bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Function of Brønsted and Lewis Acidity in the Zeolite‐Catalyzed Isomerization of Glucose to Fructose in Alcohols
Authors: Saravanamurugan Shunmugavel , Riisager Anders , Taarning Esben , Meier Sebastian
Published: September 2016

Glucose conversion via fructose to useful chemicals and fuels has attracted considerable attention. Isomerization of glucose to fructose can proceed along several different reaction pathways involving different sugar intermediates and isomeric forms. Presently, the roles of the substrate isomeric forms and of the catalyst properties remain incompletely understood. By using NMR spectroscopy, we elucidate the interplay of the catalyst active sites in converting monosaccharide forms to products, byproducts, and intermediates in alcohols.
Targeting programmed cell death 4 (PDCD4) with biogenic compounds in ARDS by Gaussian process‐based QSAR virtual screening
Authors: Wang Sheng‐Yun , Liu Jun‐Ying , Wang Lv , Duan Li‐Wei , Chen Qi‐Tong , Zheng Jin‐Hao , Lin Zhao‐Fen , Li Wen‐Fang
Published: September 2016

The programmed cell death 4 (PDCD4) has recently been recognized as a new and attractive target of acute respiratory distress syndrome. Here, we attempted to discover new and potent PDCD4 mediator ligands from biogenic compounds using a synthetic strategy of statistical virtual screening and experimental affinity assay. In the procedure, a Gaussian process‐based quantitative structure‐activity relationship regression predictor was developed and validated statistically based on a curated panel of structure‐based protein‐ligand affinity data. The predictor was integrated with pharmacokinetics analysis, chemical redundancy reduction, and flexible molecular docking to perform high‐throughput virtual screening against a distinct library of chemically diverse, drug‐like biogenic compounds. Consequently, 6 hits with top scores were selected, and their binding affinities to the recumbent protein of human PDCD4 were identified, 3 out of which were determined to have high or moderate affinity with Kd at micromolar level. Structural analysis of protein‐ligand complexes revealed that hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PDCD4 with these mediator ligands, while few hydrogen bonds, salt bridges, and/or π‐π stacking at the complex interfaces confer selectivity and specificity for the protein‐ligand recognition. It is suggested that the statistical Gaussian process‐based quantitative structure‐activity relationship screening strategy can be successfully applied to rational discovery of biologically active compounds. The newly identified molecular entities targeting PDCD4 are considered as promising lead scaffolds to develop novel chemical therapeutics for acute respiratory distress syndrome.
Enantiodivergent Synthesis of (+)‐ and (−)‐Pyrrolidine 197B: Synthesis of trans‐2,5‐Disubstituted Pyrrolidines by Intramolecular Hydroamination
Authors: Pérez Sixto J. , Purino Martín A. , Cruz Daniel A. , López‐Soria Juan M. , Carballo Rubén M. , Ramírez Miguel A. , Fernández Israel , Martín Víctor S. , Padrón Juan I.
Published: September 2016

A highly efficient, diastereoselective, iron(III)‐catalyzed intramolecular hydroamination/cyclization reaction involving α‐substituted amino alkenes is described. Thus, enantiopure trans‐2,5‐disubstituted pyrrolidines and trans‐5‐substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l‐α‐amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)‐ and (−)‐pyrrolidine 197B alkaloids from l‐glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation.
Thermal Stability of Oxidized Single‐Walled Carbon Nanotubes: Competitive Elimination and Decomposition Reaction Depending on the Degree of Functionalization
Authors: Maeda Yutaka , Sone Erika , Nishino Akane , Amagai Yuri , Wang Wei‐Wei , Yamada Michio , Suzuki Mitsuaki , Matsui Jun , Mitsuishi Masaya , Okazaki Toshiya , Nagase Shigeru
Published: September 2016

The thermal stability of oxidized single‐walled carbon nanotubes (SWNTs) with various degrees of oxidation was investigated. The oxidized SWNTs exhibited lower absorption and radial breathing mode (RBM) peaks and a higher intensity ratio of the D band to the G band (D/G) in their absorption and Raman spectra than those of the pristine SWNTs. After the thermal treatment, the D/G ratio of the oxidized SWNTs almost recovered its original intensity, regardless of the degree of oxidation. The absorption, photoluminescence (PL), and RBM peaks could not recover their original intensities when the oxidation degree was high. The results indicate that the elimination and decomposition reactions proceeded competitively depending on the degree of oxidation. In addition, a new PL peak was observed in the near‐infrared region, and the PL peak intensity increased with the subsequent thermal treatment. The theoretical calculations provided an insight into the possible pathways for the decomposition of oxidized SWNTs, showing that the O2 elimination and CO/CO2 evolution proceed competitively during thermal treatment.
Selective Co‐Encapsulation Inside an M6L4 Cage
Authors: Leenders Stefan H. A. M. , Becker René , Kumpulainen Tatu , de Bruin Bas , Sawada Tomohisa , Kato Taito , Fujita Makoto , Reek Joost N. H.
Published: September 2016

