bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Symmetry, Structure, and Self‐Assembly Mechanism of a Gigantic Seven‐Fold Symmetric {Pd84} Wheel
Authors: Scullion Rachel A. , Surman Andrew J. , Xu Feng , Mathieson Jennifer S. , Long De‐Liang , Haso Fadi , Liu Tianbo , Cronin Leroy
Published: July 2014

The symmetry, structure and formation mechanism of the structurally self‐complementary {Pd84} = [Pd84O42(PO4)42(CH3CO2)28]70− wheel is explored. Not only does the symmetry give rise to a non‐closest packed structure, the mechanism of the wheel formation is proposed to depend on the delicate balance between reaction conditions. We achieve the resolution of gigantic polyoxopalladate species through electrophoresis and size‐exclusion chromatography, the latter has been used in conjunction with electrospray mass spectrometry to probe the formation of the ring, which was found to proceed by the stepwise aggregation of {Pd6}− = [Pd6O4(CH3CO2)2(PO4)3Na6−nHn]− building blocks. Furthermore, the higher‐order assembly of these clusters into hollow blackberry structures of around 50 nm has been observed using dynamic and static light scattering.
Chlorfreie Pyrotechnik: “grüne” Emission blauen Lichtes durch Kupfer(I)‐iodid
Authors: Klapötke Thomas M. , Rusan Magdalena , Sabatini Jesse J.
Published: July 2014

Die Erzeugung blauen Lichtes in pyrotechnischen Formulierungen wurde ohne den Einsatz von chlorhaltigen Verbindungen erreicht, wobei sich Kupfer(I)‐iodid als geeigneter molekularer Emitter blauen Lichtes herausgestellt hat. Im Vergleich zu chlorhaltigen Formulierungen wurden durch die beste blau brennende Formulierung auf Basis von Kupfer(I)‐iodid eine höhere spektrale Reinheit, Lichtintensität und Brenndauer erzielt. Ebenso erwies sich diese Formulierung als unempfindlich gegenüber Schlag, Reibung und Hitze.
Baking, Ageing, Diabetes: A Short History of the Maillard Reaction
Authors: Hellwig Michael , Henle Thomas
Published: July 2014

The reaction of reducing carbohydrates with amino compounds described in 1912 by Louis‐Camille Maillard is responsible for the aroma, taste, and appearance of thermally processed food. The discovery that non‐enzymatic conversions also occur in organisms led to intensive investigation of the pathophysiological significance of the Maillard reaction in diabetes and ageing processes. Dietary Maillard products are discussed as “glycotoxins” and thus as a nutritional risk, but also increasingly with regard to positive effects in the human body. In this Review we give an overview of the most important discoveries in Maillard research since it was first described and show that the complex reaction, even after over one hundred years, has lost none of its interdisciplinary actuality.
On the Rotational Intergrowth of Hierarchical FAU/EMT Zeolites
Authors: Khaleel Maryam , Wagner Andrew J. , Mkhoyan K. Andre , Tsapatsis Michael
Published: July 2014

A structural study of a hierarchical zeolite X, which is similar to the one first synthesized by Inayat et al.,12 was performed using transmission electron microscopy imaging and diffraction. Evidence is provided, by comparison to simulations, that this material is an intergrowth of FAU and EMT and a conceptual model is presented for the growth of the FAU material with a small fraction of EMT in an atypical morphology of assembled sheets with well‐defined intersection angles.
Synthesis‐Enabled Probing of Mitosene Structural Space Leads to Improved IC50 over Mitomycin C
Authors: Zheng Zhitong , Touve Mollie , Barnes Josue , Reich Norbert , Zhang Liming
Published: July 2014

A DNA crosslinking approach, which is distinct but related to the double alkylation by mitomycin C, involving a novel electrophilic spiro‐cyclopropane intermediate is hypothesized. Rational design and substantial structural simplification permitted the expedient chemical synthesis and rapid discovery of MTSB‐6, a mitomycin C analogue which is twice as potent as mitomycin C against the prostate cancer cells. MTSB‐6 shows improvements in its selective action against noncancer prostate cells over mitomycin C. This hypothesis‐driven discovery opens novel yet synthetically accessible mitosene structural space for discovering more potent and less toxic therapeutic candidates.
Dating Archaeological Copper/Bronze Artifacts by Using the Voltammetry of Microparticles
Authors: Doménech‐Carbó Antonio , Doménech‐Carbó María Teresa , Capelo Sofia , Pasíes Trinidad , Martínez‐Lázaro Isabel
Published: July 2014

A method for dating copper/bronze archaeological objects aged in atmospheric environments is proposed based on the specific signals for cuprite and tenorite corrosion products measured through the voltammtry of microparticles method. The tenorite/cuprite ratio increased with the corrosion time and fitted to a potential law that yielded a calibration curve usable for dating purposes.
Defect Chemistry of Singly and Doubly Doped Ceria: Correlation between Ion Transport and Energetics
Authors: Buyukkilic Salih , Kim Sangtae , Navrotsky Alexandra
Published: July 2014

