bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of awareness of treatment failure among HIV‐1‐infected patients in Guinea‐Bissau – a retrospective cohort study
Authors: Jespersen Sanne , Hønge Bo Langhoff , Medina Candida , da Silva Té David , Correira Faustino Gomes , Laursen Alex Lund , Erikstrup Christian , Østergaard Lars , Wejse Christian ,   for the Bissau HIV Cohort study group
Published: September 2015

Introduction

With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second‐line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second‐line treatment and evaluated mortality related to treatment failure among HIV‐infected patients in Guinea‐Bissau.

Methods

In this retrospective cohort study, adult patients infected with HIV‐1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time‐varying coefficient, were used to estimate the hazard ratio for death and loss to follow‐up.

Results

We assessed 1,591 HIV‐1‐infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first‐ to second‐line ART. The overall switching rate was 3.1 per 100 person‐years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow‐up, patients experiencing treatment failure had a higher risk of being lost to follow‐up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8).

Conclusions

We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second‐line therapy. These factors could lead to an increased risk of resistance development and excess mortality.
Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2
Authors: McCormack Ryan M , Lyapichev Kirill , Olsson Melissa L , Podack Eckhard R , Munson George P
Published: September 2015

Perforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as Yersinia pseudotuberculosis and enteropathogenic Escherichia coli disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.
Extrinsic and intrinsic signals converge on the Runx1/CBFβ transcription factor for nonpeptidergic nociceptor maturation
Authors: Huang Siyi , O'Donovan Kevin J , Turner Eric E , Zhong Jian , Ginty David D
Published: September 2015

The generation of diverse neuronal subtypes involves specification of neural progenitors and, subsequently, postmitotic neuronal differentiation, a relatively poorly understood process. Here, we describe a mechanism whereby the neurotrophic factor NGF and the transcription factor Runx1 coordinate postmitotic differentiation of nonpeptidergic nociceptors, a major nociceptor subtype. We show that the integrity of a Runx1/CBFβ holocomplex is crucial for NGF-dependent nonpeptidergic nociceptor maturation. NGF signals through the ERK/MAPK pathway to promote expression of Cbfb but not Runx1 prior to maturation of nonpeptidergic nociceptors. In contrast, transcriptional initiation of Runx1 in nonpeptidergic nociceptor precursors is dependent on the homeodomain transcription factor Islet1, which is largely dispensable for Cbfb expression. Thus, an NGF/TrkA-MAPK-CBFβ pathway converges with Islet1-Runx1 signaling to promote Runx1/CBFβ holocomplex formation and nonpeptidergic nociceptor maturation. Convergence of extrinsic and intrinsic signals to control heterodimeric transcription factor complex formation provides a robust mechanism for postmitotic neuronal subtype specification.
Population subdivision of the surf clamMactra chinensisin the East China Sea: Changjiang River outflow is not the sole driver
Authors: Ni Gang , Li Qi , Ni Lehai , Kong Lingfeng , Yu Hong
Published: September 2015

The northwestern Pacific, characterized by unique tectonic and hydrological settings, has greatly intrigued marine phylogeographers. However, current studies mostly focus on the influence of Pleistocene isolation of sea basins in population structure of species in the region, leaving the contribution of other factors (such as freshwater outflow and environmental gradients) largely unexploited. Here we shed light on the question by investigating phylogeography of the surf clamMactra chinensisin the East China Sea (ECS). Genetic information was acquired from 501 specimens collected from its main distribution in the region, represented by mitochondrial cytochrome oxidase I (COI) and nine polymorphic microsatellite loci. A shallow and star-like phylogeny was revealed for all COI haplotypes, indicating the origin of populations from a single refugium. Although no divergent lineages existed, population subdivision was detected in both data sets. The most striking pattern was the significant differentiation between populations north and south of a biogeographic boundary—the Changjiang Estuary, suggesting a barrier effect of the freshwater outflow to gene flow. For the northern group, substructure was revealed by COI result as one southernmost population was significant different from other ones. Clear latitude gradations in allele frequencies were revealed by microsatellite analyses, likely influenced by environmental gradient factors such as temperature. Our results demonstrate that genetic subdivision can arise for populations within the ECS despite they have a single origin, and multiple mechanisms including Changjiang River outflow, environmental gradient factors and life-history traits may act in combination in the process.
Partitioning the impact of environment and spatial structure on alpha and beta components of taxonomic, functional, and phylogenetic diversity in European ants
Authors: Arnan Xavier , Cerdá Xim , Retana Javier
Published: September 2015

