bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of regional changes in skeletal metabolism following 3 and 18 months of teriparatide treatment
Authors: Moore Amelia EB , Blake Glen M , Taylor Kathleen A , Rana Asad E , Wong Mayme , Chen Peiqi , Fogelman Ignac 
Published: November 2009

Abstract
Teriparatide (TPTD) increases skeletal mass, bone turnover markers, and bone strength, but in vivo effects at individual skeletal sites have not been characterized. Quantitative radionuclide imaging studies reflect bone blood flow and osteoblast activity to assess regional changes in bone metabolism. Changes in bone plasma clearance using technetium-99m methylene diphosphonate (99mTc-MDP) were quantified and correlated with changes in bone turnover markers in 10 postmenopausal women with osteoporosis. Subjects underwent bone scintigraphy at baseline and 3 and 18 months after initiating TPTD 20 µg/day subcutaneously. Subjects were injected with 600 MBq 99mTc-MDP, and whole-body bone scan images were acquired at 10 minutes and 1, 2, 3, and 4 hours. Multiple blood samples were taken between 5 minutes and 4 hours after treatment, and free 99mTc-MDP was measured using ultrafiltration. The Patlak plot method was used to evaluate whole-skeleton 99mTc-MDP plasma clearance (Kbone) and derive regional bone clearance for the calvarium, mandible, spine, pelvis, and upper and lower extremities using gamma camera counts. Bone turnover markers were measured at baseline and 3, 12, and 18 months. Median increases from baseline in whole-skeleton Kbone were 22.3% (p = .004) and 33.7% (p = .002) at 3 and 18 months, respectively. Regional Kbone values were increased significantly in all six subregions at 3 months and in all subregions except the pelvis at 18 months. Bone markers were increased significantly from baseline at 3 and 18 months and correlated significantly with whole-skeleton Kbone. This is the first study showing a direct metabolic effect of TPTD at different skeletal sites in vivo, as measured by tracer kinetics. © 2010 American Society for Bone and Mineral Research
ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation
Authors: Dinther Maarten van , Visser Nils , de Gorter David JJ , Doorn Joyce , Goumans Marie-José , de Boer Jan , ten Dijke Peter 
Published: November 2009

Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare disabling disease characterized by heterotopic ossification for which there is currently no treatment available. FOP has been linked recently to a heterozygous R206H mutation in the bone morphogenetic protein (BMP) type I receptor activin receptor–like kinase 2 (ALK2). Expression of the mutant ALK2-R206H receptor (FOP-ALK2) results in increased phosphorylation of the downstream Smad1 effector proteins and elevated basal BMP-dependent transcriptional reporter activity, indicating that FOP-ALK2 is constitutively active. FOP-ALK2-induced transcriptional activity could be blocked by overexpressing either of the inhibitory Smads, Smad6 or -7, or by treatment with the pharmacological BMP type I receptor inhibitor dorsomorphin. However, in contrast to wild-type ALK2, FOP-ALK2 is not inhibited by the negative regulator FKBP12. Mesenchymal cells expressing the FOP-ALK2 receptor are more sensitive to undergoing BMP-induced osteoblast differentiation and mineralization. In vivo bone formation was assessed by loading human mesenchymal stem cells (hMSCs) expressing the ALK2-R206H receptor onto calcium phosphate scaffolds and implantation in nude mice. Compared with control cells FOP-ALK2-expressing cells induced increased bone formation. Taken together, the R206H mutation in ALK2 confers constitutive activity to the mutant receptor, sensitizes mesenchymal cells to BMP-induced osteoblast differentiation, and stimulates new bone formation. We have generated an animal model that can be used as a stepping stone for preclinical studies aimed at inhibiting the heterotopic ossification characteristic of FOP. © 2010 American Society for Bone and Mineral Research
Long-term leisure-time physical activity has a positive effect on bone mass gain in girls
Authors: Völgyi Eszter , Lyytikäinen Arja , Tylavsky Frances A , Nicholson Patrick HF , Suominen Harri , Alén Markku , Cheng Sulin 
Published: November 2009