Earlier studies have shown a strong correlation between the enthalpy of formation, ΔHf,ox, and the ionic conductivity, σi, near room temperature in doped ceria systems, which are promising solid electrolytes for intermediate‐temperature solid oxide fuel cells (IT‐SOFCs). The present work demonstrates that this correlation holds at the operating temperature of IT‐SOFCs, 600–700 °C. Solid solutions of Ce1−xNdxO2−0.5x, Ce1−xSmxO2−0.5x, and Ce1−xSm0.5xNd0.5xO2−0.5x are studied. The ΔHf,ox at 702 °C is determined by considering the excess heat content between 25 and 702 °C combined with the value of ΔHf,ox at 25 °C. Both σi and ΔHf,ox show maxima at x=0.15 and 0.20 for the singly and doubly doped ceria, respectively, suggesting that the number of mobile oxygen vacancies in these solid solutions reaches a maximum near those compositions. An increase in temperature results in a shift of the maximum in both ΔHf,ox and σi towards higher concentrations. This shift results from a gradual increase in dissociation of the defect associates.
Simultaneous Assessment of Kinetic, Site‐Specific, and Structural Aspects of Enzymatic Protein Phosphorylation
Authors: van de Waterbeemd Michiel , Lössl Philip , Gautier Violette , Marino Fabio , Yamashita Masami , Conti Elena , Scholten Arjen , Heck Albert J. R.
Published: July 2014

Protein phosphorylation is a widespread process forming the mechanistic basis of cellular signaling. Up to now, different aspects, for example, site‐specificity, kinetics, role of co‐factors, and structure–function relationships have been typically investigated by multiple techniques that are incompatible with one another. The approach introduced here maximizes the amount of information gained on protein (complex) phosphorylation while minimizing sample handling. Using high‐resolution native mass spectrometry on intact protein (assemblies) up to 150 kDa we track the sequential incorporation of phosphate groups and map their localization by peptide LC‐MS/MS. On two model systems, the protein kinase G and the interplay between Aurora kinase A and Bora, we demonstrate the simultaneous monitoring of various aspects of the phosphorylation process, namely the effect of different cofactors on PKG autophosphorylation and the interaction of AurA and Bora as both an enzyme–substrate pair and physical binding partners.
Imidazole‐Based Small Molecules that Promote Neurogenesis in Pluripotent Cells
Authors: Kim Gun‐Hee , Halder Debasish , Park Jinhong , Namkung Wan , Shin Injae
Published: July 2014

Reported herein are two imidazole‐based small molecules, termed neurodazine (Nz) and neurodazole (Nzl), which induce neuronal differentiation of pluripotent P19 cells. Their ability to induce neurogenesis of P19 cells is comparable to that of retinoic acid. However, Nz and Nzl were found to be more selective neurogenesis inducers than retinoic acid owing to their unique ability to suppress astrocyte differentiation of P19 cells. Our results also show that Nz and Nzl promote production of physiologically active neurons because P19‐cell‐derived neurons induced by these substances have functional glutamate responsiveness. The present study suggests that Nz and Nzl could serve as important chemical tools to induce formation of specific populations of neuronal cell types from pluripotent cells.
The Structure of a Transient Complex of a Nonribosomal Peptide Synthetase and a Cytochrome P450 Monooxygenase
Authors: Haslinger Kristina , Brieke Clara , Uhlmann Stefanie , Sieverling Lina , Süssmuth Roderich D. , Cryle Max J.
Published: July 2014

Studying the interplay between nonribosomal peptide synthetases (NRPS), a major source of secondary metabolites, and crucial external modifying enzymes is a challenging task since the interactions involved are often transient in nature. By applying a range of synthetic inhibitor‐type compounds, a stabilized complex appropriate for structural analysis was generated for such a tailoring enzyme and an NRPS domain. The complex studied comprises an NRPS peptidyl carrier protein (PCP) domain bound to the Cytochrome P450 enzyme that is crucial for the provision of β‐hydroxylated amino acid precursors in the biosynthesis of the cyclic depsipeptide skyllamycin. The structure reveals that complex formation is governed by hydrophobic interactions, the presence of which can be controlled through minor alterations in PCP structure that enable selectivity amongst multiple highly similar PCP domains.
An overview of luminescent bio‐based composites
Authors: Pinto Ricardo J. B. , Carlos Luís D. , Marques Paula A. A. P. , Silvestre Armando J. D. , Freire Carmen S. R.
Published: July 2014

The development of inorganic/organic composite materials represents a fast‐growing interdisciplinary area in materials science and engineering. In this topic, a key idea is the production of composites comprising biopolymers and functional inorganic phases that could replace conventional materials in several high‐technology applications. Following this concept, the use of different polymers from renewable sources, such as cellulose, starch, alginate, and chitosan, have gained great relevance because of their renewable nature, potential biocompatibility, and biodegradability, as well as specific physicochemical properties. The combination of these biopolymers with different fillers (including inorganic nanoparticles (NPs), clusters, or ions) allows the design of innovative bio‐based materials with specific and/or improved properties, namely, optical, mechanical, and barrier properties, luminescence, and biological properties (as antimicrobial activity and biocompatibility). This review will focus on the most important synthetic approaches, properties, and applications of luminescent bio‐based composites obtained by combining different biopolymers and fillers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41169.
Dielectric strength of Al2O3/silicone composites after high‐temperature aging
Authors: Yao Yiying , Chen Zheng , Lu Guo‐Quan , Boroyevich Dushan , Ngo Khai D. T.
Published: July 2014