We analyze the relative contribution of environmental and spatial variables to the alpha and beta components of taxonomic (TD), phylogenetic (PD), and functional (FD) diversity in ant communities found along different climate and anthropogenic disturbance gradients across western and central Europe, in order to assess the mechanisms structuring ant biodiversity. To this aim we calculated alpha and beta TD, PD, and FD for 349 ant communities, which included a total of 155 ant species; we examined 10 functional traits and phylogenetic relatedness. Variation partitioning was used to examine how much variation in ant diversity was explained by environmental and spatial variables. Autocorrelation in diversity measures and each trait’s phylogenetic signal were also analyzed. We found strong autocorrelation in diversity measures. Both environmental and spatial variables significantly contributed to variation in TD, PD, and FD at both alpha and beta scales; spatial structure had the larger influence. The different facets of diversity showed similar patterns along environmental gradients. Environment explained a much larger percentage of variation in FD than in TD or PD. All traits demonstrated strong phylogenetic signals. Our results indicate that environmental filtering and dispersal limitations structure all types of diversity in ant communities. Strong dispersal limitations appear to have led to clustering of TD, PD, and FD in western and central Europe, probably because different historical and evolutionary processes generated different pools of species. Remarkably, these three facets of diversity showed parallel patterns along environmental gradients. Trait-mediated species sorting and niche conservatism appear to structure ant diversity, as evidenced by the fact that more variation was explained for FD and that all traits had strong phylogenetic signals. Since environmental variables explained much more variation in FD than in PD, functional diversity should be a better indicator of community assembly processes than phylogenetic diversity.
Stress, sense of coherence and quality of life among Norwegian nurse students after a period of clinical practice
Authors: Kleiveland Benedicte , Natvig Gerd Karin , Jepsen Randi
Published: September 2015

Background.Previous research has found that sense of coherence is significantly related to aspects of health, but studies on nurse students with a salutogenic approach are limited.

Objectives.To investigate (1) if nurse students’ experience of stress differs among clinical practice in nursing homes and medical/surgical wards. (2) Whether sense of coherence and stress are associated with quality of life. (3) If sense of coherence acts as a moderator in the relationship between stress and quality of life.

Participants.Data were collected from 227 nurse students between January and April 2014.

Methods.Questionnaires measuring stress, sense of coherence and quality of life were completed after a period of clinical practice. Linear regression analyses were used to measure associations between stress, and sense of coherence respectively, and quality of life.

Results.The results showed that 33.92% of the students experienced moderate or high levels of stress, and there was significantly more stress in hospital wards compared to nursing homes (p= 0.027). Sense of coherence was positively associated with quality of life in the simple and multiple regression analyses (p< 0.01). Stress was negatively associated with quality of life in the simple regression analysis (p< 0.01), but not in the multiple analyses when sense of coherence was included. However, when we included an interaction term, stress was no longer associated with quality of life and sense of coherence appeared to be a significant moderator in the relationship between stress and quality of life (p= 0.015). Thus, a negative association was seen among students with the lowest levels of sense of coherence.