Abstract
The purpose of this 7-year prospective longitudinal study was to examine whether the level and consistency of leisure-time physical activity (LTPA) during adolescence affected the bone mineral content (BMC) and bone mineral density (BMD) attained at early adulthood. The study subjects were 202 Finnish girls who were 10 to 13 years of age at baseline. Bone area (BA), BMC, and BMD of the total body (TB), total femur (TF), and lumbar spine (L2–L4) were assessed by dual-energy X-ray absorptiometry (DXA). Scores of LTPA were obtained by questionnaire. Girls were divided into four groups: consistently low physical activity (GLL), consistently high (GHH), and changed from low to high (GLH) and from high to low (GHL) during 7 years of follow-up. At baseline, no differences were found in BA, BMC, and BMD among the groups in any of the bone sites. Compared with the GLL group, the GHH group had higher BMC (11.7% in the TF, p &lt; .05) and BMD at the TB (4.5%) and the TF (12.2%, all p &lt; .05) at age 18. Those in the GLH group also had higher a BMC at each site (8.5% to 9.4%, p &lt; .05) and a higher BMD in the TB (5.4%) and the TF (8.9%) than that of GLL (all p &lt; 0.05) at the age 18. Our results suggest that long-term leisure-time physical activity has a positive effect on bone mass gain of multiple bone sites in girls during the transition from prepuberty to early adulthood. In addition, girls whose physical activity increases during adolescence also benefit from bone mass gain. © 2010 American Society for Bone and Mineral Research
The Nuclear Component of a Cytonuclear Hybrid Incompatibility in Mimulus Maps to a Cluster of Pentatricopeptide Repeat Genes
Authors: Barr Camille M , Fishman Lila 
Published: November 2009

Abstract
Characterizing the genetic and molecular basis of hybrid incompatibilities is a first step toward understanding their evolutionary origins. We fine mapped the nuclear restorer (Rf) of cytoplasm-dependent anther sterility in Mimulus hybrids by identifying and targeting regions of the Mimulus guttatus genome containing large numbers of candidate pentatricopeptide repeat genes (PPRs). The single Mendelian locus Rf was first isolated to a 1.3-cM region on linkage group 7 that spans the genome's largest cluster of PPRs, then split into two tightly linked loci (Rf1 and Rf2) by &lt;10 recombination events in a large (N = 6153) fine-mapping population. Progeny testing of fertile recombinants demonstrated that a dominant M. guttatus allele at each Rf locus was sufficient to restore fertility. Each Rf locus spans a physical region containing numerous PPRs with high homology to each other, suggesting recent tandem duplication or transposition. Furthermore, these PPRs have higher homology to restorers in distantly related taxa (petunia and rice) than to PPRs elsewhere in the Mimulus genome. These results suggest that the cytoplasmic male sterility (CMS)–PPR interaction is highly conserved across flowering plants. In addition, given our theoretical understanding of cytonuclear coevolution, the finding that hybrid CMS results from interactions between a chimeric mitochondrial transcript that is modified by Rf loci identified as PPRs is consistent with a history of selfish mitochondrial evolution and compensatory nuclear coevolution within M. guttatus.
ERECT PANICLE2 Encodes a Novel Protein That Regulates Panicle Erectness in Indica Rice
Authors: Zhu Keming , Tang Ding , Yan Changjie , Chi Zhengchang , Yu Hengxiu , Chen Jianmin , Liang Jiansheng , Gu Minghong , Cheng Zhukuan 
Published: November 2009

