bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulating curvilinear crack propagation in two dimensions with universal meshes
Authors: Rangarajan Ramsharan , Chiaramonte Maurizio M. , Hunsweck Michael J. , Shen Yongxing , Lew Adrian J. 
Published: August 2014

SummaryWe formulate a class of delicately controlled problems to model the kink‐free evolution of quasistatic cracks in brittle, isotropic, linearly elastic materials in two dimensions. The evolving crack satisfies familiar principles—Griffith's criterion, local symmetry, and irreversibility. A novel feature of the formulation is that in addition to the crack path, the loading is also treated as an unknown. Specifically, a scaling factor for prescribed Dirichlet and Neumann boundary conditions is computed as part of the solution to yield an always‐propagating and ostensibly kink‐free crack and a continuous loading history beyond the initial step. A dimensionless statement of the problem depends only on the Poisson's ratio of a homogeneous material, and is in particular, independent of its Young's modulus and fracture toughness.Numerical resolution of the formulated problem relies on two new ideas. The first is an algorithm to compute triangulations conforming to cracked domains by locally deforming a given background mesh in the vicinity of evolving cracks. The algorithm is robust under mild assumptions on the sizes and angles of triangles near the crack and its smoothness. Hence, a subset, if not the entire family, of cracked domains realized during the course of a simulation can be discretized with the same background mesh; we term the latter a universal mesh for such a family of domains. Universal meshes facilitate adopting a discrete representation for the crack (as splines in our examples), preclude the need for local splitting/retriangulation operations, liberate the crack from following directions prescribed by the mesh, and enable the adoption of standard FEMs to compute the elastic fields in the cracked solid. Second, we employ a method specifically designed to approximate the stress intensity factors for curvilinear cracks. We examine the performance of the resulting numerical method with detailed examples, including comparisons with an exact solution of a crack propagating along a circular arc (which we construct) and comparisons with experimental fracture paths. In all cases, we observe convergence of computed paths, their derivatives, and loading histories with refinement of the universal mesh. Copyright © 2014 John Wiley & Sons, Ltd.
End‐of‐life care in pediatric neuro‐oncology
Authors: Vallero Stefano Gabriele , Lijoi Stefano , Bertin Daniele , Pittana Laura Stefania , Bellini Simona , Rossi Francesca , Peretta Paola , Basso Maria Eleonora , Fagioli Franca 
Published: August 2014

BackgroundThe management of children with cancer during the end‐of‐life (EOL) period is often difficult and requires skilled medical professionals. Patients with tumors of the central nervous system (CNS) with relapse or disease progression might have additional needs because of the presence of unique issues, such as neurological impairment and altered consciousness. Very few reports specifically concerning the EOL period in pediatric neuro‐oncology are available.ProcedureAmong all patients followed at our center during the EOL, we retrospectively analyzed data from 39 children and adolescents with brain tumors, in order to point out on their peculiar needs.ResultsPatients were followed‐up for a median time of 20.1 months. Eighty‐two percent were receiving only palliative therapy before death. Almost half the patients (44%) died at home, while 56% died in a hospital. Palliative sedation with midazolam was performed in 58% of cases; morphine was administered in 51.6% of cases. No patient had uncontrolled pain.ConclusionsThe EOL in children with advanced CNS cancer is a period of active medical care. Patients may develop complex neurological symptoms and often require long hospitalization. We organized a network‐based collaboration among the reference pediatric oncology center, other pediatric hospitals and domiciliary care personnel, with the aim to ameliorate the quality of care during the EOL period. In our cohort, palliative sedation was widely used while no patients died with uncontrolled pain. A precise process of data collection and a better sharing of knowledge are necessary in order to improve the management of such patients. Pediatr Blood Cancer 2014;61:2004–2011. © 2014 Wiley Periodicals, Inc.
Geography and the burden of care in pediatric cancers
Authors: Fluchel Mark N. , Kirchhoff Anne C. , Bodson Julia , Sweeney Carol , Edwards Sandra L. , Ding Qian , Stoddard Gregory J. , Kinney Anita Y. 
Published: August 2014

