bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐Lived 1H Nuclear Spin Singlet in Dimethyl Maleate Revealed by Addition of Thiols
Authors: Zhang Yuning , Soon Pei Che , Jerschow Alexej , Canary James W.
Published: March 2014

Nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) have become important techniques in many research areas. One major limitation is the relatively low sensitivity of these methods, which recently has been addressed by hyperpolarization. However, once hyperpolarization is imparted on a molecule, the magnetization typically decays within relatively short times. Singlet states are well isolated from the environment, such that they acquire long lifetimes. We describe herein a model reaction for read‐out of a hyperpolarized long‐lived state in dimethyl maleate using thiol conjugate addition. This type of reaction could lend itself to monitoring oxidative stress or hypoxia by sensitive detection of thiols. Similar reactions could be used in biosensors or assays that exploit molecular switching. Singlet lifetimes of about 4.7 min for 1H spins in [D4]MeOH are seen in this system.
Polyoxometalate Clusters Integrated into Peptide Chains and as Inorganic Amino Acids: Solution‐ and Solid‐Phase Approaches
Authors: Yvon Carine , Surman Andrew J. , Hutin Marie , Alex Jennifer , Smith Brian O. , Long De‐Liang , Cronin Leroy
Published: March 2014

General synthetic methods for the grafting of peptide chains onto polyoxometalate clusters by the use of general activated precursors have been developed. Using a solution‐phase approach, pre‐synthesized peptides can be grafted to a metal oxide cluster to produce hybrids of unprecedented scale (up to 30 residues). An adapted solid‐phase method allows the incorporation of these clusters, which may be regarded as novel hybrid unnatural amino acids, during the peptide synthesis itself. These methods may open the way for the automated synthesis of peptides and perhaps even proteins that contain “inorganic” amino acids.
Gated Electron Sharing Within Dynamic Naphthalene Diimide‐Based Oligorotaxanes
Authors: Avestro Alyssa‐Jennifer , Gardner Daniel M. , Vermeulen Nicolaas A. , Wilson Eleanor A. , Schneebeli Severin T. , Whalley Adam C. , Belowich Matthew E. , Carmieli Raanan , Wasielewski Michael R. , Stoddart J. Fraser
Published: March 2014

The controlled self‐assembly of well‐defined and spatially ordered π‐systems has attracted considerable interest because of their potential applications in organic electronics. An important contemporary pursuit relates to the investigation of charge transport across noncovalently coupled components in a stepwise fashion. Dynamic oligorotaxanes, prepared by template‐directed methods, provide a scaffold for directing the construction of monodisperse one‐dimensional assemblies in which the functional units communicate electronically through‐space by way of π‐orbital interactions. Reported herein is a series of oligorotaxanes containing one, two, three and four naphthalene diimide (NDI) redox‐active units, which have been shown by cyclic voltammetry, and by EPR and ENDOR spectroscopies, to share electrons across the NDI stacks. Thermally driven motions between the neighboring NDI units in the oligorotaxanes influence the passage of electrons through the NDI stacks in a manner reminiscent of the conformationally gated charge transfer observed in DNA.
Metal‐Only Lewis Pairs by Reversible Insertion of Ruthenium and Osmium Fragments into Metal–Boron Double Bonds
Authors: Bertsch Stefanie , Bertermann Rüdiger , Braunschweig Holger , Damme Alexander , Dewhurst Rian D. , Phukan Ashwini K. , Saalfrank Christian , Vargas Alfredo , Wennemann Benedikt , Ye Qing
Published: March 2014

New metal‐only Lewis pairs (MOLPs: Ru→Cr and Os→Cr) are prepared by the insertion of a zerovalent ruthenium or osmium complex into chromium–boron double bonds of borylene complexes. The reaction creates new borylene complexes (the first ever for osmium), and is crystallization‐controlled; re‐dissolving the complexes results in regeneration of the starting materials. A mechanism is proposed based on DFT calculations, along with a computational study of the unusual MOLPs.
Peapod‐Type Nanocomposites through the In Situ Growth of Gold Nanoparticles within Preformed Hexaniobate Nanoscrolls
Authors: Adireddy Shiva , Carbo Cecilia E. , Rostamzadeh Taha , Vargas Jose M. , Spinu Leonard , Wiley John B.
Published: March 2014

A facile in situ method to grow Au nanoparticles (NPs) in hexaniobate nanoscrolls is applied to the formation of plasmonic Au@hexaniobate and bifunctional plasmonic‐magnetic Au‐Fe3O4@hexaniobate nanopeapods (NPPs). Utilizing a solvothermal treatment, rigid multiwalled hexaniobate nanoscrolls and partially filled Fe3O4@hexaniobate NPPs were first fabricated. These nanostructures were then used as templates for the controlled in situ growth of Au NPs. The resulting peapod structures exhibited high filling fractions and long‐range uniformity. Optical measurements showed a progressive red shift in plasmonic behavior between Au NPs, Au NPPs, and Au‐Fe3O4 NPPs; magnetic studies found that the addition of gold in the Fe3O4@hexaniobate NPPs reduced interparticle coupling effects. The development of this approach allows for the routine bulk preparation of noble‐metal‐containing bifunctional nanopeapod materials.
Multi‐Objective Molecular De Novo Design by Adaptive Fragment Prioritization
Authors: Reutlinger Michael , Rodrigues Tiago , Schneider Petra , Schneider Gisbert
Published: March 2014