There is broad interest in molecular encapsulation as such systems can be utilized to stabilize guests, facilitate reactions inside a cavity, or give rise to energy‐transfer processes in a confined space. Detailed understanding of encapsulation events is required to facilitate functional molecular encapsulation. In this contribution, it is demonstrated that Ir and Rh‐Cp‐type metal complexes can be encapsulated inside a self‐assembled M6L4 metallocage only in the presence of an aromatic compound as a second guest. The individual guests are not encapsulated, suggesting that only the pair of guests can fill the void of the cage. Hence, selective co‐encapsulation is observed. This principle is demonstrated by co‐encapsulation of a variety of combinations of metal complexes and aromatic guests, leading to several ternary complexes. These experiments demonstrate that the efficiency of formation of the ternary complexes depends on the individual components. Moreover, selective exchange of the components is possible, leading to formation of the most favorable complex. Besides the obvious size effect, a charge‐transfer interaction may also contribute to this effect. Charge‐transfer bands are clearly observed by UV/Vis spectrophotometry. A change in the oxidation potential of the encapsulated electron donor also leads to a shift in the charge‐transfer energy bands. As expected, metal complexes with a higher oxidation potential give rise to a higher charge‐transfer energy and a larger hypsochromic shift in the UV/Vis spectrum. These subtle energy differences may potentially be used to control the binding and reactivity of the complexes bound in a confined space.
Preparation, characterization, and application of vertically aligned CNT sheets through template assisted pyrolysis of PBI‐Kapton
Authors: Azami Hamed , Omidkhah Mohammad Reza
Published: September 2016

This article investigates the synthesis of vertically aligned carbon nanotube (CNT) sheets through the pyrolysis of polybenzimidazole (PBI)‐Kapton inside the pores of anodized aluminium oxide (AAO). The nanocomposites of CNT/Alumina obtained were characterized by several techniques. It was found that the resulting carbon structures presented higher crystallinity compared with graphite. All of the CNT sheets had high antibacterial activity that was proportional to degree of CNT crystallinity. Moreover, the desalination of salty water using CNT sheets was performed. The results demonstrated that the vertically aligned CNT sheets could be used as an effective adsorbent for salty water desalination due to their very high adsorption capacity without CNT leakage into water.
An investigation on heat transfer of granular materials in the novel flighted rotary drum
Authors: Li Muyuan , Ling Xiang , Peng Hao , Cao Zhengyu , Wang Yan
Published: September 2016

In this study, a model is carried out to investigate heat transfer within a granular system in the novel flighted rotary drum (FRD). The model using Eulerian continuum approach (ECA) is developed and then verified by comparing with experimental data published previously. The effects of flight configuration, number of flights, rotational speed, and fill level on heat transfer characteristics are discussed. The results show that increasing rotational speed can intensify heat transfer to a certain degree, but it is not significant. The average temperature of granular materials increases with the increase of the number of flights and the decrease of the fill level. More importantly, the average temperature is strongly dependent on flight configurations (including different length ratios and flight tip angles). There is an enhancement in heat transfer when the length ratio S1/S2 is 1 or the flight tip angle is higher.
Theranostic Polyaminocarboxylate–Cyanine–Transferrin Conjugate for Anticancer Therapy and Near‐Infrared Optical Imaging
Authors: Kang Chi Soo , Ren Siyuan , Sun Xiang , Chong Hyun‐Soon
Published: September 2016

Iron chelation therapy has been recognized as a promising antitumor therapeutic strategy. Herein we report a novel theranostic agent for targeted iron chelation therapy and near‐infrared (NIR) optical imaging of cancers. The theranostic agent was prepared by incorporation of a polyaminocarboxylate‐based cytotoxic chelating agent (N‐NE3TA; 7‐[2‐[(carboxymethyl)amino]ethyl]‐1,4,7‐triazacyclononane‐1,4‐diacetic acid) and a NIR fluorescent cyanine dye (Cy5.5) onto a tumor‐targeting transferrin (Tf). The N‐NE3TA–Tf conjugate (without Cy5.5) was characterized and evaluated for antiproliferative activity in HeLa, HT29, and PC3 cancer cells, which have elevated expression levels of the transferrin receptor (TfR). The N‐NE3TA–Tf conjugate displayed significant inhibitory activity against all three cancer cell lines. The NIR dye Cy5.5 was then incorporated into N‐NE3TA–Tf, and the resulting cytotoxic and fluorescent transferrin conjugate N‐NE3TA–Tf–Cy5.5 was shown by microscopy to enter TfR‐overexpressing cancer cells. This theranostic conjugate has potential application for dual use in targeted iron chelation cancer therapy and NIR fluorescence imaging.
Regulatory Pathways for New Antimicrobial Agents: Trade‐offs to Keep the Perfect From Being the Enemy of the Good
Authors: Spellberg B , Marr KA , Brass EP
Published: September 2016

In 2002, Shlaes and Moellering warned that pharmaceutical companies were abandoning antibiotic research and development due to changing regulatory standards regarding noninferiority (NI) clinical trials. NI trials are subject to unique biases that may yield false‐positive conclusions. The US Food and Drug Administration (FDA) developed guidance to ensure that NI results truly reflect drug efficacy. These changes, intended to reduce uncertainty in trial results, have shaped trial enrollment and conduct in ways that now require reflection.
An assessment of implications of adaptive licensing for pharmaceutical intellectual property and regulatory exclusivity rights in the European Union
Authors: Meier A , Faulkner SD , Schoonderbeek C , Jong B , Kung J , Brindley D , Barker R
Published: September 2016

