bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐Delivery of Antiviral and Antifungal Therapeutics for the Treatment of Sexually Transmitted Infections using a Moldable, Supramolecular Hydrogel
Authors: Lee Ashlynn L.Z. , Ng Victor W.L. , Poon Ghim Lee , Ke Xiyu , Hedrick James L. , Yang Yi Yan
Published: September 2014

In this investigation, a therapeutic co‐delivery hydrogel system is developed to provide effective HIV prophylaxis, alongside the prevention and/or treatment of candidiasis. Two components—a HIV reverse transcriptase inhibitor, tenofovir, and a cationic macromolecular antifungal agent derived from a vitamin D‐functionalized polycarbonate (VD/BnCl (1:30))—are formulated into biodegradable vitamin D‐functionalized polycarbonate/PEG‐based supramolecular hydrogels. The hydrogels exhibit thixotropic properties and can be easily spread across surfaces for efficient drug absorption. Sustained release of tenofovir from the hydrogel is observed, where approximately 85% tenofovir is released within 3 h. VD/BnCl (1:30) does not impede drug diffusion from the hydrogel as the drug release profiles are similar with and without the polycation. Antimicrobial efficacy studies indicate that the hydrogels kill C. albicans efficiently with a minimum bactericidal concentration (MBC) of 0.25–0.5 g L−1. These hydrogels also eradicate C. albicans biofilm effectively at 4× MBC. When human dermal fibroblasts (as model mammalian cells) are treated with these hydrogels, cell viability remains high at above 80%, demonstrating excellent biocompatibility. When applied topically, this dual‐functional hydrogel can potentially prevent HIV transmission and eliminate microbes that cause infections in the vulvovagina region.
Sol–Gel Route Toward Efficient and Robust Distributed Bragg Reflectors for Light Management Applications
Authors: Brudieu Barbara , Bris A. Le , Teisseire J. , Guillemot F. , Dantelle G. , Misra S. , Cabarrocas P. Roca i , Sorin F. , Gacoin T.
Published: September 2014

The optimization of functional optical devices requires the appropriate control of light propagation, which can be achieved by using engineered dielectric structures. Innovative materials combination and fabrication strategies are required to achieve a robust gain in performance without impacting manufacturing complexity and cost. In the present work, a novel liquid‐based approach is proposed for the simple and scalable fabrication of highly efficient and robust optical multilayer dielectric coatings. In particular, a sol–gel process is developed that enables the fabrication of large‐area distributed Bragg reflectors (DBR) integrating macroporous materials of controlled closed porosity. The DBRs have a very high index contrast, excellent and tunable optical properties, and high stability of performance and structural integrity with respect to crack formation and delamination, even against harsh ageing tests or solvent exposure. The potential of this approach to be integrated within existing optoelectronic architectures is demonstrated through the integration of a DBR structure as a back reflector in an amorphous silicon solar cell (a‐Si:H), resulting in a significant increase in light absorption, photocurrent, and overall efficiency. This opens the way towards simple dielectric engineering of robust photoactive devices based on the versatile use of liquid routes for the deposition of structured dielectric coatings.
Voice and Culture: A Prospect Theory Approach
Authors: Paddock E. Layne , Ko Jaewon , Cropanzano Russell , Bagger Jessica , El Akremi Assâad , Camerman Julie , Greguras Gary J. , Mladinic Antonio , Moliner Carolina , Nam Kidok , Törnblom Kjell , Van den Bos Kees
Published: September 2014

The present study examines the congruence of individuals' minimum preferred amounts of voice with the prospect theory value function across nine countries. Accounting for previously ignored minimum preferred amounts of voice and actual voice amounts integral to testing the steepness of gain and loss functions explicated in prospect theory, we use curve fitting to show that ratings of procedural justice fit prospect theory's value function specifically. Further, we investigate the form of this function across nine countries that range in power distance. Results suggest that the form of the value function is congruent with prospect theory, showing an S‐shaped curve that is steeper in the loss than in the gain domain. Further, this pattern is similar across countries. Theoretical and practical implications of these results for both decision making and organizational justice are discussed. Copyright © 2014 John Wiley & Sons, Ltd.
HDL3 stimulates paraoxonase 1 antiatherogenic catalytic and biological activities in a macrophage model system: In vivo and in vitro studies
Authors: Rosenblat Mira , Volkova Nina , Aviram Michael
Published: September 2014

We analyzed in‐vivo and in‐vitro high density lipoprotein (HDL) effects on paraoxonase 1 (PON1) antiatherogenic properties in serum and in macrophages. Intraperitoneal injection to C57BL/6 mice of recombinant PON1 (rePON1) + HDL, in comparison to HDL or to rePON1 alone, significantly increased serum PON1 arylesterase activity (by 20%), and serum‐mediated cholesterol efflux from J774A.1 macrophages (by 18%). Similarly, in peritoneal macrophages (MPM) harvested from mice injected with HDL + rePON1 versus rePON1 alone, we observed reduction in oxidative stress (by 11%), increase in cellular PON1 activity (by 14%) and in HDL‐mediated cholesterol efflux (by 38%). Incubation of serum or HDL with rePON1, substantially increased PON1 arylesterase activity, two‐fold more than the expected additive values. HDL2 and HDL3 increased PON1 activity by 199% or 274%, respectively. Macrophage (J774A.1) cholesterol efflux rate significantly increased by HDL3 + rePON1 versus HDL3 alone (by 19%), but not by HDL2 + rePON1 versus HDL2 alone. Oxidation of HDL3 reduced its ability to induce macrophage cholesterol efflux, and abolished HDL3 stimulatory effects on rePON1. Addition of exogenous polyphenol quercetin (60 µM), but not phosphatidylcholine or apolipoprotein A1, to HDL + rePON1 increased PON1 activity (by 404%), increased the ability to reduce oxidative stress in J774A.1 macrophages (by 53%) and to stimulate macrophage cholesterol efflux (by 14%). Upon adding the hypocholesterolemic drug simvastatin (15 µg/mL) to HDL + rePON1, PON1 activity and the ability to induce macrophage cholesterol efflux increased, in comparison to HDL + rePON1. We thus concluded that HDL (mostly HDL3), stimulates PON1 antiatherogenic activities in macrophages, and these PON1 activities were further stimulated by quercetin, or by simvastatin. © 2014 BioFactors, 40(5):536–545, 2014
Conformational Flexibility in the Binding Surface of the Potassium Channel Blocker ShK
Authors: Sher Inbal , Chang Shih Chieh , Li Ying , Chhabra Sandeep , Palmer Arthur G. , Norton Raymond S. , Chill Jordan H.
Published: September 2014

