bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiosyncratic Drug Reactions and the Potential Role of Metabolism
Authors: Uetrecht Jack P. 
Published: October 2012

AbstractThere is a large amount of circumstantial evidence that supports the hypothesis that most idiosyncratic drug reactions (IDRs) are caused by reactive metabolites rather than the parent drug. When the total daily dose is included in the calculation, there is a rough correlation between the amount of covalent binding and the risk that a drug will be associated with a significant incidence of IDRs, especially those affecting the liver. However, there are drugs that form a large amount of reactive metabolites and rarely cause IDRs, and there are drugs such as ximelagatran that do not appear to form reactive metabolites and yet had to be withdrawn from the market because of an unacceptable risk of IDRs.There are a wide variety of proteins that are targets of covalent binding, and clearly, not all covalent binding is associated with the same risk of causing an IDR. It is likely that most IDRs are immune mediated, although this is not without controversy, especially with respect to idiosyncratic liver toxicity. There are several hypotheses that address the issue of how drugs initiate an immune response, but in the absence of valid animal models, they are very difficult to rigorously test. These hypotheses include the hapten hypothesis, the danger hypothesis, the p‐I (pharmacological interaction) hypothesis, epigenetic effects leading to activation of the immune system, direct activation of antigen‐presenting cells, and some of the newer biological agents simply appear to alter the balance in the immune system and do not involve reactive metabolites. It is likely that the mechanism by which different drugs induce an immune response is different, at least in detail. There are also hypotheses that do not involve the immune system such as mitochondrial toxicity and the inflammagen hypothesis.In the absence of valid animal models, it is important to use the clinical characteristics of IDRs to evaluate the hypotheses. A very important characteristic is the usual delay between starting a drug and the onset of the IDR. Another important characteristic is that different drugs can cause different types of IDRs in different people and even the same drug can cause different types of IDRs in different people. This is most easily explained by an immune mechanism in which this variability is due to variability in T‐cell‐receptor specificity, which is different even in identical twins. However, until we have a much better understanding of the detailed mechanisms of IDRs, it will be difficult to predict which drug candidates are likely to cause a relatively high incidence of IDRs and which patients are at high risk of such adverse reactions.
Single‐Step Deposition of Au‐ and Pt‐Nanoparticle‐Functionalized Tungsten Oxide Nanoneedles Synthesized Via Aerosol‐Assisted CVD, and Used for Fabrication of Selective Gas Microsensor Arrays
Authors: Vallejos Stella , Umek Polona , Stoycheva Toni , Annanouch Fatima , Llobet Eduard , Correig Xavier , De Marco Patrizia , Bittencourt Carla , Blackman Chris 
Published: October 2012

AbstractTungsten oxide nanostructures functionalized with gold or platinum NPs are synthesized and integrated, using a single‐step method via aerosol‐assisted chemical vapour deposition, onto micro‐electromechanical system (MEMS)‐based gas‐sensor platforms. This co‐deposition method is demonstrated to be an effective route to incorporate metal nanoparticles (NP) or combinations of metal NPs into nanostructured materials, resulting in an attractive way of tuning functionality in metal oxides (MOX). The results show variations in electronic and sensing properties of tungsten oxide according to the metal NPs introduced, which are used to discriminate effectively analytes (C2H5OH, H2, and CO) that are present in proton‐exchange fuel cells. Improved sensing characteristics, in particular to H2, are observed at 250 °C with Pt‐functionalized tungsten oxide films, whereas non‐functionalized tungsten oxide films show responses to low concentrations of CO at low temperatures. Differences in the sensing characteristics of these films are attributed to the different reactivities of metal NPs (Au and Pt), and to the degree of electronic interaction at the MOX/metal NP interface. The method presented in this work has advantages over other methods of integrating nanomaterials and devices, of having fewer processing steps, relatively low processing temperature, and no requirement for substrate pre‐treatment.
Size‐Controlled Synthesis of Cu2‐xE (E = S, Se) Nanocrystals with Strong Tunable Near‐Infrared Localized Surface Plasmon Resonance and High Conductivity in Thin Films
Authors: Liu Xin , Wang Xianliang , Zhou Bin , Law Wing‐Cheung , Cartwright Alexander N. , Swihart Mark T. 
Published: October 2012

