bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial testing of the investigational NEDD8‐activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program
Authors: Smith Malcolm A. , Maris John M. , Gorlick Richard , Kolb E. Anders , Lock Richard , Carol Hernan , Keir Stephen T. , Reynolds C. Patrick , Kang Min H. , Morton Christopher L. , Wu Jianrong , Smith Peter G. , Yu Jie , Houghton Peter J. 
Published: October 2011

AbstractBackgroundMLN4924 is an investigational first‐in‐class small molecule inhibitor of NEDD8‐activating enzyme (NAE). NAE is an essential component of the NEDD8 conjugation pathway, controlling the activity of a subset of ubiquitin‐proteasome system (UPS) E3 ligases, multiprotein complexes that transfer ubiquitin molecules to substrate proteins.ProceduresMLN4924 was tested against the PPTP in vitro panel using 96‐hour exposure time at concentrations ranging from 1.0 nM to 10 µM. It was tested in vivo at a dose of 100 mg/kg [66 mg/kg for the acute lymphoblastic leukemia (ALL) xenografts] administered orally twice daily × 5 days. Treatment duration was 3 weeks.ResultsThe median relative IC50 for MLN4924 against the PPTP cell lines was 143 nM, (range: 15–678 nM) with that for the Ewing panel being significantly lower (31 nM). MLN4924 induced significant differences in EFS distribution compared to control in 20 of 34 (59%) evaluable solid tumor xenografts. MLN4924 induced intermediate activity (EFS T/C values >2) in 9 of the 33 evaluable xenografts (27%), including 4 of 4 glioblastoma xenografts, 2 of 3 Wilm's tumor xenografts, 2 of 5 rhabdomyosarcoma xenografts, and 1 of 4 neuroblastoma xenografts. For the ALL panel, 5 of 8 evaluable xenografts showed intermediate activity for the EFS T/C measure. MLN4924 did not induce objective responses in the PPTP solid tumor or ALL panels.ConclusionsMLN4924 showed potent activity in vitro and in vivo showed tumor growth inhibitory activity against a subset of the PPTP solid tumor and ALL xenografts. Pediatr Blood Cancer 2012;59:246–253. © 2011 Wiley Periodicals, Inc.
Bleeding disorders in Noonan syndrome
Authors: Briggs Benjamin J. , Dickerman Joseph D. 
Published: October 2011

AbstractNoonan Syndrome (NS) is a common genetic disease with multiple organ defects including bleeding disorders, which was last reviewed in 1997. Since then significant information has been acquired regarding bleeding problems in NS, specifically on the underlying genetics. Associations between mutated genes and bleeding disorders are reviewed along with prevalence and underlying etiologies. Between 50–89% of NS patients will have a bleeding disorder and since a significant number will require surgery it is important to identify which ones are at risk prior to their procedure. Recommendations regarding screening for bleeding disorders and their treatment are discussed. Pediatr Blood Cancer 2012; 58: 167–172. © 2011 Wiley Periodicals, Inc.
Physical and mental health status and health behaviors of childhood cancer survivors: Findings from the 2009 BRFSS survey
Authors: Phillips‐Salimi Celeste R. , Lommel Karen , Andrykowski Michael A. 
Published: October 2011

AbstractBackgroundThe growing number of childhood cancer survivors makes examination of their current physical and mental health status and health behaviors an important concern. Much of what is known about the long‐term outcomes of childhood cancer survivors comes from the Childhood Cancer Cohort Study (CCSS) which uses sibling controls.ProcedureUsing data from the 2009 Behavioral Risk Factor Surveillance System survey, 651 childhood cancer survivors and 142,932 non‐cancer peer controls were identified. The two groups were compared on a variety of physical and mental health status and health behavior variables using ANCOVA and binary logistic regression.ResultsWhile controlling for differences in age, sex, and minority status, survivors significantly (P ≤ 0.001) had poorer socioeconomic outcomes, more comorbid conditions, lower life satisfaction, less social and emotional support, poorer general health, and reported more days per month of poor physical and mental health than non‐cancer individuals. Survivors were more likely to report being a current smoker [odds ratio (OR) = 2.33; 95% confidence interval (CI), 1.98–2.73; P < 0.001]; tested for human immunodeficiency virus (HIV) (OR = 1.79; 95% CI, 1.52–2.11; P < 0.001); and that at least one HIV situation applied to them (OR = 2.06; 95% CI, 1.55–2.74; P < 0.001). No significant differences were found between groups in regards alcohol use and diet.ConclusionsResults support and extend previous findings reported by the CCSS. New findings regarding survivors' increased likelihood to engage in risky behaviors proposes new directions for future research. Pediatr Blood Cancer 2012; 58: 964–970. © 2011 Wiley Periodicals, Inc.
The use of plerixafor in harvesting autologous stem cells in the pediatric setting
Authors: Vettenranta Kim , Möttönen Merja , Riikonen Pekka 
Published: October 2011