ShK is a 35‐residue peptide that binds with high affinity to human voltage‐gated potassium channels through a conserved K‐Y dyad. Here we have employed NMR measurements of backbone‐amide 15N spin‐relaxation rates to investigate motions of the ShK backbone. Although ShK is rigid on the ps to ns timescale, increased linewidths observed for 11 backbone‐amide 15N resonances identify chemical or conformational exchange contributions to the spin relaxation. Relaxation dispersion profiles indicate that exchange between major and minor conformers occurs on the sub‐millisecond timescale. Affected residues are mostly clustered around the central helix‐kink‐helix structure and the critical K22–Y23 motif. We suggest that the less structured minor conformer increases the exposure of Y23, known to contribute to binding affinity and selectivity, thereby facilitating its interaction with potassium channels. These findings have potential implications for the design of new channel blockers based on ShK.
Unusually Broad Substrate Profile of Self‐Sufficient Cytochrome P450 Monooxygenase CYP116B4 from Labrenzia aggregata
Authors: Yin Yue‐Cai , Yu Hui‐Lei , Luan Zheng‐Jiao , Li Ren‐Jie , Ouyang Peng‐Fei , Liu Jing , Xu Jian‐He
Published: September 2014

A new member of the CYP116B subfamily—P450LaMO—was discovered in Labrenzia aggregata by genomic data mining. It was successfully overexpressed in Escherichia coli, purified, and subsequently characterized spectroscopically, and its catalytic properties were assessed. Substrate profiling of the P450LaMO revealed that it was a versatile catalyst, exhibiting hydroxylation and epoxidation activities as well as O‐dealkylation and asymmetric sulfoxidation activities. Diverse compounds, including alkylbenzenes, aromatic bicyclic molecules, and terpenoids, were shown to be hydroxylated by P450LaMO. Such diverse catalytic activities are uncommon for the bacterial P450s, and the P450LaMO ‐mediated stereoselective hydroxylation of inactivated CH bonds—ubiquitous and relatively unreactive in organic molecules—is particularly unusual. The self‐sufficient nature of P450LaMO, coupled with its broad substrate range, highlights it as an ideal template for directed evolution towards various applications.
Retinoic acid can induce mouse embryonic stem cell R1/E to differentiate toward female germ cells while oleanolic acid can induce R1/E to differentiate toward both types of germ cells
Authors: Wan Qian , Lu Hua , Wu Lin‐Tao , Liu Xia , Xiang Jun‐Bei
Published: September 2014

Retinoic acid (RA) and oleanolic acid (OA) were studied about their potential to induce mouse embryonic stem cell R1/E (MESC‐R1/E) to differentiate toward germ cells. Embryoid bodies (EBs) first formed from MESC‐R1/E and EBs were allowed to attach to the bottoms of normal cell‐culturing plate and grow. Then, different compounds including RA, OA and so on were respectively added to induce MESC‐R1/E to differentiate. After 72 h, microscopy images were taken for all interventions, then total RNAs were extracted, cDNAs were synthesized and real‐time fluorescence quantitative PCR (qPCR) was performed to detect the transcriptional expression patterns of 11 reproductive‐differentiation‐related genes for different compounds respectively. During the data analysis, it was found RA significantly up‐regulated the expression levels of GDF‐9, Stra8, SCP3, Mvh, ZP1, ZP2, and ZP3, while significantly down‐regulated the levels of Itag6 and Itgb1, and the level of Oct‐4 was down‐regulated insignificantly, while the level of TP2 was up‐regulated insignificantly; OA significantly up‐regulated the expression levels of Stra8, SCP3, Mvh, ZP1, ZP2, Itgb1, and TP2, and the levels of Oct‐4, GDF‐9, ZP3, and Itga6 were up‐regulated insignificantly. The data showed that RA can induce MESC‐R1/E to differentiate toward female germ cells while OA can induce MESC‐R1/E to differentiate toward male and female germ cells.
Recombinant arginine‐degrading enzymes in metabolic anticancer therapy and bioanalytics
Authors: Stasyk Oleh V. , Boretsky Yuriy R. , Gonchar Mykhailo V. , Sibirny Andriy A.
Published: September 2014