One of the key advantages of adaptive licensing (AL) is to align the licensing of new medicines more closely with patient needs for earlier access to beneficial treatments. From an innovators perspective, “earlier” market access may seem an obvious incentive to gain earlier revenue generation. However, this is offset with an “earlier” start to patent and regulatory protection periods, which, depending on the technology, disease, population, and timing of subsequent asset protection periods, can present a conflict.
Graphitic Carbon Nitride Film: An Emerging Star for Catalytic and Optoelectronic Applications
Authors: Bian Juncao , Huang Chao , Zhang Rui‐Qin
Published: September 2016

Graphitic carbon nitride (g‐CN) is a unique organic semiconductor that has been widely applied as a visible‐light‐driven photocatalyst. However, these applications are primarily based on g‐CN powders. Applications of g‐CN in devices are hindered because of difficulties associated with the synthesis of high‐quality g‐CN films. This work reviews the latest advances in g‐CN films. The deposition methods are summarized and the structural, optical, and electronic properties of g‐CN films and their applications in catalysis, solar cells, and light‐emitting diodes are outlined. Moreover, the challenges remaining in this field are also discussed.
Increased autophagy in CD4+ T cells of rheumatoid arthritis patients results in T‐cell hyperactivation and apoptosis resistance
Authors: van Loosdregt Jorg , Rossetti Maura , Spreafico Roberto , Moshref Maryam , Olmer Merissa , Williams Gary W. , Kumar Pavanish , Copeland Dana , Pischel Ken , Lotz Martin , Albani Salvatore
Published: September 2016

Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4+ T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4+ T cells in the autoimmune process. A better knowledge of the mechanisms determining such impaired homeostasis could contribute significantly to both the understanding and the treatment of the disease. Here we investigated whether autophagy, is dysregulated in CD4+ T cells of RA patients, resulting in disturbed T‐cell homeostasis. We demonstrate that the rate of autophagy is significantly increased in CD4+ T cells from RA patients, and that increased autophagy is also a feature of in vitro activated CD4+ T cells. The increased apoptosis resistance observed in CD4+ T cells from RA patients was significantly reversed upon autophagy inhibition. These mechanisms may contribute to RA pathogenesis, as autophagy inhibition reduced both arthritis incidence and disease severity in a mouse collagen induced arthritis mouse model. Conversely, in Atg5flox/flox‐CD4‐Cre+ mice, in which all T cells are autophagy deficient, T cells showed impaired activation and proliferation. These data provide novel insight into the pathogenesis of RA and underscore the relevance of autophagy as a promising therapeutic target.
The role of Omega‐3 docosapentaenoic acid in pregnancy and early development
Authors: Li Juan , Yin Huaixia , Bibus Douglas M. , Byelashov Oleksandr A.
Published: September 2016

Docosapentaenoic acid (DPA, 22:5n‐3) is normally present in small quantities in marine products. Metabolically, it can directly convert to docosahexaenoic acid (DHA, 22:6n‐3) and retro‐convert into eicosapentaenoic acid (EPA, 20:5n‐3), suggesting that it may serve as a reservoir for these fatty acids in human body. Among other biological functions, DPA serves a precursor to anti‐inflammatory and pro‐resolving mediators. Further, either consumption of DPA or its blood levels are associated with positive human health outcomes, and in vitro and in vivo models have confirmed and highlighted DPA's biological role in mammals. Because the role of DHA in prenatal and postnatal development is well known, most infant formulas are now supplemented with DHA. Although human breast milk contains significant levels of DHA, importantly, its levels of DPA are comparable. Despite this, the importance of DPA in infant and maternal health is less recognized. Our review highlights that DPA intake (often along with EPA and DHA) by lactating mothers is linked to better neural development and bone health of children. Additionally, blood levels of DPA in mothers are associated with fewer allergic diseases such as asthma, rhinitis, and eczema in children and mothers. The daily dietary intake of DPA in breast‐fed infants in various populations ranges from 5.1 to 44.6 mg/kg body weight, which would translate to 357–3122 mg/d for a 70‐kg adult. The reported health effects of DPA suggest it may be beneficial to increase the intake of DPA during prenatal and early postnatal life stages.

Practical applications: This paper reviewed all research articles related with DPA health benefits in human development and summarized the potential function of DPA in human during pregnancy and early development. In vitro and in vivo studies both indicated that DPA has important biological role in mammals. The fact that DPA is high in human breast milk shows the potential biological function of DPA in infant development. The authors recommend infant formula manufacturers to consider adding DPA to infant food and encourage researchers to conduct human clinical studies to further prove the biological function of DPA in human development.