Silicones are widely used for electrical insulation owing to their high dielectric strength and thermal stability. However, recent studies revealed insufficient stability of silicone for high‐temperature applications. To study the effect of Al2O3 fiber on silicone stability, we measured the dielectric strength of unfilled silicone and Al2O3/silicone composites as a function of aging time at 250°C in air and analyzed data by Weibull probability distribution to determine characteristic dielectric strength (E0) and shape parameter (β). Prior to aging, unfilled silicone and composites had similar behavior, with E0 at about 20 kV/mm and β > 15. During aging, unfilled silicone developed both micro‐ and macrocracks, with β dropped below five in 240 h and E0 decreased significantly. Composites developed microcracks, with β dropped below 5 in longer time and E0 remained almost constant. Addition of Al2O3 slowed down crack growth in silicone matrix, resulting in longer lasting high‐temperature dielectric materials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41170.
The promise of perfect adult tissue repair and regeneration in mammals: Learning from regenerative amphibians and fish
Authors: Godwin James
Published: July 2014

Regenerative medicine promises to greatly impact on human health by improving repair outcomes in a range of tissues and injury contexts. Successful therapies will rely on identifying both intrinsic and extrinsic biological circuits that control wound healing, proliferation, cell survival, and developmental cell fate. Animals such as the zebrafish and the salamander display powerful examples of near‐perfect regeneration and scar‐free healing in a range of injury contexts not attained in mammals. By studying regeneration in a range of highly regenerative species that maintain regenerative potential throughout life, many instructive and permissive factors have been identified that could assist in the development of regenerative therapies. This review highlights some of the recent observations in immune regulation, epigenetic regulation, stem cell mobilization, and regenerative signatures that have improved our understanding of the regenerative process. Potential opportunities in harnessing this knowledge for future translation into the clinic are discussed.
Identification of metabolites of gardenin A in rats by combination of high‐performance liquid chromatography with linear ion trap–Orbitrap mass spectrometer based on multiple data processing techniques
Authors: Zhang Jiayu , Wang Fang , Cai Wei , Zhang Qian , Liu Ying , Li Yun , Liu Rongrong , Cao Guangshang
Published: July 2014

Gardenin A is one of the less abundant hydroxylated polymethoxyflavonoids (OH‐PMFs) in nature, and has many potential significant health benefits. In the present study, an efficient strategy was established using high‐performance liquid chromatography coupled with linear ion trap–Orbitrap mass spectrometer to profile the in vivo metabolic fate of gardenin A in rat plasma and various tissues. First, an online LC‐MSn data acquisition method was developed to trace all the probable metabolites. Second, a combination of offline data processing methods including extracted ion chromatography and multiple mass defect filters was employed to screen the common and uncommon metabolites from the background noise and endogenous components. Finally, structures of the metabolites were elucidated based on an accurate mass measurement, the diagnostic product ions of PMFs, and relevant drug biotransformation knowledge. Based on the proposed strategy, a total of 26 metabolites were observed and characterized. The results indicate that some biotransformations, such as methylation, demethoxylation, demethylation, glucuronide conjugation, sulfate conjugation and their composite reactions, have been discovered for OH‐PMFs. Moreover, some diagnostic biotransformation pathways are summarized. Overall, this study gives us a first insight into the in vivo metabolism of gardenin A. The study also provides a practical strategy for rapidly screening and identifying metabolites, which can be widely applied for the other biotransformations. Copyright © 2014 John Wiley & Sons, Ltd.
Task‐dependent recruitment of intrinsic brain networks reflects normative variance in cognition
Authors: Gess Jennifer L. , Fausett Jennifer S. , Kearney‐Ramos Tonisha E. , Kilts Clinton D. , James George Andrew
Published: July 2014

Background

Functional neuroimaging has great potential to inform clinical decisions, whether by identifying neural biomarkers of illness progression and severity, predicting therapeutic response, or selecting suitable patients for surgical interventions. Yet a persisting barrier to functional neuroimaging's clinical translation is our incomplete understanding of how normative variance in cognition, personality, and behavior shape the brain's structural and functional organization. We propose that modeling individual differences in these brain–behavior relationships is crucial for improving the accuracy of neuroimaging biomarkers for neurologic and psychiatric disorders.

Methods

We addressed this goal by initiating the Cognitive Connectome Project, which bridges neuropsychology and neuroimaging by pairing nine cognitive domains typically assessed by clinically validated neuropsychological measures with those tapped by canonical neuroimaging tasks (motor, visuospatial perception, attention, language, memory, affective processing, decision making, working memory, and executive function). To date, we have recruited a diverse sample of 53 participants (mean [SD], age = 32 [9.7] years, 31 females).

Results

As a proof of concept, we first demonstrate that our neuroimaging task battery can replicate previous findings that task performance recruits intrinsic brain networks identified during wakeful rest. We then expand upon these previous findings by showing that the extent to which these networks are recruited by task reflects individual differences in cognitive ability. Specifically, performance on the Judgment of Line Orientation task (a clinically validated measure of visuospatial perception) administered outside of the MRI scanner predicts the magnitude of task‐induced activity of the dorsal visual network when performing a direct replication of this task within the MRI scanner. Other networks (such as default mode and right frontoparietal) showed task‐induced changes in activity that were unrelated to task performance, suggesting these networks to not be involved in visuospatial perception.