Abstract
Rice (Oryza sativa L.) inflorescence (panicle) architecture is an important agronomic trait for rice breeding. A number of high-yielding japonica rice strains, characterized by an erect panicle (EP) of their architecture, have been released as commercial varieties in China. But no EP-type indica varieties are released so far. Here, we identified two allelic erect-panicle mutants in indica rice, erect panicle2-1 (ep2-1) and erect panicle2-2 (ep2-2), exhibiting the characteristic erect panicle phenotype. Both mutants were derived from spontaneous mutation. We cloned the EP2 gene by way of a map-based cloning strategy, and a transgenic complementation test rescued the phenotype of ep2-1. Anatomical investigations revealed that the ep2 mutants have more vascular bundles and a thicker stem than that of wild-type plants, explaining the panicle erectness phenotype in ep2 mutants. It was shown that EP2 was specifically expressed in the vascular bundles of internodes by GUS staining and RT–PCR. EP2 encodes a novel plant-specific protein, which localizes to the endoplasmic reticulum with unknown biochemical function. In addition, EP2 also regulates other panicle characteristics, such as panicle length and grain size, but grain number per panicle shows little change, indicating that the mutation of the ep2 gene could be applied in EP-type indica rice breeding.
Proteasomal Degradation of Rpn4 in Saccharomyces cerevisiae Is Critical for Cell Viability Under Stressed Conditions
Authors: Wang Xiaogang , Xu Haiming , Ha Seung-Wook , Ju Donghong , Xie Youming 
Published: November 2009

Abstract
The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback loop in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome. In addition to the proteasome genes, Rpn4 regulates numerous other genes involved in a wide range of cellular pathways. Therefore, the Rpn4–proteasome negative feedback circuit not only controls proteasome abundance, but also gauges the expression of other Rpn4 target genes. Our previous work has shown that Rpn4-induced gene expression is critical for cell viability under stressed conditions. Here we investigate whether proteasomal degradation of Rpn4 is also important for cell survival in response to stress. To this end, we generate a stabilized Rpn4 mutant (Rpn4*) that retains its transcription activity. We find that expression of Rpn4* severely reduces cell viability in response to various genotoxic and proteotoxic agents. This detrimental effect can be eliminated by a point mutation that abolishes the transcription activity of Rpn4*, suggesting that overexpression of some Rpn4 target genes weakens the cell's ability to cope with stress. Moreover, we demonstrate that inhibition of Rpn4 degradation causes synthetic growth defects when combined with proteasome impairment resulting from mutation of a proteasome gene or accumulation of misfolded endoplasmic reticulum membrane proteins. Rpn4 thus represents an important stress-responsive mediator whose degradation as well as availability are critical for cell survival under stressed conditions.
Relative Impact of Influenza and Respiratory Syncytial Virus in Young Children
Authors: Bourgeois Florence T. , Valim Clarissa , McAdam Alexander J. , Mandl Kenneth D. 
Published: November 2009

OBJECTIVE: We measured the relative impact of influenza and respiratory syncytial virus (RSV) infections in young children in terms of emergency department (ED) visits, clinical care requirements, and overall resource use.METHODS: Patients who were aged ≤7 years and treated in the ED of a tertiary care pediatric hospital for an acute respiratory infection were enrolled during 2 winter seasons between 2003 and 2005. We quantified health care resource use for children with influenza or RSV infections, and extrapolated results to estimate the national resource use associated with influenza and RSV infections.RESULTS: Nationally, an estimated 10.2 ED visits per 1000 children were attributable to influenza and 21.5 visits per 1000 to RSV. Children who were aged 0 to 23 months and infected with RSV had the highest rate of ED visits with 64.4 visits per 1000 children. Significantly more children required hospitalization as a result of an RSV infection compared with influenza, with national hospitalization rates of 8.5 and 1.4 per 1000 children, respectively. The total number of workdays missed yearly by caregivers of children who required ED care was 246965 days for influenza infections and 716404 days for RSV infections.CONCLUSION: For young children, RSV is associated with higher rates of ED visits, hospitalization, and caregiver resource use than is influenza. Our results provide data on the large number of children who receive outpatient care for influenza and RSV illnesses and serve to inform analyses of prevention programs and treatments for both influenza and RSV disease.
Spatial Accessibility to Providers and Vaccination Compliance Among Children With Medicaid
Authors: Fu Linda Y. , Cowan Nuala , McLaren Rosie , Engstrom Ryan , Teach Stephen J. 
Published: November 2009

