bluuebunny/crossref_metadata_2025 huggingface dataset:
Noncoding RNA blockade of autophagy is therapeutic in medullary thyroid cancer
Authors: Gundara Justin S. , Zhao JingTing , Gill Anthony J. , Lee James C. , Delbridge Leigh , Robinson Bruce G. , McLean Catriona , Serpell Jonathan , Sidhu Stan B.
Published: February 2015

Micro‐RNAs are dysregulated in medullary thyroid carcinoma (MTC) and preliminary studies have shown that miRNAs may enact a therapeutic effect through changes in autophagic flux. Our aim was to study the in vitro effect of miR‐9‐3p on MTC cell viability, autophagy and to investigate the mRNA autophagy gene profile of sporadic versus hereditary MTC. The therapeutic role of miR‐9‐3p was investigated in vitro using human MTC cell lines (TT and MZ‐CRC‐1 cells), cell viability assays, and functional mechanism studies with a focus on cell cycle, apoptosis, and autophagy. Post‐miR‐9‐3p transfection mRNA profiling of cell lines was performed using a customized, quantitative RT‐PCR gene array card. This card was also run on clinical tumor samples (sporadic: n = 6; hereditary: n = 6) and correlated with clinical data. Mir‐9‐3p transfection resulted in reduced in vitro cell viability; an effect mediated through autophagy inhibition. This was accompanied by evidence of G2 arrest in the TT cell line and increased apoptosis in both cell lines. Atg5 was validated as a predicted miR‐9‐3p mRNA target in TT cells. Post‐miR‐9‐3p transfection array studies showed a significant global decline in autophagy gene expression (most notably in PIK3C3, mTOR, and LAMP‐1). Autophagy gene mRNAs were generally overexpressed in sporadic (vs. hereditary MTC) and Beclin‐1 overexpression was shown to correlate with residual disease. Autophagy is a tumor cell survival mechanism in MTC that when disabled, is of therapeutic advantage. Beclin‐1 expression may be a useful prognostic biomarker of aggressive disease.
Children's consumption behavior in response to food product placements in movies
Authors: Matthes Jörg , Naderer Brigitte
Published: February 2015

Almost all research on the effects of product placements on children has focused on brand attitudes or behavioral intentions. Drawing on the important difference between attitudes or behavioral intentions on the one hand and actual behavior on the other, this paper tests the effects of brand placements on children's food consumption. Children from 6 to 14 years old were exposed to an excerpt of the popular movie Alvin and the Chipmunks, including placements for the product Cheese Balls. Three versions were created: one without placements, one with moderate placement frequency, and one with high placement frequency. Results showed that exposure to high‐frequency product placements exerted a significant effect on snack consumption, but no effect on brand or product attitudes. These effects were independent of children's ages. The findings are of great importance to consumer behavior scholars, nutrition experts, and policy regulators. Copyright © 2015 John Wiley & Sons, Ltd.
Raschig Super‐Ring Operating Characteristics in Unpulsed Liquid‐Liquid Extraction Columns
Authors: Hlawitschka Mark W. , Schmidt Stephan , Bart Hans‐Jörg , Schultes Michael
Published: February 2015

Raschig Super‐Rings are well‐established in the field of rectification and absorption. Instead, the efficiency of these packings in liquid‐liquid extraction was not investigated till now. The application of Raschig Super‐Ring No. 0.3 and Raschig Super‐Ring No. 1 packings in unpulsed liquid‐liquid extraction columns of diameters DN 80 and DN 150 is investigated with respect to flooding point and efficiency. As a comparative study, 15‐mm and 25‐mm Pall‐Ring packings are used. The hydrodynamic studies indicate that the Raschig Super‐Ring offers a 9–10 % higher load capacity compared to the Pall‐Rings. In addition, the mass transport investigations performed using the test system toluene/acetone/water reveal that the height of transfer units (HTU) for the Raschig Super‐Ring No. 0.3 is higher than for the comparable 15‐mm Pall‐Ring. On average, the achieved difference of the HTU unit is 0.26 m.
Electrochemically and Chemically Induced Redox Processes in Molecular Machines
Authors: Le Poul Nicolas , Colasson Benoit
Published: February 2015

The controlled motion of ions, molecules, or supramolecular entities has inspired scientists for more than 25 years, and the concept remains of great interest for the development of moveable nanoscale objects for applications in electronics, medicine, and materials chemistry. Artificial molecular machines that involve electron exchange processes induced by electrical, chemical, or photochemical energy, have been widely developed. More specifically, machines that are stimulated by electrochemical means have been the focus of particular attention because such systems can allow the change of states to be followed and can enable access to mechanistic pathways through direct monitoring. Furthermore, these devices have the ability to connect the nanoscale machine to the macroscopic world, for instance by surface immobilization. In this review, we report recent examples of redox‐based molecular machines in both fluid solution and in organized or controllable environments such as modified electrodes, nanoparticles, polymers, gels, and liquid crystals. Basic concepts of molecular machinery and general applications are also discussed.
Multinuclear Diffusion NMR Spectroscopy and DFT Modeling: A Powerful Combination for Unraveling the Mechanism of Phosphoester Bond Hydrolysis Catalyzed by Metal‐Substituted Polyoxometalates
Authors: Luong Thi Kim Nga , Shestakova Pavletta , Mihaylov Tzvetan T. , Absillis Gregory , Pierloot Kristine , Parac‐Vogt Tatjana N.
Published: February 2015