We present the development and application of a computational molecular de novo design method for obtaining bioactive compounds with desired on‐ and off‐target binding. The approach translates the nature‐inspired concept of ant colony optimization to combinatorial building block selection. By relying on publicly available structure–activity data, we developed a predictive quantitative polypharmacology model for 640 human drug targets. By taking reductive amination as an example of a privileged reaction, we obtained novel subtype‐selective and multitarget‐modulating dopamine D4 antagonists, as well as ligands selective for the sigma‐1 receptor with accurately predicted affinities. The nanomolar potencies of the hits obtained, their high ligand efficiencies, and an overall success rate of 90 % demonstrate that this ligand‐based computer‐aided molecular design method may guide target‐focused combinatorial chemistry.
A Convergent Total Synthesis of the Telomerase Inhibitor (±)‐γ‐Rubromycin
Authors: Wilsdorf Michael , Reissig Hans‐Ulrich
Published: March 2014

The total synthesis of the human telomerase inhibitor γ‐rubromycin in its racemic form was accomplished in 3.8 % overall yield. The key feature of this synthesis is an efficient acid‐catalyzed spiroketalization for the construction of the spiroketal core. The required electronically well‐balanced spiroketal precursor was obtained by the convergent assembly of a naphthyl‐substituted aldehyde, an α‐methoxyallyl‐γ‐silyl‐substituted phosphonate as the central C3 building block, and a highly functionalized aryl Grignard reagent. Another key feature is the late‐stage construction of the isocoumarin moiety and a simultaneous protodesilylation furnishing the known methyl aryl ether protected precursor of γ‐rubromycin.
Significance of Preradiographic Magnetic Resonance Imaging Lesions in Persons at Increased Risk of Knee Osteoarthritis
Authors: Sharma Leena , Chmiel Joan S. , Almagor Orit , Dunlop Dorothy , Guermazi Ali , Bathon Joan M. , Eaton Charles B. , Hochberg Marc C. , Jackson Rebecca D. , Kwoh C. Kent , Mysiw W. Jerry , Crema Michel D. , Roemer Frank W. , Nevitt Michael C.
Published: March 2014

Objective

Little is known about early knee osteoarthritis (OA). The significance of lesions on magnetic resonance imaging (MRI) in older persons without radiographic OA is unclear. Our objectives were to determine the extent of tissue pathology by MRI and evaluate its significance by testing the following hypotheses: cartilage damage, bone marrow lesions, and meniscal damage are associated with prevalent frequent knee symptoms and incident persistent symptoms; bone marrow lesions and meniscal damage are associated with incident tibiofemoral (TF) cartilage damage; and bone marrow lesions are associated with incident patellofemoral (PF) cartilage damage.

Methods

In a cohort study of 849 Osteoarthritis Initiative (OAI) participants who had a bilateral Kellgren/Lawrence (K/L) score of 0, we assessed cartilage damage, bone marrow lesions, and meniscal damage using the MRI OA Knee Score, as well as prevalent frequent knee symptoms, incident persistent symptoms, and incident cartilage damage. Multiple logistic regression (one knee per person) was used to evaluate associations between MRI lesions and each of these outcomes.

Results

Of the participants evaluated, 76% had cartilage damage, 61% had bone marrow lesions, 21% had meniscal tears, and 14% had meniscal extrusion. Cartilage damage (any; TF and PF), bone marrow lesions (any; TF and PF), meniscal extrusion, and body mass index (BMI) were associated with prevalent frequent symptoms. Cartilage damage (isolated PF; TF and PF), bone marrow lesions (any; isolated PF; TF and PF), meniscal tears, and BMI were associated with incident persistent symptoms. Hand OA, but no individual lesion type, was associated with incident TF cartilage damage, and bone marrow lesions (any; any PF) with incident PF damage. Having more lesion types was associated with a greater risk of outcomes.

Conclusion

MRI‐detected lesions are not incidental and may represent early disease in persons at increased risk of knee OA.
Modifications of Gait as Predictors of Natural Osteoarthritis Progression in STR/Ort Mice
Authors: Poulet Blandine , de Souza Roberto , Knights Chancie B. , Gentry Clive , Wilson Alan M. , Bevan Stuart , Chang Yu‐Mei , Pitsillides Andrew A.
Published: March 2014

Objective

Osteoarthritis (OA) is a common chronic disease for which disease‐modifying therapies are not currently available. Studies to seek new targets for slowing the progress of OA rely on mouse models, but these do not allow for longitudinal monitoring of disease development. This study was undertaken to determine whether gait can be used to measure disease severity in the STR/Ort mouse model of spontaneous OA and whether gait changes are related to OA joint pain.

Methods

Gait was monitored using a treadmill‐based video system. Correlations between OA severity and gait at 3 treadmill speeds were assessed in STR/Ort mice. Gait and pain behaviors of STR/Ort mice and control CBA mice were analyzed longitudinally, with monthly assessments.

Results

The best speed to identify paw area changes associated with OA severity in STR/Ort mice was found to be 17 cm · seconds−1. Paw area was modified with age in CBA and STR/Ort mice, but this began earlier in STR/Ort mice and correlated with the onset of OA at 20 weeks of age. In addition, task noncompliance appeared at 20 weeks. Surprisingly, STR/Ort mice did not show any signs of pain with OA development, even when treated with the opioid antagonist naloxone, but did exhibit normal pain behaviors in response to complete Freund's adjuvant–induced arthritis.

Conclusion

The present results identify an animal model in which OA severity and OA pain can be studied in isolation from one another. The findings suggest that paw area and treadmill noncompliance may be useful tools to longitudinally monitor nonpainful OA development in STR/Ort mice. This will help in providing a noninvasive means of assessing new therapies to slow the progression of OA.
A Phase II Randomized Study of Subcutaneous Ixekizumab, an Anti–Interleukin‐17 Monoclonal Antibody, in Rheumatoid Arthritis Patients Who Were Naive to Biologic Agents or Had an Inadequate Response to Tumor Necrosis Factor Inhibitors
Authors: Genovese Mark C. , Greenwald Maria , Cho Chul‐Soo , Berman Alberto , Jin Ling , Cameron Gregory S. , Benichou Olivier , Xie Li , Braun Daniel , Berclaz Pierre‐Yves , Banerjee Subhashis
Published: March 2014

Objective

To evaluate ixekizumab, an anti–interleukin‐17A (anti–IL‐17A) monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients: biologics‐naive patients and patients with an inadequate response to tumor necrosis factor (TNF) inhibitors.