Conclusion

These findings establish a methodological framework by which clinical neuropsychology and functional neuroimaging may mutually inform one another, thus enhancing the translation of functional neuroimaging into clinical decision making.
Person–Environment Interaction in a New Secure Forensic State Psychiatric Hospital
Authors: Eggert Jon E. , Kelly Sean P. , Margiotta David T. , Hegvik Donna K. , Vaher Kairi A. , Kaya Rachel Tamiko
Published: July 2014

This study examined the person–environment interaction effects of environmental design on ward climate, safety, job satisfaction, and treatment outcomes within a new high security forensic psychiatric facility. Participants included male and female adult psychiatric inpatients and staff members at different security stages. Data were collected once before and twice after the experimental group moved into the new building. The control group remained in the same facilities. Contrary to expectations, the new building had limited effects on the measured variables. Copyright © 2014 John Wiley & Sons, Ltd.
Duty of Care, Safety, Normalisation and the Mental Capacity Act: A Discourse Analysis of Staff Arguments about Facilitating Choices for People with Learning Disabilities in UK Services
Authors: Jingree Treena
Published: July 2014

The benefits of having choice and control for people with learning disabilitiesare well documented, and front‐line carers often make efforts ensuring that these are facilitated. However, despite this, government policy reports that disempowerment within learning disability services in the UK is a persistent problem. Using critical discursive psychology, 15 interviews with support workers about empowering people with learning disabilities were analysed. Interpretative repertoires about ‘duty of care’, ‘safety’ and ‘normalisation’ and discursive strategies involving ‘comparative evaluations’ were found, which opened speaker positions of granting or withholding choice, assuming responsibility for those in care and constructing service users as lacking capacity. These resources also allowed speakers to regulate the choices of service users and to normalise limited choice in ways that undermined taking up more empowering practices. The findings may explain the persistence of disempowerment within services by indicating how such discourses are deeply entrenched in service talk and are invoked to justify disempowering practices. This is discussed in view of the implications for empowerment and also current legislative frameworks such as the Mental Capacity Act. Copyright © 2014 John Wiley & Sons, Ltd.
Photoactivation of Molecular Oxygen by an Iron(III) Porphyrin with a Magnesium Aluminum Layered Double Hydroxide for the Aerobic Epoxidation of Cyclohexene
Authors: Teramura Kentaro , Tsuneoka Hideo , Ogura Kentaro , Sugimoto Takashi , Shishido Tetsuya , Tanaka Tsunehiro
Published: July 2014

The photocatalytic aerobic epoxidation of cyclohexene proceeded under visible‐light irradiation only if 5,10,15,20tetrakis(pentafluorophenyl)porphyrin iron(III) chloride ([FeIII(TPFPP)Cl]) was combined with Mg‐Al layered double hydroxide (Mg‐Al LDH) as a solid base in chloroform. The OH groups in the Mg‐Al LDH exchanged with the axial Cl ligands in [FeIII(TPFPP)Cl] to afford [FeIII(TPFPP)OH], which functioned photocatalytically in the presence of Mg‐Al LDH but was inactive in its absence. The band in the action spectrum agreed well with the Soret band in the UV/Vis absorption spectrum of [FeIII(TPFPP)OH]. The spectral changes indicated the reduction of [FeIII(TPFPP)OH] to [FeII(TPFPP)] under visible‐light irradiation, which in turn activates O2 that could be used for the epoxidation of cyclohexene.
Effect of Operating Conditions on Ice Characteristics in Continuous Eutectic Freeze Crystallization
Authors: Chivavava Jemitias , Rodriguez‐Pascual Marcos , Lewis Alison E.
Published: July 2014

The efficacy of eutectic freeze crystallization (EFC) in crystallizers and in subsequent downstream washing or filtration steps is a direct function of size and morphology of the crystalline products. These product characteristics are influenced by supersaturation and residence time. To investigate the effect of residence time and supercooling on ice product characteristics in a continuous EFC process, crystallization experiments were performed in an EFC crystallizer with Na2SO4 aqueous solution. Crystal size distribution and morphology during the crystallization process were analyzed by digital image processing. Longer residence times enhanced the mean crystal size and disk‐shaped ice crystals were formed. Increasing supercooling resulted in a larger mean ice equivalent diameter.
In Situ Growth Measurements of Sodium Sulfate during Cooling Crystallization
Authors: Egan Tim , Rodriguez‐Pascual Marcos , Lewis Alison
Published: July 2014

Combined rainbow Schlieren deflectometry (RSD) and liquid crystal thermography (LCT) served as in situ non‐intrusive techniques to determine local concentration and temperature fields based on refractive index gradients in solution during crystallization of sodium sulfate from aqueous solution. The combination of RSD with LCT allowed the decoupling of concentration and temperature effects. Convective mass transport happened during periods of fast, dendritic growth, but even higher levels occurred during the densification of the dendritic crystals, indicating significant mass deposition in this phase. The convection developed mainly as a result of concentration gradients as opposed to temperature gradients. A supersaturation field map was generated and growth kinetics of the sodium sulfate salt was determined. The kinetics followed a power law relationship, with constants in line with those in the literature.
Crystallization of Piroxicam Solid Forms and the Effects of Additives
Authors: Liu Guangpu , Hansen Thomas B. , Qu Haiyan , Yang Mingshi , Pajander Jari P. , Rantanen Jukka , Christensen Lars P.
Published: July 2014

The relative stabilities of the two anhydrous polymorphs and the monohydrate of piroxicam in ethanol/water mixtures and the crystallization behavior of the solid forms in the presence of 11 additives were studied. At 37 °C, form II is thermodynamically more stable than form I, while the relative stability of form II and the monohydrate depends on the water concentration in the solution. The total Hansen solubility parameter δT and the hydrogen bonding solubility parameter δH of the substances can partly explain the effects of the additives on the crystallization of the solid forms. The additives that selectively promoted the crystallization of form I are the ones with δT and δH parameters similar to those of piroxicam.
Designing Printable Medicinal Products: Solvent System and Carrier‐Substrate Screening
Authors: Raijada Dhara , Genina Natalja , Fors Daniela , Wisaeus Erik , Peltonen Jouko , Rantanen Jukka , Sandler Niklas
Published: July 2014

