bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of matrix bound parathyroid hormone on bone regeneration
Authors: Jung Ronald E. , Cochran David L. , Domken Olivier , Seibl Reinhart , Jones Archie A. , Buser Daniel , Hammerle Christoph H. F. 
Published: March 2007

AbstractIntroduction: Autogenous bone is the most successful bone‐grafting material; however, multiple disadvantages continue to drive developments of improved methods for bone regeneration.Aim: The aim of the present study was to test the hypothesis that an arginine–glycine–aspartic acid (RGD) modified polyethylene glycol‐based matrix (PEG) containing covalently bound peptides of the parathyroid hormone (PTH1−34) enhances bone regeneration to a degree similar to autogenous bone.Material and methods: Six American foxhounds received a total of 48 cylindrical titanium implants placed in the mandible between the first premolar and the second molar. Five, respectively, 7 months following tooth extraction, implants were placed into the center of surgically created defects. This resulted in a circumferential bone defect simulating an alveolar defect with a circular gap of 1.5 mm. Four treatment modalities were randomly allocated to the four defects per side: (1) PEG‐matrix containing 20 μg/ml of PTH1−34, and 350 μg/ml cys‐RGD peptide, (2) PEG alone, (3) autogenous bone and (4) empty defects. Histomorphometric analysis was performed 4 and 12 weeks after implantation. The area fraction of newly formed bone was determined within the former defect and the degree of bone‐to‐implant contact (BIC) was evaluated both in the defect region and in the apical region of the implant. For statistical analysis ANOVA and subsequent pairwise Student's t‐test were applied.Results: Healing was uneventful and all implants were histologically integrated. Histomorphometric analysis after 4 weeks showed an average area fraction of newly formed bone of 41.7±1.8% for matrix‐PTH, 26.6±4.1% for PEG alone, 43.9±4.5% for autogenous bone, and 28.9±1.5% for empty defects. After 12 weeks, the respective values were 49.4±7.0% for matrix‐PTH, 39.3±5.7% for PEG alone, 50.5±3.4% for autogenous bone and 38.7±1.9% for empty defects. Statistical analysis after 4 and 12 weeks revealed significantly more newly formed bone in the PTH1−34 group compared with PEG alone or empty defects, whereas no difference could be detected against autogenous bone. Regarding BIC no significant difference was observed between the four treatment groups neither at 4 nor at 12 weeks.Conclusion: It is concluded that an RGD‐modified PEG hydrogel containing PTH1−34 is an effective matrix system to obtain bone regeneration.
Re‐Visiting Peruvian Grassroots Women's Organisations: Where Are They Now?
Authors: Jenkins Katy 
Published: March 2007

AbstractWhile women's organising in Latin America was the subject of significant academic attention throughout the 1980s and early 1990s, there has been little more recent discussion of the ongoing role of low income women in urban community development. This article therefore re‐visits women's long‐term voluntary work in order to explore how their endeavours have been conceptualised over time, tracing the trajectory of women's popular organising in Peru. The discussion begins with understandings of women's popular organising as part of an ‘alternative development’ paradigm, before exploring more recent mainstream considerations of women's organisations as a source of social capital. This overview is complemented by a recent case study of a group of women health promoters in Lima, which emphasises the continued resilience and dedication of grassroots women activists, despite their recent low profile in the international development arena.
Evolution of Resistant M414T Mutants among Hepatitis C Virus Replicon Cells Treated with Polymerase Inhibitor A-782759
Authors: Lu Liangjun , Mo Hongmei , Pilot-Matias Tami J. , Molla Akhteruzzaman 
Published: March 2007