AbstractBackgroundChildhood cancers typically require rigorous treatment at specialized centers in urban areas, which can create substantial challenges for families residing in remote communities. We evaluated the impact of residence and travel time on the burden of care for families of childhood cancer patients.ProcedureWe conducted a cross‐sectional, self‐administered survey of 354 caregivers of pediatric cancer patients at a children's hospital serving a seven state area. Measures included the impact of cancer treatment on relocation, employment, schooling, and finances. We evaluated these domains by rural/urban residence and travel time (>1 hour and >2 hours) to the hospital in multivariable regression models.ResultsOf the 29% of caregivers who reported moving residences as their child was diagnosed, 33% reported that the move was due to their child's cancer. Rural and remote (e.g., >1 hour travel time) caregivers missed more days of work during the first month after diagnosis than did urban and local caregivers, however, these differences did not persist over the first 6 months of therapy. One‐third of caregivers reported quitting or changing jobs as a direct result of their child being diagnosed with cancer. Rural respondents had greater out‐of‐pocket travel expenses and reported a significantly greater perceived financial burden. Rural patients missed more school days and were at an increased risk of having to repeat a grade.ConclusionsChildhood cancer has an appreciable impact on the lives of patients and caregivers. The burden is greater for those living far from a treatment center. Pediatr Blood Cancer 2014;61:1918–1924. © 2014 Wiley Periodicals, Inc.
Initial solid tumor testing (Stage 1) of AZD1480, an inhibitor of Janus kinases 1 and 2 by the pediatric preclinical testing program
Authors: Houghton Peter J. , Kurmasheva Raushan T. , Lyalin Dmitry , Maris John M. , Kolb E. Anders , Gorlick Richard , Reynolds C. Patrick , Kang Min H. , Keir Stephen T. , Wu Jianrong , Smith Malcolm A. 
Published: August 2014

BackgroundAZD1480 is an ATP competitive inhibitor of Janus kinases 1 and 2 (JAK1, 2) that has been shown to inhibit the growth of solid tumor models. This agent was selected for testing the putative role of JAK/STAT signaling in the standard PPTP solid tumor models.ProceduresAZD1480 was tested against the PPTP in vitro cell line panel at concentrations from 1.0 nM to 10 μM and against the PPTP in vivo solid tumor xenograft panels at (60 mg/kg once daily (SID) × 5) for three consecutive weeks. Additional studies evaluated 5 to 20 mg/kg BID × 5 with SID dosing at 7–30 mg/kg at weekends for three consecutive weeks.ResultsIn vitro the median relative IC50 (rIC50) for the PPTP cell lines was 1.5 µM, with a range from 0.3 µM to 5.9 µM. The two cell lines with rIC50 values of 0.3 µM both had ALK activating genomic alterations. AZD1480 demonstrated statistically significant differences (P < 0.05) in EFS distribution compared to control in 89% of the solid tumor xenografts. AZD1480 induced intermediate (EFS T/C > 2) or high‐level growth inhibition in 15 of 30 (50%) solid tumor xenografts. Tumor regressions were observed in three of six Wilms tumor models at doses that induced inhibition of Stat3(Y705) phosphorylation.ConclusionsAZD1480 demonstrated significant tumor growth inhibition against most PPTP solid tumor xenografts, similar to that observed for antiangiogenic agents tested by the PPTP. Tumor regressing activity was noted for Wilms tumor xenografts. Pediatr Blood Cancer 2014;61:1972–1979. © 2014 Wiley Periodicals, Inc.
Abnormalities in renal tubular phosphate handling in children with sickle cell disease
Authors: Raj Vimal Master Sankar , Freundlich Michael , Hamideh Dima , Alvarez Ofelia , Seeherunvong Wacharee , Abitbol Carolyn , Katsoufis Chryso , Chandar Jayanthi , Ruiz Phillip , Zilleruelo Gaston 
Published: August 2014