AbstractThe mobilization of stem cells using the standard approach, chemotherapy and G‐CSF, may not be successful in all cases heavily pretreated. Plerixafor (AMD3100) has emerged as a viable option in attempts to mobilize stem cells among these patients. The use of plerixafor in the adult setting has been established, but data on pediatric use is scarce. We report on the use of plerixafor in eight pediatric cases either as add‐on to chemotherapy plus G‐CSF or in remobilization. Pediatr Blood Cancer 2012; 59: 197–198. © 2011 Wiley Periodicals, Inc.
Genotoxicity associated with hydroxyurea exposure in infants with sickle cell anemia: Results from the BABY‐HUG phase III clinical trial
Authors: McGann Patrick T. , Flanagan Jonathan M. , Howard Thad A. , Dertinger Stephen D. , He Jin , Kulharya Anita S. , Thompson Bruce W. , Ware Russell E. ,   for the BABY HUG Investigators
Published: October 2011

AbstractBackgroundThe laboratory and clinical benefits of hydroxyurea therapy for children with sickle cell anemia (SCA) are well recognized, but treatment in young patients is limited in part by concerns about long‐term genotoxicity, and specifically possible carcinogenicity.ProcedureThe Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) was a multicenter double‐blinded placebo‐controlled randomized clinical trial (NCT00006400) testing whether hydroxyurea could prevent chronic organ damage in very young patients with SCA. An important secondary objective was the measurement of acquired genotoxicity using three laboratory assays: chromosomal karyotype, illegitimate VDJ recombination events, and micronucleated reticulocyte formation.ResultsOur data indicate that hydroxyurea treatment was not associated with any significant increases in genotoxicity compared to placebo treatment.ConclusionsThese data provide additional support to the safety profile of hydroxyurea for young patients with SCA, and suggest that genotoxicity in this patient population is low. Pediatr Blood Cancer 2012;59:254–257. © 2011 Wiley Periodicals, Inc.
Effect of carbon black structure on low‐strain conductivity of polypropylene and low‐density polyethylene composites
Authors: Fathi Atefeh , Hatami Kianoosh , Grady Brian P. 
Published: October 2011

AbstractThe influences of carbon black (CB) structure on the percolation threshold, mechanical properties, and strain‐resistivity response of polymer composites are studied. Low‐density polyethylene (LDPE) and polypropylene (PP) samples were blended with five different types of CB differing in structure. Relatively low strains were studied; the maximum strain was 10%. It was found that the CB concentration for maximum strain‐sensitivity of the electrical conductivity is higher for low structure carbon blacks but is essentially independent of the CB structure for medium‐ to high‐structure carbon blacks. However, the composite containing the largest particle size carbon black clearly showed the highest strain‐sensitivity to electrical conduction. The mechanical properties and sensitivity of electrical resistivity to tensile strain of the filled composites examined in the study are also presented and discussed. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
Transparent thermoplastic resin with electron beam cross‐linking
Authors: Sano Tomomi , Nakabayashi Makoto , Ito Hiroshi 
Published: October 2011

AbstractThe mechanical, thermal and optical properties of a transparent thermoplastic resin which is based on non‐crystalline nylon with cross‐linking agents were improved by electron beam (EB) irradiation cross‐linking. When the EB irradiation power was increased, the yield stress improved by 34% and the glass transformation temperature increased from 116 to 165°C. Transformation from the brittle to the ductile state was observed by the dependence of a strange elastic module on the temperature and EB irradiation power. Above the glass transformation temperature, an optical element produced using this resin could maintain its shape. The birefringence decreased when the EB irradiation power was increased. The decrease of the birefringence was dependent on the initial birefringence value before EB cross‐linking. The molecular orientation was relaxed by EB cross‐linking. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
Velocity measurements on a polypropylene melt during extrusion through a flat coat‐hanger die
Authors: Grieß Hans Jürgen , Burghelea Teodor I. , Münstedt Helmut 
Published: October 2011

