bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐scale assimilation of root zone soil water predictions
Authors: Lü Haishen , Yu Zhongbo , Horton Robert , Zhu Yonghua , Wang Zhenlong , Hao Zhenchun , Xiang Long 
Published: February 2011

AbstractWhen hydrology model parameters are determined, a traditional data assimilation method (such as Kalman filter) and a hydrology model can estimate the root zone soil water with uncertain state variables (such as initial soil water content). The simulated result can be quite good. However, when a key soil hydraulic property, such as the saturated hydraulic conductivity, is overestimated or underestimated, the traditional soil water assimilation process will produce a persistent bias in its predictions. In this paper, we present and demonstrate a new multi‐scale assimilation method by combining the direct insertion assimilation method, particle swarm optimisation (PSO) algorithm and Richards equation. We study the possibility of estimating root zone soil water with a multi‐scale assimilation method by using observedin situdata from the Wudaogou experiment station, Huaihe River Basin, China. The results indicate there is a persistent bias between simulated and observed values when the direct insertion assimilation surface soil water content is used to estimate root zone soil water contents. Using a multi‐scale assimilation method (PSO algorithm and direct insertion assimilation) and an assumed bottom boundary condition, the results show some obvious improvement, but the root mean square error is still relatively large. When the bottom boundary condition is similar to the actual situation, the multi‐scale assimilation method can well represent the root zone soil water content. The results indicate that the method is useful in estimating root zone soil water when available soil water data are limited to the surface layer and the initial soil water content even when the soil hydraulic conductivities are uncertain. Copyright © 2011 John Wiley & Sons, Ltd.
Skeletal recovery after weaning does not require PTHrP
Authors: Kirby Beth J , Ardeshirpour Laleh , Woodrow Janine P , Wysolmerski John J , Sims Natalie A , Karaplis Andrew C , Kovacs Christopher S 
Published: February 2011

Abstract
Mice lose 20% to 25% of trabecular bone mineral content (BMC) during lactation and restore it after weaning through unknown mechanisms. We found that tibial Pthrp mRNA expression was upregulated fivefold by 7 days after weaning versus end of lactation in wild-type (WT) mice. To determine whether parathyroid hormone–related protein (PTHrP) stimulates bone formation after weaning, we studied a conditional knockout in which PTHrP is deleted from preosteoblasts and osteoblasts by collagen I promoter–driven Cre (CreColI). These mice are osteopenic as adults but have normal serum calcium, calcitriol, and parathyroid hormone (PTH). Pairs of Pthrpflox/flox;CreColI (null) and WT;CreColI (WT) females were mated and studied through pregnancy, lactation, and 3 weeks of postweaning recovery. By end of lactation, both genotypes lost lumbar spine BMC: WT declined by 20.6% ± 3.3%, and null decreased by 22.5% ± 3.5% (p &lt; .0001 versus baseline; p = NS between genotypes). During postweaning recovery, both restored BMC to baseline: WT to –3.6% ± 3.7% and null to 0.3% ± 3.7% (p = NS versus baseline or between genotypes). Similar loss and full recovery of BMC were seen at the whole body and hind limb. Histomorphometry confirmed that nulls had lower bone mass at baseline and that this was equal to the value achieved after weaning. Osteocalcin, propeptide of type 1 collagen (P1NP), and deoxypyridinoline increased equally during recovery in WT and null mice; PTH decreased and calcitriol increased equally; serum calcium was unchanged. Urine calcium increased during recovery but remained no different between genotypes. Although osteoblast-derived PTHrP is required to maintain adult bone mass and Pthrp mRNA upregulates in bone after weaning, it is not required for recovery of bone mass after lactation. The factors that stimulate postweaning bone formation remain unknown. © 2011 American Society for Bone and Mineral Research.
Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: The OCEAN study
Authors: Eastell Richard , Nagase Shinichi , Ohyama Michiyo , Small Maria , Sawyer James , Boonen Steven , Spector Tim , Kuwayama Tomohiro , Deacon Steve 
Published: February 2011