Methods

In this phase II, randomized, double‐blind study, placebo or ixekizumab was administered subcutaneously to 260 biologics‐naive patients and 188 patients with an inadequate response to TNF inhibitors at weeks 0, 1, 2, 4, 6, 8, and 10 with concomitant disease‐modifying antirheumatic drugs. The primary objective was to determine the dose‐response relationship of ixekizumab as measured by the proportion of biologics‐naive patients meeting the American College of Rheumatology 20% improvement criteria (ACR20) at week 12.

Results

Using a logistic regression model defined a priori, a statistically significant dose‐response relationship as measured by ACR20 response rates at week 12 was detected in biologics‐naive patients (P = 0.031). For patients with an inadequate response to TNF inhibitors, ACR20 responses at week 12 were significantly better with ixekizumab than placebo (P < 0.05). Decreases in the Disease Activity Score in 28 joints using the C‐reactive protein level (DAS28‐CRP), Clinical Disease Activity Index (CDAI), and CRP level from baseline were observed at week 12 in the ixekizumab groups in both populations (P < 0.05 versus placebo). Onset of action was rapid in some dose groups in both populations, with improvements in the ACR20, DAS28‐CRP, CRP levels, and CDAI observed by day 3 (P < 0.05). Adverse events occurred with similar frequencies overall in the ixekizumab and placebo groups. Infections were more frequent with ixekizumab than placebo (biologics‐naive 25% versus 19%; inadequate responders to TNF inhibitors 27% versus 25%). No mycobacterial or invasive fungal infections were reported.

Conclusion

Ixekizumab improved RA signs and symptoms in RA patients who were either naive to biologics treatment or had an inadequate response to TNF inhibitors. The safety profile was similar to that of other biologic agents, with no unexpected safety concerns.
Antibodies to Endothelial Cell Growth Factor and Obliterative Microvascular Lesions in the Synovium of Patients With Antibiotic‐Refractory Lyme Arthritis
Authors: Londoño Diana , Cadavid Diego , Drouin Elise E. , Strle Klemen , McHugh Gail , Aversa John M. , Steere Allen C.
Published: March 2014

Objective

Endothelial cell growth factor (ECGF) was recently identified as the first autoantigen known to be a target of T cell and B cell responses in ∼20% of patients with antibiotic‐refractory Lyme arthritis. The goal of the current study was to look for a pathologic correlate between ECGF autoantibody responses and histologic findings in synovial tissue.

Methods

Synovial tissue was examined from 14 patients with antibiotic‐refractory Lyme arthritis and 6 patients with other forms of chronic inflammatory arthritis, primarily rheumatoid arthritis. The tissue sections were subjected to chemical and immunostaining, and IgG antibody responses to ECGF were determined by enzyme‐linked immunosorbent assay (ELISA). Each finding was ranked for statistical analysis.

Results

In each disease, synovial tissue showed synovial hypertrophy, vascular proliferation, immune cell infiltrates, and fibrosis. However, among the 14 patients with antibiotic‐refractory arthritis, 8 (57%) had obliterative microvascular lesions in the tissue, compared with none of the 6 patients with other forms of chronic inflammatory arthritis (P = 0.04). Among the patients with Lyme arthritis, 5 (36%) had autoantibody responses to ECGF, and all 5 had obliterative lesions, as compared with only 3 of 9 patients who lacked ECGF antibody responses (P = 0.009). Moreover, the magnitude of ECGF antibody responses correlated directly with the extent of obliterative lesions (P = 0.02) and with greater vascularity in the tissue (P = 0.05).

Conclusion

The correlations of ECGF autoantibody reactivity with obliterative microvascular lesions imply that these autoantibodies may be involved in the obliterative process, suggesting that anti‐ECGF antibodies have specific pathologic consequences in the synovial tissue of patients with antibiotic‐refractory Lyme arthritis.
Bone‐ and Cartilage‐Protective Effects of a Monoclonal Antibody Against Colony‐Stimulating Factor 1 Receptor in Experimental Arthritis
Authors: Toh Myew‐Ling , Bonnefoy Jean‐Yves , Accart Nathalie , Cochin Sandrine , Pohle Sandy , Haegel Hélène , De Meyer Micael , Zemmour Christophe , Preville Xavier , Guillen Christine , Thioudellet Christine , Ancian Philippe , Lux Anja , Sehnert Bettina , Nimmerjahn Falk , Voll Reinhard E. , Schett Georg
Published: March 2014

Objective

Colony‐stimulating factor 1 receptor (CSF‐1R) essentially modulates monocyte proliferation, migration, and activation, which are considered important for the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine CSF‐1R expression in human RA as well as the efficacy of a specific anti–CSF‐1R monoclonal antibody (AFS98) in 2 different animal models of RA.

Methods

CSF‐1R expression was examined in blood, synovium, and bone samples from RA patients, osteoarthritis (OA) patients, and healthy subjects. The efficacy of AFS98 was examined by clinical assessment, histology, and bone histomorphometry in collagen‐induced arthritis (CIA) and serum‐transfer arthritis.