More flexible yet robust manufacturing solutions are needed in the pharmaceutical industry. Tablet compaction is no longer the obvious choice for commercial‐scale processing of innovative drug delivery systems. Engineering solutions have gained wide attention in the pharmaceutical industry. Technical innovations within printing are considerable solutions for future product design. Printable medicinal products of a model compound are designed and an analytical approach for imaging the model compound in the printed medicinal products is investigated. The potential implications of using a unique combination of ink solution and carrier‐substrate for designing a specific crystallization process and future directions towards continuous manufacturing of personalized medicinal products are discussed.
Carbon Monoxide‐Induced Dynamic Metal‐Surface Nanostructuring
Authors: Carenco Sophie
Published: July 2014

Carbon monoxide is a ubiquitous molecule in surface science, materials chemistry, catalysis and nanotechnology. Its interaction with a number of metal surfaces is at the heart of major processes, such as Fischer–Tropsch synthesis or fuel‐cell optimization. Recent works, coupling structural and nanoscale in situ analytic tools have highlighted the ability of metal surfaces and nanoparticles to undergo restructuring after exposure to CO under fairly mild conditions, generating nanostructures. This Minireview proposes a brief overview of recent examples of such nanostructuring, which leads to a discussion about the driving force in reversible and non‐reversible situations.
Wie die Produktion von Eierlöffeln das Image von Chemie und Physik verändern kann
Authors: Weßnigk Susanne , Euler Manfred
Published: July 2014

Im vergangenen Jahrzehnt wurden zahlreiche außerschulische Maßnahmen ins Leben gerufen, um die naturwissenschaftliche Bildung der Schülerinnen und Schüler zu verbessern. Hierbei sind insbesondere Schülerlabore zu nennen, die einen Beitrag zu naturwissenschaftlichen und technischen Bildungsprozessen leisten. Während ihr Konzept zunächst an naturwissenschaftlichen Vorgehensweisen unter wissenschaftlichen Gesichtspunkten orientiert war, werden mittlerweile Bezüge zur Wirtschaft und möglichen Berufsfeldern hergestellt. Eines dieser Schülerlabore ist das Baylab plastics. Das industrienahe Labor erweitert die Erfahrungen des außerschulischen Lernens im naturwissenschaftlichen und technischen Bereich um die Potenziale, Perspektiven und Anforderungen eines Industrieunternehmens. An der Schnittstelle von Schule und Beruf gelingen hier Imageänderungen von Chemie und Physik. Zudem ergeben sich positive Einflüsse auf die naturwissenschaftliche Berufsorientierung.
Development of Diaminoquinazoline Histone Lysine Methyltransferase Inhibitors as Potent Blood‐Stage Antimalarial Compounds
Authors: Sundriyal Sandeep , Malmquist Nicholas A. , Caron Joachim , Blundell Scott , Liu Feng , Chen Xin , Srimongkolpithak Nitipol , Jin Jian , Charman Susan A. , Scherf Artur , Fuchter Matthew J.
Published: July 2014

Modulating epigenetic mechanisms in malarial parasites is an emerging avenue for the discovery of novel antimalarial drugs. Previously we demonstrated the potent in vitro and in vivo antimalarial activity of (1‐benzyl‐4‐piperidyl)[6,7‐dimethoxy‐2‐(4‐methyl‐1,4‐diazepin‐1‐yl)‐4‐quinazolinyl]amine (BIX01294; 1), a known human G9a inhibitor, together with its dose‐dependent effects on histone methylation in the malarial parasite. This work describes our initial medicinal chemistry efforts to optimise the diaminoquinazoline chemotype for antimalarial activity. A variety of analogues were designed by substituting the 2 and 4 positions of the quinazoline core, and these molecules were tested against Plasmodium falciparum (3D7 strain). Several analogues with IC50 values as low as 18.5 nM and with low mammalian cell toxicity (HepG2) were identified. Certain pharmacophoric features required for antimalarial activity were found to be analogous to the previously published SAR of these analogues for G9a inhibition, thereby suggesting potential similarities between the malarial and human HKMT targets of this chemotype. Physiochemical, in vitro activity, and in vitro metabolism studies were also performed for a select set of potent analogues to evaluate their potential as antimalarial leads.
Colorectal cancer mortality among Hispanics in California: Differences by neighborhood socioeconomic status and nativity
Authors: Tao Li , Ladabaum Uri , Gomez Scarlett Lin , Cheng Iona
Published: July 2014

BACKGROUND

Socioeconomic status (SES) plays an important role in colorectal cancer (CRC) mortality, although the independent and joint effects with nativity and neighborhood factors have yet to be evaluated.

METHODS

With nearly one‐third of all US Hispanics residing in California, the authors obtained information from the California Cancer Registry to examine the associations between neighborhood SES and mortality in all 33,146 Hispanic individuals diagnosed with CRC from 1988 through 2010, with a particular focus on associations among US‐born and foreign‐born Hispanics. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for overall and CRC‐specific mortality.

RESULTS

Hispanics residing in lower SES neighborhoods demonstrated a higher rate of overall and CRC‐specific mortality than those residing in high SES neighborhoods (SES quintile 1[low] vs quintile 5 [high]: HR, 1.15 [95% CI, 1.05‐1.26] and HR, 1.16 [95% CI, 1.03‐1.30], respectively). Nativity modified the associations between SES and mortality (P for interaction, .02 for overall and P for interaction, .01 for CRC‐specific mortality) such that the SES associations were observed only among US‐born (P for trend < .01 for overall and CRC‐specific mortality) but not among foreign‐born Hispanics.