AbstractAn experimental investigation of various flow regimes observed during the extrusion of a polypropylene melt through a flat coat‐hanger die by laser‐Doppler velocimetry (LDV) is presented. LDV measurements of the velocity profiles across the gap of the die at various locations along the die reveal three different extrusion regimes. At small wall shear stresses, the velocity profiles can be fitted by symmetrical curves with the velocities becoming zero at the die walls. These profiles are not uniformly distributed along the die. An increase of the wall shear stress reveals a second flow regime characterized by a uniform distribution of the velocity profiles along the die. As the wall shear stress is increased even further, a third flow regime characterized by wall slip on the glass windows is observed. This flow regime is systematically characterized by measurements of the slip velocities at various temperatures and throughputs. The maximum velocities along the die are taken to assess the uniformity of flow which decisively influences the thickness of the extruded film. By measuring velocity profiles, at different throughput, and temperatures, the conditions for constant velocities along the die were determined. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
Melt grafting of maleic anhydride onto polypropylene with assistance of α‐methylstyrene
Authors: Luo Weihua , Liu Xingxing , Fu Yujuan 
Published: October 2011

AbstractMelt grafting of maleic anhydride (MA) and α‐methylstyrene (AMS) onto polypropylene (PP) was performed by reactive extrusion. Effects of AMS on the graft degree of MA, crystallization behavior, and thermal properties of the graft copolymer were investigated. Results show that the addition of AMS as a comonomer can efficiently improve the MA graft degree. When the molar ratio of AMS to MA is 0.9:1, the maximum MA graft degree is attained, which increases about 56% compared with that using single monomer of MA. The results of the graft degree of MA obtained by chemical titration (CT) agree well with those obtained by Fourier transform infrared spectroscopy (FTIR). Melt flow rate (MFR) measurements indicate that the addition of AMS effectively reduces the degradation of PP molecules. The wide‐angle X‐ray diffraction (WAXD) results show that in comparison with the PP‐g‐MA sample, the PP‐g‐(MA‐AMS) sample shows no new crystalline form, but has a slight decrease in the average crystalline domain size. According to the results of thermogravimetry (TG) and differential scanning calorimetry (DSC), the graft PP in the presence of AMS exhibits a lower melting point and a higher crystallization temperature and thermal stability in comparison with that without AMS. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Effects of phosphate and polysiloxane on flame retardancy and impact toughening behavior of poly(2,6‐dimethyl‐1,4‐phenylene oxide)
Authors: Lin Shiwen , Sun Shuangyue , He Yadong , Wang Xiaodong , Wu Dezhen 
Published: October 2011

AbstractPoly(2,6‐dimethyl‐1,4‐phenylene oxide) (PPO)‐based compounds containing resorcinol bis(diphenyl phosphate) (RDP) and poly(dimethyl‐diphenyl siloxane) (PDMDPS) were prepared through melt extrusion, and their flammability characteristics and mechanical properties were evaluated. The incorporation of RDP enhanced the flame retardancy of PPO compounds, but hardly made them obtain the UL 94 V‐0 rating unless RDP and PDMDPS were combined. Studies on the residual chars after vertical burning test suggested that the excellent flame retardancy be correlated with the retention from the combination effects of silica and phosphate in the char, whose cross‐linked silica enhanced the formation of a compact char to retard combustion. Thermogravimetric analysis indicated that the presence of PDMDPS and RDP improved the char yielding as well as the decomposition temperature of PPO compounds. Moreover, the Izod impact strength was improved significantly in the presence of RDP and PDMDPS, and this toughening effect was attributed to the deformation and multiple cracks induced by PDMDPS, which enhances the impact energy absorption of the matrix. This work provides a very effective flame retarding formulation for PPO compounds with improved impact toughness. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers
The ErbB4 extracellular region retains a tethered‐like conformation in the absence of the tether
Authors: Liu Ping , Bouyain Samuel , Eigenbrot Charles , Leahy Daniel J. 
Published: October 2011