Conclusion.These findings suggest that sense of coherence could be seen as a resource that nurse educators can build upon when supporting students in coping with stress.
Increasing sediment accumulation rates in La Fonera (Palamós) submarine canyon axis and their relationship with bottom trawling activities
Authors: Puig P. , Martín J. , Masqué P. , Palanques A.
Published: September 2015

Previous studies conducted in La Fonera (Palamós) submarine canyon (NW Mediterranean) found that trawling activities along the canyon flanks cause resuspension and transport of sediments toward the canyon axis. 210Pb chronology supported by 137Cs dating applied to a sediment core collected at 1750 m in 2002 suggested a doubling of the sediment accumulation rate since the 1970s, coincident with the rapid industrialization of the local trawling fleet. The same canyon area has been revisited a decade later, and new data are consistent with a sedimentary regime shift during the 1970s and also suggest that the accumulation rate during the last decade could be greater than expected, approaching ~2.4 cm yr−1 (compared to ~0.25 cm yr−1 pre‐1970s). These results support the hypothesis that commercial bottom trawling can substantially affect sediment dynamics and budgets on continental margins, eventually initiating the formation of anthropogenic depocenters in submarine canyon environments.
Theory and observations of upward field‐aligned currents at the magnetopause boundary layer
Authors: Wing Simon , Johnson Jay R.
Published: September 2015

The dependence of the upward field‐aligned current density (J||) at the dayside magnetopause boundary layer is well described by a simple analytic model based on a velocity shear generator. A previous observational survey confirmed that the scaling properties predicted by the analytical model are applicable between 11 and 17 MLT. We utilize the analytic model to predict field‐aligned currents using solar wind and ionospheric parameters and compare with direct observations. The calculated and observed parallel currents are in excellent agreement, suggesting that the model may be useful to infer boundary layer structures. However, near noon, where velocity shear is small, the kinetic pressure gradients and thermal currents, which are not included in the model, could make a small but significant contribution to J||. Excluding data from noon, our least squares fit returns log(J||,max_cal) = (0.96 ± 0.04) log(J||_obs) + (0.03 ± 0.01) where J||,max_cal = calculated J||,max and J||_obs = observed J||.
Virtual array beamforming of GPS TEC observations of coseismic ionospheric disturbances near the Geomagnetic South Pole triggered by teleseismic megathrusts
Authors: Gómez Demián , Smalley Robert , Langston Charles A. , Wilson Terry J. , Bevis Michael , Dalziel Ian W. D. , Kendrick Eric C. , Konfal Stephanie A. , Willis Michael J. , Piñón Diego A. , Cimbaro Sergio R. , Caccamise Dana
Published: September 2015

We identified coseismic ionospheric disturbances (CID) in Antarctica generated by the 2010 Maule and the 2011 Tohoku‐Oki earthquakes analyzing total electron content (TEC) data with a modified beamforming technique. Beamforming in Antarctica, however, is not straightforward due to the effects of array deformation and atmospheric neutral wave‐ionospheric plasma coupling. We take these effects into account and present a method to invert for the seismically generated acoustic wave using TEC observations. The back azimuths, speeds, and waveforms obtained by the beamform are in excellent agreement with the hypothesis that the TEC signals are generated by the passage of Rayleigh waves from the Maule and Tohoku‐Oki earthquakes. The Tohoku‐Oki earthquake is ~12,500 km from Antarctica, making this the farthest observation of CIDs to date using GPS.
Wavelet‐based time‐dependent travel time tomography method and its application in imaging the Etna volcano in Italy
Authors: Zhang Xin , Zhang Haijiang
Published: September 2015

It has been a challenge to image velocity changes in real time by seismic travel time tomography. If more seismic events are included in the tomographic system, the inverted velocity models do not have necessary time resolution to resolve velocity changes. But if fewer events are used for real‐time tomography, the system is less stable and the inverted model may contain some artifacts, and thus, resolved velocity changes may not be real. To mitigate these issues, we propose a wavelet‐based time‐dependent double‐difference (DD) tomography method. The new method combines the multiscale property of wavelet representation and the fast converging property of the simultaneous algebraic reconstruction technique to solve the velocity models at multiple scales for sequential time segments. We first test the new method using synthetic data constructed using real event and station distribution for Mount Etna volcano in Italy. Then we show its effectiveness to determine velocity changes for the 2001 and 2002 eruptions of Mount Etna volcano. Compared to standard DD tomography that uses seismic events from a longer time period, wavelet‐based time‐dependent tomography better resolves velocity changes that may be caused by fracture closure and opening as well as fluid migration before and after volcano eruptions.
Mapping the mechanical properties of rocks using automated microindentation tests
Authors: Masson Yder , Pride Steven R.
Published: September 2015