A detailed reaction mechanism is proposed for the hydrolysis of the phosphoester bonds in the DNA model substrate bis(4‐nitrophenyl) phosphate (BNPP) in the presence of the ZrIV‐substituted Keggin type polyoxometalate (Et2NH2)8[{α‐PW11O39Zr(μ‐OH) (H2O)}2]⋅7 H2O (ZrK 2:2) at pD 6.4. Low‐temperature 31P DOSY spectra at pD 6.4 gave the first experimental evidence for the presence of ZrK 1:1 in fast equilibrium with ZrK 2:2 in purely aqueous solution. Moreover, theoretical calculations identified the ZrK 1:1 form as the potentially active species in solution. The reaction intermediates involved in the hydrolysis were identified by means of 1H/31P NMR studies, including EXSY and DOSY NMR spectroscopy, which were supported by DFT calculations. This experimental/theoretical approach enabled the determination of the structures of four intermediate species in which the starting compound BNPP, nitrophenyl phosphate (NPP), or the end product phosphate (P) is coordinated to ZrK 1:1. In the proposed reaction mechanism, BNPP initially coordinates to ZrK 1:1 in a monodentate fashion, which results in hydrolysis of the first phosphoester bond in BNPP and formation of NPP. EXSY NMR studies showed that the bidentate complex between NPP and ZrK 1:1 is in equilibrium with monobound and free NPP. Subsequently, hydrolysis of NPP results in P, which is in equilibrium with its monobound form.
Radiofluorination of a Pre‐formed Gallium(III) Aza‐macrocyclic Complex: Towards Next‐Generation Positron Emission Tomography (PET) Imaging Agents
Authors: Bhalla Rajiv , Levason William , Luthra Sajinder K. , McRobbie Graeme , Sanderson George , Reid Gillian
Published: February 2015

As part of a study to investigate the factors influencing the development of new, more effective metal‐complex‐based positron emission tomography (PET) imaging agents, the distorted octahedral complex, [GaCl(L)]⋅2 H2O has been prepared by reaction of 1‐benzyl‐1,4,7‐triazacyclononane‐4,7‐dicarboxylic acid hydrochloride (H2L⋅HCl) with Ga(NO3)3⋅9 H2O, which is a convenient source of GaIII for reactions in water. Spectroscopic and crystallographic data for [GaCl(L)]⋅2 H2O are described, together with the crystal structure of [GaCl(L)]⋅MeCN. Fluorination of this complex by Cl−/F− exchange was achieved in high yield by treatment with KF in water at room temperature over 90 minutes, although the reaction was complete in approximately 30 minutes if heated to 80 °C, giving [GaF(L)]⋅2 H2O in good yield. The same complex was obtained by hydrothermal synthesis from GaF3⋅3 H2O and Li2L, and has been characterised by single‐crystal X‐ray analysis, IR, 1H and 19F{1H} NMR spectroscopy and ESI+ MS.

Radiofluorination of the pre‐formed [GaCl(L)]⋅2 H2O has been demonstrated on a 210 nanomolar scale in aqueous NaOAc at pH 4 by using carrier‐free 18F−, leading to 60–70 % 18F‐incorporation after heating to 80 °C for 30 minutes. The resulting radioproduct was purified easily by using a solid‐phase extraction (SPE) cartridge, leading to 98–99 % radiochemical purity. The [Ga18F(L)] is stable for at least 90 minutes in 10 % EtOH/NaOAc solution at pH 6, but defluorinates over this time scale at pH of approximately 7.5 in phosphate buffered saline (PBS) or human serum albumin (HSA). The subtle role of the Group 13 metal ion and co‐ligand donor set in influencing the pH dependence of this system is discussed in the context of developing potential new imaging agents for PET.
Recycling Nanowire Templates for Multiplex Templating Synthesis: A Green and Sustainable Strategy
Authors: Wang Jin‐Long , Liu Jian‐Wei , Lu Bing‐Zhang , Lu Yi‐Ruo , Ge Jin , Wu Zhen‐Yu , Wang Zhi‐Hua , Arshad Muhammad Nadeem , Yu Shu‐Hong
Published: February 2015

Template‐directed synthesis of nanostructures has been emerging as one of the most important synthetic methodologies. A pristine nanotemplate is usually chemically transformed into other compounds and sacrificed after templating or only acts as an inert physical template to support the new components. If a nanotemplate is costly or toxic as waste, to recycle such a nanotemplate becomes highly desirable. Recently, ultrathin tellurium nanowires (TeNWs) have been demonstrated as versatile chemical or physical templates for the synthesis of a diverse family of uniform 1D nanostructures. However, ultrathin TeNWs as template are usually costly and are discarded as toxic waste in ionic species after chemical reactions or erosion. To solve the above problem, we conceptually demonstrate that such a nanotemplate can be economically recycled from waste solutions and repeatedly used as template.
Sequential Surface Modification of Au Nanoparticles: From Surface‐Bound AgI Complexes to Ag0 Doping
Authors: Fritz Eva‐Corinna , Nimphius Corinna , Goez Albrecht , Würtz Sebastian , Peterlechner Martin , Neugebauer Johannes , Glorius Frank , Ravoo Bart Jan
Published: February 2015