LC Omega‐3 fatty acids play a critical role in human nutrition and health. DPA's role as a reservoir for DHA and EPA highlights the importance in human physiology. This study demonstrates the association between blood DPA levels and both infant and maternal health, and suggests the recommendation for DPA consumption during prenatal and early postnatal life stages.
Electrothermal Annealing of Catalytic Platinum Microwire Electrodes: Towards Membrane‐Free pH 7 Glucose Micro‐Fuel Cells
Authors: Weber James , Wain Andrew J. , Attard Gary A. , Marken Frank
Published: September 2016

Surface activation and cleaning of platinum micro‐wires of 25 micron diameter has been achieved by a short one‐second electrothermal annealing treatment in air at 0.3 A (to orange glow). Voltammetric data suggest a decrease in the electrochemically active surface area with annealing time and a change in surface structure towards the Pt(100) crystalline face. The impact of electrothermal annealing on the electrocatalytic activity towards (i) oxygen reduction and (ii) glucose oxidation in pH 7 phosphate buffered aqueous solutions is investigated. In contrast to as‐received platinum, annealed platinum produces an electrocatalytic response towards glucose oxidation with increasing glucose concentration. A short one‐second anneal step is just as effective in enhancing catalysis as prolonged electrochemical cleaning in sulphuric acid. Finally, by combining a non‐annealed and an annealed microwire electrode, a very simple membrane‐free micro‐fuel cell system is devised operating in phosphate buffer at pH 7 with linearly increasing power output reaching 2.2 nW cm−2 for high glucose levels of 0.5 M.
Basin‐scale methods for predicting salmonid spawning habitat via grain size and riffle spacing, tested in a California coastal drainage
Authors: Pfeiffer Allison M. , Finnegan Noah J.
Published: September 2016

Basin‐scale predictive geomorphic models for river characteristics, particularly grain size, can aid in salmonid habitat identification. However, these basin‐scale methods are largely untested with actual habitat usage data. Here, we develop and test an approach for predicting grain size distributions from high resolution LiDAR (Light Detection and Ranging)‐derived topographic data for a 77 km2 watershed along the central California Coast. This approach improves on previous efforts in that it predicts the full grain size distribution and incorporates an empirically calibrated shear stress partitioning factor. The predicted grain size distributions are used to calculate the fraction of the bed area movable by spawning fish. We then compare the ‘movable fraction’ with 7 years of observed spawning data. We find that predicted movable fraction explains the paucity of spawning in the upper reaches of the study drainage, but does not explain variation along the mainstem. In search of another morphologic characteristic that may help explain the variation within the mainstem, we measure riffle density, a proxy for physical habitat complexity. We find that field surveys of riffle density explain 64% of the variation in spawning in these mainstem reaches, suggesting that within reaches of appropriate sized gravel, spawning density is related to riffle density. Because riffle density varies systematically with channel width, predicting riffle spacing is straightforward with LiDAR data. Taken together, these findings demonstrate the efficacy of basin‐scale spawning habitat predictions made using high‐resolution digital elevation models. Copyright © 2016 John Wiley & Sons, Ltd.
How does anisotropy in bedrock river granitic outcrops influence pothole genesis and development?
Authors: Ortega‐Becerril Jose , Gomez‐Heras Miguel , Fort Rafael , Wohl Ellen
Published: September 2016

Pothole formation and development may be influenced by joint sets and other heterogeneities within bedrock, as well as by hydraulics. Previous research indicates that most potholes found in rivers of the mountainous Spanish Central System exhibit preferred orientations associated with dominant joints and correlate more strongly with variations in substrate resistance than with hydraulics. Weathering and erosion weaken rock surfaces, which leads to decreased mechanical resistance. We start from the hypothesis that different mechanisms of pothole formation may create around the pothole a distinctive signature in terms of ultrasound pulse velocity and surface hardness. We develop a conceptual model and test it using potholes for which we know the mechanism of formation, demonstrating that the spatial and statistical distributions of dynamical mechanical properties and surface hardness of a pothole may provide insight into its genesis. Copyright © 2016 John Wiley & Sons, Ltd.
Bias due to participant overlap in two‐sample Mendelian randomization
Authors: Burgess Stephen , Davies Neil M. , Thompson Simon G.
Published: September 2016

Mendelian randomization analyses are often performed using summarized data. The causal estimate from a one‐sample analysis (in which data are taken from a single data source) with weak instrumental variables is biased in the direction of the observational association between the risk factor and outcome, whereas the estimate from a two‐sample analysis (in which data on the risk factor and outcome are taken from non‐overlapping datasets) is less biased and any bias is in the direction of the null. When using genetic consortia that have partially overlapping sets of participants, the direction and extent of bias are uncertain. In this paper, we perform simulation studies to investigate the magnitude of bias and Type 1 error rate inflation arising from sample overlap. We consider both a continuous outcome and a case‐control setting with a binary outcome. For a continuous outcome, bias due to sample overlap is a linear function of the proportion of overlap between the samples. So, in the case of a null causal effect, if the relative bias of the one‐sample instrumental variable estimate is 10% (corresponding to an F parameter of 10), then the relative bias with 50% sample overlap is 5%, and with 30% sample overlap is 3%. In a case‐control setting, if risk factor measurements are only included for the control participants, unbiased estimates are obtained even in a one‐sample setting. However, if risk factor data on both control and case participants are used, then bias is similar with a binary outcome as with a continuous outcome. Consortia releasing publicly available data on the associations of genetic variants with continuous risk factors should provide estimates that exclude case participants from case‐control samples.
Synthesis of alkyl α‐aminomethyl‐phenylphosphinates and N,N‐bis(alkoxyphenylphosphinylmethyl)amines by the microwave‐assisted Kabachnik–Fields reaction
Authors: Bálint Erika , Tóth Regina Eszter , Keglevich György
Published: September 2016