A microindentation scanner is constructed that measures the spatial fluctuation in the elastic properties of natural rocks. This novel instrument performs automated indentation tests on the surface of a rock slab and outputs 2‐D maps of the indentation modulus at submillimeter resolution. Maps obtained for clean, well‐consolidated, sandstone are presented and demonstrate the capabilities of the instrument. We observe that the elastic structure of sandstones correlates well with their visual appearance. Further, we show that the probability distribution of the indentation modulus fluctuations across the slab surfaces can be modeled using a lognormal probability density function. To illustrate possible use of the data obtained with the microindentation scanner, we use roughly 10 cm × 10 cm scans with millimeter resolution over four sandstone planar slabs to numerically compute the overall drained elastic moduli for each sandstone sample. We show that such numerically computed moduli are well modeled using the multicomponent form of the Hashin‐Shtrikman lower bound that employs the observed lognormal probability distribution for the mesoscopic‐scale moduli (the geometric mean works almost the same). We also compute the seismic attenuation versus frequency associated with wave‐induced fluid flow between the heterogeneities in the scanned sandstones and observe relatively small values for the inverse quality factor (Q−1<10−2) in the seismic frequency band 102 Hz <f < 104 Hz. The numerically computed frequency dependence in the attenuation varies from one type of sandstone to another, and we observe significant anisotropy in the attenuation associated with waves propagating in different directions.
Novel algorithms for the synchronization control of nonlinear systems
Authors: Tomei Patrizio , Verrelli Cristiano Maria
Published: September 2015

We show how the design of repetitive learning controls, which typically require perfect knowledge of the period T characterizing the periodic reference signals to be tracked, can be generalized, through the design of novel recursive add‐on period identifiers, to face sufficiently small period uncertainties in synchronization problems. Exponential period identification is achieved so that the asymptotic convergence properties guaranteed by the classical learning controls are preserved. Simulation results concerning multi‐link robot synchronization tasks are included. Copyright © 2015 John Wiley & Sons, Ltd.
Assessment of Periodic Open Cellular Structures for Enhanced Heat Conduction in Catalytic Fixed‐Bed Reactors
Authors: Bianchi Enrico , Schwieger Wilhelm , Freund Hannsjörg
Published: September 2015

In this paper, the effective heat conductivity of periodic open cellular structures (POCS) is investigated by means of a systematic numerical study. 3D geometries of different configurations were considered, representing the unit cell volume of the modular POCS. Special emphasis is put on the strut morphology, i.e. the strut cross sectional shape and the distribution of the solid material along the strut. At the same porosity, the optimal designed structures show a higher effective heat conductivity than conventional open‐cell solid foams with random cell geometry. This possibility to exceed the effective thermal conductivity of state‐of‐the‐art open‐cell foams by optimization of their geometrical properties is an interesting novel aspect of high relevance regarding their application in catalytic reactors.
Optimized Synthesis of nTiO2 Using Murraya koenigii Leaf Extract and Its Application in iPP–EPDM Blends
Authors: Shimpi Navinchandra G. , Shirole Sharda , Suryawanshi Yogesh , Mishra Satyendra
Published: September 2015

The present study deals with the green synthesis of titanium dioxide nanoparticles (nTiO2) using Murraya koenigii leaf extract without any catalyst, template, and surfactant. Colloidal nTiO2 were synthesized by reacting aqueous titanium(IV) isopropoxide with M. koenigii leaf extract under controlled ultrasound cavitation. This study significantly deals with (i) the concentration of titanium(IV) isopropoxide, (ii) the concentration of M. koenigii leaf extract, (iii) rate and time of reaction, (iv) intensity and pulse rate of ultrasound, which had been investigated and optimized for the controllable size and shape of nTiO2 particles. The size and shape of nTiO2 particle were confirmed by using transmission electron microscopy, whereas the size was calculated from XRD spectra using Scherer's formula. Moreover, the effect of nTiO2 particle on properties of isotactic polypropylene–ethylene propylene diene monomer (iPP–EPDM) blends was studied. The physical properties (mechanical, thermal, and swelling) were found to be improved significantly with increasing amount of loading of nTiO2 particles. This increment in properties was due to uniform dispersion of nTiO2 particles, which can be clearly observed in FE‐SEM.
Solar Rechargeable Batteries Based on Lead–Organohalide Electrolyte
Authors: Wang Qiong , Chen Hongjun , McFarland Eric , Wang Lianzhou
Published: September 2015