Gold nanoparticles (Au NPs) with tailor‐made structures and properties are highly desirable for applications in catalysis and sensing. In this context, surface modifications of Au NPs are of particular relevance. Herein, we present a sequential surface modification of Au NPs with AgI coordination complexes, which can be converted into Ag0‐doped Au NPs by simple ligand‐exchange reaction. The key innovative element of this surface modification is a multifunctional bioxazoline‐based ligand that brings coordinated AgI into close proximity to the particle surface.
Tobramycin and Nebramine as Pseudo‐oligosaccharide Scaffolds for the Development of Antimicrobial Cationic Amphiphiles
Authors: Berkov‐Zrihen Yifat , Herzog Ido M. , Benhamou Raphael I. , Feldman Mark , Steinbuch Kfir B. , Shaul Pazit , Lerer Shachar , Eldar Avigdor , Fridman Micha
Published: February 2015

Antimicrobial cationic amphiphiles derived from aminoglycoside pseudo‐oligosaccharide antibiotics interfere with the structure and function of bacterial membranes and offer a promising direction for the development of novel antibiotics. Herein, we report the design and synthesis of cationic amphiphiles derived from the pseudo‐trisaccharide aminoglycoside tobramycin and its pseudo‐disaccharide segment nebramine. Antimicrobial activity, membrane selectivity, mode of action, and structure–activity relationships were studied. Several cationic amphiphiles showed marked antimicrobial activity, and one amphiphilic nebramine derivative proved effective against all of the tested strains of bacteria; furthermore, against several of the tested strains, this compound was well over an order of magnitude more potent than the parent antibiotic tobramycin, the membrane‐targeting antimicrobial peptide mixture gramicidin D, and the cationic lipopeptide polymyxin B, which are in clinical use.
Die Ammoniak‐Brennstoffzelle wird Reaktor
Authors: Jaenicke Lothar
Published: February 2015

Industriell anwendbare Alternativen zur nunmehr über hundert Jahre alten Ammoniaksynthese nach dem Haber‐Bosch‐Verfahren sind noch nicht in Sicht, als Forschungsthema ist die Ammoniaksynthese daher nach wie vor aktuell.
Relation of In‐hospital Serum Creatinine Change Patterns and Outcomes Among ST‐Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention
Authors: Shacham Yacov , Leshem‐Rubinow Eran , Gal‐Oz Amir , Ben‐Assa Eyal , Steinvil Arie , Keren Gad , Roth Arie , Arbel Yaron
Published: February 2015

Background

The worsening of serum creatinine (sCr) level is a frequent finding among ST‐segment elevation MI (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), associated with adverse short‐term and long‐term outcomes. No information is present, however, regarding the incidence and prognostic implications associated with an improvement in sCr levels throughout hospitalization, as compared with admission levels.

Hypothesis

Reversible renal impairment prior to PCI is not associated with adverse outcomes.

Methods

We retrospectively studied 1260 STEMI patients undergoing primary PCI. The incidence of in‐hospital complications and long‐term mortality was compared between patients having stable, worsened (>0.3 mg/dL increase), or improved (>0.3 mg/dL decrease) sCr levels throughout hospitalization.

Results

Overall, 127 patients (10%) had worsening in sCr levels, whereas 44 (3.5%) had an improvement of sCr compared with admission levels. Patients with worsening sCR had more complications during hospitalization, higher 30‐day (13% vs 1%; P < 0.001) and up to 5‐year all‐cause mortality (28% vs 5%; P < 0.001) compared with those with stable sCR. No significant difference was found regarding complications and mortality between patients having an improvement in sCr and stable sCr. Compared with patients with stable sCr, the adjusted hazard ratio for all‐cause mortality in patients with worsened sCr was 6.68 (95% confidence interval: 2.1‐21.6, P = 0.002).

Conclusions

In STEMI patients undergoing primary PCI, renal impairment prior to PCI is a frequent finding. In contrast to post‐PCI sCr worsening, this entity is not associated with adverse short‐term and long‐term outcomes.
Boron Nitride Nanomaterials for Thermal Management Applications
Authors: Meziani Mohammed J. , Song Wei‐Li , Wang Ping , Lu Fushen , Hou Zhiling , Anderson Ankoma , Maimaiti Halidan , Sun Ya‐Ping
Published: February 2015

Hexagonal boron nitride nanosheets (BNNs) are analogous to their two‐dimensional carbon counterparts in many materials properties, in particular, ultrahigh thermal conductivity, but also offer some unique attributes, including being electrically insulating, high thermal stability, chemical and oxidation resistance, low color, and high mechanical strength. Significant recent advances in the production of BNNs, understanding of their properties, and the development of polymeric nanocomposites with BNNs for thermally conductive yet electrically insulating materials and systems are highlighted herein. Major opportunities and challenges for further studies in this rapidly advancing field are also discussed.
On self‐organising traffic lights technology
Authors: Reztsov Andrei
Published: February 2015

Self‐organising traffic lights (SOTL) are considered a promising instrument for the development of more efficient adaptive traffic control systems. In this paper, we explain why this technology should be scrutinised and carefully reviewed. Research projects based on SOTL currently under way should be reviewed too. © 2015 Wiley Periodicals, Inc. Complexity 21: 328–330, 2016
Nighttime and daytime respiration in a headwater stream
Authors: González‐Pinzón Ricardo , Peipoch Marc , Haggerty Roy , Martí Eugènia , Fleckenstein Jan H.
Published: February 2015

