bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural studies and SH3 domain binding properties of a human antiviral salivary proline‐rich peptide
Authors: Righino Benedetta , Pirolli Davide , Radicioni Giorgia , Marzano Valeria , Longhi Renato , Arcovito Alessandro , Sanna Maria Teresa , De Rosa Maria Cristina , Paoluzi Serena , Cesareni Gianni , Messana Irene , Castagnola Massimo , Vitali Alberto 
Published: June 2016

AbstractHuman saliva contains hundreds of small proline‐rich peptides originated by the proteolytic cleavage of the salivary basic Proline‐Rich Proteins. Nevertheless only for few of them a specific biological activity has been assigned to date. Among them, the 1932 Da peptide (p1932) has been patented as an anti‐HIV agent. In order to shed light on the possible mechanism of action of this peptide, we assessed in this study, by means of molecular dynamics calculations, circular dichroism and FTIR spectroscopic techniques, that p1932 has an intrinsic propensity to adopt a polyproline‐II helix arrangement. This structural feature combined with the presence of PxxP motifs in its primary structure, represents an essential property for the exploitation of several biological activities. Next to these findings, we recently demonstrated the ability of this peptide to be internalized within cells of the oral mucosa, thus we focused onto a possible intracellular target, represented by the SH3 domains family. Its ability to interact with selected SH3 domains was finally assayed by Surface Plasmon Resonance spectroscopy. As a result, only Fyn, Hck, and c‐Src SH3 domains gave positive results in terms of interaction, showing dissociation constants ranging from nanomolar to micromolar values having the best performer a KD of 148 nM. It is noteworthy that all the interacting domains belong to the Src kinases family, suggesting a role for p1932 as a modulator of the signal transduction pathways mediated by these kinases. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714–725, 2016.
ROS‐responsive drug delivery systems
Authors: Liang Jing , Liu Bin 
Published: June 2016

AbstractReactive oxygen species (ROS) play an important role in signal transduction and metabolism. Over‐produced ROS in cells or tissues, however, often leads to oxidation stress that has implications in a series of diseases including cancer, aging, atherosclerosis and inflammation. Driven by the need for on‐demand drug delivery and fuelled by recent development of ROS‐responsive materials and nanomedicine, responsive drug delivery systems (DDSs) have gained increasing research interest. ROS‐responsive DDS is designed to release therapeutic agents only in targets of interest that produce excessive ROS, which may lead to both enhanced therapeutic efficiency and reduced side effects. Multiple‐stimuli responsive DDSs that are also sensitive to other stimuli can further enhance controlled drug release in sites where multiple stimuli coexist. Beyond drug delivery, multifunctional DDSs have great potential in achieving simultaneous imaging, combinatorial therapy and targeting ability by introducing multifunctional elements such as signal reporter, targeting elements and photosensitizer. This review will summarize the latest development of ROS‐responsive DDSs and discuss their design principle and biomedical applications.
A framework to learn graph theory using simple wireless network models
Authors: Dapena Adriana , Vázquez‐Araujo Francisco J. , Castro Paula M. , Souto‐Salorio Maria J. 
Published: June 2016

ABSTRACTIn order to improve the student learning process, we present a framework to define attractive computer laboratory lessons in Engineering Degrees. Theoretical concepts are illustrated from a practical point of view using a graphical user interface designed to establish the relationship between wireless network models and graph theory concepts. In this paper, we will explain some simple routing protocols to illustrate both Dijkstra's algorithm and the graph dominant set. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:843–852, 2016; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21753
Fluorescent Mechanism‐Based Probe for Aerobic Flavin‐Dependent Enzyme Activity
Authors: McCulloch Ian P. , La Clair James J. , Jaremko Matt J. , Burkart Michael D. 
Published: June 2016

AbstractDiversity in non‐ribosomal peptide and polyketide secondary metabolism is facilitated by interactions between biosynthetic domains with discrete monomer loading and their cognate tailoring enzymes, such as oxidation or halogenation enzymes. The cooperation between peptidyl carrier proteins and flavin‐dependent enzymes offers a specialized strategy for monomer selectivity for oxidization of small molecules from within a complex cellular milieu. In an effort to study this process, we have developed fluorescent probes to selectively label aerobic flavin‐dependent enzymes. Here we report the preparation and implementation of these tools to label oxidase, monooxygenase, and halogenase flavin‐dependent enzymes.
Semi‐supervised kernel partial least squares fault detection and identification approach with application to HGPWLTP
Authors: Jia Qilong , Du Wenyou , Zhang Yingwei 
Published: June 2016