A dye‐sensitized solar cell (DSC) with in situ energy storage capacity is demonstrated using a lead–organohalide electrolyte CH3NH3I·PbCl2 (LOC) to replace the conventional I−/I3− electrolyte. The coupling of lead and iodine in one electrolyte creates a dual‐function rechargeable solar battery that combines the working processes of photoelectrochemical cells with electrochemical batteries. Optimization of the H+ concentration in the electrolyte leads to increased photocharging efficiency and storage. The power conversion efficiency of the LOC–DSC is 8.6% under one sun illumination (AM 1.5, 100 mW cm−2) as a DSC. When operating as a battery, Faraday efficiency can be achieved as high as 81.5% using a bromide‐based CH3NH3Br·PbBr2 (LOB) electrolyte in a DSC configuration. This new cell design suggests a means of combining photovoltaic energy conversion and electrical energy storage.
The behavioral characteristics of Sotos syndrome
Authors: Sheth Krupa , Moss Joanna , Hyland Sarah , Stinton Chris , Cole Trevor , Oliver Chris
Published: September 2015

In this study we describe the levels of clinically significant behavior in participants with Sotos syndrome relative to three matched contrast groups in which the behavioral phenotype is well documented (Autism Spectrum Disorder, ASD; Prader–Willi, and Down syndromes). Parents and carers of 38 individuals with Sotos syndrome (mean age = 17.3; SD = 9.36), completed questionnaires regarding self‐injury, aggression, repetitive behavior, autism spectrum phenomenology, overactivity, impulsivity and mood, interest and pleasure. Individuals with Sotos syndrome showed an increased risk of self‐injurious behavior, physical aggression, and destruction of property relative to the Down syndrome group but not a greater risk of stereotyped behavior. Impulsivity and levels of activity were also significantly higher relative to those with Down syndrome and comparable to those with ASD. A large proportion of participants met the cut off score for ASD (70.3%) and Autism (32.4%) on the Social Communication Questionnaire. Social impairments were particularly prominent with repetitive behavior and communication impairments less characteristic of the syndrome. Interestingly, preference for routine and repetitive language were heightened in individuals with Sotos syndrome and the repetitive behavior profile was strikingly similar to that observed in individuals with Prader–Willi syndrome. These findings build upon previous research and provide further evidence of the behavioral phenotype associated with Sotos syndrome. © 2015 Wiley Periodicals, Inc.
N‐Heterocyclic‐Carbene‐Catalysed Diastereoselective Vinylogous Mukaiyama/Michael Reaction of 2‐(Trimethylsilyloxy)furan and Enones
Authors: Wang Ying , Du Guang‐Fen , Xing Fen , Huang Kuo‐Wei , Dai Bin , He Lin
Published: September 2015

N‐heterocyclic carbenes have been utilised as highly efficient nucleophilic organocatalysts to mediate vinylogous Mukaiyama/Michael reactions of 2‐(trimethylsilyloxy)furan with enones to afford γ‐substituted butenolides in 44–99 % yield with 3:1–32:1 diastereoselectivity.
Redox‐Modulation der PTEN‐Phosphataseaktivität durch Wasserstoffperoxid und Bisperoxidovanadium‐Komplexe
Authors: Lee Chang‐Uk , Hahne Gernot , Hanske Jonas , Bange Tanja , Bier David , Rademacher Christoph , Hennig Sven , Grossmann Tom N.
Published: September 2015