AbstractA facile method for preparing highly self‐doped Cu2‐xE (E = S, Se) nanocrystals (NCs) with controlled size in the range of 2.8–13.5 nm and 7.2–16.5 nm, for Cu2‐xS and Cu2‐xSe, respectively, is demonstrated. Strong near‐infrared localized surface plasmon resonance absorption is observed in the NCs, indicating that the as‐prepared particles are heavily p‐doped. The NIR plasmonic absorption is tuned by varying the amount of oleic acid used in synthesis. This effect is attributed to a reduction in the number of free carriers through surface interaction of the deprotonated carboxyl functional group of oleic acid with the NCs. This approach provides a new pathway to control both the size and the cationic deficiency of Cu2‐xSe and Cu2‐xS NCs. The high electrical conductivity exhibited by these NPs in metal‐semiconductor‐metal thin film devices shows promise for applications in printable field‐effect transistors and microelectronic devices.
A Novel Method to Precisely Assemble Loose Nanofiber Structures for Regenerative Medicine Applications
Authors: Beachley Vince , Katsanevakis Eleni , Zhang Ning , Wen Xuejun 
Published: October 2012

AbstractPolymer nanofibers are favorable for tissue engineering scaffolds because of their high surface‐to‐volume ratio and biomimicry of the extracellular matrix. Random and uniaxially oriented polymer nanofibers are easily fabricated by conventional electrospinning techniques; however, control over fiber organization within nanofiber structures is limited when they are collected directly from an electrospinning jet. The regenerative medicine applications of electrospun scaffolds could be expanded by developing assembly methods that allow better control of fiber organization. Here, a novel technique is presented that utilizes parallel automated tracks to orient and collect nanofibers from an electrospinning jet. The stabilized fibers are then subsequently assembled into desirable structures. It is difficult to assemble complex structures directly from an electrospinning jet because of high electrical charge and velocities, so this technology adds an intermediate step where nanofibers are immobilized on automated tracks. The result is a continuous steady‐state delivery of static stabilized nanofibers that provides a unique and promising platform for automated post processing into useful nanofiber structures. This technique also allows for an indefinite amount of time, as determined by design parameters, for fibers to dry or cool before they contact other nanofibers in the collection site, thus eliminating potential for fiber‐to‐fiber adhesions even with slow evaporating solvents or high‐temperature melts. To demonstrate potential in regenerative medicine applications, several nanofiber structures were fabricated, including: 2D structures with well‐controlled fiber density; 3D loosely assembled aligned nanofiber structures with good cell penetration properties; and, complex layer‐by‐layer 3D aligned fiber structures assembled by integration with post‐processing techniques.
Extension of the Stöber Method to Construct Mesoporous SiO2 and TiO2 Shells for Uniform Multifunctional Core–Shell Structures
Authors: Li Wei , Zhao Dongyuan 
Published: October 2012

AbstractCore–shell nanoparticles (CSNs) have attracted considerable attention because of their promising applications in a wide range of fields. Recently, substantial efforts have been focused on the development of facile and versatile methods for preparing CSNs with mesoporous SiO2 or TiO2 shells because of their fascinating properties, such as high surface area, large pore channels and high pore volume. This Research News reviews the recent progress in facile, versatile and reproducible approaches which are simply extended from the well‐known Stöber method to construct mesoporous SiO2 and TiO2 shells for uniform multifunctional core–shell nanostructures. Several strategies, including the surfactant‐templating process, the long‐chain organosilane‐assisted approach, the phase transfer assisted surfactant‐templating process, and the kinetics‐controlled coating approach, are discussed. In addition, new trends in this field for the creation of multifunctional CSNs and novel nanostructures are highlighted.
Synthesis and Selective Human Monoamine Oxidase B Inhibition of Heterocyclic Hybrids Based on Hydrazine and Thiazole Scaffolds
Authors: Carradori Simone , D'Ascenzio Melissa , De Monte Celeste , Secci Daniela , Yáñez Matilde 
Published: October 2012

AbstractA new scaffold of hydrazothiazoles has been designed as monoamine oxidase (MAO) inhibitors combining the hydrazine moiety of iproniazid and the thiazole nucleus of glitazones, a class of peroxisome proliferator‐activated receptor (PPAR)γ agonists recently co‐crystallized with human MAO‐B. The resulting derivatives were synthesized and assayed to evaluate their in vitro activity against both the A and B isoforms of hMAO. All compounds were shown to be selective hMAO‐B inhibitors with IC50 values in the low micromolar/high nanomolar range. Such results suggest that the hydrazothiazole scaffold could be considered as an interesting pharmacophore for the future design of new lead compounds as coadjuvants for the treatment of neurodegenerative diseases.
Brain estrogen signaling effects acute modulation of acoustic communication behaviors: A working hypothesis
Authors: Remage‐Healey Luke 
Published: October 2012

