bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐Nanofiller‐Content Graphene Oxide–Polymer Nanocomposites via Vacuum‐Assisted Self‐Assembly
Authors: Putz Karl W. , Compton Owen C. , Palmeri Marc J. , Nguyen SonBinh T. , Brinson L. Catherine 
Published: August 2010

AbstractHighly ordered, homogeneous polymer nanocomposites of layered graphene oxide are prepared using a vacuum‐assisted self‐assembly (VASA) technique. In VASA, all components (nanofiller and polymer) are pre‐mixed prior to assembly under a flow, making it compatible with either hydrophilic poly(vinyl alcohol) (PVA) or hydrophobic poly(methyl methacrylate) (PMMA) for the preparation of composites with over 50 wt% filler. This process is complimentary to layer‐by‐layer assembly, where the assembling components are required to interact strongly (e.g., via Coulombic attraction). The nanosheets within the VASA‐assembled composites exhibit a high degree of order with tunable intersheet spacing, depending on the polymer content. Graphene oxide–PVA nanocomposites, prepared from water, exhibit greatly improved modulus values in comparison to films of either pure PVA or pure graphene oxide. Modulus values for graphene oxide–PMMA nanocomposites, prepared from dimethylformamide, are intermediate to those of the pure components. The differences in structure, modulus, and strength can be attributed to the gallery composition, specifically the hydrogen bonding ability of the intercalating species
18F‐flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trial
Authors: Vandenberghe Rik , Van Laere Koen , Ivanoiu Adrian , Salmon Eric , Bastin Christine , Triau Eric , Hasselbalch Steen , Law Ian , Andersen Allan , Korner Alex , Minthon Lennart , Garraux Gaëtan , Nelissen Natalie , Bormans Guy , Buckley Chris , Owenius Rikard , Thurfjell Lennart , Farrar Gill , Brooks David J. 
Published: August 2010

AbstractObjectiveThe most widely studied positron emission tomography ligand for in vivo β‐amyloid imaging is 11C‐Pittsburgh compound B (11C‐PIB). Its availability, however, is limited by the need for an on‐site cyclotron. Validation of the 18F‐labeled PIB derivative 18F‐flutemetamol could significantly enhance access to this novel technology.MethodsTwenty‐seven patients with early‐stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of 18F‐flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for 18F‐flutemetamol and its parent molecule 11C‐PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test‐retest variability of 18F‐flutemetamol SUVRs in 5 of the AD subjects.ResultsBlinded visual assessments of 18F‐flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical 18F‐flutemetamol SUVRs and 11C‐PIB SUVRs ranged from 0.89 to 0.92. Test‐retest variabilities of regional SUVRs were 1 to 4%.Interpretation18F‐Flutemetamol performs similarly to the 11C‐PIB parent molecule within the same subjects and provides high test‐retest replicability and potentially much wider accessibility for clinical and research use. ANN NEUROL 2010
Glut1 deficiency: Inheritance pattern determined by haploinsufficiency
Authors: Rotstein Michael , Engelstad Kristin , Yang Hong , Wang Dong , Levy Brynn , Chung Wendy K. , De Vivo Darryl C. 
Published: August 2010

AbstractTwo families manifesting Glut1 deficiency syndrome (DS) as an autosomal recessive trait are described. In 1 family, a severely affected boy inherited a mutated allele from his asymptomatic heterozygous mother. A de novo mutation developed in the paternal allele, producing compound heterozygosity. In another family, 2 mildly affected sisters inherited mutations from their asymptomatic heterozygous consanguineous parents. Red blood cell glucose uptake residual activity, a surrogate of haploinsufficiency, correlated with the clinical severity. These cases demonstrate that Glut1 DS may present as an autosomal recessive trait. The clinical pattern of inheritance is determined by the relative pathogenicity of the mutation and the resulting degree of haploinsufficiency. Ann Neurol 2010
A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease
Authors: Laxton Adrian W. , Tang‐Wai David F. , McAndrews Mary Pat , Zumsteg Dominik , Wennberg Richard , Keren Ron , Wherrett John , Naglie Gary , Hamani Clement , Smith Gwenn S. , Lozano Andres M. 
Published: August 2010