PTEN ist eine dualspezifische Protein‐Tyrosin‐Phosphatase. Sie ist einer der zentralen Tumorsuppressoren, weshalb eine genaue Regulierung ihrer Aktivität essenziell für die richtige zelluläre Homöostase ist. Die genauen Auswirkungen der Inhibition von PTEN durch reaktive Sauerstoffspezies (z. B. H2O2) und deren strukturelle Folgen sind bisher wenig verstanden. Wichtige Instrumente für das Studium der Wirkung von PTEN‐Inhibition sind Bisperoxidovanadium(bpV)‐Komplexe, mit dem Potenzial für die Behandlung von Nervenverletzungen oder kardialer Ischämie. Allerdings ist ihr Wirkmechanismus unbekannt, was weitere Optimierungen und therapeutische Anwendungen erschwert. Mithilfe der Proteinkristallographie, Massenspektrometrie und NMR‐Spektroskopie untersuchen wir hier die molekularen Grundlagen der PTEN‐Inhibition durch H2O2 und bpV‐Komplexe. Dabei zeigen wir, dass PTEN in beiden Fällen oxidativ inhibiert wird und sich die gleiche intramolekulare Disulfidbrücke bildet. Dies ermöglicht die Reaktivierung von PTEN unter reduzierenden Bedingungen.
Di‐N‐Methylation of Anti‐Gram‐Positive Aminoglycoside‐Derived Membrane Disruptors Improves Antimicrobial Potency and Broadens Spectrum to Gram‐Negative Bacteria
Authors: Benhamou Raphael I. , Shaul Pazit , Herzog Ido M. , Fridman Micha
Published: September 2015

The effect of di‐N‐methylation of bacterial membrane disruptors derived from aminoglycosides (AGs) on antimicrobial activity is reported. Di‐N‐methylation of cationic amphiphiles derived from several diversely structured AGs resulted in a significant increase in hydrophobicity compared to the parent compounds that improved their interactions with membrane lipids. The modification led to an enhancement in antibacterial activity and a broader antimicrobial spectrum. While the parent compounds were either modestly active or inactive against Gram‐negative pathogens, the corresponding di‐N‐methylated compounds were potent against the tested Gram‐negative as well as Gram‐positive bacterial strains. The reported modification offers a robust strategy for the development of broad‐spectrum membrane‐disrupting antibiotics for topical use.
Manganese(I)‐Catalyzed C–H Aminocarbonylation of Heteroarenes
Authors: Liu Weiping , Bang Jonas , Zhang Yujiao , Ackermann Lutz
Published: September 2015

A versatile manganese(I) catalyst was employed in CH aminocarbonylation reactions of heteroarenes with aryl as well as with alkyl isocyanates using a removable directing group approach. Detailed experimental mechanistic studies were suggestive of an organometallic CH manganesation step, followed by a rate‐determining migratory insertion.
Understanding P450‐mediated Bio‐transformations into Epoxide and Phenolic Metabolites
Authors: Tomberg Anna , Pottel Joshua , Liu Zhaomin , Labute Paul , Moitessier Nicolas
Published: September 2015

Adverse drug reactions are commonly the result of cytochrome P450 enzymes (CYPs) converting the drugs into reactive metabolites. Thus, information about the CYP bioactivation of drugs would not only provide insight into metabolic stability, but also into the potential toxicity. For example, oxidation of phenyl rings may lead to either toxic epoxides or safer phenols. Herein, we demonstrate that the potential to form reactive metabolites is encoded primarily in the properties of the molecule to be oxidized. While the enzyme positions the molecule inside the binding pocket (selects the site of metabolism), the subsequent reaction is only dependent on the substrate itself. To test this hypothesis, we used this observation as a predictor of drug inherent toxicity. This approach was used to successfully identify the formation of reactive metabolites in over 100 drug molecules. These results provide a new perspective on the impact of functional groups on aromatic oxidation of drugs and their effects on toxicity.
Alkali‐Metal‐Mediated Magnesiations of an N‐Heterocyclic Carbene: Normal, Abnormal, and “Paranormal” Reactivity in a Single Tritopic Molecule
Authors: Martínez‐Martínez Antonio J. , Fuentes M. Ángeles , Hernán‐Gómez Alberto , Hevia Eva , Kennedy Alan R. , Mulvey Robert E. , O'Hara Charles T.
Published: September 2015