Results

CSF‐1R expression was increased in the synovium of RA patients compared to OA patients and healthy controls in fibroblast‐like synoviocytes, follicular dendritic cells, macrophages, and osteoclasts. Circulating RA monocytes and neutrophils but not lymphocytes were CSF‐1R+. In mice, blockade of CSF‐1R abrogated cartilage damage, bone erosion, and systemic bone loss, and this was associated with the depletion of osteoclasts in both models. While blockade of CSF‐1R did not affect inflammation in passive serum‐transfer arthritis, it significantly reduced inflammation in CIA, and this was associated with the absence of synovial macrophages and reduced splenic CD11b+Gr‐1− monocytes.

Conclusion

CSF‐1R was broadly expressed in human RA. Blockade of CSF‐1R protected against bone and cartilage destruction in both mouse models and also showed significant antiinflammatory effects in the CIA model. These data provide evidence for CSF‐1R as a therapeutic target in RA.
Anatomical knowledge gain through a clay‐modeling exercise compared to live and video observations
Authors: Kooloos Jan G.M. , Schepens‐Franke Annelieke N. , Bergman Esther M. , Donders Rogier A.R.T. , Vorstenbosch Marc A.T.M.
Published: March 2014

Clay modeling is increasingly used as a teaching method other than dissection. The haptic experience during clay modeling is supposed to correspond to the learning effect of manipulations during exercises in the dissection room involving tissues and organs. We questioned this assumption in two pretest–post‐test experiments. In these experiments, the learning effects of clay modeling were compared to either live observations (Experiment I) or video observations (Experiment II) of the clay‐modeling exercise. The effects of learning were measured with multiple choice questions, extended matching questions, and recognition of structures on illustrations of cross‐sections. Analysis of covariance with pretest scores as the covariate was used to elaborate the results. Experiment I showed a significantly higher post‐test score for the observers, whereas Experiment II showed a significantly higher post‐test score for the clay modelers. This study shows that (1) students who perform clay‐modeling exercises show less gain in anatomical knowledge than students who attentively observe the same exercise being carried out and (2) performing a clay‐modeling exercise is better in anatomical knowledge gain compared to the study of a video of the recorded exercise. The most important learning effect seems to be the engagement in the exercise, focusing attention and stimulating time on task. Anat Sci Educ 7: 420–429. © 2014 American Association of Anatomists.
Modified team‐based learning strategy to improve human anatomy learning: A pilot study at the Universidad del Norte in Barranquilla, Colombia
Authors: Martínez Emilio G. , Tuesca Rafael
Published: March 2014

As part of an institutional program sponsored by the Centre for Teaching Excellence at the Universidad del Norte, Barranquilla, Colombia, we developed an educational research study on two sessions of human anatomy in which we combined team‐based learning (TBL) and the use of iPads. Study data included the TBL, assessments applied during the course, student's grades on mid‐term examinations and students' perceptions of their experiences. Students reported a positive attitude toward the use of the TBL sessions, and the results showed a significant improvement in their learning between the first and second sessions. Significantly positive correlations (P < 0.05) were obtained between (a) the individual students' readiness test performance 1 and mid‐term examination 1, (b) the individual readiness test performances from Session 1 to Session 2, and (c) the group readiness test performances from the first and second sessions. These results point to positive learning experiences for these students. Analyses of the students' reflections on their activities also pointed toward future challenges. Anat Sci Educ 7: 399–405. © 2014 American Association of Anatomists.
Information and ontologies: Challenges in scaling knowledge for development
Authors: Seddon Jessica , Srinivasan Ramesh
Published: March 2014

This article calls for a conceptual and empirical research agenda on ways in which policymakers and researchers can aggregate socioeconomic information shared by diverse communities without losing contextual information that is important for extracting meaning from the data. We describe the knowledge loss that occurs when information is aggregated across diverse ontologies into databases or archives relying on a single schema and use a series of illustrative examples demonstrate the significance of this information loss for policy design and implementation. While there are important gains from information aggregation across ontologies, the potential trade‐offs involved in creating large‐scale databases are significant. The differences between locally constituted ways of knowing and the organizing ontology used for larger scale databases affects the extent to which these collections, or “knowledge banks,” provide accurate guidance for policy and action. The article draws on insights from information science and social science to discuss two classes of socio‐technical approaches for overcoming information loss at the interface between ontologies: first, technology‐enabled efforts to soften ontological interfaces by making data open, unconstructed, and available and/or creating ontologies collaboratively and, second, organizational changes that reduce the need for information to cross interfaces, such as reconstructing knowledge platforms to be more interactive, thereby decentralizing decision‐making. The framing of the challenges involved in building large‐scale knowledge banks as a matter of ontology mismatch creates an opportunity for an interdisciplinary and analytically integrated research agenda to implement and test these potential approaches.
Ranking methods for entity‐oriented semantic web search
Authors: Koumenides Christos L. , Shadbolt Nigel R.
Published: March 2014

This article provides a technical review of semantic search methods used to support text‐based search over formal Semantic Web knowledge bases. Our focus is on ranking methods and auxiliary processes explored by existing semantic search systems, outlined within broad areas of classification. We present reflective examples from the literature in some detail, which should appeal to readers interested in a deeper perspective on the various methods and systems implemented in the outlined literature. The presentation covers graph exploration and propagation methods, adaptations of classic probabilistic retrieval models, and query‐independent link analysis via flexible extensions to the PageRank algorithm. Future research directions are discussed, including development of more cohesive retrieval models to unlock further potentials and uses, data indexing schemes, integration with user interfaces, and building community consensus for more systematic evaluation and gradual development.
Metadata quality in digital repositories: Empirical results from the cross‐domain transfer of a quality assurance process
Authors: Palavitsinis Nikos , Manouselis Nikos , Sanchez‐Alonso Salvador
Published: March 2014