Abstract
Osteoporosis occurs when there is an imbalance between resorption and formation of bone, with resorption predominating. Inhibitors of cathepsin K may rebalance this condition. This is the first efficacy study of a new cathepsin K inhibitor, ONO-5334. The objective of the study was to investigate the efficacy and safety of ONO-5334 in postmenopausal osteoporosis. This was a 12-month, randomized, double-blind, placebo- and active-controlled parallel-group study conducted in 13 centers in 6 European countries. Subjects included 285 postmenopausal women aged 55 to 75 years with osteoporosis. Subjects were randomized into one of five treatment arms: placebo; 50 mg twice daily, 100 mg once daily, or 300 mg once daily of ONO-5334; or alendronate 70 mg once weekly. Lumbar spine, total hip, and femoral neck BMD values were obtained along with biochemical markers of bone turnover and standard safety assessments. All ONO-5334 doses and alendronate showed a significant increase in BMD for lumbar spine, total hip (except 100 mg once daily), and femoral neck BMD. There was little or no suppression of ONO-5334 on bone-formation markers compared with alendronate, although the suppressive effects on bone-resorption markers were similar. There were no clinically relevant safety concerns. With a significant increase in BMD, ONO-5334 also demonstrated a new mode of action as a potential agent for treating osteoporosis. Further clinical studies are warranted to investigate long-term efficacy as well as safety of ONO-5334. © 2011 American Society for Bone and Mineral Research.
Bone turnover markers and bone mineral density response with risedronate therapy: Relationship with fracture risk and patient adherence
Authors: Eastell Richard , Vrijens Bernard , Cahall David L , Ringe Johann D , Garnero Patrick , Watts Nelson B 
Published: February 2011

Abstract
Surrogate markers of fracture risk—bone turnover markers (BTMs) and bone mineral density (BMD)—can be used to monitor treatment response. We assessed whether changes in these markers greater than the least significant change (LSC) were associated with fracture risk reduction and greater adherence. This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment (IMPACT) study—a multinational prospective, open-label, cluster-randomized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks—assessed adherence by electronic monitors. Urinary N-terminal cross-linked telopeptide of type 1 collagen (uNTX) and serum C-terminal cross-linked telopeptide of type 1 collagen (sCTX) levels were assessed at baseline and weeks 10 and 22, and BMD at baseline and week 52. Fractures were recorded as adverse events. In 2302 women, responses beyond LSC in BTMs (uNTX and sCTX) and BMD (spine only) were associated with a reduced risk of nonvertebral fractures (NVFs) and all fractures. NVF incidence was about 50% lower in patients with 30% or more of uNTX reduction at week 22 (1.6%) than in those with less than 30% reduction (3.2%, p = .015). NVFs also were reduced in patients with more than 3% spine BMD increase at 52 weeks than those with 3% or less. Responses greater than LSC in BTMs and BMD were associated with greater adherence, but there was no association between adherence and fracture outcomes at 52 weeks. Changes greater than the LSC in BTMs and BMD reflect better treatment adherence, were associated with fracture risk reduction, and identify differences in individual responsiveness to risedronate. © 2011 American Society for Bone and Mineral Research.
CYR61 downregulation reduces osteosarcoma cell invasion, migration, and metastasis
Authors: Fromigue Olivia , Hamidouche Zahia , Vaudin Pascal , Lecanda Fernando , Patino Ana , Barbry Pascal , Mari Bernard , Marie Pierre J 
Published: February 2011