BackgroundThe mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients.MethodsRenal tubular phosphate handling and circulating levels of various analytes including FGF23 and parathyroid hormone (PTH) were measured in 24 children with SCD and normal estimated GFR in a cross sectional study. Correlation and regression analysis were employed to derive relationships between serum phosphorus and several variables.ResultsMost children showed elevated age‐ adjusted serum phosphorus (5.1 ± 0.7 mg/dl) levels. Tubular re‐absorption of phosphorus(TRP) (96.3 ± 2.1%) and tubular maximum re‐absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9 ± 0.6 mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81 ± 38 pg/ml) while the average PTH values were normal in most patients (50 ± 27 pg/ml). Univariate analysis showed significant correlations of serum phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH), and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r = 0.5, P< or = 0.01) but not with PTH. Multiple regression analysis yielded an independent relationship of serum phosphorus with TMP/GFR.ConclusionThe elevated serum phosphorus concentrations with simultaneously increased TMP/GFR and elevated FGF23 levels collectively suggest that patients with SCD display proximal tubular resistance to the action of FGF23 before any decline in GFR. Pediatr Blood Cancer 2014;61:2267–2270. © 2014 Wiley Periodicals, Inc.
Extraordinarily large swelling energy of iodine‐treated poly(vinyl alcohol) demonstrated by jump of a film
Authors: Takamura Tatsuro , Nozawa Kazuya , Sugimoto Yoshiki , Shioya Masatoshi 
Published: August 2014

ABSTRACTOrganic material characteristics of volume change and stress generation have attracted the attention of many researchers aiming to develop chemomechanical systems such as artificial muscles and polymer engines having the advantages of high energy density and silent operation. Although polymer gels offer a relatively large actuator stroke, their mechanical properties are relatively poor and the working temperature is relatively low, often limited by the evaporation of liquid if contained. We have developed an iodine‐treated poly(vinyl alcohol) having extraordinarily large vapor‐induced deswelling stress reaching 59 MPa, which is one to two orders of magnitude greater than those of ordinary polymer gels. Furthermore, this material has extremely large volumetric and gravimetric energy densities reaching 1.3 × 106 J m−3 and 9.6 × 102 J kg−1, respectively, and an elastic modulus of a few GPa and is heat‐resistant to at least 200 °C. The high performance of this material can be demonstrated by a jump of a film. © 2014 The Authors. Journal of Polymer Science Part B: Polymer Physics published by Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 1357–1365
High risk of adult asthma following severe wheezing in early life
Authors: Goksör Emma , Åmark Mainor , Alm Bernt , Ekerljung Linda , Lundbäck Bo , Wennergren Göran 
Published: August 2014

SummaryBackground: Severe wheezing in early life is associated with an increased risk of asthma during childhood and adolescence. The aim of the present follow‐up was to investigate the asthma prevalence and risk factors for asthma in adulthood. Methods: We have prospectively studied asthma development in 101 children hospitalized due to severe wheezing before the age of 24 months. The cohort was re‐investigated at a mean age of 27 years and tested for bronchial hyper‐responsiveness and allergic sensitization. The response rate in adulthood was 81% (82/101). The results were compared with a population‐based, age‐matched control group (n = 1,210) recruited from the West Sweden Asthma Study. Results: Current doctor‐diagnosed asthma was found in 37% (30/82) compared with 7% (82/1,210) in the control group. The risk of adult asthma in the cohort compared with the control group was increased 10‐fold (adjusted OR 10.0, 95% CI 5.3–18.7), independently of allergic rhinitis, gender, smoking and heredity. Within the cohort, current allergy (aOR 9.6, 95% CI 3.0–31.2) and female gender (aOR 3.2, 95% CI 1.1–9.3) independently increased the risk of adult asthma. Females with current allergy had the highest risk of adult asthma (OR 29.4, 95% CI 5.0–173.3), compared with males without allergy. When separately adjusting for factors present at admission in early life within the cohort, a family history of asthma was a significant risk factor for asthma in adulthood (aOR 4.0, 95% CI 1.3–12.5). Conclusion: Subjects with severe early wheezing have a 10‐fold increase in the risk of adult asthma compared to an age‐matched control group, adjusted for allergic rhinitis, gender, smoking and heredity. Pediatr Pulmonol. 2015; 50:789–797. © 2014 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.
Dual effects of familial Alzheimer's disease mutations (D7H, D7N, and H6R) on amyloid β peptide: Correlation dynamics and zinc binding
Authors: Xu Liang , Chen Yonggang , Wang Xiaojuan 
Published: August 2014