AbstractAlthough estrogens are widely considered circulating “sex steroid hormones” typically associated with female reproduction, recent evidence suggests that estrogens can act as local modulators of brain circuits in both males and females. The functional implications of this newly characterized estrogen signaling system have begun to emerge. This essay summarizes evidence in support of the hypothesis that the rapid production of estrogens in brain circuits can drive acute changes in both the production and perception of acoustic communication behaviors. These studies have revealed two fundamental neurobiological concepts: (1) estrogens can be locally produced in brain circuits, independent of levels in nearby circuits and in the circulation and (2) estrogens can have very rapid effects within these brain circuits to modulate social vocalizations, acoustic processing, and sensorimotor integration. This vertebrate‐wide span of research, including vocalizing fishes, amphibians, and birds, emphasizes the importance of comparative model systems in understanding principles of neurobiology.
Quantification and validation of HPLC‐UV and LC‐MS assays for therapeutic drug monitoring of ertapenem in human plasma
Authors: Pickering Matthew , Brown Stacy 
Published: October 2012

ABSTRACTRapid and simple HPLC‐UV and LC‐MS methods were developed and validated for the quantification of ertapenem (Invanz™) in human plasma. Ertapenem is a unique drug in that current dosing recommendations call for a 1 g dose for normal renal function patients, despite body weight. These assays, which involve a protein precipitation followed by liquid–liquid extraction, allow for fast therapeutic drug monitoring of ertapenem in patients, which is especially useful in special populations. Both methods were sufficient to baseline resolve meropenem (internal standard) and ertapenem, and were validated over 3 days using a six‐point calibration curve (0.5–50 µg/mL). Validation was collected using four different points on the calibrations curve yielding acceptable precision (<15% inter‐day and intra‐day; <20% for lower limit of quantitation, LLOQ) as well as accuracy (<15% inter‐day and intra‐day; <20% for LLOQ). The lower limit of detection (LOD) was determined to be 0.1 and 0.05 µg/mL for the HPLC‐UV and LC‐MS methods, respectively. The developed HPLC‐UV and LC‐MS methods for ertapenem quantification are fast, accurate and reproducible over the calibration range and can be used to determine ertapenem plasma concentrations for monitoring clinical efficacy. Copyright © 2012 John Wiley & Sons, Ltd.
Oriented immobilized anti‐hIgG via Fc fragment‐imprinted PHEMA cryogel for IgG purification
Authors: Bereli Nilay , Ertürk Gizem , Tümer M.Aşkın , Say Rıdvan , Denizli Adil 
Published: October 2012

ABSTRACTAntibodies are used in many applications, especially as diagnostic and therapeutic agents. Among the various techniques used for the purification of antibodies, immunoaffinity chromatography is by far the most common. For this purpose, oriented immobilization of antibodies is an important step for the efficiency of purification step. In this study, Fc fragment‐imprinted poly(hydroxyethyl methacrylate) cryogel (MIP) was prepared for the oriented immobilization of anti‐hIgG for IgG purification from human plasma. Non‐imprinted poly(hydroxyethyl methacrylate) cryogel (NIP) was also prepared for random immobilization of anti‐hIgG to compare the adsorption capacities of oriented (MIP/anti‐hIgG) and random (NIP/anti‐hIgG) cryogel columns. The amount of immobilized anti‐hIgG was 19.8 mg/g for the NIP column and 23.7 mg/g for the MIP column. Although the amount of immobilized anti‐hIgG was almost the same for the NIP and MIP columns, IgG adsorption capacity was found to be three times higher than the NIP/anti‐hIgG column (29.7 mg/g) for the MIP/anti‐hIgG column (86.9 mg/g). Higher IgG adsorption capacity was observed from human plasma (up to 106.4 mg/g) with the MIP/anti‐hIgG cryogel column. Adsorbed IgG was eluted using 1.0 m NaCl with a purity of 96.7%. The results obtained here are very encouraging and showed the usability of MIP/anti‐hIgG cryogel prepared via imprinting of Fc fragments as an alternative to conventional immunoaffinity techniques for IgG purification. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis and Structural Characterisation of Selective Non‐Carbohydrate‐Based Inhibitors of Bacterial Sialidases
Authors: Brear Paul , Telford Judith , Taylor Garry L. , Westwood Nicholas J. 
Published: October 2012