AbstractIn this paper, fault detection and identification methods based on semi‐supervised Laplacian regularization kernel partial least squares (LRKPLS) are proposed. In Laplacian regularization learning framework, unlabeled and labeled samples are used to improve estimate of data manifold so that one can establish a more robust data model. We show that LRKPLS can avoid the over‐fitting problem which may be caused by sample insufficient and outliers present. Moreover, the proposed LRKPLS approach has no special restriction on data distribution, in other words, it can be used in the case of nonlinear or non‐Gaussian data. On the basis of LRKPLS, corresponding fault detection and identification methods are proposed. Those methods are used to monitor a numerical example and Hot Galvanizing Pickling Waste Liquor Treatment Process (HGPWLTP), and the cases study show effeteness of the proposed approaches. Copyright © 2016 John Wiley & Sons, Ltd.
Gold‐Catalyzed Oxidation/C−H Functionalization of Ynones: Efficient and Rapid Access to Functionalized Polycyclic Salicyl Ketones
Authors: Ji Kegong , Yang Fang , Gao Shiyue , Tang Jiangjiang , Gao Jinming 
Published: June 2016

AbstractAn efficient strategy to construct salicyl ketones through gold‐catalyzed oxidation/C−H functionalization of ynones is reported. A variety of functionalized salicyl ketones are readily accessed by utilizing this non‐diazo approach, thus providing a viable alternative to synthetically useful salicyl ketones with a yield up to 98 %. The α‐oxo gold carbenes generated in situ through gold‐catalyzed oxidation of ynones can be trapped effectively by internal aryl and heteroaromatic groups. Electronic and steric effects were also investigated in this reaction. The anticancer activity of one salicyl ketone analogue was investigated and its cytotoxicity assays against the PC‐3 prostate cancer cell line and SKOV‐3 human ovarian carcinoma cell line yield IC50 were 0.81±0.05 and 0.87±0.15 μm, respectively, demonstrating that salicyl ketone analogues showed good anticancer activity.
New Experimental Insight into the Nature of Metal−Metal Bonds in Digallium Compounds: J Coupling between Quadrupolar Nuclei
Authors: Kobera Libor , Southern Scott A. , Rao Gyandshwar Kumar , Richeson Darrin S. , Bryce David L. 
Published: June 2016

AbstractMultiple bonding between atoms is of ongoing fundamental and applied interest. Here, we report a multinuclear (1H, 13C, and 71Ga) solid‐state magnetic resonance spectroscopic study of digallium compounds which have been proposed, albeit somewhat controversially, to contain single, double, and triple Ga−Ga bonds. Of particular relevance to the nature of these bonds, we have carried out two‐dimensional 71Ga J/D‐resolved NMR experiments which provide a direct measurement of J(71Ga,71Ga) spin–spin coupling constants across the gallium−gallium bonds. When placed in the context of clear‐cut experimental data for analogous singly, doubly, and triply bonded carbon spin pairs or boron spin pairs, the 71Ga NMR data clearly support the notion of a different bonding paradigm in the gallium systems. Our findings are consistent with an increasing role across the purported gallane–gallene–gallyne series for classical and/or slipped π‐type bonding orbitals.
Formation of Oxazoles from Elusive Gold(I) α‐Oxocarbenes: A Mechanistic Study
Authors: Schulz Jiří , Jašík Juraj , Gray Andrew , Roithová Jana 
Published: June 2016

AbstractThe gold(I) catalyzed reaction between phenylacetylene, pyridine N‐oxide and acetonitrile leading, via a putative gold‐α‐oxocarbene intermediate, towards an oxazole product has been investigated. A novel mass spectrometric method called “delayed reactant labeling” is used to track consecutive and parallel reactions. It clearly shows that the intramolecular formation of a pyridine adduct of gold‐α‐oxocarbene is in competition with the formation of the oxazole product. The reaction mechanism most probably corresponds to competition between acetonitrile and pyridine in an almost barrierless reaction with putative gold‐α‐oxocarbene within the solvent cage. The detected ionic species have been characterized by helium tagging infrared photodissociation spectroscopy.
Cobalt‐Catalyzed C(sp2)−H Methylation by using Dicumyl Peroxide as both the Methylating Reagent and Hydrogen Acceptor
Authors: Li Qun , Li Yanrong , Hu Weipeng , Hu Renjian , Li Guigen , Lu Hongjian 
Published: June 2016