AbstractObjectiveAlzheimer disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions. We hypothesized that fornix/hypothalamus deep brain stimulation (DBS) could modulate neurophysiological activity in these pathological circuits and possibly produce clinical benefits.MethodsWe conducted a phase I trial in 6 patients with mild AD receiving ongoing medication treatment. Patients received continuous stimulation for 12 months. Three main lines of investigation were pursued including: (1) mapping the brain areas whose physiological function was modulated by stimulation using standardized low‐resolution electromagnetic tomography, (2) assessing whether DBS could correct the regional alterations in cerebral glucose metabolism in AD using positron emission tomography (PET), and 3) measuring the effects of DBS on cognitive function over time using clinical scales and instruments.ResultsDBS drove neural activity in the memory circuit, including the entorhinal, and hippocampal areas and activated the brain's default mode network. PET scans showed an early and striking reversal of the impaired glucose utilization in the temporal and parietal lobes that was maintained after 12 months of continuous stimulation. Evaluation of the Alzheimer's Disease Assessment Scale cognitive subscale and the Mini Mental State Examination suggested possible improvements and/or slowing in the rate of cognitive decline at 6 and 12 months in some patients. There were no serious adverse events.InterpretationThere is an urgent need for novel therapeutic approaches for AD. Modulating pathological brain activity in this illness with DBS merits further investigation. Ann Neurol 2010
The Cutaneous Microvascular Architecture of Human Diabetic Toe Studied by Corrosion Casting and Scanning Electron Microscopy Analysis
Authors: Sangiorgi S. , Manelli A. , Reguzzoni M. , Ronga M. , Protasoni M. , Dell'Orbo C. 
Published: August 2010

AbstractIn this morphological study, we report on the three‐dimensional microvascular architecture constituting the toes of a patient affected by diabetic microangiopathy. We applied corrosion casting (CC) technique to the toes of a patient affected by Type 2 diabetes, who underwent surgery for explantation of inferior left limb due to necrotic processes of soft tissues. The toes of a foot traumatically explanted in a motorcycle accident were kept as controls. According to technical protocols, toes were injected with a low‐viscosity acrylic resin (Mercox) through the major digital artery, tissues were corroded in KOH solution (8%), and resulting casts processed for SEM observations. Already at low magnification, in diabetic toes, we found an impairment of the linear track‐like disposition of the vessels of plantar side, with signs of vascular disruption and obliterations, stopped resin, and leakages. Capillaries under the nail and a lot of vascular villi in eponychium and nail borders were damaged, and vascular regression phenomena acting on them were clearly visible. Resin leakages and impairment of normal vascular architecture were also observed in the root of the nail. This preliminary report represents only the first step for further investigations regarding morphological three‐dimensional appearance of diabetic microangiopathy. CC and scanning electron microscopy technique well documented these morphological modifications, highlighting on both structural and ultrastructural features of diabetic toes microvessels. In conclusion, our qualitative data try to better focus on the pathophysiological mechanisms involved in diabetic dermopathy and microangiopathy, proposing CC as useful method to investigate on them. Anat Rec 293:1639–1645, 2010. © 2010 Wiley‐Liss, Inc.
Toward the total chemical synthesis of the cancer protein NY‐ESO‐1
Authors: Harris Paul W. R. , Brimble Margaret A. 
Published: August 2010