ABSTRACTAlthough the N‐terminal region of Amyloid β (Aβ) peptides plays dual roles as metal‐coordinating sites and conformational modulator, few studies have been performed to explore the effects of mutations at this region on the overall conformational ensemble of Aβ and the binding propensity of metal ions. In this work, we focus on how three familial Alzheimer's disease mutations (D7H, D7N, and H6R) alter the structural characteristics and thermodynamic stabilities of Aβ42 using molecular dynamics simulations. We observe that each mutation displays increased β‐sheet structures in both N and C termini. In particular, both the N terminus and central hydrophobic region of D7H can form stable β‐hairpin structures with its C terminus. The conserved turn structure at Val24–Lys28 in all peptides and Zn2+‐bound Aβ42 is confirmed as the common structural motif to nucleate folding of Aβ. Each mutant can significantly increase the solvation free energy and thus enhance the aggregation of Aβ monomers. The correlation dynamics between Aβ(1–16) and Aβ(17–42) fragments are elucidated by linking the domain motions with the corresponding structured conformations. We characterize the different populations of correlated domain motions for each mutant from a more macroscopic perspective, and unexpectedly find that Zn2+‐bound Aβ42 ensemble shares the same populations as Aβ42, indicating that the binding of Zn2+ to Aβ follows the conformational selection mechanism, and thus is independent of domain motions, even though the structures of Aβ have been modified at a residue level. Proteins 2014; 82:3286–3297. © 2014 Wiley Periodicals, Inc.
Reversing cancer multidrug resistance: insights into the efflux by ABC transports from in silico studies
Authors: Ferreira Ricardo J. , Ferreira Maria‐José U. , dos Santos Daniel J. V. A. 
Published: August 2014

One of the greatest threats to cancer treatment is the development, by some tumors, of resistance to the pharmacological action of several structurally unrelated cytotoxic agents—multidrug resistance (MDR). As P‐glycoprotein (P‐gp) is one of the most studied ATP‐dependent efflux pumps that are frequently involved in drug efflux from cancer cells, the development of MDR modulators with the ability to inhibit P‐gp efflux is considered a promising approach for overcoming MDR. However, the development of P‐gp modulators have been hampered due to the absence of knowledge on the intrinsic molecular aspects by which efflux occurs, namely the specific steps that correlates drug recognition, ATP binding and efflux‐related conformational changes. Experimental evidences for these processes are also difficult to obtain and only provide small pieces of information that need to be assembled for better comprehension of a wider and complex process that is drug efflux. A promising alternative relies on cutting‐edge computational techniques to provide new insights on key aspects that are determinant to understand how P‐gp efflux can be effectively reversed. With the contribution of ligand‐based or structure‐based computational methods, P‐gp drug efflux is slowly becoming a dynamic and reactive process rather than a simple response to drug binding, with the complex architecture of ABC transporters playing a determinant role not only in drug recognition but in the coordination of ATP‐driven conformational changes that ultimately drives drug efflux. The major enlightenments that computational studies provided toward a better comprehension of MDR and P‐gp efflux phenomena are hereby described. WIREs Comput Mol Sci 2015, 5:27–55. doi: 10.1002/wcms.1196This article is categorized under:

Structure and Mechanism > Computational Biochemistry and Biophysics
Effects of sea surface temperature accuracy on offshore wind resource assessment using a mesoscale model
Authors: Shimada Susumu , Ohsawa Teruo , Kogaki Tetsuya , Steinfeld Gerald , Heinemann Detlev 
Published: August 2014