Metadata quality presents a challenge faced by many digital repositories. There is a variety of proposed quality assurance frameworks applied in repositories that are deployed in various contexts. Although studies report that there is an improvement of the quality of the metadata in many of the applications, the transfer of a successful approach from one application context to another has not been studied to a satisfactory extent. This article presents the empirical results of the application of a metadata quality assurance process that has been developed and successfully applied in an educational context (learning repositories) to 2 different application contexts to compare results with the previous application and assess its generalizability. More specifically, it reports results from the adaptation and application of this process in a library context (institutional repositories) and in a cultural context (digital cultural repositories). Initial empirical findings indicate that content providers seem to be gaining a better understanding of metadata when the proposed process is put in place and that the quality of the produced metadata records increases.
The Association Between Social Cognition and Executive Functioning and Symptoms of Anxiety and Depression in Adolescents With Autism Spectrum Disorders
Authors: Hollocks Matthew J. , Jones Catherine R.G. , Pickles Andrew , Baird Gillian , Happé Francesca , Charman Tony , Simonoff Emily
Published: March 2014

While high levels of anxiety and depression are now recognized as major co‐occurring problems in children and young people with an autism spectrum disorder (ASD), research examining possible associations with individual differences in neurocognitive functioning has been limited. This study included 90 adolescents with an ASD aged 14–16 years with a full‐scale IQ > 50. Using structural equation modeling, we examined the independent relationships between multiple measures of executive functioning and social cognition on severity of anxiety or depressive symptoms. Results indicated a significant association between poorer executive functioning and higher levels of anxiety, but not depression. In contrast, social cognition ability was not associated with either anxiety or depression. This study is the first to report significant associations between executive functions and anxiety in ASD. This may suggest that poor executive functioning is one factor associated with the high prevalence of anxiety disorder in children and adolescents with ASD. Autism Res 2014, 7: 216–228. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
Disposition of d‐penicillamine, a promising drug for preventing alcohol‐relapse. Influence of dose, chronic alcohol consumption and age: studies in rats
Authors: Orrico Alejandro , Martí‐Prats Lucía , Cano‐Cebrián M. José , Polache Ana , Zornoza Teodoro , Granero Luis
Published: March 2014

Pharmacokinetic studies concerning d‐penicillamine (an acetaldehyde sequestering agent) are scarce and have not evaluated the influence of chronic ethanol consumption and age on its disposition. Since recent preclinical studies propose d‐penicillamine as a promising treatment for alcohol relapse, the main aim of the present work was to evaluate the influence of these two factors on d‐penicillamine disposition in order to guide future clinical studies on the anti‐relapse efficacy of this drug in alcoholism. Additionally, the effect of the administered dose was also evaluated. To this end, three studies were carried out. Study 1 assessed the influence of dose on d‐penicillamine disposition, whereas studies 2 and 3 evaluated, respectively, the influence of chronic alcohol consumption and age. Rapid intravenous administrations of 2, 10 and 30 mg/kg of d‐penicillamine were performed using young or adult ethanol‐naïve rats or adult ethanol‐experienced (subjected to a long‐term ethanol self‐administration protocol) rats. Pharmacokinetic parameters were derived from the biexponential model. Statistical analysis of CL, normalized AUC0∞, V1 and k10 revealed that disposition, in the range plasma concentrations assayed, is non‐linear both in young ethanol‐naïve and in adult ethanol‐experienced rats. Notably, no significant changes in t1/2 were detected. Chronic ethanol consumption significantly reduced CL values by 35% without affecting t1/2. d‐Penicillamine disposition was equivalent in young and adult animals. In conclusion, although DP pharmacokinetics is non‐linear, the lack of significant alterations of the t1/2 would potentially simplify the clinical use of this drug. Chronic consumption of ethanol also alters d‐penicillamine disposition but, again, does not modify t1/2. Copyright © 2014 John Wiley & Sons, Ltd.
Dietary intake of choline and neural tube defects in Mexican Americans
Authors: Lavery Amy M. , Brender Jean D. , Zhao Hongwei , Sweeney Anne , Felkner Marilyn , Suarez Lucina , Canfield Mark A.
Published: March 2014

Background

Low maternal intake of dietary choline and betaine (a choline derivative) has recently been investigated as a possible risk factor for neural tube defects (NTDs)

Methods

This case‐control study examined the NTD risk associated with choline and betaine in 409 Mexican‐American women who gave birth during 1995 to 2000 in the 14‐county border region of Texas

Results

Using data from the food frequency questionnaire and the lowest quartiles of intake as the reference categories, a protective association was suggested between higher intakes of choline and betaine and NTD risk although the 95% confidence intervals for all risk estimates included 1.0. For choline intake in the second, third, and fourth quartiles, adjusted odds ratios were 1.2, 0.80, and 0.89, respectively. Betaine appeared more protective with odds ratios of 0.62, 0.73, and 0.61, respectively, for the second, third, and fourth quartiles of intake

Conclusion

Study findings suggest that dietary betaine may help to prevent NTDs. Birth Defects Research (Part A) 100:463–471, 2014. © 2014 Wiley Periodicals, Inc.
Characterization of the interaction of a mono‐6‐thio‐β‐cyclodextrin‐capped CdTe quantum dots–methylene blue/methylene green system with herring sperm DNA using a spectroscopic approach
Authors: Shen Yizhong , Liu Shaopu , Wang Lei , Yin Pengfei , He Youqiu
Published: March 2014