We investigated changes in respiration across nighttime and daytime in a headwater stream. For this, we conducted consecutive nighttime and daytime experiments injecting the bioreactive tracer resazurin in two reaches with different riparian canopy densities (different levels of photosynthetically active radiation) to compare respiration rate coefficients. We found that even though stream water temperatures measured above the streambed at day and night (half‐day timescale) were different within each reach and across reaches (95% confidence level), apparent respiration rate coefficients were not different across nighttime and daytime conditions (95% confidence level). A likely explanation for this is that the bulk of stream respiration takes place in the hyporheic zone, where diel fluctuations of stream temperature and photosynthetically active radiation are considerably attenuated and where temperature is not measured in routine investigations of stream metabolism. Our results suggest that community respiration in headwater streams may not need to be ‘corrected’ for temperature between daytime and nighttime, even though instantaneous changes in respiration are expected to occur from a pure biological perspective. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation of ground motion selection and modification procedures using synthetic ground motions
Authors: Kwong N. Simon , Chopra Anil K. , McGuire Robin K.
Published: February 2015

This study presents a novel approach for evaluating ground motion selection and modification (GMSM) procedures in the context of probabilistic seismic demand analysis. In essence, synthetic ground motions are employed to derive the benchmark seismic demand hazard curve (SDHC), for any structure and response quantity of interest, and to establish the causal relationship between a GMSM procedure and the bias in its resulting estimate of the SDHC. An example is presented to illustrate how GMSM procedures may be evaluated using synthetic motions. To demonstrate the robustness of the proposed approach, two significantly different stochastic models for simulating ground motions are considered. By quantifying the bias in any estimate of the SDHC, the proposed approach enables the analyst to rank GMSM procedures in their ability to accurately estimate the SDHC, examine the sufficiency of intensity measures employed in ground motion selection, and assess the significance of the conditioning intensity measure in probabilistic seismic demand analysis. Copyright © 2015 John Wiley & Sons, Ltd.
Larval exposure to polychlorinated biphenyl 126 (PCB-126) causes persistent alteration of the amphibian gut microbiota
Authors: Kohl Kevin D. , Cary Tawnya L. , Karasov William H. , Dearing M. Denise
Published: February 2015

Interactions between gut microbes and anthropogenic pollutants have been under study. The authors investigated the effects of larval exposure to polychlorinated biphenyl 126 (PCB-126) on the gut microbial communities of tadpoles and frogs. Frogs treated with PCBs exhibited increased species richness in the gut and harbored communities significantly enriched in Fusobacteria. These results suggest that anthropogenic pollutants alter gut microbial populations, which may have health and fitness consequences for hosts. Environ Toxicol Chem 2015;34:1113–1118. © 2015 SETAC
Altered salience processing in attention deficit hyperactivity disorder
Authors: Tegelbeckers Jana , Bunzeck Nico , Duzel Emrah , Bonath Björn , Flechtner Hans‐Henning , Krauel Kerstin
Published: February 2015

Attentional problems in patients with attention deficit hyperactivity disorder (ADHD) have often been linked with deficits in cognitive control. Whether these deficits are associated with increased sensitivity to external salient stimuli remains unclear. To address this issue, we acquired functional brain images (fMRI) in 38 boys with and without ADHD (age: 11–16 years). To differentiate the effects of item novelty, contextual rareness and task relevance, participants performed a visual oddball task including four stimulus categories: a frequent standard picture (62.5%), unique novel pictures (12.5%), one repeated rare picture (12.5%), and a target picture (12.5%) that required a specific motor response. As a main finding, we can show considerable overlap in novelty‐related BOLD responses between both groups, but only healthy participants showed neural deactivation in temporal as well as frontal regions in response to novel pictures. Furthermore, only ADHD patients, but not healthy controls, engaged wide parts of the novelty network when processing the rare but familiar picture. Our results provide first evidence that ADHD patients show enhanced neural activity in response to novel but behaviorally irrelevant stimuli as well as reduced habituation to familiar items. These findings suggest an inefficient use of neuronal resources in children with ADHD that could be closely linked to increased distractibility. Hum Brain Mapp 36:2049–2060, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment
Authors: Čeko Marta , Shir Yoram , Ouellet Jean A. , Ware Mark A. , Stone Laura S. , Seminowicz David A.
Published: February 2015