AbstractOffshore wind simulations were performed with the Weather Research and Forecasting (WRF) model driven by three different sea surface temperature (SST) datasets for Japanese coastal waters to investigate the effect of the SST accuracies on offshore wind simulations. First, the National Centers for Environmental Prediction Final analysis (FNL) (1° × 1° grid resolution) and the Operational Sea Surface Temperature and Sea Ice Analysis (OSTIA) (0.05° × 0.05° grid resolution) datasets were compared with in situ measurements. The results show a decrease in accuracy of these datasets toward the coast from the open ocean. Aiming at an improved accuracy of SST data, we developed a new high‐resolution SST dataset (0.02° × 0.02° grid resolution). The new dataset referred to as MOSST is based on the Moderate Resolution Imaging Spectroradiometer (MODIS) product, provided by the Japan Aerospace Exploration Agency (JAXA). MOSST was confirmed to be more accurate than FNL and OSTIA for the coastal waters. Then, WRF simulations were carried out for 1 year with a 2 km grid resolution and by using the FNL, OSTIA and MOSST datasets. The use of the OSTIA dataset for a WRF simulation was found to improve the accuracy when compared with the FNL dataset, and further improvement was obtained when the MOSST dataset was applied. The sensitivity of wind speed and wind energy density to SST is also discussed. We conclude that the use of an accurate SST is a key factor not only for realistic offshore wind simulations near the surface but also for accurate wind resource assessments at the hub height of wind turbines. Copyright © 2014 John Wiley & Sons, Ltd.
Model of wind shear conditional on turbulence and its impact on wind turbine loads
Authors: Dimitrov Nikolay , Natarajan Anand , Kelly Mark 
Published: August 2014

AbstractWe analyse high‐frequency wind velocity measurements from two test stations over a period of several years and at heights ranging from 60 to 200 m, with the objective to validate wind shear predictions as used in load simulations for wind turbine design. A validated wind shear model is thereby proposed for flat terrain and that can significantly decrease the uncertainty associated with fatigue load predictions for wind turbines with large rotors. An essential contribution is the conditioning of wind shear on the 90% quantile of wind turbulence, such that the appropriate magnitude of the design fatigue load is achieved. The proposed wind shear model based on the wind measurements is thereby probabilistic in definition, with shear jointly distributed with wind turbulence. A simplified model for the wind shear exponent is further derived from the full stochastic model. The fatigue loads over different turbine components are evaluated under the full wind measurements, using the developed wind shear model and with standard wind conditions prescribed in the IEC 61400‐1 ed. 3. The results display the effect of the Wöhler exponent and reveal that under moderate turbulence, the effect of wind shear is most pronounced on the blade flap loads. It is further shown that under moderate wind turbulence, the wind shear exponents may be over‐specified in the design standards, and a reduction of wind shear exponent based on the present measurements can contribute to reduced fatigue damage equivalent loads on turbine blades. Although the influence of wind shear on extreme loads was found to be negligible, the IEC 61400‐1 wind shear definition was found to result in non‐conservative estimates of the 50 year extreme blade deflection toward the tower, especially under extreme turbulence conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Syntheses, Crystal Structures, and Fluorescence Properties of Two Transition Metal‐Organic Coordination Polymers Based on 4,4′‐Dimethyl‐2,2′‐bipyridine
Authors: Shan Yuexia , Chen Qin , Wang Lei , Zhang Wenli , Ni Liang 
Published: August 2014

AbstractTwo transition metal‐organic coordination polymers, [Mn2(1,3‐bdc)2(Me2bpy)2]·Me2bpy (1) and [Co(4,4′‐oba)(Me2bpy)] (2) were hydrothermally synthesized and structurally characterized by elemental analysis, IR spectroscopy, TG, and single‐crystal X‐ray diffraction [1,3‐H2bdc = benzene‐1,3‐dicarboxylic acid, H2oba = 4,4′‐oxybis(benzoic acid) Me2bpy = 4,4′‐dimethyl‐2,2′‐bipyridine]. Compound 1 crystallizes in the orthorhombic system, space group P212121, with a = 23.371(5), b = 14.419(3), and c = 14.251(3) Å. Compound 2 crystallizes in the monoclinic system, space group P21/c, with a = 7.4863(15), b = 18.272(4), c = 16.953(5) Å, and β = 107.44(3)°. The crystal structure of complex 1 is a wave‐like layer with central Mn2+ atoms bridged by 1,3‐bdc ligands, whereas the structure of compound 2 presents a ladder chain of hexacoordinate Co2+ atoms, in which the metal atoms are bridged by 4,4′‐oba ligands and decorated by Me2bpy ligands. The two compounds are further extended into 3D supramolecular structures through π–π stacking interactions. Additionally, the compounds show intense fluorescence in solid state at room temperature.