As a novel extension, the Kabachnik–Fields reaction was applied to the synthesis of alkyl α‐aminomethyl‐phenylphosphinates, and the double phospha‐Mannich reaction was utilized in the preparation of bis(alkoxyphenylphosphinylmethyl)amines. A total of 27 new aminophosphinate derivatives were synthesized by the microwave‐assisted solvent‐free condensation of alkyl phenyl‐H‐phosphinates, paraformaldehyde, and primary or secondary amines. The starting P‐species were also prepared under microwave conditions. The formation of the N‐methylated aminomethyl‐phenylphosphinate by‐products was also investigated.
Variable relationship of the recurrent laryngeal nerve to the inferior thyroid artery: A meta‐analysis and surgical implications
Authors: Henry Brandon Michael , Vikse Jens , Graves Matthew J. , Sanna Silvia , Sanna Beatrice , Tomaszewska Iwona M. , Hsieh Wan Chin , Tubbs R. Shane , Tomaszewski Krzysztof A.
Published: September 2016

Background

The relationship between the recurrent laryngeal nerve (RLN) and inferior thyroid artery (ITA) is highly variable and traceable back to embryological life.

Methods

Comprehensive database searches were conducted, followed by judgment of eligibility, assessment, and extraction of data concerning the RLN/ITA relationship. The data were pooled into a meta‐analysis and subjected to sex, side‐based, geographic origin of study, and study modality subgroup analyses.

Results

Seventy‐nine studies (n = 14,269 nerves) reported data on the relationship of the RLN to the ITA. The left versus right‐sided comparison revealed stark differences: RLNs were predominantly posterior (62.6% vs 37.0%) and anterior (17.2% vs 37.1%) on the left and right sides, respectively.

Conclusion

Symmetry of neurovascular relationships should not be assumed. Extra care should be taken during procedures on the right side, because the nerves are significantly more likely to present in patterns (anterior and between) associated with greater risk of iatrogenic injury. © 2016 Wiley Periodicals, Inc. Head Neck 39: 177–186, 2017
Fast Efficient and General PASE Approach to Medicinally Relevant 4H,5H‐Pyrano‐[4,3‐b]pyran‐5‐one and 4,6‐Dihydro‐5H‐pyrano‐[3,2‐c]pyridine‐5‐one Scaffolds
Authors: Elinson Michail N. , Ryzhkov Fedor V. , Nasybullin Ruslan F. , Vereshchagin Anatoly N. , Egorov Mikhail P.
Published: September 2016

The general ‘on‐solvent’ PASE approach was found to be medicinally relevant for 4H,5H‐pyrano[4,3‐b]pyran‐5‐one and 4,6‐dihydro‐5H‐pyrano[3,2‐c]pyridine‐5‐one scaffolds. Ammonium acetate‐catalyzed multicomponent reaction of aldehydes and two different C–H acids in the presence of small amounts of EtOH results in fast (3 – 15 min) and efficient formation of scaffolds, promising for many diverse oriented medical applications.
Life cycle of petroleum biodegradation metabolite plumes, and implications for risk management at fuel release sites
Authors: Zemo Dawn A , O'Reilly Kirk T , Mohler Rachel E , Magaw Renae I , Espino Devine Catalina , Ahn Sungwoo , Tiwary Asheesh K
Published: September 2016

This paper summarizes the results of a 5-y research study of the nature and toxicity of petroleum biodegradation metabolites in groundwater at fuel release sites that are quantified as diesel-range “Total Petroleum Hydrocarbons” (TPH; also known as TPHd, diesel-range organics (DRO), etc.), unless a silica gel cleanup (SGC) step is used on the sample extract prior to the TPH analysis. This issue is important for site risk management in regulatory jurisdictions that use TPH as a metric; the presence of these metabolites may preclude site closure even if all other factors can be considered “low-risk.” Previous work has shown that up to 100% of the extractable organics in groundwater at petroleum release sites can be biodegradation metabolites. The metabolites can be separated from the hydrocarbons by incorporating an SGC step; however, regulatory agency acceptance of SGC has been inconsistent because of questions about the nature and toxicity of the metabolites. The present study was conducted to answer these specific questions. Groundwater samples collected from source and downgradient wells at fuel release sites were extracted and subjected to targeted gas chromatography-mass spectrometry (GC-MS) and nontargeted two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-MS) analyses, and the metabolites identified in each sample were classified according to molecular structural classes and assigned an oral reference dose (RfD)–based toxicity ranking. Our work demonstrates that the metabolites identified in groundwater at biodegrading fuel release sites are in classes ranked as low toxicity to humans and are not expected to pose significant risk to human health. The identified metabolites naturally attenuate in a predictable manner, with an overall trend to an increasingly higher proportion of organic acids and esters, and a lower human toxicity profile, and a life cycle that is consistent with the low-risk natural attenuation paradigm adopted by many regulatory agencies for petroleum release sites. Integr Environ Assess Manag 2017;13:714–727. © 2016 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points

Petroleum metabolite mixtures in groundwater are primarily organic acids or esters, with variable alcohols and ketones, and few aldehydes or phenols. Petroleum metabolites in groundwater are in molecular structural classes ranked as low toxicity to humans. Metabolites in groundwater have a life cycle that is consistent with the natural attenuation (NA) paradigm. Risk management focus at fuel release sites should be the hydrocarbons and not the metabolites, and silica gel cleanup (SGC) should be used to separate the two.
Safety and Tolerability of Neladenoson Bialanate, a Novel Oral Partial Adenosine A1 Receptor Agonist, in Patients With Chronic Heart Failure
Authors: Voors Adriaan Alexander , Düngen Hans‐Dirk , Senni Michele , Nodari Savina , Agostoni Piergiuseppe , Ponikowski Piotr , Bax Jeroen J. , Butler Javed , Kim Raymond J. , Dorhout Bernard , Dinh Wilfried , Gheorghiade Mihai
Published: September 2016