AbstractThe epidermal growth factor receptor (EGFR) and its homologs ErbB3 and ErbB4 adopt a tethered conformation in the absence of ligand in which an extended hairpin loop from domain II contacts the juxtamembrane region of domain IV and tethers the domain I/II pair to the domain III/IV pair. By burying the hairpin loop, which is required for formation of active receptor dimers, the tether contact was thought to prevent constitutive activation of EGFR and its homologs. Amino‐acid substitutions at key sites within the tether contact region fail to result in constitutively active receptors however. We report here the 2.5 Å crystal structure of the N‐terminal three extracellular domains of ErbB4, which bind ligand but lack domain IV and thus the tether contact. This ErbB4 fragment nonetheless adopts a domain arrangement very similar to the arrangement adopted in the presence of the tether suggesting that regions in addition to the tether contribute to maintaining this conformation and inactivity in the absence of the tether contact. We suggest that the tether conformation may have evolved to prevent crosstalk between different EGFR homologs and thus allow diversification of EGFR and its homologs.
Temperature‐dependent study reveals that dynamics of hydrophobic residues plays an important functional role in the mitochondrial Tim9–Tim10 complex
Authors: Ivanova Ekaterina , Pang Jiayun , Jowitt Thomas A. , Yan Guanhua , Warwicker Jim , Sutcliffe Michael J. , Lu Hui 
Published: October 2011

AbstractProtein–protein interaction is a fundamental process in all major biological processes. The hexameric Tim9–Tim10 (translocase of inner membrane) complex of the mitochondrial intermembrane space plays an essential chaperone‐like role during import of mitochondrial membrane proteins. However, little is known about the functional mechanism of the complex because the interaction is weak and transient. This study investigates how electrostatic and hydrophobic interactions affect the conformation and function of the complex at physiological temperatures, using both experimental and computational methods. The results suggest that, first, different complex conformational states exist at equilibrium, and the major difference between these states is the degree of hydrophobic interactions. Second, the conformational change mimics the biological activity of the complex as measured by substrate binding at the same temperatures. Finally, molecular dynamics simulation and detailed energy decomposition analysis provided supporting evidence at the atomic level for the presence of an excited state of the complex, the formation of which is largely driven by the disruption of hydrophobic interactions. Taken together, this study indicates that the dynamics of the hydrophobic residues plays an important role in regulating the function of the Tim9–Tim10 complex. Proteins 2012. © 2011 Wiley Periodicals, Inc.
Ligand‐induced formation of transient dimers of mammalian 12/15‐lipoxygenase: A key to allosteric behavior of this class of enzymes?
Authors: Ivanov Igor , Shang Weifeng , Toledo Lea , Masgrau Laura , Svergun Dmitri I. , Stehling Sabine , Gómez Hansel , Di Venere Almerinda , Mei Giampiero , Lluch José M. , Skrzypczak‐Jankun Ewa , González‐Lafont Àngels , Kühn Hartmut 
Published: October 2011

AbstractMammalian lipoxygenases (LOXs) have been implicated in cellular defense response and are important for physiological homeostasis. Since their discovery, LOXs have been believed to function as monomeric enzymes that exhibit allosteric properties. In aqueous solutions, the rabbit 12/15‐LOX is mainly present as hydrated monomer but changes in the local physiochemical environment suggested a monomer–dimer equilibrium. Because the allosteric character of the enzyme can hardly be explained using a single ligand binding‐site model, we proposed that the binding of allosteric effectors may shift the monomer–dimer equilibrium toward dimer formation. To test this hypothesis, we explored the impact of an allosteric effector [13(S)‐hydroxyoctadeca‐9(Z),11(E)‐dienoic acid] on the structural properties of rabbit 12/15‐LOX by small‐angle X‐ray scattering. Our data indicate that the enzyme undergoes ligand‐induced dimerization in aqueous solution, and molecular dynamics simulations suggested that LOX dimers may be stable in the presence of substrate fatty acids. These data provide direct structural evidence for the existence of LOX dimers, where two noncovalently linked enzyme molecules might work in unison and, therefore, such mode of association might be related to the allosteric character of 12/15‐LOX. Introduction of negatively charged residues (W181E + H585E and L183E + L192E) at the intermonomer interface disturbs the hydrophobic dimer interaction of the wild‐type LOX, and this structural alteration may lead to functional distortion of mutant enzymes. Proteins 2011. © 2012 Wiley Periodicals, Inc.
From implant planning to surgical execution: an integrated approach for surgery in oral implantology
Authors: Chiarelli Tommaso , Franchini Federico , Lamma Achille , Lamma Evelina , Sansoni Tommaso 
Published: October 2011