AbstractThe first cobalt‐catalyzed direct methylation of a C(sp2)−H bond using dicumyl peroxide (DCP) as both the methylating reagent and hydrogen acceptor has been established. The reaction proceeded without the use of any additives, and was proven to be applicable to various amides bearing a 2‐pyridinylisopropyl (PIP) directing group, providing an efficient access to o‐methyl aryl amides with high functional‐group tolerance. Preliminary mechanistic studies suggest a radical process would be involved in the catalytic process.
c‐FOS expression in the visual system of tree shrews after monocular inactivation
Authors: Takahata Toru , Kaas Jon H. 
Published: June 2016

ABSTRACTTree shrews possess an unusual segregation of ocular inputs to sublayers rather than columns in the primary visual cortex (V1). In this study, the lateral geniculate nucleus (LGN), superior colliculus (SC), pulvinar, and V1 were examined for changes in c‐FOS, an immediate‐early gene, expression after 1 or 24 hours of monocular inactivation with tetrodotoxin (TTX) in tree shrews. Monocular inactivation greatly reduced gene expression in LGN layers related to the blocked eye, whereas normally high to moderate levels were maintained in the layers that receive inputs from the intact eye. The SC and caudal pulvinar contralateral to the blocked eye had greatly (SC) or moderately (pulvinar) reduced gene expressions reflective of dependence on the contralateral eye. c‐FOS expression in V1 was greatly reduced contralateral to the blocked eye, with most of the expression that remained in upper layer 4a and lower 4b and lower layer 6 regions. In contrast, much of V1 contralateral to the active eye showed normal levels of c‐FOS expression, including the inner parts of sublayers 4a and 4b and layers 2, 3, and 6. In some cases, upper layer 4a and lower 4b showed a reduction of gene expression. Layers 5 and sublayer 3c had normally low levels of gene expression. The results reveal the functional dominance of the contralateral eye in activating the SC, pulvinar, and V1, and the results from V1 suggest that the sublaminar organization of layer 4 is more complex than previously realized. J. Comp. Neurol. 525:151–165, 2017. © 2016 Wiley Periodicals, Inc.
Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Piragliatin, a Glucokinase Activator, and Glyburide, a Sulfonylurea, in Type 2 Diabetic Patients
Authors: Zhai S. , Georgy A. , Liang Z. , Zhi J. 
Published: June 2016

AbstractA glucokinase activator and a sulfonylurea might be coprescribed to synergize treatment success for type 2 diabetes (T2D). This clinical pharmacology study was designed to investigate the potential glucose‐lowering effect or pharmacodynamic (PD), pharmacokinetic (PK), and safety/tolerability interactions between piragliatin and glyburide in T2D patients already taking glyburide but not adequately controlled. This was an open‐label, multiple‐dose, 3‐period, single‐sequence crossover design: on days –1, 6, and 12, PD and PK samples were drawn with glyburide alone (period 0), piragliatin + glyburide (period 1), and piragliatin alone (period 2) treatments. The glucose‐lowering effect, including fasting plasma glucose (FPG), of piragliatin was more pronounced when it was administered concomitantly with glyburide as compared to piragliatin or glyburide administered alone. However, this enhancement cannot be explained by a potential PK interaction between piragliatin and glyburide. Other than hypoglycemia, there were no clinically relevant safety findings. Thus, the enhanced PD effect warrants further investigation to define the optimal dose combination between glucokinase activators and sulfonylureas with regard to efficacy, safety, and tolerability.
Pharmacokinetic Interactions Between Isavuconazole and the Drug Transporter Substrates Atorvastatin, Digoxin, Metformin, and Methotrexate in Healthy Subjects
Authors: Yamazaki Takao , Desai Amit , Goldwater Ronald , Han David , Lasseter Kenneth C. , Howieson Corrie , Akhtar Shahzad , Kowalski Donna , Lademacher Christopher , Rammelsberg Diane , Townsend Robert 
Published: June 2016