We previously reported that effective treatment of chronic low back pain (CLBP) reversed abnormal brain structure and functional MRI (fMRI) activity during cognitive task performance, particularly in the left dorsolateral prefrontal cortex (DLPFC). Here, we used resting‐state fMRI to examine how chronic pain affects connectivity of brain networks supporting cognitive functioning and the effect of treatment in 14 CLBP patients and 16 healthy, pain‐free controls (scans were acquired at baseline for all subjects and at 6‐months post‐treatment for patients and a matched time‐point for 10 controls). The main networks activated during cognitive task performance, task‐positive network (TPN) and task‐negative network (TNN) (aka default mode) network, were identified in subjects' task fMRI data and used to define matching networks in resting‐state data. The connectivity of these cognitive resting‐state networks was compared between groups, and before and after treatment. Our findings converged on the bilateral insula (INS) as the region of aberrant cognitive resting‐state connectivity in patients pretreatment versus controls. These findings were complemented by an independent, data‐driven approach showing altered global connectivity of the INS. Detailed investigation of the INS confirmed reduced connectivity to widespread TPN and TNN areas, which was partially restored post‐treatment. Furthermore, analysis of diffusion‐tensor imaging (DTI) data revealed structural changes in white matter supporting these findings. The left DLPFC also showed aberrant connectivity that was restored post‐treatment. Altogether, our findings implicate the bilateral INS and left DLPFC as key nodes of disrupted cognition‐related intrinsic connectivity in CLBP, and the resulting imbalance between TPN and TNN function is partially restored with treatment. Hum Brain Mapp 36:2075–2092, 2015. © 2015 Wiley Periodicals, Inc.
Investigation of N‐ and C‐Phosphanylation of [1,2,4]Triazolo[4,3‐a]pyridines
Authors: Marchenko Anatoliy P. , Koidan Heorgiy N. , Kirilchuk Andrey A. , Rozhenko Alexander B. , Yurchenko Aleksandr A. , Kostyuk Aleksandr N.
Published: February 2015

Synthesis and deprotonation of N‐phosphanylated[1,2,4]triazolo[4,3‐a]pyridinium triflates were investigated. Phosphanylation by t‐Bu2PCl proceeds at N1 of starting triazolo‐pyridines. According to density functional theory calculations, deprotonation of the formed salt gives abnormal carbenes, which decompose by opening of the triazole cycle. Treatment by chlorodiphenylphosphane leads to an equilibrium mixture of N1‐ and N2‐phosphanylated salts, which under addition of base yields normal carbene that rapidly rearranges to form C‐phosphanylated product. Mechanisms of the reactions are discussed.
Naturally Occurring Polyphenolic Glucosidase Inhibitors
Authors: Yang You , Lian Gaoyan , Yu Biao
Published: February 2015

Polyphenols, which are abundantly distributed in plants such as fruits, vegetables, and tea, constitute a large group of aromatic compounds, mainly including phenolic acids and flavonoids. These natural metabolites have been demonstrated to possess a wide range of biological activities associated with health benefits, including the α‐glucosidase inhibitory activity. In contrast to the classical α‐glucosidase inhibitors, e.g., aza/imino sugars, polyphenols serve as a new type of α‐glucosidase inhibitor with different, yet unknown, mechanisms of action, which could lead to novel dietary supplements and therapeutic agents for the prevention and treatment of metabolic disorders. In this review, we report a collection of 137 naturally occurring phenolic acids and flavonoids with α‐glucosidase inhibitory activities.
Peptide Nanostructures with π‐Ways: Photophysical Consequences of Peptide/π‐Electron Molecular Self‐Assembly
Authors: Tovar John D.
Published: February 2015

This article provides a summary of the electronic outcomes that result as oligopeptides with embedded π‐conjugated units are drawn together into hierarchical 1D assemblies reminiscent of amyloid plaques or other protein deposits associated with neurodegenerative diseases. The baseline photophysics of prototype molecules are presented, followed by a description of how subtle molecular variations further perturb these responses in manners relevant to several cutting‐edge optoelectronic applications. For example, the influence of amino acid residue steric bulk/hydrophobicity and peptide N‐to‐C sequence variation are explicated, showing excited‐state variations in the excimeric or excitonic nature of the intermolecular π‐electron delocalization that result as the π‐conjugated peptides are driven to assemble into extended 1D fibrillar assemblies.
Response of Quinoa to Different Water Management Strategies: Field Experiments and Saltmed Model Application Results
Authors: Fghire Rachid , Wahbi Said , Anaya Fatima , Issa Ali Oudou , Benlhabib Ouafae , Ragab Ragab
Published: February 2015

Given the current water shortage in North Africa, improving water management to produce more crop per drop is vital. In addition, the introduction of drought‐tolerant, less water‐consuming crops such as quinoa is of great interest. To understand the response of quinoa to water stress in terms of biomass and grain yield under various irrigation management strategies, the SALTMED model was employed using field measurements during the cropping seasons of 2011 and 2012 at a site in the Marrakech region, south Morocco. Quinoa showed its ability to grow in the south of Morocco and give a good yield under full irrigation. However, the experimental and modelling results showed that under rainfed and deficit irrigation, the grain yield was lower than under the full irrigation treatment and was dependent on water deficit level. The study revealed that a reasonable grain yield of quinoa can only be obtained if it was subjected to moderate water stress conditions. The results indicated that the SALTMED model is able to simulate the quinoa biomass and grain yield under various water deficit levels and that the model can be used in the evaluation of different irrigation strategies. Copyright © 2015 John Wiley & Sons, Ltd.
Accurate reaction barrier heights of pericyclic reactions: Surprisingly large deviations for the CBS‐QB3 composite method and their consequences in DFT benchmark studies
Authors: Karton Amir , Goerigk Lars
Published: February 2015