CONCLUSIONS

Neighborhood SES demonstrates significant differential effects on overall and CRC‐specific mortality between US‐born and foreign‐born Hispanics. Future efforts should investigate the underlying contextual and individual‐level factors that could account for these differential associations by nativity. Cancer 2014;120:3510–3518. © 2014 American Cancer Society.
Pancreatic neuroendocrine tumors: Accurate grading with Ki‐67 index on fine‐needle aspiration specimens using the WHO 2010/ENETS criteria
Authors: Farrell Jessica M. , Pang Judy C. , Kim Grace E. , Tabatabai Z. Laura
Published: July 2014

BACKGROUND

The natural history of pancreatic neuroendocrine tumors (panNETs) is extremely variable. One of the most controversial problems in diagnosis is the accurate prediction of the clinical behavior of these tumors. PanNETs that behave aggressively with a malignant course may have bland cytologic features, while some tumors with previously described “malignant” features may behave in a benign or indolent fashion. Various classification schemes have been proposed for grading panNETs. The European Neuroendocrine Tumor Society (ENETS) and 2010 World Health Organization (WHO) classification schemes include counting the mitotic index and/or the Ki‐67 proliferation index for grading. The current study was undertaken to determine whether tumors sampled by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) can be accurately graded based on the Ki‐67 index when compared to surgical samples.

METHODS

Corresponding EUS‐FNA cytology and surgical tissue specimens were obtained for 22 tumors and stained for hematoxylin and eosin (H&E) and the Ki‐67 proliferation marker (MIB‐1 antibody). Samples were graded by scoring Ki‐67 staining indices in accordance with the 2010 ENETS/WHO criteria. The grading scores assigned to the EUS‐FNA cytology samples were compared with the scores assigned to the corresponding histological samples.

RESULTS

The majority (86%) of EUS‐FNA cytology samples and corresponding surgical tissue specimens demonstrated concordant grading based on Ki‐67 indices.

CONCLUSIONS

These results indicate that EUS‐FNA cytology samples can be accurately graded based on the WHO Ki‐67 labeling scheme. Thus, Ki‐67 scoring in EUS‐FNA cytology samples is an alternative approach for establishing the grade of panNETs. Accurate grading of panNETs is critical for predicting tumor biology, patient prognosis, and making informed decisions regarding patient management and treatment. Cancer (Cancer Cytopathol) 2014;122:770–778. © 2014 American Cancer Society.
Personalizing flow‐diverter intervention for cerebral aneurysms: from computational hemodynamics to biochemical modeling
Authors: Peach T. W. , Ngoepe M. , Spranger K. , Zajarias‐Fainsod D. , Ventikos Y.
Published: July 2014

This paper presents the computational modeling of a variety of flow‐diverting stents, deployed in a number of patient‐specific aneurysm geometries. We consider virtual device deployment and hemodynamics as well as thrombus formation, with the scope to assess pre‐operatively the efficacy of specific devices in treating particular aneurysms. An algorithm based on a linear and torsional spring analogy is developed for the fast virtual deployment of stents and similar minimally invasive devices in patient‐specific vessel geometries. The virtual deployment algorithm is used to accurately deploy a total of four stent designs in three aneurysm geometries. A variety of different flow‐diverting stent designs, representing the commercially available and the entirely novel, are presented, varying in both mesh design and porosity. Transient computational hemodynamics simulations are performed on multiple patient‐specific geometries to predict the reduction in aneurysm inflow after the deployment of each device. Further, a thrombosis initiation and growth model is implemented, coupled with the hemodynamic computations. Hemodynamic simulations show large variations in flow reduction between devices and across different aneurysm geometries. The industry standard of flow‐diverters with 70% porosity, assumed to offer the best compromise in flexibility and flow reduction, is challenged in at least one aneurysm geometry. Copyright © 2014 John Wiley & Sons, Ltd.
Decabrominated diphenyl ether and methylmercury impair fetal nervous system development in mice at documented human exposure levels
Authors: Mariani Alessandro , Fanelli Roberto , Re Depaolini Andrea , De Paola Massimiliano
Published: July 2014

The central nervous system (CNS) is extremely vulnerable to the toxic effects of environmental pollutants during development. Polybrominated diphenyl ethers (PBDEs) are persistent contaminants, increasingly present in the environment and in human tissues. Recent investigations identified a correlation between maternal exposure to PBDEs and impairment in fetal neurobehavioral development, suggesting that these contaminants pose a potential risk for children. We investigated on the potential effects of environmental decabrominated diphenyl ether (decaBDE, the fully brominated congener) on key neurodevelopmental molecules (e.g., synaptic proteins and immature neuron markers) in fetal mouse neurons. Methylmercury was used as reference neurotoxic contaminant and to evaluate its possible synergism with decaBDE. The neurotoxic effects of decaBDE and methylmercury were determined in developing cultured neurons from mouse fetal hippocampus and cerebellum. Neuron death, dendritic branching, synaptic protein expression, markers of immature neurons, and microglia activation were evaluated by immunocytochemistry. Brain samples from prenatally treated embryos were also examined for neurotoxicity signs by immunoblotting and histochemistry. DecaBDE significantly affected (down to 0.4 nM) the number of dendritic branches, and the levels of synaptic proteins and doublecortin in cultured neurons. Prenatal exposure to decaBDE decreased the synaptic proteins and increased the expression of the immature neuron and microglial markers in mouse fetuses. In conclusion, prenatal exposure to realistic (relevant for human exposure) concentrations of decaBDE induces impairment of fetal CNS development in mice, suggesting a potential risk of fetotoxicity in humans. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 23–38, 2015
Control of Spectrum for Improvement of Color Rendering Spectrum Affected by Scandium Vapor Mixed with Argon Arc
Authors: Mitsuyasu Eriko , Iwao Toru , Yumoto Motoshige
Published: July 2014