AbstractThis article summarizes 4 phase 1 trials that explored interactions between the novel, triazole antifungal isavuconazole and substrates of the drug transporters breast cancer resistance protein (BCRP), multidrug and toxin extrusion protein‐1 (MATE1), organic anion transporters 1/3 (OAT1/OAT3), organic anion‐transporting polypeptide 1B1 (OATP1B1), organic cation transporters 1/2 (OCT1/OCT2), and P‐glycoprotein (P‐gp). Healthy subjects received single doses of atorvastatin (20 mg; OATP1B1 and P‐gp substrate), digoxin (0.5 mg; P‐gp substrate), metformin (850 mg; OCT1, OCT2, and MATE1 substrate), or methotrexate (7.5 mg; BCRP, OAT1, and OAT3 substrate) in the presence and absence of clinical doses of isavuconazole (200 mg 3 times a day for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased mean area under the plasma concentration‐time curves (90% confidence interval) of atorvastatin, digoxin, and metformin to 137% (129, 145), 125% (117, 134),  and 152% (138, 168) and increased mean maximum plasma concentrations to 103% (88, 121), 133% (119, 149), and 123% (109, 140), respectively. Methotrexate parameters were unaffected by isavuconazole. There were no serious adverse events. These findings indicate that isavuconazole is a weak inhibitor of P‐gp, as well as OCT1, OCT2, MATE1, or a combination thereof but not of BCRP, OATP1B1, OAT1, or OAT3.
Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects
Authors: Yamazaki Takao , Desai Amit , Goldwater Ronald , Han David , Howieson Corrie , Akhtar Shahzad , Kowalski Donna , Lademacher Christopher , Pearlman Helene , Rammelsberg Diane , Townsend Robert 
Published: June 2016

AbstractThis report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23). Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration‐time curves (AUC∞) and maximum concentrations (Cmax) as follows: bupropion, AUC∞ reduced 42%, Cmax reduced 31%; repaglinide, AUC∞ reduced 8%, Cmax reduced 14%; caffeine, AUC∞ increased 4%, Cmax reduced 1%; dextromethorphan, AUC∞ increased 18%, Cmax increased 17%; R‐methadone, AUC∞ reduced 10%, Cmax increased 3%; S‐methadone, AUC∞ reduced 35%, Cmax increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2‐, CYP2C8‐, or CYP2D6‐mediated metabolism.
Pharmacokinetic Assessment of Drug‐Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults
Authors: Groll Andreas H. , Desai Amit , Han David , Howieson Corrie , Kato Kota , Akhtar Shahzad , Kowalski Donna , Lademacher Christopher , Lewis William , Pearlman Helene , Mandarino Debra , Yamazaki Takao , Townsend Robert 
Published: June 2016

AbstractThis report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration‐time curves (AUC0–∞) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (Cmax) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; Cmax of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism.
Pharmacokinetic Evaluation of CYP3A4‐Mediated Drug‐Drug Interactions of Isavuconazole With Rifampin, Ketoconazole, Midazolam, and Ethinyl Estradiol/Norethindrone in Healthy Adults
Authors: Townsend Robert , Dietz Albert , Hale Christine , Akhtar Shahzad , Kowalski Donna , Lademacher Christopher , Lasseter Kenneth , Pearlman Helene , Rammelsberg Diane , Schmitt‐Hoffmann Anne , Yamazaki Takao , Desai Amit 
Published: June 2016

