bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary inner ear schwannomas: A case series and systematic review of the literature
Authors: Van Abel Kathryn M. , Carlson Matthew L. , Link Michael J. , Neff Brian A. , Beatty Charles W. , Lohse Christine M. , Eckel Laurence J. , Lane John I. , Driscoll Colin L. 
Published: January 2013

Objectives/HypothesisTo describe the natural history of primary inner ear schwannomas (PIES) and evaluate management outcomes and relationship between PIES location, clinical presentation, and time to diagnosis.Study DesignRetrospective chart review and systematic review of the literature.MethodsVestibular schwannoma confined to or arising from the inner ear were included. PIES classification was based on anatomic subsite(s) involved. Detailed clinical history and outcomes were recorded.ResultsIn a systematic review (1933–2011), including 14 patients from the authors' institution (1999–2009), a total of 72 studies comprising 234 patients were evaluated. Mean follow‐up was 32.8 ± 39.1 months (range, 0–183 months). The cochlea was the most commonly involved subsite (51%). Hearing loss was the most frequent presenting symptom (99%). Vertigo and abnormal balance were more common among tumors involving the vestibular system (P < .01). Average delay between symptom onset and diagnosis was 7.0 ± 8.0 years (median, 5 years; range, 0–40 years). Recent onset hearing loss was more likely to elicit an earlier diagnosis (P = .01). The majority of patients were observed without treatment (53%). Tumor progression was seen in 52% of patients.Conclusions PIES are rare tumors and most commonly involve the cochlea. Tumor location is often associated with clinical presentation and correlates with delay between symptom onset and diagnosis. A watch‐and‐scan approach is the management strategy of choice in the absence of intractable vertigo or extensive tumor growth. The majority of patients report stable or improved symptoms over time, regardless of treatment. Laryngoscope, 123:1957–1966, 2013
Shrinking Hydrogel‐DNA Spots Generates 3D Microdots Arrays
Authors: Le Goff Gaelle C. , Blum Loïc J. , Marquette Christophe A. 
Published: January 2013

AbstractThis report describes a straightforward approach for the achievement of sub‐100 micrometers size hydrogel dots supporting DNA immobilization. Hydrogel‐DNA spots are arrayed and UV‐crosslinked on PolyShrink, an innovative polymer material having the remarkable property of isotropically shrinking under high temperature. Curing the microarray enables then spot miniaturization, resulting in 6 µm thick and 60 µm wide hydrogel dots in which oligonucleotides are immobilized in a 3D hydrophilic environment. The probe immobilization within the hydrogel network and its capacity to detect targets specifically and quantitatively is demonstrated using chemiluminescent as well as colorimetric detection techniques. The hydrogel material improves probe accessibility within the spot, leading to an enhanced sensitivity. magnified image
Emulsion Self‐Assembly Synthesis of Chitosan/Poly(lactic‐co‐glycolic acid) Stimuli‐Responsive Amphiphiles
Authors: Niu Xufeng , Wang Lizhen , Chen Pin , Li Xiaoming , Zhou Gang , Feng Qingling , Fan Yubo 
Published: January 2013

AbstractAn amphiphilic graft copolymer using chitosan (CS) as a hydrophilic main chain and poly(lactic‐co‐glycolic acid) (PLGA) as a hydrophobic side chain is prepared through an emulsion self‐assembly synthesis. CS aqueous solution is used as a water phase and PLGA in chloroform is served as an oil phase. A water‐in‐oil (W/O) emulsion is fabricated in the presence of the surfactant span‐80. The self‐assembly reaction is performed between PLGA and CS under the condensation of EDC. Fourier transform IR (FTIR) spectroscopy reveals that PLGA is grafted onto the backbone of CS through the interactions between end carboxyl and amino groups of the two components. 1H NMR spectroscopy directly indicates the grafting content of PLGA in the CS‐graft‐PLGA (CS‐g‐PLGA) copolymer is close to 25%. X‐ray diffraction (XRD) confirms that the copolymer exhibits an amorphous structure. The CS‐g‐PLGA amphiphile can self‐assemble to form micelles with size in the range of ≈100–300 nm, which makes it easy to apply in various targeted‐drug‐release and biomaterial fields.
Temporal Gödel‐Gentzen and Girard translations
Authors: Kamide Norihiro 
Published: January 2013