Accurate barrier heights are obtained for the 26 pericyclic reactions in the BHPERI dataset by means of the high‐level Wn‐F12 thermochemical protocols. Very often, the complete basis set (CBS)‐type composite methods are used in similar situations, but herein it is shown that they in fact result in surprisingly large errors with root mean square deviations (RMSDs) of about 2.5 kcal mol−1. In comparison, other composite methods, particularly G4‐type and estimated coupled cluster with singles, doubles, and quasiperturbative triple excitations [CCSD(T)/CBS] approaches, show deviations well below the chemical‐accuracy threshold of 1 kcal mol−1. With the exception of SCS‐MP2 and the herein newly introduced MP3.5 approach, all other tested Møller‐Plesset perturbative procedures give poor performance with RMSDs of up to 8.0 kcal mol−1. The finding that CBS‐type methods fail for barrier heights of these reactions is unexpected and it is particularly troublesome given that they are often used to obtain reference values for benchmark studies. Significant differences are identified in the interpretation and final ranking of density functional theory (DFT) methods when using the original CBS‐QB3 rather than the new Wn‐F12 reference values for BHPERI. In particular, it is observed that the more accurate Wn‐F12 benchmark results in lower statistical errors for those methods that are generally considered to be robust and accurate. Two examples are the PW6B95‐D3(BJ) hybrid‐meta‐general‐gradient approximation and the PWPB95‐D3(BJ) double‐hybrid functionals, which result in the lowest RMSDs of the entire DFT study (1.3 and 1.0 kcal mol−1, respectively). These results indicate that CBS‐QB3 should be applied with caution in computational modeling and benchmark studies involving related systems. © 2015 Wiley Periodicals, Inc.
Quantifying electro/nucleophilicity by partitioning the dual descriptor
Authors: Tognetti Vincent , Morell Christophe , Joubert Laurent
Published: February 2015

Translating local electro/nucleophilicities into the language of reactive sites is an appealing theoretical challenge that could be conducive to strengthen the collaborative dialogue between experimentalists and quantum chemists. The usual schemes for such condensation, relying on atomic charges, may however lead to important information loss, due to a sometimes inappropriate averaging of the reactivity anisotropy. In this article, we present instead an approach based on the dual descriptor Δf, which aims at partitioning real space into nonoverlapping reactive domains that feature a constant Δf sign. This strategy enables not only to identify the nucleo/electrophilic regions inside a molecule but also to quantify meaningful properties (mean value, volume, electron population…). Its interest is then illustrated on two specific chemical problems: the measure of σ‐holes in the context of halogen bonds, and of the electrophilicity of organic carbocations, casting the light on the versatility of this method. © 2015 Wiley Periodicals, Inc.
Assessment of the persistence of anacetrapib and evacetrapib concentrations using two pharmacokinetic modeling approaches
Authors: Small David S. , Ke Alice Ban , Hall Stephen D. , Mantlo Nathan , Rotelli Matthew , Friedrich Stuart
Published: February 2015

Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor, has been reported to have longer elimination half‐life after longer treatment. Two pharmacokinetic model‐based approaches were used to assess whether evacetrapib, another CETP inhibitor, could behave similarly. Using population pharmacokinetic (PopPK) modeling, evacetrapib and anacetrapib pharmacokinetics were characterized using available concentration‐time data, and steady‐state conditions were simulated. Published 2‐compartment models for each compound were adapted to include a hypothetical third compartment representing a depot into which drug could partition. Physiologically based pharmacokinetic (PBPK) modeling was used to predict steady‐state conditions and terminal half‐life based on known physicochemical and dispositional properties. The PopPK model described the anacetrapib data well, showing a likely third compartment with estimated apparent volume of 40,700 L. Anacetrapib's estimated half‐life for this compartment was 550 days. Simulations for evacetrapib using a hypothetical 3‐compartment model, the third compartment being consistent with that of the anacetrapib model, produced predictions inconsistent with reported results, indicating that evacetrapib did not substantially accumulate into a large compartment. The PBPK simulations were consistent with PopPK results, predicting accumulation for anacetrapib (but not evacetrapib) followed by very slow elimination. Based on available data and known physicochemical properties, evacetrapib is not expected to accumulate substantially during long‐term treatment.
Management of lipid disorders in patients living with HIV
Authors: Myerson Merle , Malvestutto Carlos , Aberg Judith A.
Published: February 2015

Since the discovery and development of antiretroviral therapy (ART), HIV has become a chronic disease with patients living longer lives and to ages where co‐morbidities, such as cardiovascular disease (CVD) are prevalent. Diagnosis and management of risk factors for CVD, in particular dyslipidemia, have become an important part of the overall care for patients living with HIV infection. Existing guidelines and recommendations for the management of dyslipidemia for persons with HIV infection are largely based on guidelines for the general population. Clinical and epidemiologic research efforts are ongoing to provide information specific to patients living with HIV. This review offers a detailed guide for clinicians who manage dyslipidemia in patients infected with HIV. The first sections provide background information on dyslipidemia, risk stratification, and targets for lipid therapy. This is followed by a step‐by‐step approach for diagnosis and treatment with specific information on lipid drug use for patients with HIV. The recommendations presented here are based on existing guidelines for the general population, evidence from research in patients infected with HIV, and the clinical experience of the authors. Management issues for which little or no information is available specific to this patient population are noted and serve to highlight the many gaps in our knowledge that will need to be addressed.
Self‐reported confidence in prescribing skills correlates poorly with assessed competence in fourth‐year medical students
Authors: Brinkman David J. , Tichelaar Jelle , van Agtmael Michiel A. , de Vries Theo P. G. M. , Richir Milan C.
Published: February 2015