Herein the sodium alkylmagnesium amide [Na4Mg2(TMP)6(nBu)2] (TMP=2,2,6,6‐tetramethylpiperidide), a template base as its deprotonating action is dictated primarily by its 12 atom ring structure, is studied with the common N‐heterocyclic carbene (NHC) IPr [1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene]. Remarkably, magnesiation of IPr occurs at the para‐position of an aryl substituent, sodiation occurs at the abnormal C4 position, and a dative bond occurs between normal C2 and sodium, all within a 20 atom ring structure accommodating two IPr2−. Studies with different K/Mg and Na/Mg bimetallic bases led to two other magnesiated NHC structures containing two or three IPr− monoanions bound to Mg through abnormal C4 sites. Synergistic in that magnesiation can only work through alkali‐metal mediation, these reactions add magnesium to the small cartel of metals capable of directly metalating a NHC.
CH Oxidation of Ingenanes Enables Potent and Selective Protein Kinase C Isoform Activation
Authors: Jin Yehua , Yeh Chien‐Hung , Kuttruff Christian A. , Jørgensen Lars , Dünstl Georg , Felding Jakob , Natarajan Swaminathan R. , Baran Phil S.
Published: September 2015

Ingenol derivatives with varying degrees of oxidation were prepared by two‐phase terpene synthesis. This strategy has allowed access to analogues that cannot be prepared by semisynthesis from natural ingenol. Complex ingenanes resulting from divergent CH oxidation of a common intermediate were found to interact with protein kinase C in a manner that correlates well with the oxidation state of the ingenane core. Even though previous work on ingenanes has suggested a strong correlation between potential to activate PKCδ and induction of neutrophil oxidative burst, the current study shows that the potential to activate PKCβII is of key importance while interaction with PKCδ is dispensable. Thus, key modifications of the ingenane core allowed PKC isoform selectivity wherein PKCδ‐driven activation of keratinocytes is strongly reduced or even absent while PKCβII‐driven activation of neutrophils is retained.
Lanthanum histidine with pentaerythritol and zinc stearate as thermal stabilizers for poly(vinyl chloride)
Authors: Li Mei , Duan Cheng , Wang Haiou , Liu Zhaogang , Wang Mitang , Hu Yanhong
Published: September 2015

Lanthanum histidine [La(His)2·(NO3)·2H2O or La(His)2] was synthesized via the reaction of histidine and lanthanum nitrate, and it was investigated as a stabilizer for poly(vinyl chloride) (PVC). The results show that La(His)2 exhibited a stabilizing effect on PVC as a long‐term stabilizer because it prolonged the stability time of PVC to 76 min, which was about 24 times longer than the stability time of the pure PVC. The stabilizing effect of La(His)2 as a costabilizer with pentaerythritol (Pe) and zinc stearate (ZnSt2) was also studied. The results show that the use of La(His)2 with Pe or Pe/ZnSt2 improved the stability time of PVC. La(His)2/Pe/ZnSt2 provided PVC with a good initial color and long‐term stability, and when it was prepared at mass ratios of 0.8:2.4:0.8 and 1.6:1.6:0.8, the stability times of PVC were improved to 86 and 88 min, respectively. As a nontoxic stabilizer, La(His)2/Pe/ZnSt2 has the potential to replace the toxic stabilizers widely used in PVC manufacturing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42878.
Laccase‐catalyzed synthesis of conducting polyaniline‐lignosulfonate composite
Authors: Zhang Ya , Dong Aixue , Fan Xuerong , Wang Qiang , Zhang Ying , Yu Yuanyuan , Cavaco‐Paulo Artur
Published: September 2015