We studied safety and tolerability of neladenoson bialanate, a novel oral selective partial adenosine A1 receptor agonist that maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist, in 2 pilot studies in patients with heart failure with reduced ejection fraction (HFrEF). The β‐blocker interaction study was a single‐blind, placebo‐controlled study on the effects of a 30‐mg single dose of neladenoson bialanate on atrioventricular (AV) conduction in 11 patients with HFrEF treated with β‐blockers. The PARSiFAL pilot study was a double‐blind, placebo‐controlled study on the effects of a 7‐day treatment with 10 or 20 mg neladenoson bialanate or placebo in 31 patients with HFrEF on β‐blocker therapy. In the β‐blocker interaction study with 11 HFrEF patients, no second‐ or third‐degree AV block was detected on 48‐hour Holter monitoring. In the 31 HFrEF patients included in the PARSiFAL pilot study, no second‐ or third‐degree AV blocks were observed during 24‐hour Holter monitoring, and no effects were seen on heart rate and blood pressure. Median absolute changes in LVEF, measured by cardiac magnetic resonance, were 1.9% (interquartile range –1.1 to 4.3), 0.3% (–1.4 to 2.7), and 2.2% (0.4 to 4.5), in the placebo, 10‐mg, and 20‐mg groups, respectively. Treatment of HFrEF patients with the novel partial adenosine A1 agonist neladenoson bialanate appeared to be safe in 2 small pilot studies, and no atrioventricular conduction disorders or neurological side effects were observed. No significant early changes in cardiac function were detected.
The syntheses of isotopically labelled CB‐1 antagonists for the treatment of obesity
Authors: Tran Scott B. , Maxwell Brad D. , Burrell Richard , Bonacorsi Samuel J.
Published: September 2016

BMS‐725519, BMS‐811064, and BMS‐812204 are potent and selective central cannabinoid receptor antagonists that have been investigated for the treatment of human obesity. To further understand their biotransformation profiles, radiolabelled and stable‐labelled products were required. This paper describes the utility of [14C]1,1‐carbonyldiimidazole as a radiolabelling reagent for the syntheses of carbonyl‐labelled [14C]BMS‐725519, [14C]BMS‐811064, and [14C]BMS‐812204. The syntheses of stable‐labelled [13C6]BMS‐725519 and [13CD313CD2]BMS‐812204 synthesized from of [13C6]4‐chloroacetophenone and [13CD313CD2]iodoethane, respectively, are also described.
Morphological variation among the inner ears of extinct and extant baleen whales (Cetacea: Mysticeti)
Authors: Ekdale Eric G.
Published: September 2016

Living mysticetes (baleen whales) and odontocetes (toothed whales) differ significantly in auditory function in that toothed whales are sensitive to high‐frequency and ultrasonic sound vibrations and mysticetes to low‐frequency and infrasonic noises. Our knowledge of the evolution and phylogeny of cetaceans, and mysticetes in particular, is at a point at which we can explore morphological and physiological changes within the baleen whale inner ear. Traditional comparative anatomy and landmark‐based 3D‐geometric morphometric analyses were performed to investigate the anatomical diversity of the inner ears of extinct and extant mysticetes in comparison with other cetaceans. Principal component analyses (PCAs) show that the cochlear morphospace of odontocetes is tangential to that of mysticetes, but odontocetes are completely separated from mysticetes when semicircular canal landmarks are combined with the cochlear data. The cochlea of the archaeocete Zygorhiza kochii and early diverging extinct mysticetes plot within the morphospace of crown mysticetes, suggesting that mysticetes possess ancestral cochlear morphology and physiology. The PCA results indicate variation among mysticete species, although no major patterns are recovered to suggest separate hearing or locomotor regimes. Phylogenetic signal was detected for several clades, including crown Cetacea and crown Mysticeti, with the most clades expressing phylogenetic signal in the semicircular canal dataset. Brownian motion could not be excluded as an explanation for the signal, except for analyses combining cochlea and semicircular canal datasets for Balaenopteridae. J. Morphol. 277:1599–1615, 2016. © 2016 Wiley Periodicals, Inc.
Malignancy characterization of hepatocellular carcinomas based on texture analysis of contrast‐enhanced MR images
Authors: Zhou Wu , Zhang Lijuan , Wang Kaixin , Chen Shuting , Wang Guangyi , Liu Zaiyi , Liang Changhong
Published: September 2016

Purpose

To investigate the performance of texture analysis in characterizing malignancy of hepatocellular carcinomas (HCCs) based on contrast‐enhanced magnetic resonance imaging (MRI).

Materials and Methods

Gd‐DTPA contrast‐enhanced MRI data of 46 consecutive subjects with resected HCC were retrieved. The mean intensity and gray‐level run‐length nonuniformity (GLN) were quantified as the discriminative features based on the arterial phase images and compared between groups with different histological grading using independent Student's t‐test or Welch–Satterthwaite approximate t‐test for data following a normal distribution and Mann–Whitney U‐test for data violating the normal distribution. The performance of texture features in differentiating the biological aggressiveness of HCC was assessed using receiver operating characteristic (ROC) analysis. P < 0.05 was set as the significance level.