AbstractThe major human pathogen Streptococcus pneumoniae plays a key role in several disease states including septicaemia, meningitis and community‐acquired pneumonia. Although vaccines against S. pneumoniae are available as prophylactics, there remains a need to identify and characterise novel chemical entities that can treat the diseases caused by this pathogen. S. pneumoniae expresses three sialidases, enzymes that cleave sialic acid from carbohydrate‐based surface molecules. Two of these enzymes, NanA and NanB, have been implicated in the pathogenesis of S. pneumoniae and are considered to be validated drug targets. Here we report our studies on the synthesis and structural characterisation of novel NanB‐selective inhibitors that are inspired by the β‐amino‐sulfonic acid family of buffers.
When the Leader Gets Loose: In Vivo Biosynthesis of a Leaderless Prenisin Is Stimulated by a trans‐Acting Leader Peptide
Authors: Khusainov Rustem , Kuipers Oscar P. 
Published: October 2012

AbstractThe nisin leader is believed to be crucial for nisin biosynthesis. Here, by using a construct completely lacking the leader peptide, we show that an up to fivefold‐dehydrated leaderless prenisin can be obtained, as judged by MALDI‐TOF MS, and that some of these species are biologically active, thus suggesting that at least three lanthionine rings are present. Notably, by expressing the leader peptide in trans together with the leaderless prenisin, we were able to increase the dehydration/cyclization efficiency of both NisB and NisC, but still with limited efficiency until the fifth dehydratable residue (Thr13) was processed, thereby enabling three rings to form. This, for the first time, demonstrates that 1) the leader is not absolutely necessary for the dehydration reaction of class I lantibiotics to occur in vivo; 2) the leader acts in trans in vivo; 3) the leader increases the efficiency of modification. Based on previous work and our current study, a model for the interactions of NisB and NisC with prenisin is proposed, in which the leader induces a more active conformation and/or productive complex formation of the biosynthetic machinery, and, when covalently bound, is involved in increasing the efficiency of dehydration to the C‐terminal end of the prenisin substrate molecule.
Residue 75 of Interleukin‐8 is Crucial for its Interactions with Glycosaminoglycans
Authors: Nordsieck Karoline , Pichert Annelie , Samsonov Sergey A. , Thomas Lars , Berger Christian , Pisabarro M. Teresa , Huster Daniel , Beck‐Sickinger Annette G. 
Published: October 2012

AbstractThe interactions between regulatory proteins such as interleukin‐8 (IL‐8) and glycosaminoglycans are of great interest both for the general understanding of regulatory processes in biology and for the development of implant coatings and innovative materials that suppress undesired immune responses and improve wound healing. In previous work, a number of residues of IL‐8 that interact strongly with several glycosaminoglycans (GAGs) have been identified. In particular, the negatively charged Glu75 was reported to be involved in interactions with charged GAGs. To improve understanding of the role of this residue, we generated a selectively 15N‐labeled E75K variant of IL‐8(1–77) by expressed protein ligation. NMR and fluorescence spectroscopy in combination with molecular modeling were applied to evaluate the particular role of residue 75 in interactions with GAGs. Remarkably, more residues in the variant responded to GAG binding than in the wild‐type. For the first time, we identified amino acids 34 to 36 as additional residues in the loop region of IL‐8(1–77) that participate in the interactions with GAGs. These findings indicate that the N terminus of the E75K variant is more important as a second binding site for GAGs than that of the wild‐type IL‐8(1–77).
Deprotonation‐Induced Aromaticity Enhancement and New Conjugated Networks in meso‐Hexakis(pentafluorophenyl)[26]hexaphyrin
Authors: Cha Won‐Young , Lim Jong Min , Yoon Min‐Chul , Sung Young Mo , Lee Byung Sun , Katsumata Sho , Suzuki Masaaki , Mori Hirotaka , Ikawa Yoshiya , Furuta Hiroyuki , Osuka Atsuhiro , Kim Dongho 
Published: October 2012

Abstractmeso‐Hexakis(pentafluorophenyl)‐substituted neutral hexaphyrin with a 26π‐electronic circuit can be regarded as a real homolog of porphyrin with an 18π‐electronic circuit with respect to a quite flat molecular structure and strong aromaticity. We have investigated additional aromaticity enhancement of meso‐hexakis(pentafluorophenyl)[26]hexaphyrin(1.1.1.1.1.1) by deprotonation of the inner NH groups in the macrocyclic molecular cavity to try to induce further structural planarization. Deprotonated mono‐ and dianions of [26]hexaphyrin display sharp B‐like bands, remarkably strong fluorescence, and long‐lived singlet and triplet excited‐states, which indicate enhanced aromaticity. Structural, spectroscopic, and computational studies have revealed that deprotonation induces structural deformations, which lead to a change in the main conjugated π‐electronic circuit and cause enhanced aromaticity.
Heteroleptic FeII Complexes of 2,2′‐Biimidazole and Its Alkylated Derivatives: Spin‐Crossover and Photomagnetic Behavior
Authors: Phan Hoa V. , Chakraborty Pradip , Chen Meimei , Calm Yitzi M. , Kovnir Kirill , Keniley Lawrence K. , Hoyt Jordan M. , Knowles Elisabeth S. , Besnard Céline , Meisel Mark W. , Hauser Andreas , Achim Catalina , Shatruk Michael 
Published: October 2012