AbstractDuring the course of developing a synthetic route for the cancer protein NY‐ESO‐1 using native chemical ligation, a number of the required thioester polypeptide fragments were unable to be synthesized effectively using Boc solid phase peptide synthesis. Modification of the SPPS protocols to include an arginine tag at the C terminus linked via the thioester resulted in a better purity profile and enhanced solubility, facilitating purification by HPLC. During preparation of another reactive partner for ligation that contained an internal Cys(Acm) residue by Fmoc SPPS, extensive loss of the Acm group occurred during cleavage from the resin while substitution with Cys(tBu) resulted in no loss of protecting group. It was shown that native chemical ligation of N‐terminal cysteine peptide 155–180 containing the Cys(tBu) residue with thioester 140–154 was slow, incomplete and led to extensive HPLC column fouling. Subsequent incorporation of a C‐terminal arginine tag into the N‐terminal NY‐ESO‐1 155‐180 fragment joined by a base labile 4‐hydroxymethylbenzoic acid (HMBA) linker facilitated rapid quantitative ligation. The HMBA linker was demonstrated to be stable to the conditions required for native chemical ligation, subsequent transformations and final purification. Importantly it was effectively removed at pH = 10. © 2010 Wiley Periodicals, Inc.Biopolymers (Pept Sci) 94: 542–550, 2010.
Peptide reporters of kinase activity in whole cell lysates
Authors: Wu Ding , Sylvester Juliesta E. , Parker Laurie L. , Zhou Guangchang , Kron Stephen J. 
Published: August 2010

AbstractKinase assays are used to screen for small‐molecule inhibitors that may show promise as targeted pharmaceutical therapies. Using cell lysates instead of purified kinases provides a more accurate estimate of inhibitor sensitivity and selectivity in a biological setting. This review summarizes the range of homogeneous (solution‐phase) and heterogeneous (solid‐supported) formats available for using peptide substrates to monitor kinase activities in cell lysates. With a focus on heterogeneous kinase assays, the peptide substrate Abltide is used as a model to optimize presentation geometries and the modular arrangement of short sequences for kinase recognition. We present results from peptides immobilized on two‐ and three‐dimensional surfaces such as hydrogels on 96‐well plates and glass slides, and fluorescent Luminex beads. We discuss methods to increase assay sensitivity using chemifluorescent ELISAs, antibody‐based recognition, and label‐free mass spectrometry. Monitoring the activity of specific kinases in cell lysates presents challenges that can be overcome by manipulating peptide substrates to optimize assay conditions. In particular, signal‐to‐background ratios were improved by (1) adding long branched hydrophilic linkers between the substrate and the surface, (2) changing the orientation of peptides relative to the surface, and (3) including peptide ligands in cis or in trans to recruit kinases to the surface. By improving the accessibility of immobilized peptide substrates to kinases in solution, the apparent rate of phosphorylation increased and assays were more sensitive to changes in endogenous kinase activities. These strategies can be generalized to improve the reactivity of most peptide substrates used in heterogeneous kinase assays with cell lysates. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 475–486, 2010.
1‐O‐alkenyl‐sn‐glyceryl‐3‐phosphorylcholine may be a novel posttranslational modification used by the placenta
Authors: Lowry Philip 
Published: August 2010

AbstractNeurokinin B (NKB) secreted by the placenta was previously found to be raised in preeclampsia and most of the symptoms in this disease appeared to be through progressive activation of the three neurokinin receptors. Further characterization of placental NKB revealed that placental NKB eluted in the approximate position of a 13mer and this was confirmed by TOF mass spectrometry which gave a mass of 1580. Although this is consistent with dimethylated NKB‐Gly‐Lys‐Arg, further characterization (immunological and mass spectrometric fragment analysis) suggested a novel posttranslational modification containing phosphocholine (PC) with some evidence for glycerol and a coordinated alkene. The structure that fits all the data is that a form of platelet activating factor is attached to the aspartyl side chain at position 4 of NKB and thus now implicates placental NKB in the platelet pathology seen in preeclampsia. As it has been reported that it is the PC group per se attached to certain proteins secreted by filarial nematodes imparts them with immune inhibitory properties and thus survival in the host over long periods, attaching PC to placental secretory peptide hormones (also be found on the placental precursors of CRF, ACTH, and activin) may result in a similar situation. © 2010 Wiley Periodicals,Inc. Biopolymers (Pept Sci) 96: 189–192, 2011.
Peptide inhibitors of xenoreactive antibodies mimic the interaction profile of the native carbohydrate antigens
Authors: Agostino Mark , Sandrin Mauro S. , Thompson Philip E. , Ramsland Paul A. , Yuriev Elizabeth 
Published: August 2010