Tumor cells often exhibit specific metabolic defects due to the aberrations in oncogene‐dependent regulatory and/or signaling pathways that distinguish them from normal cells. Among others, many malignant cells are deficient in biosynthesis of certain amino acids and concomitantly exhibit elevated sensitivity to deprivation of these amino acids. Although the underlying causes of such metabolic changes are still not fully understood, this feature of malignant cells is exploited in metabolic enzymotherapies based on single amino acid, e.g., arginine, deprivation. To achieve efficient arginine depletion in vivo, two recombinant enzymes, bacterial arginine deiminase and human arginase I have been evaluated and are undergoing further development. This review is aimed to summarize the current knowledge on the application of arginine‐degrading enzymes as anticancer agents and as bioanalytical tools for arginine assays. The problems that have to be solved to optimize this therapy for clinical application are discussed.
Tuning the Selectivity in the Hydrogenation of Aromatic Ketones Catalyzed by Similar Ruthenium and Rhodium Nanoparticles
Authors: Llop Castelbou Jessica , Bresó‐Femenia Emma , Blondeau Pascal , Chaudret Bruno , Castillón Sergio , Claver Carmen , Godard Cyril
Published: September 2014

Ru and Rh nanoparticles (NPs) RuI, RuII, RhI and RhII, stabilised by triphenylphosphine (PPh3) and diphenylphosphinobutane (dppb) were synthesised, characterised and applied as catalysts in the hydrogenation of several aromatic ketones. The effects of the nature of the metal and of the stabilising agent on the aryl versus ketone hydrogenation were studied. For Rh NPs, the coordination of arene dominates the interaction of the substrate with the NP, whereas the coordination of the ketone group was not evidenced. For Ru NPs, however, the results show that both arene and ketone coordinate to the NPs surface in a competitive manner. The properties of the stabilising ligands have a clear influence on the outcome of the reaction, and for the Rh‐catalysed reactions, products of hydrogenolysis were only formed if PPh3 was used as the stabiliser. The structure of the substrate was also a key factor for the selectivity.
An Analysis of Anion‐Specific Effects on the Standard Potential Shifts of 9‐Fluorenone in Room‐Temperature Ionic Liquids with a Silver Electrode as a Cathode Material
Authors: Reche Irene , Gallardo Iluminada , Guirado Gonzalo
Published: September 2014

This study aims to show the interesting possibilities offered by the use of electrochemical techniques in several ionic liquids by establishing the potential use of silver electrodes in reduction processes. A range of fundamental electrochemical studies are described based on the determination of the diffusion coefficients, the standard potential shifts, and solvation effects for the electrochemical reduction of 9‐fluorenone by several room‐temperature ionic liquids (RTILs). The RTILs are composed of an unsymmetrical organic cation (1‐butyl or 1‐ethyl‐3‐methylimidazolium) and a range of inorganic anions. The catalytic properties of RTILs combined with a silver working electrode mean that this system could be a good starting point for establishing the design of new, more environmentally friendly and efficient electrosynthetic routes, as well as fluorenone‐based devices.
Highly Efficient Low‐Temperature Plasma‐Assisted Modification of TiO2 Nanosheets with Exposed {001} Facets for Enhanced Visible‐Light Photocatalytic Activity
Authors: Li Beibei , Zhao Zongbin , Zhou Quan , Meng Bo , Meng Xiangtong , Qiu Jieshan
Published: September 2014

Anatase TiO2 nanosheets with exposed {001} facets have been controllably modified under non‐thermal dielectric barrier discharge (DBD) plasma with various working gas, including Ar, H2, and NH3. The obtained TiO2 nanosheets possess a unique crystalline core/amorphous shell structure (TiO2@TiO2−x), which exhibit the improved visible and near‐infrared light absorption. The types of dopants (oxygen vacancy/surface Ti3+/substituted N) in oxygen‐deficient TiO2 can be tuned by controlling the working gases during plasma discharge. Both surface Ti3+ and substituted N were doped into the lattice of TiO2 through NH3 plasma discharge, whereas the oxygen vacancy or Ti3+ (along with the oxygen vacancy) was obtained after Ar or H2 plasma treatment. The TiO2@TiO2−x from NH3 plasma with a green color shows the highest photocatalytic activity under visible‐light irradiation compared with the products from Ar plasma or H2 plasma due to the synergistic effect of reduction and simultaneous nitridation in the NH3 plasma.
Population pharmacokinetic analysis of thrombomodulin alfa to support dosing rationale in patients with renal impairment
Authors: Mouksassi Mohamad‐Samer , Marier Jean‐Francois , Bax Leon , Osawa Yutaka , Tsuruta Kazuhisa
Published: September 2014

Thrombomodulin alfa is a soluble recombinant human thrombomodulin that was reported to enhance the reversal of disseminated intravascular coagulation (DIC) in subjects with sepsis or hematologic malignancy and reduce mortality in subjects with sepsis and DIC. Population pharmacokinetic (PK) analysis of thrombomodulin alfa was performed based on rich samples collected in 24 healthy subjects (0.02 and 0.06 mg/kg) and sparse samples collected in 368 subjects with sepsis and DIC (0.06 mg/kg). Sources of variability (baseline characteristics, markers of renal/liver function, hematocrit, and disease severity) were explored using non‐linear mixed effect modeling to support dosing rationale in patients with sepsis and DIC. Plasma concentrations of thrombomodulin alfa were best fitted with a one‐compartment model. Body weight and creatinine clearance were important covariates describing the PK of thrombomodulin alfa. Typical CL values in patients with normal renal function, or mild, moderate and severe renal impairment were 0.158, 0.145, 0.128, and 0.105 L/h, respectively. Based on simulations, a 0.06 mg/kg dosing of thrombomodulin alfa is expected to result in drug exposure within the therapeutic range of the product (300–5,400 ng/mL), with minimum risks of bleeding in patient with normal and impaired renal functions.
Pharmacokinetic and bioequivalence evaluation of single‐tablet and separate‐tablet regimens for once‐daily cobicistat‐boosted elvitegravir in healthy Japanese male subjects: A randomized, two‐way crossover study
Authors: Shiomi Mari , Matsuki Shunji , Ikeda Atsushi , Ishikawa Tomohiro , Nishino Noriaki , Kimura Miyuki , Kumagai Yuji , Irie Shin
Published: September 2014