AbstractThree iron(II) complexes, [Fe(TPMA)(BIM)](ClO4)2⋅0.5H2O (1), [Fe(TPMA)(XBIM)](ClO4)2 (2), and [Fe(TPMA)(XBBIM)](ClO4)2 ⋅0.75CH3OH (3), were prepared by reactions of FeII perchlorate and the corresponding ligands (TPMA=tris(2‐pyridylmethyl)amine, BIM=2,2′‐biimidazole, XBIM=1,1′‐(α,α′‐o‐xylyl)‐2,2′‐biimidazole, XBBIM=1,1′‐(α,α′‐o‐xylyl)‐2,2′‐bibenzimidazole). The compounds were investigated by a combination of X‐ray crystallography, magnetic and photomagnetic measurements, and Mössbauer and optical absorption spectroscopy. Complex 1 exhibits a gradual spin crossover (SCO) with T1/2=190 K, whereas 2 exhibits an abrupt SCO with approximately 7 K thermal hysteresis (T1/2=196 K on cooling and 203 K on heating). Complex 3 is in the high‐spin state in the 2–300 K range. The difference in the magnetic behavior was traced to differences between the inter‐ and intramolecular interactions in 1 and 2. The crystal packing of 2 features a hierarchy of intermolecular interactions that result in increased cooperativity and abruptness of the spin transition. In 3, steric repulsion between H atoms of one of the pyridyl substituents of TPMA and one of the benzene rings of XBBIM results in a strong distortion of the FeII coordination environment, which stabilizes the high‐spin state of the complex. Both 1 and 2 exhibit a photoinduced low‐spin to high‐spin transition (LIESST effect) at 5 K. The difference in the character of intermolecular interactions of 1 and 2 also manifests in the kinetics of the decay of the photoinduced high‐spin state. For 1, the decay rate constant follows the single‐exponential law, whereas for 2 it is a stretched exponential, reflecting the hierarchical nature of intermolecular contacts. The structural parameters of the photoinduced high‐spin state at 50 K are similar to those determined for the high‐spin state at 295 K. This study shows that N‐alkylation of BIM has a negligible effect on the ligand field strength. Therefore, the combination of TPMA and BIM offers a promising ligand platform for the design of functionalized SCO complexes.
Control of Light‐Promoted [2+2] Cycloaddition Reactions by a Remote Ancillary Regulatory Group That Is Covalently Attached to Rhenium Rectangles
Authors: Lu Zong‐Zhan , Lee Chung‐Chou , Velayudham Murugesan , Lee Li‐Wei , Wu Jing‐Yun , Kuo Ting‐Shen , Lu Kuang‐Lieh 
Published: October 2012

AbstractThe high‐yielding self‐assembly of three neutral rhenium(I) rectangles, [Re2(CO)6(L)(bpe)]2 (1 a, L=2,2′‐biimidazolate (biim); 1 b, L=2,2′‐bisbenzimidazolate (bbim); 1 c, L=2,2′‐bis(4,5‐dimethylimidazolate) (bdmim); bpe=trans‐1,2‐bis(4‐pyridyl)ethylene), under hydrothermal conditions is described. The rectangles were structurally characterized by spectroscopic techniques and further confirmed by single‐crystal X‐ray diffraction. Upon irradiation with a Hg lamp at 365 nm, the bpe ligands of rectangles 1 a and 1 b underwent [2+2] photocycloaddition reactions to produce [{(Re(CO)3)2L}2(4,4′‐tpcb)2] (2 a, L=biim; 2 b, L=bbim; 4,4′‐tpcb=1,2,3,4‐tetrakis(4‐pyridyl)cyclobutane) through a single‐crystal‐to‐single‐crystal (SCSC) transformation. However, rectangle 1 c, which contained methyl groups on the 2,2′‐biimidazolate ligand, failed to undergo cycloaddition, even after prolonged irradiation. This result indicates that the light‐induced cycloaddition reaction can be preferentially controlled by the remote regulatory substituents, which are attached onto the same backbone of the rectangle complex. This transformation is the first reported utilization of a remote ancillary regulatory ligand that is covalently attached onto a coordination compound to control the [2+2] cycloaddition reaction.