Results

Low‐grade HCCs had increased mean intensity and decreased GLN in four directions, as compared with high‐grade HCCs (P < 0.0005). A cutoff value of 739.37 for the average intensity resulted in an optimal sensitivity of 76% and specificity of 100% for histological grading discrimination. Cutoff values of 34.18, 66.59, 36.82, and 80.31 for the GLN in four directions (0°, 45°, 90°, 135°) resulted in an optimal sensitivity of 92%, 84%, 68%, 76% and specificity 66.70%, 71.40%, 85.70%, 76.20%, respectively. The areas under the ROC curve for the average intensity and GLN in four directions were 0.918, 0.846, 0.836, 0.827, and 0.838, respectively.

Conclusion

Texture features indexed by mean and GLN based on the arterial phase images reflect biologic aggressiveness, and may have potential applications in predicting the histological grading of HCC preoperatively.

Evidence level: 4

J. MAGN. RESON. IMAGING 2017;45:1476–1484
Quantifying right atrial filling and emptying: A 4D‐flow MRI study
Authors: Callaghan Fraser M. , Arnott Clare , Figtree Gemma A. , Kutty Shelby , Celermajer David S. , Grieve Stuart M.
Published: September 2016

Purpose

To quantitatively characterize the central role of vortex formation on the flow patterns and energy transfer within the right atrium (RA).

Materials and Methods

4D‐flow magnetic resonance imaging (MRI) data with multiple encoding velocities was acquired in 12 healthy subjects at 3T. Particles entering the RA were classified according to the origin of entry. Vortex membership was numerically derived by assessing the location of pathline center of curvature relative to the vortex core, defined by Q‐criteria. Flow dynamics and energetics were assessed using paired t‐tests.

Results

The majority of flow (74%) passes through the RA in a single beat, with a very small volume fraction retained longer than two beats (<1%). RA flow was dominated by a governing vortex, comprising 79% of total flow, and acting to preserve kinetic energy. Flow comprising the vortex enters the RA significantly earlier than nonvortex flow (P < 0.01). The majority of nonvortex flow enters the RA during systole, traversing the RA via a direct path with a significantly shorter residence time and distance traveled (both P < 0.01).

Conclusion

Blood flow momentum is preserved during systole within a dominant vortex, which we are able to characterize numerically using a semiautomated approach. Our analytical approach has potential for application to understanding right heart function in health and disease.

Level of Evidence: 1

J. Magn. Reson. Imaging 2017;45:1046–1054
Brain white matter changes in CPAP‐treated obstructive sleep apnea patients with residual sleepiness
Authors: Xiong Ying , Zhou Xiaohong Joe , Nisi Robyn A. , Martin Kelly R. , Karaman M. Muge , Cai Kejia , Weaver Terri E.
Published: September 2016

Purpose

To investigate white matter (WM) structural alterations using diffusion tensor imaging (DTI) in obstructive sleep apnea (OSA) patients, with or without residual sleepiness, following adherent continuous positive airway pressure (CPAP) treatment. Possible quantitative relationships were explored between the DTI metrics and two clinical assessments of somnolence.

Materials and Methods

Twenty‐nine male patients (30–55 years old) with a confirmed diagnosis of OSA were recruited. The patients were treated with CPAP therapy only. The Psychomotor Vigilance Task (PVT) and Epworth Sleepiness Scale (ESS) were performed after CPAP treatment and additionally administered at the time of the magnetic resonance imaging (MRI) scan. Based on the PVT results, the patients were divided into a nonsleepy group (lapses ≤5) and a sleepy group (lapses >5). DTI was performed at 3T, followed by an analysis using tract‐based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (λ23) between the two groups.

Results

A higher MD (P < 0.05) was observed in the sleepy group than the nonsleepy group in the whole‐brain TBSS analysis in the WM. The increased MD (17.8% of the fiber tracts; P < 0.05) was caused primarily by an elevated λ23. Axial diffusivity (λ1) exhibited no significant difference (P > 0.17). The alterations in FA or MD of individual fiber tracts occurred mainly in the internal/external capsule, corona radiata, corpus callosum, and sagittal stratum regions. The FA and MD values correlated with the PVT and ESS assessments from all patients (R ≥ 0.517, P < 0.05).

Conclusion

Global and regional WM alterations, as revealed by DTI, can be a possible mechanism to explain why OSA patients with high levels of CPAP use can have differing responses to treatment. Compromised myelin sheath, indicated by increased radial diffusivity, can be involved in the underlying WM changes.