OBJECTIVE: We examined the relationship between spatial accessibility to pediatric immunization providers and vaccination compliance in a low-income, urban population of children.
METHODS: In 2007, we accessed the Washington, DC, Immunization Information System (IIS) to collect data on the immunization statuses and residential addresses of children who were aged 19 to 35 months and had Medicaid insurance. In addition, we calculated each child's spatial accessibility to pediatric vaccination providers by assessing the provider-to-population ratio at each residential address. Spatial accessibility was divided into tertiles (low, medium, and high) of access. The relationship between spatial accessibility to providers and vaccination compliance was examined by using logistic regression analysis adjusting for age, type of vaccination provider, and enrollment in child care status.
RESULTS: Overall for our cohort of 4195 children, 80.5% of the children were up-to-date with vaccinations. Vaccination coverage ranged from 61.6% to 100% (median: 79.2%) among different neighborhoods. Having the highest level of access to pediatric vaccination providers was associated with 36% higher odds of being up-to-date as compared with having the lowest level of access. The middle tertile of access was associated with 25% higher odds of being up-to-date.
CONCLUSIONS: Within our low-income, urban population, children with higher spatial accessibility to pediatric vaccination providers were more likely to be up-to-date with vaccinations. This association may guide future studies and efforts to ensure adequate immunization coverage for children regardless of where they live.
Association of Tobacco and Lead Exposures With Attention-Deficit/Hyperactivity Disorder
Authors: Froehlich Tanya E. , Lanphear Bruce P. , Auinger Peggy , Hornung Richard , Epstein Jeffery N. , Braun Joe , Kahn Robert S. 
Published: November 2009

OBJECTIVE: The study objective was to determine the independent and joint associations of prenatal tobacco and childhood lead exposures with attention-deficit/hyperactivity disorder (ADHD), as defined by current diagnostic criteria, in a national sample of US children.METHODS: Data are from the 2001–2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the US population. Participants were 8 to 15 years of age (N = 2588). Prenatal tobacco exposure was measured by report of maternal cigarette use during pregnancy. Lead exposure was assessed by using current blood lead levels. The Diagnostic Interview Schedule for Children was used to ascertain the presence of ADHD in the past year, on the basis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria.RESULTS: A total of 8.7% (95% confidence interval [CI]: 7.3%–10.1%) of children met criteria for ADHD. Prenatal tobacco exposure (adjusted odds ratio [aOR]: 2.4 [95% CI: 1.5–3.7]) and higher current blood lead concentrations (aOR for third versus first tertile: 2.3 [95% CI: 1.5–3.8]) were independently associated with ADHD. Compared with children with neither exposure, children with both exposures (prenatal tobacco exposure and third-tertile lead levels) had an even greater risk of ADHD (aOR: 8.1 [95% CI: 3.5–18.7]) than would be expected if the independent risks were multiplied (tobacco-lead exposure interaction term, P &lt; .001).CONCLUSIONS: Prenatal tobacco and childhood lead exposures are associated with ADHD in US children, especially among those with both exposures. Reduction of these common toxicant exposures may be an important avenue for ADHD prevention.
Preschool-Aged Children's Television Viewing in Child Care Settings
Authors: Christakis Dimitri A. , Garrison Michelle M. 
Published: November 2009