Arc lighting to produce environments for evacuation, rescue, safety, and comfort is a subject of interest. The lack of a radiation intensity and color rendering spectrum is a problem because of inappropriate energy balance. This paper elucidates the improvement of the color rendering spectrum with control of the spectrum affected by scandium vapor mixed with an argon arc. The temperature with maintenance of color rendering increases with the contamination ratio of metal vapor because of the chromaticity diagram. In addition, volume incrementation of the low‐temperature region and the periphery of the arc is effective the color rendering. The radiation power increases with increasing metal vapor content even if the temperature is low. In particular, the maximum radiation power with metal vapor is 10 times that without metal vapor. The radiation power increases with maintenance of color rendering and the radiation power increases when the appropriate temperature is chosen with consideration of the chromaticity diagram. Improvement of the color rendering spectrum is expected to result from control of the balance between the broad continuous spectrum of argon and the line spectrum of scandium, with a temperature distribution derived from current increase and/or arc pinch.
Spin‐State‐Dependent Properties of an Iron(III) Hydrogenase Mimic
Authors: Edler Eileen , Stein Matthias
Published: July 2014

A biomimetic mononuclear iron(III) model complex was investigated in detail by density functional theory (DFT) calculations. Structural and energetic criteria were employed to confirm the S = 3/2 intermediate state to be the ground state. The ground state was verified by using both pure and hybrid functionals with different amounts of exact Hartree–Fock exchange. A comprehensive study of the influence of the functional as well as thermodynamic corrections to the energetic ordering of spin states was performed. A modified B3LYP functional with 10 % Hartree–Fock exchange was able to reproduce the structural properties in excellent agreement with the experimental data. The thermodynamics of two possible spin‐crossover transitions [intermediate‐spin to high‐spin (IS–HS) and low‐spin to high‐spin (LS–HS)] were investigated. A torsional profile obtained by rotation of the axial ligand revealed a spin‐dependent preference of the ligand orientation. The structure solved by X‐ray crystallography corresponds to the global energetic minimum of the complex in the S = 3/2 and 5/2 states but not in the S = 1/2 state. This study demonstrates that the spin multiplicity affects not only the structural properties but may also influence the chemical reactivity of this transition metal complex in general.
A Direct Electrochemical Detection Method of Melanoma Based on Melanoma Biomarker
Authors: Mossberg Michal , Vernick Sefi , Ortenberg Rona , Markel Gal , Diamand Yosi Shacham‐ , Rishpon Judith
Published: July 2014

A new method of detecting and diagnosing melanoma based on melanoma biomarker was developed and its feasibility demonstrated. The method is based on an electrochemical biosensor platform comprised of a special biochip and device, performing a multi‐channel amperometric detection of the enzymatic activity of tyrosinase, an enzyme biomarker of melanoma. The newly developed biosensor platform is able to electrochemically detect tyrosinase activity in fresh biopsy samples. This bioelectrochemical detection method is rapid, yielding results within minutes from biopsy removal. Using “as is” biopsy samples, without pretreatment, simplifies the process, saves time and reduces cost and labor dramatically. Using modern portable microelectronics provides an accurate biomarker expression measurement at the “point of care” increasing the accessibility of new bio‐chip technologies to the public.
Multispecies acute toxicity evaluation of wastewaters from different treatment stages in a coking wastewater-treatment plant
Authors: Zhao Jian-Liang , Jiang Yu-Xia , Yan Bo , Wei Chaohai , Zhang Li-Juan , Ying Guang-Guo
Published: July 2014

Coking wastewater contributes approximately 5% of the total discharge volume of industrial wastewaters every year in China. The toxicity of coking wastewater to aquatic organisms is still unknown. The authors evaluated the toxicity of wastewater from different treatment stages in a coking wastewater treatment plant, South China, using 5 test species belonging to different trophic levels: luminous bacteria, green alga, a crustacean, duckweed, and zebrafish embryos. The raw influent displayed the highest toxicity to the test species, with toxic units ranging from 16.2 to 1176. The toxicity in the wastewater was then gradually removed by sequential primary treatment, biological fluidized-bed treatment, and secondary clarifier treatment. The toxic unit of the final effluent was reduced to 2.26 for the green alga (Pseudokirchneriella subcapitata) and to 0 for the other 4 organisms. Quantitative analysis of metals and polycyclic aromatic hydrocarbons (PAHs) and qualitative scanning by gas chromatography–mass spectrometry showed the presence of a variety of pollutants in the coking wastewaters. Multivariate statistical analysis revealed that the toxicity in the coking wastewater was correlated to the chemical oxygen demand, total nitrogen, ammonia nitrogen, volatile phenols, sulfide, metals (Cr, As, Sb, Hg, Pb, and Ni), and ΣPAHs. Based on the results, it is required to set a safety emission limit value for the discharge of coking wastewater to protect aquatic organisms in the receiving water bodies. Environ Toxicol Chem 2014; 33:1967–1975. © 2014 SETAC
Low cost 3D global instability analysis and flow sensitivity based on dynamic mode decomposition and high‐order numerical tools
Authors: Ferrer Esteban , de Vicente Javier , Valero Eusebio
Published: July 2014