This randomized, two‐way crossover study evaluated the bioavailability of elvitegravir administered as the new individual tablet containing 150 mg and a cobicistat 150 mg tablet, concomitantly with a fixed‐dose combination tablet containing 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (EVG + COBI + FTC/TDF), in comparison with a single‐tablet regimen containing the same dose of each component (EVG/COBI/FTC/TDF). Twenty‐four healthy Japanese male subjects received the two different elvitegravir treatments, the separate‐tablet or single‐tablet regimen, once‐daily for 10 days in each. The pharmacokinetic parameters (Cmax, AUCtau, and Ctau) of elvitegravir were investigated at Day 10 after each treatment, together with safety and tolerability. Relative to EVG/COBI/FTC/TDF, the geometric least‐squares mean ratios (GMR) and 90% confidence intervals (CIs) for elvitegravir Cmax and AUCtau were within the boundary of 0.8–1.25, while the upper limit of the 90% CI of GMR for Ctau was narrowly below the lack of bioequivalence boundary (0.79). No deaths, serious AEs, or drug‐related AEs occurred. In conclusion, Cmax and AUCtau of elvitegravir met the strict definition of bioequivalence, indicating that the two regimens were essentially bioequivalent. Treatment with both regimens for 10 days appeared to be safe and well tolerated.
Pharmacokinetics of cytisine, an α4β2 nicotinic receptor partial agonist, in healthy smokers following a single dose
Authors: Jeong Soo Hee , Newcombe David , Sheridan Janie , Tingle Malcolm
Published: September 2014

Cytisine, an α4β2 nicotinic receptor partial agonist, is a plant alkaloid that is commercially extracted for use as a smoking cessation medication. Despite its long history of use, there is very little understanding of the pharmacokinetics of cytisine. To date, no previous studies have reported cytisine concentrations in humans following its use as a smoking cessation agent. A high performance liquid chromatography‐ultraviolet (HPLC‐UV) method was developed and validated for analysis of Tabex® and nicotine‐free oral strips, two commercial products containing cytisine. A sensitive liquid chromatography‐mass spectrometry (LC‐MS) method was developed and validated for the quantification of cytisine in human plasma and for the detection of cytisine in urine. Single‐dose pharmacokinetics of cytisine was studied in healthy smokers. Subjects received a single 3 mg oral dose administration of cytisine. Cytisine was detected in all plasma samples collected after administration, including 15 min post‐dose and at 24 h. Cytisine was renally excreted and detected as an unchanged drug. No metabolites were detected in plasma or urine collected in the study. No adverse reactions were reported. Copyright © 2014 John Wiley & Sons, Ltd.
Shaping a New Generation of Culturally Responsive Evaluators: Program Director Perspectives on the Role of the Internship Experience
Authors: Bryan Michelle L. , O'Sullivan Rita
Published: September 2014

In this chapter, we reflect on the role of the internship experience (also known as the practical evaluation project placement) within the overall design and function of the Graduate Education Diversity Internship (GEDI) program as well as its relationship to program goals and outcomes. We argue that explicit consideration of the program's cultural context is critical for understanding the impact of the internship experience on the program's overall quality and effectiveness. Drawing on our experiences as former codirectors, as well as our former interns’ reflections, we address the ways in which cultural and contextual factors within their internship sites, and within the larger program itself, affected the interns’ ability to incorporate tenets of culturally responsive evaluation into their internship experience. Framing the internship as both a pedagogical and a practical space for merging evaluation theory and practice, we discuss our attempts to understand its role in supporting interns’ evolving understanding of culturally responsive evaluation.
EWSR1‐PBX3: A novel gene fusion in myoepithelial tumors
Authors: Agaram Narasimhan P. , Chen Hsiao‐Wei , Zhang Lei , Sung Yun‐Shao , Panicek David , Healey John H. , Nielsen G. Petur , Fletcher Christopher D. M. , Antonescu Cristina R.
Published: September 2014

The genetics of myoepithelial tumors (ME) of soft tissue and bone have recently been investigated, with EWSR1‐related gene fusions being seen in approximately half of the tumors. The fusion partners of EWSR1 so far described include POU5F1, PBX1, ZNF444 and, in a rare case, ATF1. We investigated by RNA sequencing an index case of EWSR1‐rearranged ME of the tibia, lacking a known fusion partner, and identified a novel EWSR1‐PBX3 fusion. The fusion was further validated by reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH). To evaluate if this is a recurrent event, an additional cohort of 22 EWSR1‐rearranged ME cases lacking a fusion partner were screened by FISH for abnormalities in PBX3 gene. Thus, two additional cases were identified showing an EWSR1‐PBX3 gene fusion. One of them was also intraosseous involving the ankle, while the other occurred in the soft tissue of the index finger. The morphology of the EWSR1‐PBX3 fusion positive cases showed similar findings, with nests or sheets of epithelioid to spindle cells in a partially myxoid to collagenous matrix. All three cases showed expression of S100 and EMA by immunohistochemistry. In summary, we report a novel EWSR1‐PBX3 gene fusion in a small subset of ME, thereby expanding the spectrum of EWSR1‐related gene fusions seen in these tumors. This gene fusion seems to occur preferentially in skeletal ME, with two of the three study cases occurring in intraosseous locations. © 2014 Wiley Periodicals, Inc.
In response to O'Reilly et al. (2014)
Authors: Van Metre Peter C , Mahler Barbara J
Published: September 2014