AbstractA theorem for embedding a first‐order linear‐time temporal logic LTL into its intuitionistic counterpart ILTL is proved using Baratella‐Masini's temporal extension of the Gödel‐Gentzen negative translation of classical logic into intuitionistic logic. A substructural counterpart LLTL of ILTL is introduced, and a theorem for embedding ILTL into LLTL is proved using a temporal extension of the Girard translation of intuitionistic logic into intuitionistic linear logic. These embedding theorems are proved syntactically based on Gentzen‐type sequent calculi.
Complex calcaneal defect reconstruction with osteotomized free fibula–flexor hallucis longus osteomuscular flap
Authors: Lykoudis Efstathios G. , Gantsos Apostolos , Dimou Apostolos Od. 
Published: January 2013

AbstractComplex calcaneal defects represent a reconstructive challenge since calcaneous plays a key role in standing and gait. We report the case of a 35‐year‐old patient with a complex calcaneal defect due to chronic osteomyelitis after a high energy Gustillo type IIIB calcaneal fracture that was reconstructed with a free fibula–flexor hallucis longus osteomuscular flap. The fibula was osteotomized into two segments, which were used to reconstruct the bone defect, and the muscular component of the flap was used for coverage of the reconstructed calcaneal skeleton. Fifteen days later permanent skin coverage was ensured with a local random pattern rhomboid skin flap. Early and late postoperative periods were uneventful. Bone maturation was radiographically evident at a follow up of 12 weeks, and complete bone incorporation at 3 years. Full weight bearing was possible at 6 months postop. Final follow up, at 3 years postop, verified a very good functional and aesthetic outcome. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.
Anomalous behavior of bilinear quadrilateral finite elements for modeling cohesive cracks with XFEM/GFEM
Authors: Ahmed A. , Sluys L.J. 
Published: January 2013

SUMMARYThe performance of partition‐of‐unity based methods such as the generalized finite element method or the extended finite element method is studied for the simulation of cohesive cracking. The focus of investigation is on the performance of bilinear quadrilateral finite elements using these methods. In particular, the approximation of the displacement jump field, representing cohesive cracks, by extended finite element method/generalized finite element method and its effect on the overall behavior at element and structural level is investigated. A single element test is performed with two different integration schemes, namely the Newton‐Cotes/Lobatto and the Gauss integration schemes, for the cracked interface contribution. It was found that cohesive crack segments subjected to a nonuniform opening in unstructured meshes (or an inclined crack in a structured finite element mesh) result in an unrealistic crack opening. The reasons for such behavior and its effect on the response at element level are discussed. Furthermore, a mesh refinement study is performed to analyze the overall response of a cohesively cracked body in a finite element analysis. Copyright © 2013 John Wiley & Sons, Ltd.
Skeletal muscle adiposity is associated with serum lipid and lipoprotein levels in Afro‐Caribbean men
Authors: Miljkovic I. , Kuipers A.L. , Kuller L.H. , Sheu Y. , Bunker C.H. , Patrick A.L. , Wheeler V.W. , Evans R.W. , Zmuda J.M. 
Published: January 2013

Objective: When compared with other ethnic groups, African ancestry individuals have lower triglycerides and higher High‐density lipoprotein cholesterol (HDL‐C) levels, although the mechanisms for these differences remain unclear. A comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men was evaluated.Design and Methods: Men (1,821) underwent dual‐energy X‐ray absorptiometry measures of total body fat and quantitative computed tomography assessments of calf skeletal muscle adiposity [subcutaneous and intermuscular adipose tissue (AT), and muscle density as a measure of intra‐muscular AT].Results: Multivariable linear regression analysis identified age (−), total body fat (+), subcutaneous AT (−), fasting glucose (+), fasting insulin (+), diastolic blood pressure (+), and non‐African ancestry (+) as independent correlates of triglycerides (all P < 0.05). Total body fat (+), intra‐muscular AT (−), and diastolic blood pressure (+) were independent correlates of Low‐density lipoprotein cholesterol (LDL‐C) (all P < 0.001). Age (+), waist circumference (−), fasting insulin (−), physical activity (+), and alcohol intake (+) were independent correlates of HDL‐C (all P < 0.05).Conclusions: A novel relationship between skeletal muscle adiposity and serum lipid and lipoprotein levels in African ancestry men, independent of total and central adiposity was illuminated. In African ancestry populations, genetic factors are likely a significant determinant of triglycerides levels.
Influence of a clinical lifestyle‐based weight loss program on the metabolic risk profile of metabolically normal and abnormal obese adults
Authors: Liu Rebecca H. , Wharton Sean , Sharma Arya M. , Ardern Chris I. , Kuk Jennifer L. 
Published: January 2013