Novel, water‐soluble CdTe quantum dots (QDs) capped with β‐cyclodextrin (β‐CD) and ~ 4.0 nm in diameter were synthesized in aqueous solution, and characterized using transmission electron microscopy (TEM). A fluorescence‐sensing system based on the photoinduced electron transfer (PET) of (mono‐6‐thio‐β‐CD)–CdTe QDs was then designed to measure the interaction of phenothiazine dyes [methylene blue (MB) and methylene green (MG)] with herring sperm DNA (hsDNA). This fluorescence‐sensing system was based on a fluorescence “OFF–ON” mode. First, MB/MG adsorbed on the surface of (mono‐6‐thio‐β‐CD)–CdTe QDs effectively quenches the fluorescence of (mono‐6‐thio‐β‐CD)–CdTe QDs through PET. Then, addition of hsDNA restores the fluorescence intensity of (mono‐6‐thio‐β‐CD)–CdTe QDs, because hsDNA can bind with MB/MG and remove it from the as‐prepared (mono‐6‐thio‐β‐CD)–CdTe QDs. In addition, detailed reaction mechanisms of the (mono‐6‐thio‐β‐CD)–CdTe QDs–MB/MG–hsDNA solution system were studied using optical methods, by comparison with the TGA–CdTe QDs–MB/MG–hsDNA solution system. Copyright © 2014 John Wiley & Sons, Ltd.
The pharmacokinetic study of sinomenine, paeoniflorin and paeonol in rats after oral administration of a herbal product Qingfu Guanjiesu capsule by HPLC
Authors: Xie Ying , Jiang Zhi‐Hong , Zhou Hua , Ma Wen‐Zhe , Wong Yuen‐Fan , Liu Zhong‐Qiu , Liu Liang
Published: March 2014

An accurate and reliable high‐performance liquid chromatography–diode array detector (HPLC‐DAD) method was developed and validated for determination of sinomenine (SI), paeoniflorin (PF) and paeonol (PA), which was further applied to assess the pharmacokinetics of SI, PF and PA in an anti‐arthritic herbal product, Qingfu Guanjieshu (QFGJS) capsule, in rats. Successful separation was achieved with a C18 column and a mobile phase composed of acetonitrile and aqueous phase (containing 0.1% formic acid, adjusted with triethylamine to pH 3.5 ± 0.2). The method was validated with excellent precision, accuracy, recovery and stability in calibration ranges from 0.06 to 11.62 µg/mL for SI, from 0.09 to 35.70 µg/mL for PF, and from 0.15 to 4.53 µg/mL for PA (with r2 > 0.999 for all three compounds). Our results showed that absorption of PF after administration of QFGJS was similar to that after oral administration of PF alone; the absorption of SI was decreased while the absorption of PA was increased after giving QFGJS orally compared with pure compounds. We may conclude that pharmacokinetic studies of complex herbal products are not only necessary but also feasible by using representative bioactive chemicals as indicators of establishing quality control standards and of determining pharmacokinetic behavior of herbal medicines. Copyright © 2014 John Wiley & Sons, Ltd.
Functional Investigations of Thromboxane Synthase (CYP5A1) in Lipid Bilayers of Nanodiscs
Authors: Das Aditi , Varma Snehita Sri , Mularczyk Christopher , Meling Daryl D.
Published: March 2014

CYP5A1 is a membrane‐associated cytochrome P450 that metabolizes the cyclooxygenase product prostaglandin (PGH2) into thromboxane A2 (TXA2), a potent inducer of vasoconstriction and platelet aggregation. Although CYP5A1 is an ER‐bound protein, the role of membranes in modulating the thermodynamics and kinetics of substrate binding to this protein has not been elucidated. In this work, we incorporated thromboxane synthase into lipid bilayers of nanodiscs for functional studies. We measured the redox potential of CYP5A1 in nanodiscs and showed that the redox potential is within a similar range of other drug‐metabolizing P450 enzymes in membranes. Further, we showed that binding of substrate to CYP5A1 can induce conformational changes in the protein that block small‐molecule ligand egress by measuring the kinetics of cyanide binding to CYP5A1 as a function of substrate concentration. Notably, we observed that sensitivity to cyanide binding was different for two substrate analogues, U44069 and U46619, thus indicating that they bind differently to the active site of CYP5A1. We also characterized the effects of the different lipids on CYP5A1 catalytic activity by using nanodiscs to create unary, binary, and ternary lipid systems. CYP5A1 activity increased dramatically in the presence of charged lipids POPS and POPE, as compared to the unary POPC system. These results suggest the importance of lipid composition on modulating the activity of CYP5A1 to increase thromboxane formation.
Arginine Arrangement of Bacteriophage λ N‐Peptide Plays a Role as a Core Motif in GNRA Tetraloop RNA Binding
Authors: Furusawa Hiroyuki , Fukusho Shinobu , Okahata Yoshio
Published: March 2014

A simple α‐helical N‐model‐peptide was designed to investigate the role of the arginine‐rich motif of bacteriophage λ N‐peptide in selective binding with boxB RNA. The five‐arginine arrangement of native N‐peptide was retained; all other residues were replaced with alanine. In vitro selection of RNA (30 random‐nucleotide region) was carried out with N‐model‐peptide immobilized on a 27 MHz quartz‐crystal microbalance (QCM). Selected RNAs were evaluated on the same QCM plate to obtain binding constants (Ka=107–108 M−1). Many selected RNAs contained GNR(N)A‐type loops (similar to the boxB RNA motif recognized by the native N‐peptide). Fragments and minimal RNAs containing the GNRA‐type loop also bound to N‐model‐peptide (Ka=106–107 M−1). The RNA recognition specificity of the peptide was studied by changing the “closing” U–A base pair and one base in the tetraloop of the RNA aptamers, and by peptide mutations (18th residue of N‐model‐peptide). It was concluded that the five‐arginine arrangement of the peptide performs selective recognition of the GNRA tetraloop and GNR(N)A pentaloop RNA structures, and that substitution of another functional amino acid residue at the 18th position in N‐peptide adds the recognition ability for a loop‐RNA sequence.
Long‐term safety and efficacy of second‐generation everolimus‐eluting stents compared to other limus‐eluting stents and bare metal stents in patients with acute coronary syndrome
Authors: Omar Alfazir , Torguson Rebecca , Kitabata Hironori , Pendyala Lakshmana K. , Loh Joshua P. , Magalhaes Marco A. , Satler Lowell F. , Suddath William O. , Pichard Augusto D. , Waksman Ron
Published: March 2014

Objectives

This study aimed to investigate the long‐term safety and efficacy of everolimus‐eluting stents (EES) compared with other limus‐eluting stents and bare metal stents (BMS) in ACS patients.