Key Points

Coal-tar-based pavement sealant, a black liquid that is sprayed or painted on asphalt pavement, typically is 15 to 35% by weight coal tar or low- or high-temperature coal-tar pitch. USGS, other governmental, and academic research that has concluded that coal-tar-based pavement sealants are a major source of urban PAHs have relied on a wide array of forensic methods. Published academic and government research on effects of coal-tar-based pavement sealants has produced results consistent with those of the USGS. PAH contamination concerns associated with coal-tar-based sealcoat are not limited to stream and lake sediments; coal-tar-based sealcoat is a major source of PAHs to many environmental compartments.
Evaluating cost when selecting performance reference compounds for the environmental deployment of polyethylene passive samplers
Authors: Perron Monique M , Burgess Robert M , Cantwell Mark G , Fernandez Loretta A
Published: September 2014

A challenge in environmental passive sampling is determining when equilibrium is achieved between the sampler, target contaminants, and environmental phases. A common approach is the use of performance reference compounds (PRCs) to estimate target contaminant sampling rates and indicate degree of sampler equilibrium. One logistical issue associated with using PRCs is their sometimes exorbitant cost. To address PRC expense, this investigation 1) compared the performance of inexpensive PRCs (deuterated PAHs) and expensive PRCs (13C-labeled PCBs) to estimate dissolved PCB concentrations in freshwater and marine deployments, and 2) evaluated the use of smaller quantities of PRC relative to regular amounts used for estimating dissolved PAH and PCB concentrations. Saltwater and freshwater site average differences between total dissolved PCB concentrations calculated using the 2 classes of PRCs was 34 pg/L (20%) and 340 pg/L (51%), respectively, and in some deployments, statistical differences in PCB concentrations generated by the 2 types of PRCs were detected. However, no statistical differences were detected between total dissolved PAH and PCB for the 3 quantities of PRCs. In both investigations, individual dissolved PCB congeners and PAH compounds demonstrated comparable behavior as those expressed as total PCB or PAH dissolved concentrations. This research provides evidence that in some applications passive sampling using inexpensive and smaller quantities of PRCs can yield cost savings of approximately 75%. This approach appears most promising in the marine water column and when focusing on dissolved concentrations of low and medium molecular weight congeners or total PCBs. Integr Environ Assess Manag 2015;11:256–265. Published 2014 SETAC. This article is a US Government work and, as such, is in the public domain in the USA.

Key Points

Inexpensive performance reference compounds (PRCs) were scientifically effective in water column passive sampling Inexpensive PRCs were most effective in the marine deployments For some applications, cost-savings may be realized while retaining scientific accuracy using inexpensive PRCs Suggested applications for inexpensive PRCs include the preliminary assessment/site inspection portion of the Superfund site assessments
Total, caffeinated and decaffeinated coffee and tea intake and gastric cancer risk: Results from the EPIC cohort study
Authors: Sanikini Harinakshi , Dik Vincent K. , Siersema Peter D. , Bhoo‐Pathy Nirmala , Uiterwaal Cuno S.P.M. , Peeters Petra H.M. , González Carlos A. , Zamora‐Ros Raul , Overvad Kim , Tjønneland Anne , Roswall Nina , Boutron‐Ruault Marie‐Christine , Fagherazzi Guy , Racine Antoine , Kühn Tilman , Katzke Verena , Boeing Heiner , Trichopoulou Antonia , Trichopoulos Dimitrios , Lagiou Pagona , Palli Domenico , Grioni Sara , Vineis Paolo , Tumino Rosario , Panico Salvatore , Weiderpass Elisabete , Skeie Guri , Braaten Tonje , Huerta José María , Sánchez‐Cantalejo Emilio , Barricarte Aurelio , Sonestedt Emily , Wallstrom Peter , Nilsson Lena Maria , Johansson Ingegerd , Bradbury Kathryn E , Khaw Kay‐Tee , Wareham Nick , Huybrechts Inge , Freisling Heinz , Cross Amanda J. , Riboli Elio , Bueno‐de‐Mesquita H. B(as)
Published: September 2014

Prospective studies examining the association between coffee and tea consumption and gastric cancer risk have shown inconsistent results. We investigated the association between coffee (total, caffeinated and decaffeinated) and tea consumption and the risk of gastric cancer by anatomical site and histological type in the European Prospective Investigation into Cancer and Nutrition study. Coffee and tea consumption were assessed by dietary questionnaires at baseline. Adjusted hazard ratios (HRs) were calculated using Cox regression models. During 11.6 years of follow up, 683 gastric adenocarcinoma cases were identified among 477,312 participants. We found no significant association between overall gastric cancer risk and consumption of total coffee (HR 1.09, 95%‐confidence intervals [CI]: 0.84–1.43; quartile 4 vs. non/quartile 1), caffeinated coffee (HR 1.14, 95%‐CI: 0.82–1.59; quartile 4 vs. non/quartile 1), decaffeinated coffee (HR 1.07, 95%‐CI: 0.75–1.53; tertile 3 vs. non/tertile 1) and tea (HR 0.81, 95%‐CI: 0.59–1.09; quartile 4 vs. non/quartile 1). When stratified by anatomical site, we observed a significant positive association between gastric cardia cancer risk and total coffee consumption per increment of 100 mL/day (HR 1.06, 95%‐CI: 1.03–1.11). Similarly, a significant positive association was observed between gastric cardia cancer risk and caffeinated coffee consumption (HR 1.98, 95%‐CI: 1.16–3.36, p‐trend=0.06; quartile 3 vs. non/quartile 1) and per increment of 100 mL/day (HR 1.09, 95%‐CI: 1.04–1.14). In conclusion, consumption of total, caffeinated and decaffeinated coffee and tea is not associated with overall gastric cancer risk. However, total and caffeinated coffee consumption may be associated with an increased risk of gastric cardia cancer. Further prospective studies are needed to rule out chance or confounding.
Tuning the binding of coumarin 6 with DNA by molecular encapsulators: effect of β‐cyclodextrin and C‐hexylpyrogallol[4]arene
Authors: Chandrasekaran Sowrirajan , Sameena Yousuf , Enoch Israel V.
Published: September 2014