ObjectiveIt is unclear whether all obese individuals should be prescribed weight loss (WL) treatment. The effect of a clinically significant WL of 5% on metabolic factors among metabolically normal and abnormal overweight and obese (MNO and MAO) individuals was examined.Design and MethodsThe sample included 392 overweight and obese adults from the Wharton Medical Clinic. MAO was defined as having one or more clinically relevant aberrations in glucose, triglycerides, blood pressure (BP), high‐density lipoprotein‐C, low‐density lipoprotein‐C, preexisting, or current medication use for metabolic conditions.ResultsOf the 392 patients, 21.2% of the sample was MNO at baseline and 41.3% of the sample attained a 5% WL. Regardless of initial metabolic health status, improvements in most risk factors were observed with a 5% WL in comparison with those who did not lose weight. Even MAO patients who did not achieve a 5% WL still significantly improved BP and cholesterol over the treatment period.ConclusionsA clinically significant WL is beneficial for the cardiometabolic risk profile of both MNO and MAO. However, a 5% WL is not necessarily required to improve the cardiometabolic risk profile of MAO. Thus, lifestyle‐based WL provides beneficial metabolic effects for all overweight and obese individuals, particularly those with significant metabolic aberrations.
How maltose influences structural changes to bind to maltose‐binding protein: Results from umbrella sampling simulation
Authors: Mascarenhas Nahren Manuel , Kästner Johannes 
Published: January 2013

AbstractA well‐studied periplasmic‐binding protein involved in the abstraction of maltose is maltose‐binding protein (MBP), which undergoes a ligand‐induced conformational transition from an open (ligand‐free) to a closed (ligand‐bound) state. Umbrella sampling simulations have been us to estimate the free energy of binding of maltose to MBP and to trace the potential of mean force of the unbinding event using the center‐of‐mass distance between the protein and ligand as the reaction coordinate. The free energy thus obtained compares nicely with the experimentally measured value justifying our theoretical basis. Measurement of the domain angle (N‐terminal‐domain – hinge – C‐terminal‐domain) along the unbinding pathway established the existence of three different states. Starting from a closed state, the protein shifts to an open conformation during the initial unbinding event of the ligand then resides in a semi‐open conformation and later resides predominantly in an open‐state. These transitions along the ligand unbinding pathway have been captured in greater depth using principal component analysis. It is proposed that in mixed‐model, both conformational selection and an induced‐fit mechanism combine to the ligand recognition process in MBP. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Toward optimal fragment generations for ab initio protein structure assembly
Authors: Xu Dong , Zhang Yang 
Published: January 2013

AbstractFragment assembly using structural motifs excised from other solved proteins has shown to be an efficient method for ab initio protein‐structure prediction. However, how to construct accurate fragments, how to derive optimal restraints from fragments, and what the best fragment length is are the basic issues yet to be systematically examined. In this work, we developed a gapless‐threading method to generate position‐specific structure fragments. Distance profiles and torsion angle pairs are then derived from the fragments by statistical consistency analysis, which achieved comparable accuracy with the machine‐learning‐based methods although the fragments were taken from unrelated proteins. When measured by both accuracies of the derived distance profiles and torsion angle pairs, we come to a consistent conclusion that the optimal fragment length for structural assembly is around 10, and at least 100 fragments at each location are needed to achieve optimal structure assembly. The distant profiles and torsion angle pairs as derived by the fragments have been successfully used in QUARK for ab initio protein structure assembly and are provided by the QUARK online server at http://zhanglab.ccmb. med.umich.edu/QUARK/. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Coarse‐grained and all‐atom modeling of structural states and transitions in hemoglobin
Authors: Tekpinar Mustafa , Zheng Wenjun 
Published: January 2013