Background

There have been concerns about the long‐term safety of drug‐eluting stents in the setting of acute coronary syndrome.

Methods

The study cohort included 1,612 patients presenting with acute coronary syndrome who underwent BMS, SES, E‐ZES, or EES implantation. End points included probable or definite stent thrombosis and major adverse cardiovascular events (MACE), defined as a composite of all‐cause death, Q‐wave myocardial infarction, and target lesion revascularization up to 3 years.

Results

The overall MACE rates were significantly higher for both BMS and SES, but not E‐ZES, when compared with EES (EES vs. BMS: HR 2.68, 95% CI 1.91–3.78, P <0.001; EES vs. SES: HR 1.75, 95% CI 1.24–2.47, P = 0.001 and EES vs. E‐ZES: HR 1.08, 95% CI 0.65–1.77, P = 0.72). Stent thrombosis rates were similar for EES, E‐ZES, and BMS but higher for SES throughout the 3‐year follow‐up (EES vs. BMS: HR 1.02, 95% CI: 0.31–3.35, P = 0.973; EES vs. SES: HR 4.90, 95% CI: 1.75–13.69, P = 0.002 and EES vs. E‐ZES: HR 1.63, 95% CI 0.37–7.31, P = 0.449).

Conclusions

There was an improvement in the long‐term outcome for MACE with EES when compared to earlier‐generation stents, but this was comparable with the 2nd‐generation E‐ZES. There was no additional risk of early or late stent thrombosis in EES when compared with BMS. © 2014 Wiley Periodicals, Inc.
Improved Photocatalytic Performance of the Ultra‐small Ag Nanocrystallite‐Decorated TiO2 Hollow Sphere Heterostructures
Authors: Li Qian , Zhang Caihong , Ma Jianmin , Wang Guozhong , Ng Dickon H. L.
Published: March 2014

The ultra‐small Ag nanocrystallite‐decorated TiO2 hollow sphere heterostructures were fabricated by using a two‐step hydrothermal method. These heterostructures demonstrated an excellent photodegradation performance of rhodamine B. The photodegradation efficiency could reach up to 100 % within 20 min under simulated sunlight irradiation. XRD, field emission SEM, TEM, scanning TEM, high‐resolution TEM coupled with energy‐dispersive X‐ray spectroscopy, UV/Vis absorption and photoluminescence spectroscopy, X‐ray photoelectron spectroscopy, Mott–Schottky analysis, and hydroxyl radical measurements were used to correlate the structure, surface property, and energy band alignment of rhodamine B to its photocatalytic activity. In these metal–semiconductor heterostructures, the Ag nanocrystallites were highly crystalline and were distributed evenly on the surface of TiO2 hollow spheres with compact interfaces. They reduced the recombination rate of charge carriers and favoured the charge transfer across the interfaces. The increased surface adsorbed oxygen facilitated the generation of hydroxyl radicals, and the reduced surface defects increased the lifetime of charge carriers upon Ag loading. The Schottky barriers between Ag and illuminated TiO2, the upward shift of the Fermi level, and increased electron density due to Ag coupling contributed to the charge transfer and increase in quantum efficiency. These key factors involved in photocatalysis are of great importance to design functional and effective photocatalysts.
Role of the Base and Control of Selectivity in the Suzuki–Miyaura Cross‐Coupling Reaction
Authors: Lima Carlos F. R. A. C. , Rodrigues Ana S. M. C. , Silva Vera L. M. , Silva Artur M. S. , Santos Luís M. N. B. F.
Published: March 2014

The outcome of the Suzuki–Miyaura cross‐coupling for the direct competition reaction between two boronic acids was evaluated under routine synthesis conditions. The reaction selectivity was found to depend on the amount of the base used, with fewer bases favoring the reactivity of the boronic acid with lower pKa (stronger acid). The dependence of the reaction selectivity on base stoichiometry was found to increase with the increase in the difference in the pKa values of the competing boronic acids. These results confirm a relationship between acid–base chemistry and the Suzuki–Miyaura reaction catalytic cycle. Moreover, the results indicate that under these specific conditions, the most reactive organoboron species toward transmetalation is the borate anion RB(OH)3− instead of the neutral boronic acid RB(OH)2. Hence, the main role of the base in the reaction mechanism is to increase the reactivity of the boronic acid toward the Pd–halide complex by converting it into the respective organoborate. In addition, boric acid, an important reaction byproduct, affects the selectivity in the Suzuki reaction because its gradual formation in the reaction medium disturbs the acid–base equilibrium.
NaBr/DMSO‐Induced Synthesis of 2,5‐Diformylfuran from Fructose or 5‐(Hydroxymethyl)furfural
Authors: Laugel Caroline , Estrine Boris , Le Bras Jean , Hoffmann Norbert , Marinkovic Sinisa , Muzart Jacques
Published: March 2014

