid Coronary Stents
Authors: Nishio Soji , Kosuga Kunihiko , Igaki Keiji , Okada Masaharu , Kyo Eisho , Tsuji Takafumi , Takeuchi Eiji , Inuzuka Yasutaka , Takeda Shinsaku , Hata Tatsuhiko , Takeuchi Yuzo , Kawada Yoshitaka , Harita Takeshi , Seki Junya , Akamatsu Shunji , Hasegawa Shinichi , Bruining Nico , Brugaletta Salvatore , de Winter Sebastiaan , Muramatsu Takashi , Onuma Yoshinobu , Serruys Patrick W. , Ikeguchi Shigeru 
Published: April 2012

Background—

The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-
l
-lactic acid.

Methods and Results—
Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change.

Conclusion—
Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.
Wind Speeds at Heights Crucial for Wind Energy: Measurements and Verification of Forecasts
Authors: Drechsel Susanne , Mayr Georg J. , Messner Jakob W. , Stauffer Reto 
Published: April 2012

AbstractWind speed measurements from one year from meteorological towers and wind turbines at heights between 20 and 250 m for various European sites are analyzed and are compared with operational short-term forecasts of the global ECMWF model. The measurement sites encompass a variety of terrain: offshore, coastal, flat, hilly, and mountainous regions, with low and high vegetation and also urban influences. The strongly differing site characteristics modulate the relative contribution of synoptic-scale and smaller-scale forcing to local wind conditions and thus the performance of the NWP model. The goal of this study was to determine the best-verifying model wind among various standard wind outputs and interpolation methods as well as to reveal its skill relative to the different site characteristics. Highest skill is reached by wind from a neighboring model level, as well as by linearly interpolated wind from neighboring model levels, whereas the frequently applied 10-m wind logarithmically extrapolated to higher elevations yields the largest errors. The logarithmically extrapolated 100-m model wind reaches the best compromise between availability and low cost for data even when the vertical resolution of the model changes. It is a good choice as input for further statistical postprocessing. The amplitude of measured, height-dependent diurnal variations is underestimated by the model. At low levels, the model wind speed is smaller than observed during the day and is higher during the night. At higher elevations, the opposite is the case.
On Imbalance Generated by Vortical Flows in a Two-Layer Spherical Boussinesq Primitive Equation Model
Authors: Mirzaei Mohammad , Mohebalhojeh Ali R. , Ahmadi-Givi Farhang 
Published: April 2012

Abstract
The spontaneous adjustment emission of inertia–gravity waves is investigated by examining the amount of imbalance generated during the evolution of unstable jets in an isentropic two-layer primitive equation model on the sphere. To determine the balance and thus the imbalance, potential vorticity (PV) inversion by means of the first-, second-, and third-order plain-δδ, plain-δγ, and plain-γγ balance relations, as well as the Bolin–Charney balance relations, is applied. Five sets of experiments are carried out by (i) changing the upper-layer potential temperature with a fixed initial jet speed and (ii) changing the initial jet speed with a fixed upper-layer potential temperature. For each set, the relation between the optimal measure of imbalance with the corresponding measure of balanced vortical flow is sought at the peak of instability. The minimal imbalance obtained by 1 of the above 10 PV inversion procedures is considered as the optimal.
The focus herein is on the magnitude of imbalance and its scaling with various measures of balanced flow. It is shown that for the magnitude of imbalance it is always possible to find the proper measure with an exponentially small scaling. For the imbalance-to-balance ratio, however, a power law is obtained when either the jet or the stratification is weak. The latter difference in scaling behavior of the imbalance and imbalance-to-balance ratio may be an artifact of the inevitable numerical errors whose effects are felt more strongly when the signature of vortical flow is weak.
DART/CAM: An Ensemble Data Assimilation System for CESM Atmospheric Models
Authors: Raeder Kevin , Anderson Jeffrey L. , Collins Nancy , Hoar Timothy J. , Kay Jennifer E. , Lauritzen Peter H. , Pincus Robert 
Published: April 2012