ABSTRACT
Treatment of hepatitis C virus (HCV) replicon cells with any single specific anti-HCV inhibitor in vitro leads to a rapid selection of resistant mutants. However, the source and the kinetic evolution of these resistant mutants during treatment are poorly understood. In this study we developed allele-specific real-time PCR assays for quantitative detection of the M414T mutant that was selected by a number of benzothiadiazine HCV polymerase inhibitors. Low levels of preexisting M414T mutants were detected in both 1b-con1 (0.22%) and 1b-N (0.18%) subgenomic replicon cell lines, as well as in 6 of 15 HCV RNA isolated from the sera of treatment-naive HCV-infected patients ranging from 0.11 to 0.60%. The proportion of M414T mutants in replicons rapidly increased in a dose-dependent manner upon treatment with benzothiadiazine inhibitor A-782759. After 4 days of treatment, 2.5, 26, or 60% of the replicon population contained M414T mutants with the use of A-782759 at 1×, 10×, or 100× its 50% effective concentration, respectively. In addition, the short 4-day treatment resulted in significant changes in inhibitor susceptibility in the replicon cells. Our results indicated that the resistant mutant preexisted as a minor population in replicon cells and that the mutant was selected within days of treatment with the inhibitor. The findings from this study suggested that early application of combination therapy of an HCV-specific inhibitor with interferon-based regimens or other classes of available inhibitors will be necessary to avoid quick viral rebound or treatment failure.
Lack of Effect of DX-619, a Novel Des-Fluoro(6)-Quinolone, on Glomerular Filtration Rate Measured by Serum Clearance of Cold Iohexol
Authors: Sarapa Nenad , Wickremasingha Prachi , Ge NanXiang , Weitzman Richard , Fuellhart Merynda , Yen Cindy , Lloyd-Parks Julia 
Published: March 2007

ABSTRACTDX-619 is a novel des-fluoro(6)-quinolone with activity against a broad range of bacterial strains, including methicillin-resistantStaphylococcus aureus. The effects of DX-619 on the glomerular filtration rate (GFR) were evaluated because drug-related increases in serum creatinine levels were observed in studies with healthy volunteers. Forty-one healthy subjects were randomized to receive intravenous DX-619 at 800 mg or placebo once daily for 4 days, and the GFR was directly measured by determination of the clearance of a bolus iohexol injection in 33 subjects who completed the study per protocol. DX-619 was noninferior to placebo for the GFR on the basis of a criterion for a clinically significant difference of −12 ml/min/1.73 m2. The mean GFRs on day 4 were 101.1 ± 14.2 ml/min/1.73 m2and 100.2 ± 15.6 ml/min/1.73 m2for the volunteers receiving placebo and DX-619, respectively. On day 4 the mean serum creatinine concentration for volunteers receiving DX-619 increased by 30 to 40%, with a corresponding decrease in mean creatinine clearance. Both parameters normalized within 7 days after the cessation of DX-619 treatment. Nonclinical studies suggest that DX-619 increases the serum creatinine concentration by inhibiting excretory tubular transporters. In conclusion, DX-619 administered intravenously at 800 mg once a day for 4 days did not affect the GFR in healthy volunteers. Glomerular toxicity is not expected to present a risk to patients receiving DX-619 in clinical trials, but monitoring of the renal function, with an emphasis on the serum creatinine concentration, is still warranted.
Broad-Spectrum Antiviral Activity of Small Interfering RNA Targeting the Conserved RNA Termini of Lassa Virus
Authors: Müller Stefanie , Günther Stephan 
Published: March 2007

ABSTRACT
Small interfering RNAs targeting the conserved RNA termini upstream of NP and L gene were found to reduce reporter gene expression from Lassa virus replicon and Lassa virus mRNA expression construct and to inhibit replication of different Lassa virus strains, lymphocytic choriomeningitis virus, and Mopeia virus in cell culture.
In Vitro Activities of Miltefosine and Two Novel Antifungal Biscationic Salts against a Panel of 77 Dermatophytes
Authors: Tong Zhongsheng , Widmer Fred , Sorrell Tania C. , Guse Zofia , Jolliffe Katrina A. , Halliday Catriona , Lee Ok Cha , Kong Fanrong , Wright Lesley C. , Chen Sharon C. A. 
Published: March 2007

ABSTRACT

The susceptibilities of 77 dermatophytes to miltefosine (MI), 1,12-bis(4-pentylpyridinium)dodecane (PYR), 1,12-bis(tributylammonium)dodecane (AM), itraconazole (ITC), terbinafine (TRB), and butenafine (BTF) were compared. Geometric mean MICs of TRB, BTF, ITC, MI, PYR, and AM were 0.039, 0.059, 1.718, 0.671, 6.006, and 4.771 μg/ml, respectively. MI was more active than ITC (
P
< 0.001).
Assessment and Continued Validation of the Malaria SYBR Green I-Based Fluorescence Assay for Use in Malaria Drug Screening
Authors: Johnson Jacob D. , Dennull Richard A. , Gerena Lucia , Lopez-Sanchez Miriam , Roncal Norma E. , Waters Norman C. 
Published: March 2007