The objective of this study was to investigate the relationship between students' self‐reported confidence and their objectively assessed competence in prescribing. We assessed the competence in several prescribing skills of 403 fourth‐year medical students at the VU University Medical Center, the Netherlands, in a formative simulated examination on a 10‐point scale (1 = very low; 10 = very high). Afterwards, the students were asked to rate their confidence in performing each of the prescribing skills on a 5‐point Likert scale (1 = very unsure; 5 = very confident). Their assessments were then compared with their self‐confidence ratings. Students' overall prescribing performance was adequate (7.0 ± 0.8), but they lacked confidence in 2 essential prescribing skills. Overall, there was a weak positive correlation (r = 0.2, P < .01, 95%CI 0.1–0.3) between reported confidence and actual competence. Therefore, this study suggests that self‐reported confidence is not an accurate measure of prescribing competence, and that students lack insight into their own strengths and weaknesses in prescribing. Future studies should focus on developing validated and reliable instruments so that students can assess their prescribing skills.
Redox activity and multiple copper(I) coordination of 2His–2Cys oligopeptide
Authors: Choi DongWon , Alshahrani Aisha A. , Vytla Yashodharani , Deeconda Manogna , Serna Victor J. , Saenz Robert F. , Angel Laurence A.
Published: February 2015

Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide‐2 (amb2) with the sequence acetyl–His1–Cys2–Tyr3–Pro4–His5–Cys6 was investigated using ion mobility–mass spectrometry (IM‐MS) and UV–Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra‐ and intermolecular Cys–Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)]+ which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM‐MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV–Vis spectrophotometric study. The results show that IM‐MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides. Copyright © 2015 John Wiley & Sons, Ltd.
Fast alternating direction implicit method for efficient transient thermal simulation of integrated circuits
Authors: Heh Ding Yu , Tan Eng Leong , Tay Wei Choon
Published: February 2015

This paper presents fast alternating direction implicit (FADI) method for efficient transient thermal simulation of integrated circuits. The FADI method is formulated from Peaceman–Rachford's ADI and Douglas–Gunn's ADI methods. The update procedure of the proposed method has basic implicit form that features derivative‐free right‐hand side and hence, better efficiency and conciseness. Subsequently, through the basic implicit form of FADI method, the relationship between classical Peaceman–Rachford's and Douglas–Gunn's ADI methods can be clarified and elucidated in detail. A unified boundary condition that can cater to common kinds of boundary conditions in thermal simulation is also introduced. To further accelerate FADI method, the graphics processing unit is also utilized through Compute Unified Device Architecture implementation. It is shown that high efficiency gain can be achieved using the proposed FADI method through large time step size and data parallelism, while maintaining stability and good accuracy. As numerical illustration, an integrated circuit structure with microchannel cooling is demonstrated. Numerical results further ascertain the cooling effect of the microchannels. Copyright © 2015 John Wiley & Sons, Ltd.
Rapid prototyping of MIMO‐OFDM based on parity bit selected and permutation spreading
Authors: Moussa Sherif , M. Abdel Razik Ahmed , Dahmane Adel Omar , D'Amours Claude , Hamam Habib
Published: February 2015

In this paper, a novel MIMO‐OFDM transmission scheme is developed to effectively enable multi‐access by joint code design across multiple antennas, subcarriers, OFDM frames, and users. It achieves better spectrum efficiency while improving bit error rate performance. The proposed scheme uses either parity bit selected or permutation techniques to assign spreading codes at the transmitter side. As a result, the detection at the receiver is greatly improved because of the fact that identifying the spreading code(s) directly yields the transmitted data symbols. The paper also investigates the field‐programmable gate array implementation of the proposed algorithms; optimization techniques are proposed to reduce area, power, and time. These techniques include a pipelined architecture for inverse FFT/FFT blocks, an efficient low complexity algorithm for despreading based on counters and comparators and an optimized architecture for complex matrix inversion using Gauss–Jordan elimination (GJ‐elimination). Finally, the fixed‐point optimized field‐programmable gate array architecture for MIMO‐OFDM transceiver is developed, where the maximum allowed performance loss because of quantization is defined, the tradeoffs between BER performance and area reduction are investigated. Copyright © 2015 John Wiley & Sons, Ltd.
Complete delay modeling of sub‐threshold CMOS logic gates for low‐power application
Authors: Chanda Manash , Chakraborty Ananda Sankar , Sarkar Chandan Kumar
Published: February 2015

In this paper, the propagation delay of a complementary metal‐oxide semiconductor (CMOS) inverter circuit in sub‐threshold regime has been analyzed thoroughly with respect to variable loads, rise and fall time of input, device dimensions and temperature, without neglecting the significant drain induced barrier lowering (DIBL) and body bias effects. In particular, sub‐threshold slope factor and current strength have been modeled with respect to temperature, which would be efficacious for the analysis of sub‐threshold circuit as temperature plays an important role in propagation delay. Transistor stacking has also been modeled considering variation in threshold voltage, sub‐threshold slope factor and DIBL coefficient owing mainly to fluctuation in doping levels. The CMOS inverter delay model together with transistor stacking model has been incorporated in the analysis of propagation delays of NAND and NOR gates. Extensive simulations have been performed under 45 and 22 nm CMOS technology using simulation program with integrated circuit emphasis (SPICE) to ensure the correctness of the analysis. Simulation shows that this model is applicable for the analysis of digital sub‐threshold circuit in sub‐90 nm technology. Copyright © 2015 John Wiley & Sons, Ltd.
Maintaining the presynaptic glutamate supply for excitatory neurotransmission
Authors: Marx Mari‐Carmen , Billups Daniela , Billups Brian
Published: February 2015