We report in this paper that the binding of coumarin 6 (C6) to DNA can be tuned by complexing it with host structures, viz. β‐cyclodextrin (β‐CD) and C‐hexylpyrogallol‐4‐arene (C‐HPA). Because host molecules are used as carriers of small molecules onto target sites, the exposed part of the guest molecule needs to be found out, and the relationship between the host : guest ratio and the mode of binding with the target macromolecule, that is, the DNA needs to be analyzed, in order to comprehend the preferred binding moiety and tune the binding. In this paper, the formation of the inclusion complex of C6 with β‐CD and with C‐HPA is studied by UV‐visible, fluorescence, 2D rotating‐frame nuclear Overhauser effect correlation spectroscopy and diffusion‐ordered spectroscopy nuclear magnetic resonance spectra and molecular modeling. C6 forms a 1:1 complex with β‐CD and a 1:2 complex with C‐HPA. The studies on the protonation of C6 in the presence and the absence of the host molecules suggest that the chromone part of C6 is outside the β‐CD molecule, whereas it is fully covered by C‐HPA. The binding of C6 with calf thymus DNA (ctDNA) occurs through intercalation and hydrogen bonding, and the host–guest structures remain intact on binding with ctDNA. The oxygens of the C6 molecules are exposed when inside the host molecules and aid in the hydrogen bonding with DNA. Copyright © 2014 John Wiley & Sons, Ltd.
Molecular recognition of HER‐1 in whole‐blood samples
Authors: Moldoveanu Iuliana , Stanciu Gavan Camelia , Stefan‐van Staden Raluca‐Ioana
Published: September 2014

Multimode sensing was proposed for molecular screening and recognition of HER‐1 in whole blood. The tools used for molecular recognition were platforms based on nanostructured materials such as the complex of Mn(III) with meso‐tetra (4‐carboxyphenyl) porphyrin, and maltodextrin (dextrose equivalence between 4 and 7), immobilized in diamond paste, graphite paste or C60 fullerene paste. The identification of HER‐1 in whole‐blood samples, at molecular level, is performed using stochastic mode and is followed by the quantification of it using stochastic and differential pulse voltammetry modes. HER‐1 can be identified in the concentration range between 280 fg/ml and 4.86 ng/ml using stochastic mode, this making possible the early detection of cancers such as gastrointestinal, pancreatic and lung cancers. The recovery tests performed using whole‐blood samples proved that the platforms can be used for identification and quantification of HER‐1 with high sensitivity and reliability in such samples, these making them good molecular screening tools. Copyright © 2014 John Wiley & Sons, Ltd.
Probing interactions between human lung adenocarcinoma A549 cell and its aptamers at single‐molecule resolution
Authors: Wang Qing , Zhou Chenchen , Yang Xiaohai , Liu Lin , Wang Kemin
Published: September 2014

Because cell‐specific aptamers have high potential for biomedical applications, investigation of the interaction between cell and its aptamers may be of key importance for an improved understanding of biochemical processes. Herein, the interaction between human lung adenocarcinoma A549 cell and its four aptamers was explored using single‐molecule force spectroscopy (SMFS). The values of the unbinding force varied from 117.1 to 171.0 pN at the loading rate of 1.8 × 105 pN/s. Based on the dependence of singe molecule force on the atomic force microscopy loading rate, the corresponding kinetic parameters were obtained. The results revealed two activation barriers and two transient states in the unbinding process of aptamer/cell interaction. More importantly, the binding sites on A549 cells with its four aptamers were defined to be different using SMFS and flow cytometry. This work demonstrated that SMFS can be used as a powerful tool for exploring the aptamer/cell binding behavior at the single‐molecule level, and may provide valuable information for the design and application of aptamer probes. Copyright © 2014 John Wiley & Sons, Ltd.
Ratiometric fluorescent scaffold giving discrete response towards iodide ion: a combined experimental and DFT study
Authors: Patil Rahul , Tayade Kundan , Sahoo Suban K , Singh Jasminder , Singh Narinder , Hundiwale Dilip , Kuwar Anil
Published: September 2014

A novel ratiometric fluorescent receptor (Z)‐2‐(4‐[diethylamino]‐2‐hydroxybenzylideneamino) pyridine‐3‐carbaldehyde (3) bearing one phenolic OH and one aldehyde group as recognition sites was synthesized and characterized. The anion recognition behaviour of receptor 3 was evaluated by various spectroscopic (UV‐visible, fluorescence and 1H nuclear magnetic resonance) methods and was validated by computational studies. The receptor showed fast response time, excellent selectivity and reproducibility towards iodide ion detection among the other surveyed anions, with a binding constant of 6.12 × 104 M−1 and a detection limit of 0.24 μM, thus confirming its potential applicability as a fluorescent sensor for iodide Copyright © 2014 John Wiley & Sons, Ltd.
Specificity, polyspecificity, and heterospecificity of antibody‐antigen recognition
Authors: Van Regenmortel Marc H. V.
Published: September 2014