ABSTRACT

Several new fluorescence malaria in vitro drug susceptibility microtiter plate assays that detect the presence of malarial DNA in infected erythrocytes have recently been reported, in contrast to traditional isotopic screens that involve radioactive substrate incorporation to measure in vitro malaria growth inhibition. We have assessed and further characterized the malaria SYBR Green I-based fluorescence (MSF) assay for its ability to monitor drug resistance. In order to use the MSF assay as a drug screen, all assay conditions must be thoroughly examined. In this study we expanded upon the capabilities of this assay by including antibiotics and antifolates in the drug panel and testing folic acid-free growth conditions. To do this, we evaluated a more expansive panel of antimalarials in combination with various drug assay culture conditions commonly used in drug sensitivity screening for their activity against
Plasmodium falciparum
strains D6 and W2. The detection and quantitation limits of the MSF assay were 0.04 to 0.08% and ∼0.5% parasitemia, respectively. The MSF assay quality was significantly robust, displaying a Z′ range of 0.73 to 0.95. The 50% inhibitory concentrations for each drug and culture condition combination were determined by using the MSF assay. Compared to the standard [
3
H]hypoxanthine assay, the MSF assay displayed the expected parasite drug resistance patterns with a high degree of global and phenotypic correlation (
r
2
≥ 0.9238), regardless of which culture condition combination was used. In conclusion, the MSF assay allows for reliable one-plate high-throughput, automated malaria in vitro susceptibility testing without the expense, time consumption, and hazard of other screening assays.
Candida albicans
Iff11, a Secreted Protein Required for Cell Wall Structure and Virulence
Authors: Bates Steven , de la Rosa José M. , MacCallum Donna M. , Brown Alistair J. P. , Gow Neil A. R. , Odds Frank C. 
Published: March 2007

ABSTRACT

The
Candida albicans
cell wall is the immediate point of contact with the host and is implicated in the host-fungal interaction and virulence. To date, a number of cell wall proteins have been identified and associated with virulence. Analysis of the
C. albicans
genome has identified the
IFF
gene family as encoding the largest family of cell wall-related proteins. This family is also conserved in a range of other
Candida
species. Iff11 differs from other family members in lacking a GPI anchor, and we have demonstrated it to be O glycosylated and secreted in
C. albicans
. A null mutant lacking
IFF11
was hypersensitive to cell wall-damaging agents, suggesting a role in cell wall organization. In a murine model of systemic infection the null mutant was highly attenuated in virulence, and survival-standardized infections suggest it is required to establish an infection. This work provides the first evidence of the importance of this gene family in the host-fungal interaction and virulence.
Genetic and Epigenetic Regulation of the Human Prostacyclin Synthase Promoter in Lung Cancer Cell Lines
Authors: Stearman Robert S. , Grady Michael C. , Nana-Sinkam Patrick , Varella-Garcia Marileila , Geraci Mark W. 
Published: March 2007

Abstract
The importance of the arachidonic acid pathway has been established in colon and lung cancers, as well as in inflammatory diseases. In these diseases, prostacyclin I2 (PGI2) and prostaglandin E2 (PGE2) are thought to have antagonistic activities, with PGI2 exerting anti-inflammatory and antiproliferative activities, whereas PGE2 is proinflammatory and antiapoptotic. In human lung cancer, prostacyclin synthase (PGIS) and PGI2 are down-regulated, whereas PGE2 synthase (PGES) and PGE2 are up-regulated. Murine carcinogenesis models of human lung cancer reciprocate the relationship between PGIS and PGES expression. PGIS-overexpressing transgenic mice are protected from carcinogen- and tobacco smoke–induced lung tumor formation, suggesting that PGI2 may play a role in chemoprevention. We investigated several potential mechanisms for the down-regulation of PGIS in human lung cancer. Using transcription reporter assays, we show that single nucleotide polymorphisms in the PGIS promoter can affect transcriptional activity. In addition, PGIS expression in several human lung cancer cell lines is silenced by CpG methylation, and we have mapped these sites across the variable number of tandem repeats (VNTR) sequence in the promoter, as well as CpGs within exon 1 and the first intron. Finally, using fluorescence in situ hybridization, we show that human lung cancer cell lines and lung cancer tissues do not have a loss of the PGIS genomic region but multiple copies. These results show that an individual's PGIS promoter haplotype can play an important role in the predisposition for lung cancer and CpG methylation provides an epigenetic mechanism for the down-regulated PGIS expression. (Mol Cancer Res 2007;5(3):295–308)
Protease-Activated Receptor-1 (hPar1), A Survival Factor Eliciting Tumor Progression
Authors: Salah Zaidoun , Maoz Myriam , Pokroy Elisheva , Lotem Michal , Bar-Shavit Rachel , Uziely Beatrice 
Published: March 2007