Evidence level: 1

J. MAGN. RESON. IMAGING 2017;45:1371–1378
Enhancing employee creativity via individual skill development and team knowledge sharing: Influences of dual‐focused transformational leadership
Authors: Dong Yuntao , Bartol Kathryn M. , Zhang Zhi‐Xue , Li Chenwei
Published: September 2016

Addressing the challenges faced by team leaders in fostering both individual and team creativity, this research developed and tested a multilevel model connecting dual‐focused transformational leadership (TFL) and creativity and incorporating intervening mechanisms at the two levels. Using multilevel, multisource survey data from individual members, team leaders, and direct supervisors in high‐technology firms, we found that individual‐focused TFL had a positive indirect effect on individual creativity via individual skill development, whereas team‐focused TFL impacted team creativity partially through its influence on team knowledge sharing. We also found that knowledge sharing constituted a cross‐level contextual factor that moderated the relationship among individual‐focused TFL, skill development, and individual creativity. We discuss the theoretical and practical implications of this research and offer suggestions for future research. Copyright © 2016 John Wiley & Sons, Ltd.
From oil spills to barley growth – oil‐degrading soil bacteria and their promoting effects
Authors: Mikolasch Annett , Reinhard Anne , Alimbetova Anna , Omirbekova Anel , Pasler Lisa , Schumann Peter , Kabisch Johannes , Mukasheva Togzhan , Schauer Frieder
Published: September 2016

Heavy contamination of soils by crude oil is omnipresent in areas of oil recovery and exploitation. Bioremediation by indigenous plants in cooperation with hydrocarbon degrading microorganisms is an economically and ecologically feasible means to reclaim contaminated soils. To study the effects of indigenous soil bacteria capable of utilizing oil hydrocarbons on biomass production of plants growing in oil‐contaminated soils eight bacterial strains were isolated from contaminated soils in Kazakhstan and characterized for their abilities to degrade oil components. Four of them, identified as species of Gordonia and Rhodococcus turned out to be effective degraders. They produced a variety of organic acids from oil components, of which 59 were identified and 7 of them are hitherto unknown acidic oil metabolites. One of them, Rhodococcus erythropolis SBUG 2054, utilized more than 140 oil components. Inoculating barley seeds together with different combinations of these bacterial strains restored normal growth of the plants on contaminated soils, demonstrating the power of this approach for bioremediation. Furthermore, we suggest that the plant promoting effect of these bacteria is not only due to the elimination of toxic oil hydrocarbons but possibly also to the accumulation of a variety of organic acids which modulate the barley's rhizosphere environment.
Effects of seed priming, salinity and methyl jasmonate treatment on bioactive composition of Brassica oleracea var. capitata (white and red varieties) sprouts
Authors: Hassini Ismahen , Baenas Nieves , Moreno Diego A , Carvajal Micaela , Boughanmi Neziha , Martinez Ballesta Maria Del Carmen
Published: September 2016

BACKGROUND

Brassica spp. sprouts are rich in nutrients and bioactive compounds, especially glucosinolates and phenolic acid derivatives, and the composition of these young germinating seeds can be altered by several external factors. In this study two cabbage varieties (Brassica oleracea var. capitata, red and white) were studied using seed priming (KCl 50 mmol L−1; NaCl 150 mmol L−1) and MeJA spraying (25 µmol L−1) to elicit the phytochemical content of edible sprouts.

RESULTS

The red variety was richer in glucosinolates and phenolic compounds than the white one but not in mineral nutrients. Seed priming enhanced the potassium (K) content and flavonols in both varieties, while the total content of glucosinolates was reduced after seed priming only in the red variety. The white variety responded better than the red one to KCl seed priming, increasing the flavonols (89%). Salinity did not induce any change in the phytochemical content of these two varieties. Elicitation with sprayed MeJA was effective in significantly increasing the content of indolic glucosinolates glucobrassicin (5.7‐fold) and neoglucobrassicin (9.7‐fold) in the red cultivar. In the white variety, in addition to glucobrassicin (19.4‐fold) and neoglucobrassicin (9.4‐fold), 4‐hydroxyglucobrassicin (2.3‐fold) was also enhanced. MeJA also elicited significant amounts of anthocyanins (41%) and chlorogenic acid derivatives (329%) in the white variety.

CONCLUSION

KCl seed priming and MeJA elicitation promoted the phytochemical composition of the cabbage varieties, especially in the white variety. The application of NaCl resulted in less efficient elicitation. © 2016 Society of Chemical Industry
Screening and identifying antioxidants from Oplopanax elatus using 2,2ʹ‐diphenyl‐1‐picrylhydrazyl with off‐line two‐dimensional HPLC coupled with diode array detection and tandem time‐of‐flight mass spectrometry
Authors: Shao Li , Nie Ming‐Kun , Chen Man‐Yun , Wang Jin , Wang Chong‐Zhi , Huang Wei‐Hua , Yuan Chun‐Su , Zhou Hong‐Hao
Published: September 2016

The root of Oplopanax elatus (Nakai) Nakai has a well‐known history of use for the treatment of diseases such as neurasthenia, cardiovascular disorders, and cancer by the native people in northeast China. It is important to screen and identify the bioactive molecules from its root rapidly. Hereby, an off‐line two‐dimensional high performance liquid chromatography coupled with diode array detection and tandem time‐of‐flight mass spectrometry together with 2,2ʹ‐diphenyl‐1‐picrylhydrazyl was established to screen antioxidants from the root of O. elatus. A Waters cyanogen column (150 × 3.9 mm, id, 4 μm) was used for the first dimensional liquid chromatography, while a Hypersil BDS‐C18 column (250 × 4.6 mm, id, 5 μm) was installed for the second dimension liquid chromatographic analysis. Twenty‐eight compounds had been tentatively identified from the methanol extract of the air‐dried root of O. elatus including six polyynes and eight phenolic derivatives were screened with antioxidant activity. The developed method could be expedient for screening and identifying antioxidants from O. elatus.