Abstract
Osteosarcoma is the most common primary tumor of bone. The rapid development of metastatic lesions and resistance to chemotherapy remain major mechanisms responsible for the failure of treatments and the poor survival rate for patients. We showed previously that the HMGCoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor statin exhibits antitumoral effects on osteosarcoma cells. Here, using microarray analysis, we identify Cyr61 as a new target of statins. Transcriptome and molecular analyses revealed that statins downregulate Cyr61 expression in human and murine osteosarcoma cells. Cyr61 silencing in osteosarcoma cell lines enhanced cell death and reduced cell migration and cell invasion compared with parental cells, whereas Cyr61 overexpression had opposite effects. Cyr61 expression was evaluated in 231 tissue cores from osteosarcoma patients. Tissue microarray analysis revealed that Cyr61 protein expression was higher in human osteosarcoma than in normal bone tissue and was further increased in metastatic tissues. Finally, tumor behavior and metastasis occurrence were analyzed by intramuscular injection of modified osteosarcoma cells into BALB/c mice. Cyr61 overexpression enhanced lung metastasis development, whereas cyr61 silencing strongly reduced lung metastases in mice. The results reveal that cyr61 expression increases with tumor grade in human osteosarcoma and demonstrate that cyr61 silencing inhibits in vitro osteosarcoma cell invasion and migration as well as in vivo lung metastases in mice. These data provide a novel molecular target for therapeutic intervention in metastatic osteosarcoma. © 2011 American Society for Bone and Mineral Research.
Trabecular bone microstructure and local gene expression in iliac crest biopsies of men with idiopathic osteoporosis
Authors: Patsch Janina M , Kohler Thomas , Berzlanovich Andrea , Muschitz Christian , Bieglmayr Christian , Roschger Paul , Resch Heinrich , Pietschmann Peter 
Published: February 2011

Abstract
Male idiopathic osteoporosis (MIO) is a metabolic bone disease that is characterized by low bone mass, microstructural alterations, and increased fracture risk in otherwise healthy men. Although the detailed pathophysiology of MIO has yet to be clarified, evidence increasingly suggests an osteoblastic defect as the underlying cause. In this study we tested the hypothesis that the expression profile of certain osteoblastic or osteoblast-related genes (ie, WNT10B, RUNX2, Osterix, Osteocalcin, SOST, RANKL, and OPG) is different in iliac crest biopsies of MIO patients when compared with healthy controls. Furthermore, we investigated the relation of local gene expression characteristics with histomorphometric, microstructural, and clinical features. Following written informed consent and diligent clinical patient characterization, iliac crest biopsies were performed in nine men. While RNA extraction, reverse-transcription, and real-time polymerase chain reactions (PCRs) were performed on one biopsy, a second biopsy of each patient was submitted for histomorphometry and micro–computed tomography (µCT). Age-matched bone samples from forensic autopsies served as controls. MIO patients displayed significantly reduced WNT10B, RUNX2, RANKL, and SOST expression. Performing µCT for the first time in MIO biopsies, we found significant decreases in trabecular number and connectivity density. Trabecular separation was increased significantly, but trabecular thickness was similar in both groups. Histomorphometry revealed decreased BV/TV and osteoid volume and fewer osteoclasts in MIO. By providing evidence for reduced local WNT10B, RUNX2, and RANKL gene expression and histomorphometric low turnover, our data support the osteoblast dysfunction model discussed for MIO. Further, MIO seems to lead to a different microstructural pathology than age-related bone loss. © 2011 American Society for Bone and Mineral Research.
Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism
Authors: Atkins Gerald J , Rowe Peter S , Lim Hui P , Welldon Katie J , Ormsby Renee , Wijenayaka Asiri R , Zelenchuk Lesya , Evdokiou Andreas , Findlay David M 
Published: February 2011