AbstractCarbohydrate–antibody interactions mediate many cellular processes and immune responses. Carbohydrates expressed on the surface of cells serve as recognition elements for particular cell types, for example, in the ABO(H) blood group system. Antibodies that recognize host‐incompatible ABO(H) system antigens exist in the bloodstream of all individuals (except AB individuals), preventing bloodtransfusion and organ transplantation between incompatible donors and recipients. A similar barrier exists for cross‐species transplantation (xenotransplantation), in particular for pig‐to‐human transplantation. All humans express antibodies against the major carbohydrate xenoantigen, Galα(1,3)Gal (αGal), preventing successful xenotransplantation. Although antibody binding sites are precisely organized so as to selectively bind a specific antigen, many antibodies recognize molecules other than their native antigen. A range of peptides have been identified that can mimic carbohydrates and inhibit anti‐αGal antibodies. However, the structural basis of how the peptides achieved this was not known. Previously, we developed an in silico method which we used to investigate carbohydrate recognition by a panel of anti‐αGal antibodies. The method involves molecular docking of carbohydrates to antibodies and uses the docked carbohydrate poses to generate maps of the antibody binding sites in terms of prevalent hydrogen bonding and van der Waals interactions. We have applied this method to investigate peptide recognition by the anti‐αGal antibodies. It was found that the site maps of the peptides and the carbohydrates were similar, indicating that the peptides interact with the same residues as those involved in carbohydrate recognition. This study demonstrates the potential for “design by mapping” of anti‐carbohydrate antibody inhibitors. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 177–180, 2011.
Molecular recognition at protein surface in solution and gas phase: Five VEGF peptidic ligands show inverse affinity when studied by NMR and CID‐MS
Authors: Dyachenko Andrey , Goldflam Michael , Vilaseca Marta , Giralt Ernest 
Published: August 2010

AbstractProtein‐protein interactions comprise of collection of molecular recognition events that take place at protein surfaces. A better understanding of the mechanism behind these interactions would provide deeper insight into the nature of many diseases, caused by the malfunction of protein networks, and contribute to design of molecules for efficient modulating of these interactions. One major factor in molecular recognition mechanism is interaction of reacting species with aqueous media. Thus, comparative study of noncovalent complex behavior in solution and gas phase can provide valuable information about the role of the solvent. Here examined interactions of vascular endothelial growth factor (VEGF) protein with five peptidic ligands of the same molecular weight but with different affinities. Interactions of VEGF with ligands in solution were studied by ITC and NMR, and KDs were determined. Gas phase stability was addressed using CID‐MS approach. The energy transfer model was taken and adapted for the calculation of binding energy. Peptides were ranked on the basis of both solution and gas phase affinity to VEGF. The results indicate that the ranking of peptides in terms of affinity in solution is reversed compared with the gas phase ranking. This observation opens up a vast field for the future study of the system, and the determination and characterization of factors, responsible for the change of stability of noncovalent protein‐ligand complexes upon complete or partial removal of the solvent. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 689–700, 2010.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Alternative chemistries for the synthesis of thrombospondin‐1 type 1 repeats
Authors: Tiefenbrunn Theresa K. , Blanco‐Canosa Juan , Dawson Philip E. 
Published: August 2010