Abstract
Although ample evidence point to the central involvement of protease activated receptor-1 (PAR1) in tumor progression, little is known about the fate of the tumor when hPar1 is being silenced. We observed that hPar1 antisense clones exhibit low PAR1 levels, attenuated cell proliferation and invasion in vitro, and tumor formation in vivo. These clones showed noticeably reduced paxillin phosphorylation compared with the parental A375SM cells, whereas no change in the integrin levels was noticed. Antisense clones injected into the mice resulted in very few and only occasional small tumors, whereas advanced and vascularized tumors were observed in A375SM cells. The antisense-derived tumor sections expressed active caspase-3, increased terminal deoxynucleotidyl transferase–mediated nick-end labeling staining, and a markedly reduced proliferating cell nuclear antigen level compared with A375SM cell–derived tissue sections. Likewise, ablation of the hPar1 gene in a tetracycline-inducible hPar1 system leads to apoptosis in immature blood vessels, whereas mature vessels were unaffected. The activation of PAR1-induced pAkt/protein kinase B abrogated serum-deprived BimEL induction and also markedly inhibited Bax levels. On the other hand, small interfering RNA silencing of the hPar1 gene induced the expression of BimEL, a direct substrate of Akt/protein kinase B and also induced expression of active caspase-9 and caspase-3. These results altogether identify PAR1 as a survival factor that protects cells from undergoing apoptosis. We conclude that whereas PAR1 gene expression correlates with tumor progression, its neutralization effectively initiates an apoptotic pathway leading at least in part to significantly reduced tumor formation. (Mol Cancer Res 2007;5(3):229–40)
Direct Insertion of MODIS Radiances in a Global Aerosol Transport Model
Authors: Weaver Clark , da Silva Arlindo , Chin Mian , Ginoux Paul , Dubovik Oleg , Flittner Dave , Zia Aahmad , Remer Lorraine , Holben Brent , Gregg Watson 
Published: March 2007

Abstract
In this paper results are presented from a simple offline assimilation system that uses radiances from the Moderate Resolution Imaging Spectroradiometer (MODIS) channels that sense atmospheric aerosols over land and ocean. The MODIS information is directly inserted into the Goddard Chemistry and Aerosol Radiation Transport model (GOCART), which simulates the following five aerosol types: dust, sea salt, black carbon, organic carbon, and sulfate. The goal is to produce three-dimensional fields of these aerosol types for radiative forcing calculations.
Products from this assimilation system are compared with ground-based measurements of aerosol optical depth (AOD) from the Aerosol Robotic Network (AERONET). Insertion of MODIS radiances draws the GOCART model closer to the AERONET AOD. However, there are still uncertainties with surface reflectivity over moderately bright surfaces and with the amount of absorbing aerosol.
Also described is the assimilation cycle. The forward model takes the aerosol information from the GOCART model and calculates radiances based on optical parameters of the aerosol type, satellite viewing angle, and the particle growth from relative humidity. Because the GOCART model is driven by previously assimilated meteorology, these forward model radiances can be directly compared with the observed MODIS level-2 radiances. The offline assimilation system simply adjusts the aerosol loading in the GOCART model so that the observed minus forward model radiances agree. Minimal change is made to the GOCART aerosol vertical distribution, size distribution, and the ratio of the five different aerosol types. The loading in the GOCART model is updated with new MODIS observations every 6 h. Since the previously assimilated meteorology provides surface wind speed, radiance sensitivity to wind speed over rough ocean is taken into account. Over land the dark target approach, also used by the MODIS–atmosphere group retrieval, is used. If the underlying land surface is deemed dark enough, the surface reflectances at the 0.47- and 0.66-μm wavelengths are constant multiples of the observed 2.13-μm reflectance. Over ocean the assimilation AOD compares well with AERONET, over land less so. The results herein are also compared with AERONET-retrieved single-scattering albedo. This research is part of an ongoing effort at NASA Goddard to integrate aerosols into the Goddard Modeling and Assimilation Office (GMAO) products.
A Mechanism for the Poleward Propagation of Zonal Mean Flow Anomalies
Authors: Lee Sukyoung , Son Seok-Woo , Grise Kevin , Feldstein Steven B. 
Published: March 2007