AbstractThis report describes the phase 1 trials that evaluated the metabolism of the novel triazole antifungal isavuconazole by cytochrome P450 3A4 (CYP3A4) and isavuconazole's effects on CYP3A4‐mediated metabolism in healthy adults. Coadministration of oral isavuconazole (100 mg once daily) with oral rifampin (600 mg once daily; CYP3A4 inducer) decreased isavuconazole area under the concentration‐time curve (AUCτ) during a dosing interval by 90% and maximum concentration (Cmax) by 75%. Conversely, coadministration of isavuconazole (200 mg single dose) with oral ketoconazole (200 mg twice daily; CYP3A4 inhibitor) increased isavuconazole AUC from time 0 to infinity (AUC0‐∞) and Cmax by 422% and 9%, respectively. Isavuconazole was coadministered (200 mg 3 times daily for 2 days, then 200 mg once daily) with single doses of oral midazolam (3 mg; CYP3A4 substrate) or ethinyl estradiol/norethindrone (35 μg/1 mg; CYP3A4 substrate). Following coadministration, AUC0‐∞ increased 103% for midazolam, 8% for ethinyl estradiol, and 16% for norethindrone; Cmax increased by 72%, 14%, and 6%, respectively. Most adverse events were mild to moderate in intensity; there were no deaths, and serious adverse events and adverse events leading to study discontinuation were rare. These results indicate that isavuconazole is a sensitive substrate and moderate inhibitor of CYP3A4.
Crystallographic and Dynamic Aspects of Solid‐State NMR Calibration Compounds: Towards ab Initio NMR Crystallography
Authors: Li Xiaozhou , Tapmeyer Lukas , Bolte Michael , van de Streek Jacco 
Published: June 2016

AbstractThe excellent results of dispersion‐corrected density functional theory (DFT‐D) calculations for static systems have been well established over the past decade. The introduction of dynamics into DFT‐D calculations is a target, especially for the field of molecular NMR crystallography. Four 13C ss‐NMR calibration compounds are investigated by single‐crystal X‐ray diffraction, molecular dynamics and DFT‐D calculations. The crystal structure of 3‐methylglutaric acid is reported. The rotator phases of adamantane and hexamethylbenzene at room temperature are successfully reproduced in the molecular dynamics simulations. The calculated 13C chemical shifts of these compounds are in excellent agreement with experiment, with a root‐mean‐square deviation of 2.0 ppm. It is confirmed that a combination of classical molecular dynamics and DFT‐D chemical shift calculation improves the accuracy of calculated chemical shifts.
Exploring the Loading Capacity of Generation Six to Eight Dendronized Polymers in Aqueous Solution
Authors: Maltar‐Strmečki Nadica , Yu Hao , Messmer Daniel , Zhang Baozhong , Schlüter A. Dieter , Hinderberger Dariush 
Published: June 2016

AbstractAspects of size, structural (im)perfection, inner density, and guest molecule loading capacity of dendronized polymers (DPs) of high generation (6≤g≤8) in aqueous solution are studied using electron paramagnetic resonance spectroscopy on amphiphilic, spin‐labeled guest molecules. The results show that the interior of the charged DPs is strongly polar, especially in comparison to their lower generation (1–4) analogues. This is a direct sign that large amounts of water penetrate the DP surface, reflecting the structural (im)perfections of these high‐generation DPs and much lower segmental densities than theoretically achievable. Images obtained with atomic force microscopy reveal that the high‐generation DPs do not aggregate and give further insights into the structural imperfections. Electron paramagnetic resonance spectroscopic data further show that despite their structural imperfections, these DPs can bind and release large numbers of amphiphilic molecules. It is concluded that attention should be paid to their synthesis, for which a protocol needs to be developed that avoids the relatively large amount of defects generated in the direct conversion of a generation g=4 DP to a generation g=6 DP, which had to be used here.
Dimethylsilanone Generation from Pyrolysis of Polysiloxanes Filled with Nanosized Silica and Ceria/Silica
Authors: Kulyk Kostiantyn , Zettergren Henning , Gatchell Michael , Alexander John D. , Borysenko Mykola , Palianytsia Borys , Larsson Mats , Kulik Tetiana 
Published: June 2016

AbstractTemperature‐programmed desorption mass spectrometry (TPD MS) was used to study the pyrolysis of PDMS and its composites with nanosized silica and ceria/silica. The results suggest that the elusive organosilicon compound, dimethylsilanone, is generated from PDMS over a broad temperature range (in some cases starting at 70 °C). The presence of nano‐oxides catalyzes this process. Ions characteristic of the fragmentation of dimethylsilanone under electron ionization are assigned with the aid of DFT structure calculations. Possible reaction mechanisms for dimethylsilanone generation are discussed in the context of the calculated kinetic parameters. Observed accompanying products of PDMS pyrolysis, such as tetramethylcyclodisiloxane and hexamethylcyclotrisiloxane, indicate that multiple channels are involved in the dimethylsilanone release.