Glutamate released from synapses during excitatory neurotransmission must be rapidly recycled to maintain neuronal communication. This review evaluates data from physiological experiments at hippocampal CA3 to CA1 synapses and the calyx of Held synapse in the brainstem to analyze quantitatively the rates of release and resupply of glutamate required to sustain neurotransmission. We calculate that, without efficient recycling, the presynaptic glutamate supply will be exhausted within about a minute of normal synaptic activity. We also discuss replenishment of the presynaptic pool by diffusion from the soma, direct uptake of glutamate back into the presynaptic terminal, and uptake of glutamate precursor molecules. Diffusion of glutamate from the soma is calculated to be fast enough to resupply presynaptic glutamate in the hippocampus but not at the calyx of Held. However, because the somatic cytoplasm will also quickly run out of glutamate and synapses can function continually even if the presynaptic axon is severed, mechanisms other than diffusion must be present to resupply glutamate for release. Direct presynaptic uptake of glutamate is not present at the calyx of Held but may play a role in glutamate recycling in the hippocampus. Alternatively, glutamine or tricarboxylic acid cycle intermediates released from glia can serve as a precursor for glutamate in synaptic terminals, and we calculate that the magnitude of presynaptic glutamine uptake is sufficient to supply enough glutamate to sustain neurotransmission. The nature of these mechanisms, their relative abundance, and the co‐ordination between them remain areas of intensive investigation. © 2015 Wiley Periodicals, Inc.
A comparative study of primary secondary amino (PSA) and multi‐walled carbon nanotubes (MWCNTs) as QuEChERS absorbents for the rapid determination of diazepam and its major metabolites in fish samples by high‐performance liquid chromatography–electrospray ionisation–tandem mass spectrometry
Authors: Li Jincheng , Zhang Jing , Liu Huan , Wu Lidong
Published: February 2015

BACKGROUND

A simple and fast modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) method is presented for the determination of diazepam and its three major metabolites, nordiazepam, temazepam and oxazepam (benzodiazepines) in fish samples by liquid chromatography–electrospray ionisation–tandem mass spectrometry.

RESULTS

Muscle tissues were extracted with acetonitrile, and then cleaned with primary secondary amino (PSA) adsorbents. The cleanup effect of PSA was compared with that of multi‐walled carbon nanotubes (MWCNTs) in term of extraction efficiency. The better results were obtained when PSA was used. The chromatography separation was achieved within 5.0 min on a C18 column. The limit of detection was 0.5 µg kg−1 and the limit of quantification was 2.5 µg kg−1. Average recoveries of diazepam and its main metabolites were in the range of 88.5–110.1%, with a relative standard deviation lower than 10.0%.

CONCLUSION

The proposed method for fish samples gives good recoveries, linearity, precision and accuracy. © 2015 Society of Chemical Industry
Fractional carbon dioxide laser resurfacing of rhytides and photoaged skin – A prospective clinical study on patient expectation and satisfaction
Authors: Kohl Elisabeth , Meierhöfer Julia , Koller Michael , Zeman Florian , Groesser Leopold , Karrer Sigrid , Hohenleutner Ulrich , Landthaler Michael , Hohenleutner Silvia
Published: February 2015

Background

Fractional CO2‐laser resurfacing is increasingly used for treating rhytides and photoaged skin because of its favorable benefit‐risk ratio. A key outcome measure and treatment goal in aesthetic laser therapy is patient satisfaction. However, few data are available on patient‐reported outcomes after fractional ablative skin‐resurfacing.

Objectives

To compare patient expectations before and patient satisfaction after three fractional CO2‐laser treatments and to correlate objectively measured wrinkle reduction with patient satisfaction after treatment.

Methods

We investigated patient expectation and satisfaction using a 14‐item questionnaire in 24 female patients. We assessed the skin‐related quality of life and patient satisfaction with skin appearance. We profilometrically measured wrinkle size in four facial areas before and three months after treatment and investigated correlations between wrinkle reduction and patient satisfaction.

Results

The high patient expectations before treatment (ceiling effect) were actually slightly exceeded. The average score of 14 items delineating patient satisfaction with laser treatment was higher (4.64 ± 0.82; n = 24) than the respective expectations before treatment (4.43 ± 0.88; n = 24). Skin‐related quality of life and patient satisfaction with skin appearance had significantly improved after the last treatment. Patients dissatisfied with their skin appearance before treatment (mean 2.1 ± 1.5; evaluated on a scale ranging from 0–6) were satisfied (mean 5.1 ± 1.2) (P < 0.001) with skin appearance at the follow‐up. Patient satisfaction with skin appearance was not correlated to the profilometrically measured reduction of wrinkle size of any facial area.

Conclusions

Our results show high patient satisfaction with ablative fractional skin resurfacing, also regarding improved self‐esteem and self‐satisfaction despite high pre‐treatment expectations. Skin‐specific quality of life had significantly improved. Thus, this treatment modality can be recommended for patients with photoaged skin wishing to improve skin appearance. Lasers Surg. Med. 47:111–119, 2015. © 2015 Wiley Periodicals, Inc.