2,5‐Diformylfuran (DFF) was obtained by heating a solution of 5‐(hydroxymethyl)furfural in DMSO. The addition of acids or salts improved the selectivity, especially if bromides were employed. Good yields of DFF were obtained with HBr or NaBr as the catalyst. One‐pot procedures were developed from fructose, which led to DFF in medium yields. This transformation occurs through the formation of 5‐(bromomethyl)furan‐2‐carbaldehyde followed by a Kornblum‐type reaction. In the presence of bromide salts, the in situ formation of the catalyst involves the thermolysis of DMSO and the association of the resulting strong acids with the bromides.
First Pre‐Functionalised Polymeric Aromatic Framework from Mononitrotetrakis(iodophenyl)methane and its Applications
Authors: Verde‐Sesto Ester , Pintado‐Sierra Mercedes , Corma Avelino , Maya Eva M. , de la Campa Jose G. , Iglesias Marta , Sánchez Felix
Published: March 2014

Starting from mononitrotetrakis(iodophenyl)methane as monomer, we report the preparation of the first pre‐functionalised porous aromatic frameworks (PAFs) and their application as supports for organometallic catalysts. Neutral coordinate imino‐pyridine Schiff base (PAF‐NPy) or chiral bis‐amino (PAF‐NPro) ligands were obtained by post‐synthetic treatment of PAF‐NH2 and treated with copper(I) or rhodium(I) to yield the corresponding supported transition‐metal catalysts. The as‐prepared PAF‐NN‐M catalysts exhibited activity and selectivity similar to that of the corresponding homogeneous catalysts and were easily removed from reaction media and recycled without loss of activity or selectivity.
The Use of a Microreactor for Rapid Screening of the Reaction Conditions and Investigation of the Photoluminescence Mechanism of Carbon Dots
Authors: Lu Yue , Zhang Ling , Lin Hengwei
Published: March 2014

A microreactor is applied and reported, for the first time, in the field of research of carbon dots (CDs), including rapid screening of the reaction conditions and investigation of the photoluminescence (PL) mechanism. Various carbonaceous precursors and solvents were selected and hundreds of reaction conditions were screened (ca. 15 min on average per condition). Through analyzing the screened conditions, tunable PL emission maxima, from about 330 to 550 nm with respectable PL quantum yields, were achieved. Moreover, the relationship between different developmental stages of the CDs and the PL properties was explored by using the microreactor. The PL emission was observed to be independent of the composition, carbonization extent, and morphology/size of the CDs. This study unambiguously presents that a microreactor could serve as a promising tool for the research of CDs.
Synthesis of Nanoporous Carbon–Cobalt‐Oxide Hybrid Electrocatalysts by Thermal Conversion of Metal–Organic Frameworks
Authors: Chaikittisilp Watcharop , Torad Nagy L. , Li Cuiling , Imura Masataka , Suzuki Norihiro , Ishihara Shinsuke , Ariga Katsuhiko , Yamauchi Yusuke
Published: March 2014

Nanoporous carbon–cobalt‐oxide hybrid materials are prepared by a simple, two‐step, thermal conversion of a cobalt‐based metal–organic framework (zeolitic imidazolate framework‐9, ZIF‐9). ZIF‐9 is carbonized in an inert atmosphere to form nanoporous carbon–metallic‐cobalt materials, followed by the subsequent thermal oxidation in air, yielding nanoporous carbon–cobalt‐oxide hybrids. The resulting hybrid materials are evaluated as electrocatalysts for the oxygen‐reduction reaction (ORR) and the oxygen‐evolution reaction (OER) in a KOH electrolyte solution. The hybrid materials exhibit similar catalytic activity in the ORR to the benchmark, commercial, Pt/carbon black catalyst, and show better catalytic activity for the OER than the Pt‐based catalyst.
Stereochemistry and Conformation of Skyllamycin, a Non‐Ribosomally Synthesized Peptide from Streptomyces sp. Acta 2897
Authors: Schubert Vivien , Di Meo Florent , Saaidi Pierre‐Loïc , Bartoschek Stefan , Fiedler Hans‐Peter , Trouillas Patrick , Süssmuth Roderich D.
Published: March 2014

Skyllamycin is a non‐ribosomally synthesized cyclic depsipeptide from Streptomyces sp. Acta 2897 that inhibits PDGF‐signaling. The peptide scaffold contains an N‐terminal cinnamoyl moiety, a β‐methylation of aspartic acid, three β‐hydroxylated amino acids and one rarely occurring α‐hydroxy glycine. With the exception of α‐hydroxy glycine, the stereochemistry of the amino acids was assigned by comparison to synthetic reference amino acids applying chiral GC‐MS and Marfey‐HPLC analysis. The stereochemistry of α‐hydroxy glycine, which is unstable under basic and acidic conditions, was determined by conformational analysis, employing a combination of data from NOESY‐NMR spectroscopy, simulated annealing and free MD simulations. The simulation procedures were applied for both R‐ and S‐configured α‐hydroxy glycine of the skyllamycin structure and compared to the NOESY data. Both methods, simulated annealing and free MD simulations independently support S‐configured α‐hydroxy glycine thus enabling the assignment of all stereocenters in the structure of skyllamycin and devising the role of two‐component flavin dependent monooxygenase (Sky39) as S‐selective.
Direct Olefination of Fluorinated Benzothiadiazoles: A New Entry to Optoelectronic Materials
Authors: Xiao Yu‐Lan , Zhang Bo , He Chun‐Yang , Zhang Xingang
Published: March 2014

Fluorinated olefin‐containing benzothiadiazoles have important applications in optoelectronic materials. Herein, we reported the direct olefination of fluorinated benzothiadiazoles, as catalyzed by palladium. The reaction proceeds under mild reaction conditions and shows high functional‐group compatibility. A preliminary study of the properties of the resulting symmetrical and unsymmetrical olefin‐containing fluorinated benzothiadiazoles in red‐light‐emitting dyes has also been conducted.