The concept of antibody specificity is analyzed and shown to reside in the ability of an antibody to discriminate between two antigens. Initially, antibody specificity was attributed to sequence differences in complementarity determining regions (CDRs), but as increasing numbers of crystallographic antibody‐antigen complexes were elucidated, specificity was analyzed in terms of six antigen‐binding regions (ABRs) that only roughly correspond to CDRs. It was found that each ABR differs significantly in its amino acid composition and tends to bind different types of amino acids at the surface of proteins. In spite of these differences, the combined preference of the six ABRs does not allow epitopes to be distinguished from the rest of the protein surface. These findings explain the poor success of past and newly proposed methods for predicting protein epitopes. Antibody polyspecificity refers to the ability of one antibody to bind a large variety of epitopes in different antigens, and this property explains how the immune system develops an antibody repertoire that is able to recognize every antigen the system is likely to encounter. Antibody heterospecificity arises when an antibody reacts better with another antigen than with the one used to raise the antibody. As a result, an antibody may sometimes appear to have been elicited by an antigen with which it is unable to react. The implications of antibody polyspecificity and heterospecificity in vaccine development are pointed out. Copyright © 2014 John Wiley & Sons, Ltd.
Prognostic value of pathologic fracture in patients with high grade localized osteosarcoma: A systemic review and meta‐analysis of cohort studies
Authors: Sun Lingling , Li Yingiun , Zhang Jian , Li Hengyuan , Li Binghao , Ye Zhaoming
Published: September 2014

Consensus has not been reached regarding the ability of pathologic fracture to predict local recurrence and survival in osteosarcoma. We aim to review the available evidence to examine the association between pathologic fracture and osteosarcoma prognosis. A comprehensive literature search for relevant studies published until March 2014 was performed using PubMed, Cochrane and Web of Science. The studies investigating pathologic fracture of osteosarcoma patients were systematically analyzed. The overall relative risk (RR) was estimated using a fixed‐effect model or random‐effect model according to heterogeneity between the trials. We included nine cohort studies involving 2,187 patients (311 with pathologic fracture and 1,876 without fracture) for the analysis of survival rate and local recurrence. Studies were assessed for quality using the Newcastle–Ottawa Assessment Scale. In the fixed‐effects model, the meta‐analysis showed that pathologic fracture in osteosarcoma patients predicted poor 3‐year overall survival (OS) (RR = 1.86, 95% CI: 1.37–2.53, p < 0.001) and 5‐year OS (RR = 1.34, 95% CI: 1.06–1.70, p = 0.016). Similarly, pathologic fracture was significantly correlated with worse 3‐year event free survival (EFS) (RR = 1.52, 95% CI: 1.21–1.92, p < 0.001) and 5‐year EFS (RR = 1.24, 95% CI: 1.03–1.49, p = 0.021), whereas no significant association was noted with local recurrence (RR = 1.30, 95% CI: 0.84–2.02, p = 0.233). The meta‐analysis confirmed that pathologic fracture in osteosarcoma was a prognostic marker for both OS and EFS but not for local recurrence. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:131–139, 2015.
Improved purification of immunoglobulin G from plasma by mixed‐mode chromatography
Authors: Chai Dong‐Sheng , Sun Yan , Wang Xiao‐Ning , Shi Qing‐Hong
Published: September 2014

Efficient loading of immunoglobulin G in mixed‐mode chromatography is often a serious bottleneck in the chromatographic purification of immunoglobulin G. In this work, a mixed‐mode ligand, 4‐(1H‐imidazol‐1‐yl) aniline, was coupled to Sepharose Fast Flow to fabricate AN SepFF adsorbents with ligand densities of 15–64 mmol/L, and the chromatographic performances of these adsorbents were thoroughly investigated to identify a feasible approach to improve immunoglobulin G purification. The results indicate that a critical ligand density exists for immunoglobulin G on the AN SepFF adsorbents. Above the critical ligand density, the adsorbents showed superior selectivity to immunoglobulin G at high salt concentrations, and also exhibited much higher dynamic binding capacities. For immunoglobulin G purification, both the yield and binding capacity increased with adsorbent ligand density along with a decrease in purity. It is difficult to improve the binding capacity, purity, and yield of immunoglobulin G simultaneously in AN SepFF chromatography. By using tandem AN SepFF chromatography, a threefold increase in binding capacity as well as high purity and yield of immunoglobulin G were achieved. Therefore, the tandem chromatography demonstrates that AN SepFF adsorbent is a practical and feasible alternative to MEP HyperCel adsorbents for immunoglobulin G purification.
Computer‐assisted design and synthesis of molecularly imprinted polymers for the simultaneous determination of six carbamate pesticides from environmental water
Authors: Qi Peipei , Wang Xiangyun , Wang Xinquan , Zhang Hu , Xu Hao , Jiang Kezhi , Wang Qiang
Published: September 2014