OBJECTIVE: The goal was to quantify television viewing in day care settings and to investigate the characteristics of programs that predict viewing.
METHODS: A telephone survey of licensed child care programs in Michigan, Washington, Florida, and Massachusetts was performed. The frequency and quantity of television viewing for infants, toddlers, and preschool-aged children were assessed.
RESULTS: With the exception of infants, children in home-based child care programs were exposed to significantly more television on an average day than were children in center-based programs (infants: 0.2 vs 0 hours; toddlers: 1.6 vs 0.1 hours; preschool-aged children: 2.4 vs 0.4 hours). In a regression analysis of daily television time for preschool-aged children in child care, center-based programs were found to have an average of 1.84 fewer hours of television each day, controlling for the other covariates. Significant effect modification was found, in that the impact of home-based versus center-based child care programs differed somewhat depending on educational levels for staff members; having a 2- or 4-year college degree was associated with 1.41 fewer hours of television per day in home-based programs, but no impact of staff education on television use was observed in center-based programs.
CONCLUSIONS: For many children, previous estimates of screen time significantly underestimated actual amounts. Pediatricians should council parents to minimize screen time in child care settings.
Water-Injection Optimization for a Complex Fluvial Heavy-Oil Reservoir by Integrating Geological, Seismic, and Production Data
Authors: Feng Xin , Wen Xian-Huan , Li Bo , Liu Ming , Zhou Dengen , Ye Qiucheng , Huo Dongmei , Yang Qinghong , Lan Lichuan 
Published: November 2009

Summary
BZ25-1s field in Bohai Bay, China, is characterized as a complex channelized fluvial reservoir in which small meandering channels were deposited at different geological times stacking and cross cutting each other. There are many isolated small reservoir systems following channel distributions. Early production showed steep pressure and production decline. Quick implementation of water injection was needed to arrest the fast production decline and to stabilize reservoir pressure.
While designing the water-injection plan, we faced a number of challenges, such as high oil viscosity (≈200 cp), strong heterogeneity, poor reservoir connectivity, complex channel geometry, and irregular well patterns. A workflow integrating geological, well-log, seismic, and dynamic production data was developed to optimize a water injection plan for this field after a short production history. Focuses of this workflow are the selection of injection wells (converted from existing producers), timing of water injection, and the optimization of injection rates.
Following the workflow, the optimal water-injection design for the areas around Platforms D and E was developed and quickly implemented within the first year of production. We started with a relatively small water-injection rate and gradually increased the injection rate to avoid the fast water breakthrough and yet to limit the pressure-decline rate.
The responses from the water injection were very positive and resulted in stable reservoir pressure and increase of oil production. Before water injection, the production-decline rates were 26 and 47% in Platforms D and E, respectively. After 1 year of water injection, oil-production-decline rates in these two platforms were reduced to 19 and 14%, respectively. The responses of water injection for different well groups were analyzed in a timely fashion and adjustments to injection/production strategies were implemented accordingly. New information revealed from the water-injection response analysis was used to update the geological model to reduce the model uncertainty, as well as to adjust the water-injection strategies for better sweep efficiency. Our experiences showed that such dynamic adjustment of injection and production schedule is very important to achieve better water-injection efficiency for this heavy-oil reservoir with complex channel geometry.
Compressible Streamline-Based Simulation With Changes in Oil Composition
Authors: Beraldo V. T. , Blunt M. J. , Schiozer D. J. 
Published: November 2009

Summary
In Brazil, there are several offshore oil fields with horizontal oil-density variations. API tracking, which is available in some commercial finite difference simulators, can deal with such cases by allowing the definition of an initial oil-gravity distribution and tracking variations of oil density owing to the movement of oil.
Streamline-based simulators can be much faster than conventional finite-difference simulators when applied to large and heterogeneous models. However, this approach is most accurate and efficient when it is assumed that the rock and fluids are incompressible. In previous work, Beraldo et al. (2007) presented an incompressible formulation for streamline simulation with an API tracking option using two components in the oleic phase.
This paper presents a compressible formulation for streamlines that also considers API tracking. It has an approach similar to the one presented by Cheng et al. (2006) and Osako and Datta-Gupta (2007). However, cumulative volume is used in the streamline solution, instead of time of flight, which reduces mass-conservation errors.
The method was implemented in a 3D two-phase streamline-based simulator. Tests based on a Brazilian oilfield model demonstrate that the implementation can reproduce the results of a conventional simulator, even when significant liquid compressibilities are considered. Another test, using the SPE 10th Comparative Case, indicates that it can be substantially faster for finely resolved models.