Abstract
The identity of the cell type responsive to sclerostin, a negative regulator of bone mass, is unknown. Since sclerostin is expressed in vivo by mineral-embedded osteocytes, we tested the hypothesis that sclerostin would regulate the behavior of cells actively involved in mineralization in adult bone, the preosteocyte. Differentiating cultures of human primary osteoblasts exposed to recombinant human sclerostin (rhSCL) for 35 days displayed dose- and time-dependent inhibition of in vitro mineralization, with late cultures being most responsive in terms of mineralization and gene expression. Treatment of advanced (day 35) cultures with rhSCL markedly increased the expression of the preosteocyte marker E11 and decreased the expression of mature markers DMP1 and SOST. Concomitantly, matrix extracellular phosphoglycoprotein (MEPE) expression was increased by rhSCL at both the mRNA and protein levels, whereas PHEX was decreased, implying regulation through the MEPE-ASARM axis. We confirmed that mineralization by human osteoblasts is exquisitely sensitive to the triphosphorylated ASARM-PO4 peptide. Immunostaining revealed that rhSCL increased the endogenous levels of MEPE-ASARM. Importantly, antibody-mediated neutralization of endogenous MEPE-ASARM antagonized the effect of rhSCL on mineralization, as did the PHEX synthetic peptide SPR4. Finally, we found elevated Sost mRNA expression in the long bones of HYP mice, suggesting that sclerostin may drive the increased MEPE-ASARM levels and mineralization defect in this genotype. Our results suggest that sclerostin acts through regulation of the PHEX/MEPE axis at the preosteocyte stage and serves as a master regulator of physiologic bone mineralization, consistent with its localization in vivo and its established role in the inhibition of bone formation. © 2011 American Society for Bone and Mineral Research.
13 years of cultured limbal epithelial cell therapy: A review of the outcomes
Authors: Baylis Oliver , Figueiredo Francisco , Henein Christin , Lako Majlinda , Ahmad Sajjad 
Published: February 2011

AbstractThe cornea is the clear tissue at the front of the eye which enables the transmission of light to the retina for normal vision. The surface of the cornea is composed of an epithelium which is renewed by stem cells located at the periphery of the cornea, a region known as the limbus. These limbal stem cells can become deficient as a result of various diseases of the eye's surface, resulting in the blinding disease of limbal stem cell deficiency. The treatment of this disease is often difficult and complex. In 1997, it was proposed that a small amount of limbal tissue containing limbal stem cells could be culture expanded and then transplanted. Since then various case reports and case series have been reported showing promising results. Here, we review the outcomes of this procedure over the past 13 years with the aim of highlighting the best culture and surgical techniques to date. J. Cell. Biochem. 112: 993–1002, 2011. © 2011 Wiley‐Liss, Inc.
Role of C/EBP‐β, p38 MAPK, and MKK6 in IL‐1β‐mediated C3 gene regulation in astrocytes
Authors: Maranto Jeffrey , Rappaport Jay , Datta Prasun K. 
Published: February 2011

AbstractComplement component C3, the central player in the complement cascade and the pro‐inflammatory cytokine IL‐1β is expressed by activated glial cells and may contribute to neurodegeneration. This study examines the regulation of the expression of C3 by IL‐1β in astroglial cells focusing on the role of the upstream kinase MKK6, p38‐α MAPK, and C/EBP‐β isoforms (LAP1, LAP2, or LIP) in astroglial cells. Activation of human astroglial cell line, U373 with IL‐1β, led to the induction of C3 mRNA and protein expression as determined by real‐time RT‐PCR and Western blot analysis, respectively. This induction was suppressed by the pharmacological inhibitor of p38 MAPK (i.e., SB202190‐HCl), suggesting the involvement of p38 MAPK in C3 gene expression. IL‐1β also induced C3 promoter activity in U373 cells in a MAP kinase‐ and C/EBP‐β‐dependent manner. Cotransfection of C3 luciferase reporter construct with constitutively active form of the upstream kinase in the MAP kinase cascade, that is, MKK6 (the immediate upstream activator of p38 kinase) resulted in marked stimulation of the promoter activity, whereas overexpression of a dominant negative forms of MKK6 and p38α MAPK inhibited C3 promoter activity. Furthermore, a mutant form of C/EBP‐β, LAPT235A showed reduction in IL‐1β‐mediated C3 promoter activation. These results suggest that the p38α, MAPK, and MKK6 play prominent roles in IL‐1β and C/EBP‐β‐mediated C3 gene expression in astrocytes. J. Cell. Biochem. 112: 1168–1175, 2011. © 2011 Wiley‐Liss, Inc.
Web servers and services for electrostatics calculations with APBS and PDB2PQR
Authors: Unni Samir , Huang Yong , Hanson Robert M. , Tobias Malcolm , Krishnan Sriram , Li Wilfred W. , Nielsen Jens E. , Baker Nathan A. 
Published: February 2011