The computer‐assisted design and synthesis of molecularly imprinted polymers for the simultaneous capture of six carbamate pesticides from environmental water are reported in this work. The quantum mechanical computational approach was employed to design the molecularly imprinted polymers with carbofuran as template. The interaction energies between the template molecule and different functional monomers in various solvents were calculated to assist in the selection of the functional monomer and porogen. The optimised molecularly imprinted polymer was subsequently used as a class‐selective sorbent in solid‐phase extraction for pre‐concentration and determination of carbamates from environmental water. The parameters influencing the extraction efficiency of the molecularly imprinted solid‐phase extraction procedure were systematically investigated to facilitate the class‐selective extraction. For the proposed method, linearity was observed over the range of 2–500 ng/mL with the correlation coefficient ranging from 0.9760 to 1.000. The limits of detection ranged from 0.2 to 1.2 ng/mL, and the limit of quantification was 4 ng/mL. These results confirm that computer‐assisted design is an effective evaluation tool for molecularly imprinted polymers synthesis, and that molecularly imprinted solid‐phase extraction can be applied to the simultaneous analysis of carbamates in environmental water.
Characterization of natural organic colorants in historical and art objects by high‐performance liquid chromatography
Authors: Pauk Volodymyr , Barták Petr , Lemr Karel
Published: September 2014

High‐performance liquid chromatography plays an important role in analysis of historical organic colorants. A number of papers have been published in this field over the last 30 years. Classification of the most commonly used natural dyes and an overview of high‐performance liquid chromatography methods with main focus on recent works (2008 to the beginning of 2014) are provided. The review deals with an entire analytical protocol covering sample preparation, chromatographic separation, and suitable detection (UV/visible and fluorescent spectroscopy and mass spectrometric techniques). High‐performance liquid chromatography has been successfully used in the complete characterization of some organic dyestuffs present in historical and art objects. The possibilities and difficulties for identification of natural sources of historical colorants are also discussed.
Enantioseparation of aldols by high‐performance liquid chromatography on polysaccharide‐based chiral stationary phases that bear chlorinated substituents
Authors: Pedotti Sonia , Patti Angela
Published: September 2014

Two families of aldols, obtained from the condensation of aromatic aldehydes with cyclohexanone or acetone (ten examples in each group), were analyzed by high‐performance liquid chromatography in normal phase elution mode on three polysaccharide‐based chiral stationary phases of the Lux series, namely, Lux Cellulose‐2, Lux Cellulose‐4 and Lux Amylose‐2, which share the common feature of chlorinated substituents in the chiral selectors. Following simple optimization steps, the enantioseparation of all aldols derived from cyclohexanone was achieved and the highest values of separation factor (α, 1.32 < α < 2.20) and resolution (Rs, 4.5 < Rs <17.2) were observed on Lux Cellulose‐2, with the only exception of the 4‐nitro‐substituted derivative that was better resolved on Lux Cellulose‐4. On the contrary, Lux Amylose‐2 was the best choice for aldols derived from acetone and only specific analytes in this group were resolved on the cellulose‐based supports. A variable‐temperature study of selected compounds allowed us to determine thermodynamic parameters of the enantioseparation process, which was enthalpy‐controlled in all the cases except one.
Investigation of mechanical properties of unidirectional steel fiber/polyester composites: Experiments and micromechanical predictions
Authors: Durai Prabhakaran R.T. , Andersen Tom Løgstrup , Bech Jakob Ilsted , Lilholt Hans
Published: September 2014

The article introduces steel fiber reinforced polymer composites, which is considered new for composite product developments. These composites consist of steel fibers or filaments of 0.21 mm diameter embedded in a polyester resin. The goal of this investigation is to characterize the mechanical performance of steel fiber reinforced polyester composites at room temperature. The mechanical properties of unidirectional steel fiber reinforced polyester composites (SFRP) are evaluated experimentally and compared with the predicted values by micro‐mechanical models. These predictions help to understand the role of material and process parameters on material properties. Two types of SFRP were studied: polyester resin reinforced by both steel fabric containing unidirectional fibers and steel fibers wound on a metal frame with 0° orientations. The effects of the fiber volume fraction and the role of polymer yarns (weft) on mechanical properties were analyzed through tensile, compressive, and shear tests. These tests were performed as per the standard test procedures. In particular, issues related to processing difficulties, polymer yarns effect on properties, standardized testing, and properties under various loading conditions were addressed. Microscopic observations were analyzed to assess the laminate quality and the macroscopic fracture surfaces of shear test specimens were studied by standard techniques. POLYM. COMPOS., 37:627–644, 2016. © 2014 Society of Plastics Engineers
A study of structure and tensile properties of polyamide 12/clay nanocomposites
Authors: Stojšić Josip , Raos Pero , Kalendova Alena
Published: September 2014

The nanocomposites are multiphase materials where at least one phase is in nanoscale, less than 100 nm, whereby a higher specific interfacial area is achieved. Due to their characteristic properties, the nanocomposites are nowadays being increasingly used for the engineering applications, and certainly will have a significant role in the materials production in the future. An important class of nanocomposite materials are polymer layered silicates, in which the layered filler (mostly modified natural clay minerals) is dispersed in the polymer matrix. Many of parameters (i.e., type of polymer matrix, type and amount of nanofiller, and a number of process parameters as melting temperature, screw speed, number and shape of mixing screws, etc) affect properties of nanocomposites. As part of the paper, the samples of PA12/nanoclay nanocomposite mixture were made by adjusting various parameters (content of nanoclay, the screw rotation frequency and mixture temperature). Afterward, the tensile properties of obtained specimens were analysed. The mathematical models that show dependence of tensile properties on the mixture parameters were obtained as the result of analysis. POLYM. COMPOS., 37:684–691, 2016. © 2014 Society of Plastics Engineers