AbstractHemoglobin (Hb), an oxygen‐binding protein composed of four subunits (α1, α2, β1, and β2), is a well‐known example of allosteric proteins that are capable of cooperative ligand binding. Despite decades of studies, the structural basis of its cooperativity remains controversial. In this study, we have integrated coarse‐grained (CG) modeling, all‐atom simulation, and structural data from X‐ray crystallography and wide‐angle X‐ray scattering (WAXS), aiming to probe dynamic properties of the two structural states of Hb (T and R state) and the transitions between them. First, by analyzing the WAXS data of unliganded and liganded Hb, we have found that the structural ensemble of T or R state is dominated by one crystal structure of Hb with small contributions from other crystal structures of Hb. Second, we have used normal mode analysis to identify two distinct quaternary rotations between the α1β1 and α2β2 dimer, which drive the transitions between T and R state. We have also identified the hot‐spot residues whose mutations are predicted to greatly change these quaternary motions. Third, we have generated a CG transition pathway between T and R state, which predicts a clear order of quaternary and tertiary changes involving α and β subunits in Hb. Fourth, we have used the accelerated molecular dynamics to perform an all‐atom simulation starting from the T state of Hb, and we have observed a transition toward the R state of Hb. Further analysis of crystal structural data and the all‐atom simulation trajectory has corroborated the order of quaternary and tertiary changes predicted by CG modeling. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Crystal structure and nucleic acid‐binding activity of the CRISPR‐associated protein Csx1 of Pyrococcus furiosus
Authors: Kim Young Kwan , Kim Yeon‐Gil , Oh Byung‐Ha 
Published: January 2013

AbstractIn many prokaryotic organisms, chromosomal loci known as clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR‐associated (CAS) genes comprise an acquired immune defense system against invading phages and plasmids. Although many different Cas protein families have been identified, the exact biochemical functions of most of their constituents remain to be determined. In this study, we report the crystal structure of PF1127, a Cas protein of Pyrococcus furiosus DSM 3638 that is composed of 480 amino acids and belongs to the Csx1 family. The C‐terminal domain of PF1127 has a unique β‐hairpin structure that protrudes out of an α‐helix and contains several positively charged residues. We demonstrate that PF1127 binds double‐stranded DNA and RNA and that this activity requires an intact β‐hairpin and involve the homodimerization of the protein. In contrast, another Csx1 protein from Sulfolobus solfataricus P2 that is composed of 377 amino acids does not have the β‐hairpin structure and exhibits no DNA‐binding properties under the same experimental conditions. Notably, the C‐terminal domain of these two Csx1 proteins is greatly diversified, in contrast to the conserved N‐terminal domain, which appears to play a common role in the homodimerization of the protein. Thus, although P. furiosus Csx1 is identified as a nucleic acid‐binding protein, other Csx1 proteins are predicted to exhibit different individual biochemical activities. Proteins 2013. © 2012 Wiley Periodicals, Inc.
HIV‐1 ENV gp120 structural determinants for peptide triazole dual receptor site antagonism
Authors: Tuzer Ferit , Madani Navid , Kamanna Kantharaju , Zentner Isaac , LaLonde Judith , Holmes Andrew , Upton Elizabeth , Rajagopal Srivats , McFadden Karyn , Contarino Mark , Sodroski Joseph , Chaiken Irwin 
Published: January 2013

AbstractDespite advances in HIV therapy, viral resistance and side‐effects with current drug regimens require targeting new components of the virus. Dual antagonist peptide triazoles (PT) are a novel class of HIV‐1 inhibitors that specifically target the gp120 component of the viral spike and inhibit its interaction with both of its cell surface protein ligands, namely the initial receptor CD4 and the co‐receptor (CCR5/CXCR4), thus preventing viral entry. Following an initial survey of 19 gp120 alanine mutants by ELISA, we screened 11 mutants for their importance in binding to, and inhibition by the PT KR21 using surface plasmon resonance. Key mutants were purified and tested for their effects on the peptide's affinity and its ability to inhibit binding of CD4 and the co‐receptor surrogate mAb 17b. Effects of the mutations on KR21 viral neutralization were measured by single‐round cell infection assays. Two mutations, D474A and T257A, caused large‐scale loss of KR21 binding, as well as losses in both CD4/17b and viral inhibition by KR21. A set of other Ala mutants revealed more moderate losses in direct binding affinity and inhibition sensitivity to KR21. The cluster of sensitive residues defines a PT functional epitope. This site is in a conserved region of gp120 that overlaps the CD4 binding site and is distant from the co‐receptor/17b binding site, suggesting an allosteric mode of inhibition for the latter. The arrangement and sequence conservation of the residues in the functional epitope explain the breadth of antiviral activity, and improve the potential for rational inhibitor development. Proteins 2013. © 2012 Wiley Periodicals, Inc.
The translocation kinetics of antibiotics through porin OmpC: Insights from structure‐based solvation mapping using WaterMap
Authors: Tran Que‐Tien , Williams Sarah , Farid Ramy , Erdemli Gül , Pearlstein Robert 
Published: January 2013