AbstractAPBS and PDB2PQR are widely utilized free software packages for biomolecular electrostatics calculations. Using the Opal toolkit, we have developed a Web services framework for these software packages that enables the use of APBS and PDB2PQR by users who do not have local access to the necessary amount of computational capabilities. This not only increases accessibility of the software to a wider range of scientists, educators, and students but also increases the availability of electrostatics calculations on portable computing platforms. Users can access this new functionality in two ways. First, an Opal‐enabled version of APBS is provided in current distributions, available freely on the web. Second, we have extended the PDB2PQR web server to provide an interface for the setup, execution, and visualization of electrostatic potentials as calculated by APBS. This web interface also uses the Opal framework which ensures the scalability needed to support the large APBS user community. Both of these resources are available from the APBS/PDB2PQR website: http://www.poissonboltzmann.org/. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Consideration of data load time on modern processors for the Verlet table and linked‐cell algorithms
Authors: Fomin Eduard S. 
Published: February 2011

AbstractNeighbor search algorithms are widely used in molecular dynamics for the direct computation of short‐range pairwise interatomic potentials. These algorithms are based on the Verlet table (VT) and linked‐cell (LC) methods. It is widely believed that the VT is more efficient than the LC. The analysis of these methods shows that in case when the average number of interactions per particle is relatively large, or more specifically, the particle density ρ and skin radius rskin meet the condition (4π/6) ρr/27 ≫ 1, which may be true for most simulations of liquids, the number of memory data load operations in the LC is much less than that in the VT. Because memory access on modern processors is a bottleneck, this advantage of the LC should be and was in fact used, and a code outperforming the VT by a factor of almost 2 was obtained. Some modifications of the VT were proposed to reduce its disadvantage concerning memory data loading. The key modifications included automated skin radius tuning during simulations and compression of the VT to minimize duplications of atom identifiers in its nearby rows. Although these modifications had improved the performance, the VT failed to regain the superiority over the LC. The methods were tested in the MOLKERN simulation software by using SIMD and multithreading. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Bringing about matrix sparsity in linear‐scaling electronic structure calculations
Authors: Rubensson Emanuel H. , Rudberg Elias 
Published: February 2011

AbstractThe performance of linear‐scaling electronic structure calculations depends critically on matrix sparsity. This article gives an overview of different strategies for removal of small matrix elements, with emphasis on schemes that allow for rigorous control of errors. In particular, a novel scheme is proposed that has significantly smaller computational overhead compared with the Euclidean norm‐based truncation scheme of Rubensson et al. (J Comput Chem 2009, 30, 974) while still achieving the desired asymptotic behavior required for linear scaling. Small matrix elements are removed while ensuring that the Euclidean norm of the error matrix stays below a desired value, so that the resulting error in the occupied subspace can be controlled. The efficiency of the new scheme is investigated in benchmark calculations for water clusters including up to 6523 water molecules. Furthermore, the foundation of matrix sparsity is investigated. This includes a study of the decay of matrix element magnitude with distance between basis function centers for different molecular systems and different methods. The studied methods include Hartree–Fock and density functional theory using both pure and hybrid functionals. The relation between band gap and decay properties of the density matrix is also discussed. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Sensitivity analysis and uncertainty calculation for dispersion corrected density functional theory
Authors: Hanke Felix 
Published: February 2011

AbstractThe precision of binding energies and distances computed with dispersion‐corrected density functional theory (DFT‐D) is investigated by propagation of uncertainties, yielding relative uncertainties of several percent. Sensitivity analysis is used to calculate the geometry‐dependent relative importance of each input parameter for the dispersion correction. While DFT‐Ds are exact at asymptotically large distances, their damping functions are shown to play a significant role in binding geometries. This is demonstrated in detail for the interlayer binding of graphite. The techniques presented allow practitioners to quickly compute error bars and to get an a posteriori estimate about the transferability of their results. They can also aid the development of future dispersion corrections. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011