We explore the recently developed snapshot‐based dynamic mode decomposition (DMD) technique, a matrix‐free Arnoldi type method, to predict 3D linear global flow instabilities. We apply the DMD technique to flows confined in an L‐shaped cavity and compare the resulting modes to their counterparts issued from classic, matrix forming, linear instability analysis (i.e. BiGlobal approach) and direct numerical simulations. Results show that the DMD technique, which uses snapshots generated by a 3D non‐linear incompressible discontinuous Galerkin Navier–Stokes solver, provides very similar results to classical linear instability analysis techniques. In addition, we compare DMD results issued from non‐linear and linearised Navier–Stokes solvers, showing that linearisation is not necessary (i.e. base flow not required) to obtain linear modes, as long as the analysis is restricted to the exponential growth regime, that is, flow regime governed by the linearised Navier–Stokes equations, and showing the potential of this type of analysis based on snapshots to general purpose CFD codes, without need of modifications. Finally, this work shows that the DMD technique can provide three‐dimensional direct and adjoint modes through snapshots provided by the linearised and adjoint linearised Navier–Stokes equations advanced in time. Subsequently, these modes are used to provide structural sensitivity maps and sensitivity to base flow modification information for 3D flows and complex geometries, at an affordable computational cost. The information provided by the sensitivity study is used to modify the L‐shaped geometry and control the most unstable 3D mode. Copyright © 2014 John Wiley & Sons, Ltd.
Reaction of Seleno‐ or Thiofenchone with Propiolic Acid: Wagner–Meerwein Rearrangement
Authors: Okuma Kentaro , Matsui Hiroyuki , Mori Yuichi
Published: July 2014

A reaction of selenofenchone with propiolic acid in refluxing chloroform produced 1,3‐oxaselenin‐6‐one, which further reacted with acid to afford the ring‐opened product. A reaction of 1,3‐oxathiin‐6‐one prepared from thiofenchone with trifluoroacetic acid gave a Wagner–Meerwein rearranged product. In the presence of AlCl3, thiofenchone reacted with methyl propiolate to afford the corresponding rearranged ester.
Modulation of auditory deviance detection by acute nicotine is baseline and deviant dependent in healthy nonsmokers: a mismatch negativity study
Authors: Knott Verner , Impey Danielle , Philippe Tristan , Smith Dylan , Choueiry Joelle , de la Salle Sara , Dort Heather
Published: July 2014

Objective

Cognitive enhancement resulting from nicotinic acetylcholine receptor stimulation may be evidenced by increased efficiency of the auditory‐frontal cortex network of auditory discrimination, which is impaired in schizophrenia, a cognitive disorder associated with excessive tobacco use. Investigating automatic (preattentive) detection of acoustic change with the mismatch negativity (MMN) brain event‐related potential in response to nicotine in individuals with varying baseline levels of auditory discrimination may provide useful insight into the cholinergic regulation of this neural network and its potential amelioration with novel nicotinic agents.

Methods

Sixty healthy, non‐smoking male volunteers were presented with an ‘optimal’ multi‐feature MMN paradigm in a randomized, placebo controlled double‐blind design with 6 mg of nicotine gum.

Results

Participants with low, medium, and high baseline amplitudes responded differently to nicotine (vs. placebo), and nicotine response was feature specific. Whereas MMN in individuals with high amplitudes was diminished by nicotine, MMN increased in those with low amplitudes. Nicotine effects were not shown in medium amplitude participants.

Conclusions

These findings provide preliminary support for the role of nicotinic neurotransmission in sensory memory processing of auditory change and suggest that nicotinic receptor modulation can both enhance and diminish change detection, depending on baseline MMN and its eliciting stimulus feature. Copyright © 2014 John Wiley & Sons, Ltd.
Effect of polymorphisms on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers
Authors: Cabaleiro Teresa , Ochoa Dolores , López‐Rodríguez Rosario , Román Manuel , Novalbos Jesús , Ayuso Carmen , Abad‐Santos Francisco
Published: July 2014

Objective

To identify genetic markers capable of predicting the pharmacokinetics, pharmacodynamics, and adverse effects of risperidone.

Methods

Genotyping was performed in 70 healthy volunteers receiving a single 1 mg oral dose of risperidone. Risperidone and hydroxyrisperidone plasma levels were measured using high‐performance liquid chromatography combined with tandem mass spectrometry. Prolactin concentration was quantified by direct chemiluminescence.

Results

Poor CYP2D6 metabolizers showed higher risperidone Cmax, area under the curve (AUC), and t1/2, as well as lower clearance. They also showed lower Cmax and AUC and higher t1/2 for hydroxyrisperidone. Furthermore, individuals with a mutant VKORC1 genotype had a lower risperidone AUC and t1/2 and higher clearance. The hydroxyrisperidone AUC was lower in individuals with the COMT mutant genotype. Risperidone increased prolactin levels (iAUC and iCmax), which were higher in women than in men. The most frequent reactions were somnolence (47.1%), headache (21.4%), and dizziness (17.1%). Women had neurological effects and headache more frequently than men. The incidence of headache was associated with polymorphisms in the AGTR1 and NAT2; neurological effects were associated with CYP2C19.

Conclusions

Differences in the pharmacokinetics of risperidone are due to polymorphisms in CYP2D6, COMT, and VKORC1. Differences in adverse reactions can be explained by gender and polymorphisms in CYP2C19, AGTR1, and NAT2. Copyright © 2014 John Wiley & Sons, Ltd.