AbstractPoor permeability of the lipopolysaccharide‐based outer membrane of Gram‐negative bacteria is compensated by the existence of protein channels (porins) that selectively admit low molecular weight substrates, including many antibiotics. Improved understanding of the translocation mechanisms of porin substrates could help guide the design of antibiotics capable of achieving high intracellular exposure. Energy barriers to channel entry and exit govern antibiotic fluxes through porins. We have previously reported a hypothesis that the costs of transferring protein solvation to and from bulk medium underlie the barriers to protein‐ligand association and dissociation, respectively, concomitant with the gain and loss of protein‐ligand interactions during those processes. We have now applied this hypothesis to explain the published rates of entry (association) and exit (dissociation) of six antibiotics to/from reconstituted E. coli porin OmpC. WaterMap was used to estimate the total water transfer energies resulting from transient occupation by each antibiotic. Our results suggest that solvation within the porin cavity is highly energetically favorable, and the observed moderately fast entry rates of the antibiotics are consistent with replacement of protein‐water H‐bonds. The observed ultrafast exit kinetics is consistent with the lack of intrachannel solvation sites that convey unfavorable resolvation during antibiotic dissociation. These results are aligned with known general relationships between antibiotic efficacy and physicochemical properties, namely unusually low logP, reflecting an abundance of H‐bond partners. We conclude that antibiotics figuratively “melt” their way through porin solvation at a rate determined by the cost of exchanging protein‐solvent for protein‐antibiotic H‐bonds. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Solution structures of polcalcin Phl p 7 in three ligation states: Apo‐, hemi‐Mg2+‐bound, and fully Ca2+‐bound
Authors: Henzl Michael T. , Sirianni Arthur G. , Wycoff Wei G. , Tan Anmin , Tanner John J. 
Published: January 2013

AbstractPolcalcins are small EF‐hand proteins believed to assist in regulating pollen‐tube growth. Phl p 7, from timothy grass (Phleum pratense), crystallizes as a domain‐swapped dimer at low pH. This study describes the solution structures of the recombinant protein in buffered saline at pH 6.0, containing either 5.0 mM EDTA, 5.0 mM Mg2+, or 100 μM Ca2+. Phl p 7 is monomeric in all three ligation states. In the apo‐form, both EF‐hand motifs reside in the closed conformation, with roughly antiparallel N‐ and C‐terminal helical segments. In 5.0 mM Mg2+, the divalent ion is bound by EF‐hand 2, perturbing interhelical angles and imposing more regular helical structure. The structure of Ca2+‐bound Phl p 7 resembles that previously reported for Bet v 4—likewise exposing apolar surface to the solvent. Occluded in the apo‐ and Mg2+‐bound forms, this surface presumably provides the docking site for Phl p 7 targets. Unlike Bet v 4, EF‐hand 2 in Phl p 7 includes five potential anionic ligands, due to replacement of the consensus serine residue at –x (residue 55 in Phl p 7) with aspartate. In the Phl p 7 crystal structure, D55 functions as a helix cap for helix D. In solution, however, D55 apparently serves as a ligand to the bound Ca2+. When Mg2+ resides in site 2, the D55 carboxylate withdraws to a distance consistent with a role as an outer‐sphere ligand. 15N relaxation data, collected at 600 MHz, indicate that backbone mobility is limited in all three ligation states. Proteins 2013. © 2012 Wiley Periodicals, Inc.