Abstract
The Community Atmosphere Model (CAM) has been interfaced to the Data Assimilation Research Testbed (DART), a community facility for ensemble data assimilation. This provides a large set of data assimilation tools for climate model research and development. Aspects of the interface to the Community Earth System Model (CESM) software are discussed and a variety of applications are illustrated, ranging from model development to the production of long series of analyses. CAM output is compared directly to real observations from platforms ranging from radiosondes to global positioning system satellites. Such comparisons use the temporally and spatially heterogeneous analysis error estimates available from the ensemble to provide very specific forecast quality evaluations. The ability to start forecasts from analyses, which were generated by CAM on its native grid and have no foreign model bias, contributed to the detection of a code error involving Arctic sea ice and cloud cover. The potential of parameter estimation is discussed. A CAM ensemble reanalysis has been generated for more than 15 yr. Atmospheric forcings from the reanalysis were required as input to generate an ocean ensemble reanalysis that provided initial conditions for decadal prediction experiments. The software enables rapid experimentation with differing sets of observations and state variables, and the comparison of different models against identical real observations, as illustrated by a comparison of forecasts initialized by interpolated ECMWF analyses and by DART/CAM analyses.
Colorado River Basin Hydroclimatic Variability
Authors: Nowak Kenneth , Hoerling Martin , Rajagopalan Balaji , Zagona Edith 
Published: April 2012

Abstract
An analysis of annual hydroclimatic variability in the Upper Colorado River basin (UCRB) for the period of 1906–2006 was performed to understand the dominant modes of multidecadal variability. First, wavelet-based spectral analysis was employed for streamflow at Lees Ferry, Arizona (aggregate location for UCRB flow), which identified two significant modes: a “low frequency” (~64-yr period) mode and a strong “decadal” (~15-yr period) component active only in recent decades. Subsequent investigation of temperature and precipitation data for the UCRB indicated that the low-frequency variability is associated with temperature via modulation of runoff efficiency while the decadal is strongly tied to moisture delivery. Simple hydrology and climate model experiments are also provided to support the aforementioned findings.
Correlation of UCRB precipitation with global sea surface temperature (SST) anomalies showed a strong link with the equatorial and northern Pacific during periods of heightened variability of the decadal mode. The correlation of UCRB temperature with global SST anomalies showed strongest values in the Atlantic consistent with the Atlantic multidecadal oscillation mode. Wavelet spectral analysis of paleo-reconstructed streamflow at Lees Ferry shows both the low-frequency and decadal flow variability features. Furthermore, the strength of the decadal mode is modulated at an ~75-yr time scale, and these are consistent with epochal variations of overall streamflow variance.
Quantifying the Influence of Atlantic Heat on Barents Sea Ice Variability and Retreat*
Authors: Årthun M. , Eldevik T. , Smedsrud L. H. , Skagseth Ø. , Ingvaldsen R. B. 
Published: April 2012

Abstract
The recent Arctic winter sea ice retreat is most pronounced in the Barents Sea. Using available observations of the Atlantic inflow to the Barents Sea and results from a regional ice–ocean model the authors assess and quantify the role of inflowing heat anomalies on sea ice variability. The interannual variability and longer-term decrease in sea ice area reflect the variability of the Atlantic inflow, both in observations and model simulations. During the last decade (1998–2008) the reduction in annual (July–June) sea ice area was 218 × 103 km2, or close to 50%. This reduction has occurred concurrent with an increase in observed Atlantic heat transport due to both strengthening and warming of the inflow. Modeled interannual variations in sea ice area between 1948 and 2007 are associated with anomalous heat transport (r = −0.63) with a 70 × 103 km2 decrease per 10 TW input of heat. Based on the simulated ocean heat budget it is found that the heat transport into the western Barents Sea sets the boundary of the ice-free Atlantic domain and, hence, the sea ice extent. The regional heat content and heat loss to the atmosphere scale with the area of open ocean as a consequence. Recent sea ice loss is thus largely caused by an increasing “Atlantification” of the Barents Sea.