AbstractBackgroundUsing oral implantology software and transferring the preoperative planning into a stereolithographic model, prosthodontists can produce the related surgical guide. This procedure has some disadvantages: bone‐supported stent invasiveness, lack of references due to scattering and non‐negligible stereolithography cost. An alternative solution is presented that provides an ideal surgical stent (not invasive, precise, and cheap) as a result. This work focuses on the third phase of a fully 3D approach to oral implant planning, that starts by CT scanning a patient who wears a markers‐equipped radiological stent, continues exploiting built‐on‐purpose preoperative planning software, and finishes producing the ideal surgical template.MethodsA 5‐axes bur‐equipped robot has been designed able to reproduce the milling vectors planned by the software. Software–robot interfacing has been achieved properly matching the stent reference frame and the software and robot coordinate systems. Invasiveness has been avoided achieving the surgical stent from the mucosa‐supported radiological mask wax‐up. Scattering is ignored because of the surgical stent independency from the bone structure radiography. Production cost has been strongly reduced by avoiding the stereolithographic model. Finally, software–robot interfacing precision has been validated comparing digitally a multi‐marker base and its planning transfer.ResultsAverage position and orientation errors (respectively 0.283 mm ± 0.073 mm and 1.798° ± 0.496°) were significantly better than those achieved using methods based on stereolithography (respectively, 1.45 mm ± 1.42 mm and 7.25° ± 2.67°, with a general best maximum translation discrepancy of about 1.1 mm).ConclusionsThis paper describes the last step of a fully 3D approach in which implant planning can be done in a 3D environment, and the correct position, orientation and depth of the planned implants are easily computed and transferred to the surgical phase. Copyright © 2011 John Wiley & Sons, Ltd.
Synchronization of epicardial crawling robot with heartbeat and respiration for improved safety and efficiency of locomotion
Authors: Patronik Nicholas A. , Ota Takeyoshi , Zenati Marco A. , Riviere Cameron N. 
Published: October 2011

AbstractBackgroundHeartLander is a miniature mobile robot designed to navigate over the epicardium of the beating heart for minimally invasive therapy. This paper presents a technique to decrease slippage and improve locomotion efficiency by synchronizing the locomotion with the intrapericardial pressure variations of the respiration and heartbeat cycles.MethodsRespiratory and heartbeat phases were detected in real time using a chest‐mounted accelerometer during locomotion in a porcine model in vivo. Trials were conducted over the lateral aspect of the heart surface to test synchronized locomotion against an unsynchronized control.ResultsOffline evaluation showed that the respiration and heartbeat algorithms had accuracies of 100% and 88%, respectively. Synchronized trials exhibited significantly lower friction, higher efficiency, and greater total distance traveled than control trials.ConclusionSynchronization of the locomotion of HeartLander with respiration and heartbeat is feasible and results in safer and more efficient travel on the beating heart. Copyright © 2011 John Wiley & Sons, Ltd.
Virtual network stacks: from theory to practice
Authors: Matos Alfredo , Ferreira Rui , Sargento Susana , Aguiar Rui L. 
Published: October 2011

ABSTRACTPrivacy is becoming a pressing requirement that spawns across different network layers and user interactions. Using multiple identifiers for the same user, pseudonyms, as means for preserving privacy, is becoming an important approach that has not seen proper discussion or validation. This paper presents formalization on pseudonymity specially considering its influence on the network stack. It presents a study on privacy requirements and its implementation cost, both at theoretical and practical levels, through the support of multiple network stack instantiations and network identifiers per user. We discuss how pseudonyms can be used to preserve users' privacy, and what key issues and requirements are needed, to use, control, and evaluate a pseudonym‐based solution at network level. The paper further presents an architecture that builds a pseudonym‐based solution supported throughout the network stack, describes its implementation in a real testbed, and depicts the results obtained related to both efficiency and costs of such a privacy approach. Finally, it discusses the characteristics of the architecture according to the identified privacy requirements, its impacts and constraints. Copyright © 2011 John Wiley & Sons, Ltd.