Abstract
Observational studies have shown that tropospheric zonal mean flow anomalies frequently undergo quasi-periodic poleward propagation. A set of idealized numerical model runs is examined to investigate the physical mechanism behind this poleward propagation.
This study finds that the initiation of the poleward propagation is marked by the formation of negative zonal wind anomalies in the Tropics. These negative anomalies arise from meridional overturning/breaking of waves that originate in midlatitudes. This wave breaking homogenizes the potential vorticity (PV) within the region of negative zonal wind anomalies, and also leads to the formation of positive zonal wind anomalies in the subtropics. Subsequent equatorward radiation of midlatitude waves is halted, which results in wave breaking at the poleward end of the homogenized PV region. This in turn generates new positive and negative zonal wind anomalies, which enables a continuation of the poleward propagation. The shielding of the homogenized PV region from equatorward wave propagation allows the model’s radiative relaxation to reestablish undisturbed westerlies in the Tropics, while extratropical westerly anomalies arise from eddy vorticity fluxes.
The above process indicates that the poleward zonal mean anomaly propagation is caused by an orchestrated combination of linear Rossby wave propagation, nonlinear wave breaking, and radiative relaxation. The importance of the meridional wave propagation and breaking is consistent with the fact that the poleward propagation occurs only in the parameter space of the model where the PV gradient is of moderate strength. Implications for predictability are briefly discussed.
Interaction between Near-Annual and ENSO Modes in a CGCM Simulation: Role of the Equatorial Background Mean State
Authors: Dewitte Boris , Cibot Carole , Périgaud Claire , An Soon-Il , Terray Laurent 
Published: March 2007

Abstract
A 260-yr-long coupled general circulation model (CGCM) simulation is used to investigate the interaction between ENSO mode and near-annual variability and its sensitivity to the equatorial background mean stratification and seasonal cycles. Although the thermocline mean vertical structure of the model favors the high-order baroclinic modes that are associated with the slow time scales of the coupled variability, the simulated ENSO oscillates at a dominant quasi-biennial frequency. Biases of the climatological velocity field are favorable to the dominance of the zonal advective feedback over the thermocline feedback, the model exhibiting an overenergetic westward seasonal zonal current in the central-western equatorial Pacific, and an upwelling rate that is about half the observations. This sets the conditions for the enhancement of a near-annual mode that is observed to oscillate at an 8-month period in the model. Using an intermediate coupled model of the tropical Pacific where the climatological fields are prescribed to the ones derived from the CGCM, it is demonstrated that the quasi-biennial ENSO variability simulated by the CGCM is mostly due to the biases in the climatological currents of the CGCM. These biases favor the dominance of the fast “zonal advective feedback” over the slow “thermocline feedback” in the coupled system and enhance a fast coupled basin mode. This fast mode differs from the theoretical Pacific Ocean basin mode in that, besides mean temperature advection by the zonal current anomalies, it is also driven by anomalous temperature advection by the total current. Results suggest that the near-annual mode destabilizes the ENSO mode to produce overenergetic quasi-biennial oscillations in the model. It also contributes to the ENSO asymmetry and the cold bias of the CGCM mean state by nonlinear accumulation of temperature zonal advection, which works toward the cold in the western Pacific more than the warm in the east. It is suggested that the model equilibrium results from the interaction between the ENSO mode, the near-annual mode, and the mean state.