AbstractSynthetic protein engineering has benefited from the development of diverse methods for the synthesis of functionalized peptide fragments and approaches for their subsequent assembly into full length polypeptides. Here we describe a series of synthetic approaches for the total chemical synthesis of the second type 1 repeat of thrombospondin‐1 (TSR2) that vary in both the location of the ligation site and α‐amine protecting group strategy (Boc/Fmoc) used for the synthesis of the associated peptide fragments. These syntheses illustrate that challenging peptide sequences can result from the protecting group strategy as well as from sequence‐dependent factors. Importantly, we find that such challenges can be overcome by altering the chemistry used for solid phase peptide synthesis, the choice of ligation site, and the resin used as a solid support. From these studies, we have developed a robust synthetic route to the TSR2 polypeptide consisting of native chemical ligation between an N‐terminal fragment synthesized by Boc‐SPPS and a C‐terminal fragment synthesized by Fmoc‐SPPS. Finally, the folded TSR2 domain is obtained following an optimized oxidative folding protocol using an excess of oxidized glutathione. This optimized synthesis will enable the use of unnatural amino acids to probe the unusual structure and anti‐angiogenic activity of this protein domain. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 405–413, 2010.
Deletion of Ac‐NMePhe1from [NMePhe1]arodyn under acidic conditions, part 2: Effects of substitutions on pharmacological activity
Authors: Fang Wei‐Jie , Bennett Marco A. , Murray Thomas F. , Aldrich Jane V. 
Published: August 2010

AbstractArodyn (Ac[Phe1,2,3,Arg4,D‐Ala8]Dyn A(1–11)NH2) is an acetylated dynorphin A (Dyn A) analog that is a potent and selective κ opioid receptor antagonist (Bennett et al., J Med Chem 2002, 45, 5617), and its analog [NMePhe1]arodyn shows even higher affinity and selectivity for κ opioid receptors (Bennett et al., J Pept Res 2005, 65, 322). However, the latter compound is prone to deletion of the Ac‐NMePhe moiety from the N‐terminus of the peptide during acidic cleavage as described in the accompanying paper. Several stable analogs of [NMePhe1]arodyn and [NMePhe1,Trp3]arodyn where the acetyl group was substituted with a heteroatom‐containing group were evaluated for their opioid receptor affinity, selectivity, and efficacy. Methoxycarbonyl derivatives exhibited the highest κ opioid receptor affinity among the analogs. Additional [CH3OCO‐NMePhe1]arodyn analogs where position 3 was substituted with other aromatic or nonaromatic residues were also evaluated for κ receptor affinity, selectivity, and efficacy. [CH3OCO‐NMePhe1]arodyn has similar κ opioid receptor affinity as [NMePhe1]arodyn, retains high κ opioid receptor selectivity, and is a potent κ opioid receptor antagonist. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 103–110, 2011.
Zirconia with Defined Particle Morphology and Hierarchically Structured Pore System Synthesized via Combined Exo‐ and Endotemplating
Authors: With P. , Heinrich A. , Lutecki M. , Fichtner S. , Böhringer B. , Gläser R. 
Published: August 2010

AbstractHighly porous zirconia with defined particle morphology can be prepared by impregnation of spherical activated carbon as an exotemplate with a zirconia nanoparticle sol. The resulting zirconia spheres show a particle size distribution between 0.2 and 0.4 mm and exhibit high specific surface areas and specific pore volumes up to 104 m2g–1 and 0.56 cm3g–1, respectively. Addition of a triblockcopolymer (TBC) as an endotemplate during the synthesis leads to the formation of an additional pore system. The corresponding spherical zirconia products possess a hierarchically structured pore system with a bimodal pore size distribution with maxima at ca. 3 and 20 nm. The relative fraction of pores originating from the endotemplate can be varied by changing the endotemplate content in the zirconia nanoparticle sol. The presence of the TBC also has an influence on the specific surface area and the specific pore volume. Using the ratio of TBC to zirconium of nTBC/nZr = 0.027, a material can be prepared that exhibits a specific surface area and a specific pore volume of 161 m2g–1 and 0.62 cm3g–1, respectively. These values are more than twice as high as for zirconia prepared by a conventional precipitation method (68 m2g–1 and 0.11 cm3g–1, respectively).