Enzymatic polymerization of aniline was first performed in lignosulfonate (LGS) template system. High‐redox‐potential catalyst laccase, isolated from Aspergillus, was used as a biocatalyst in the synthesis of conducting polyaniline/lignosulfonate (PANI‐ES‐LGS) complex using atmospheric oxygen as the oxidizing agent. The linear templates (LGS), also serving as the dopants, could facilitate the directional alignment of the monomer and improve the solubility of the conducting polymer. The process of the polymerization was monitored using UV‐Vis spectroscopy, by which the conditions for laccase‐catalyzed synthesis of PANI‐ES‐LGS complex were also optimized. The structure characterizations and solubility of the complex were carried out using corresponding characterization techniques respectively. The PANI‐ES‐LGS suspensions obtained was used as coating for cotton with a conventional padder to explore the applications of the complex. The variable optoelectronic properties of the coated cotton were confirmed by cyclic voltammetry and color strength test. The molecular weight changes of LGS treated by laccase were also studied to discuss the mechanism of laccase catalyzed aniline polymerization in LGS template system. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42941.
An efficient thermostable organophosphate hydrolase and its application in pesticide decontamination
Authors: Del Giudice Immacolata , Coppolecchia Rossella , Merone Luigia , Porzio Elena , Carusone Teresa Maria , Mandrich Luigi , Worek Franz , Manco Giuseppe
Published: September 2015

In vitro evolution of enzymes represents a powerful device to evolve new or to improve weak enzymatic functions. In the present work a semi‐rational engineering approach has been used to design an efficient and thermostable organophosphate hydrolase, starting from a lactonase scaffold (SsoPox from Sulfolobus solfataricus). In particular, by in vitro evolution of the SsoPox ancillary promiscuous activity, the triple mutant C258L/I261F/W263A has been obtained which, retaining its inherent stability, showed an enhancement of its hydrolytic activity on paraoxon up to 300‐fold, achieving absolute values of catalytic efficiency up to 105 M−1s−1. The kinetics and structural determinants of this enhanced activity were thoroughly investigated and, in order to evaluate its potential biotechnological applications, the mutant was tested in formulations of different solvents (methanol or ethanol) or detergents (SDS or a commercial soap) for the cleaning of pesticide‐contaminated surfaces. Biotechnol. Bioeng. 2016;113: 724–734. © 2015 Wiley Periodicals, Inc.
Enzymatic pretreatment of low‐grade oils for biodiesel production
Authors: Nordblad Mathias , Pedersen Anders K. , Rancke‐Madsen Anders , Woodley John M.
Published: September 2015

The alkaline process for making biodiesel (fatty acid methyl esters, or FAME) is highly efficient at the transesterification of glycerides. However, its performance is poor when it comes to using oil that contain significant amounts of free fatty acids (FFA). The traditional approach to such feedstocks is to employ acid catalysis, which is slow and requires a large excess of methanol, or to evaporate FFA and convert that in a separate process. An attractive option would be to convert the FFA in oil feedstocks to FAME, before introducing it into the alkaline process. The high selectivity of enzyme catalysis makes it a suitable basis for such a pretreatment process. In this work, we present a characterization of the pretreatment of high‐FFA rapeseed oil using immobilized Candida antarctica lipase B (Novozym 435), focused on the impact of initial FFA and methanol concentration. Based on experimental results, we have identified limitations for the process in terms of FFA concentration in the feedstock and make suggestions for process operation. It was found that, using 5% catalyst and 4% methanol at 35°C, the FFA concentration could be reduced to 0.5% within an hour for feedstock containing up to 15% FFA. Further, the reaction was observed to be under kinetic control, in that the biocatalyst converts FFA (and FAME) at a much higher rate than glyceride substrates. There is thus, both a minimum and a maximum reaction time for the process to achieve the desired concentration of FFA. Finally, an assessment of process stability in a continuous packed bed system indicates that as much as 15 m3 oil could potentially be pretreated by 1 kg of biocatalyst at the given process conditions. Biotechnol. Bioeng. 2016;113: 754–760. © 2015 Wiley Periodicals, Inc.
A Study on the Separation of Co(II), Ni(II), and Mg(II) by Solvent Extraction with Cationic Extractants
Authors: Liu Yang , Nam Sang‐Ho , Lee Man‐Seung
Published: September 2015

Solvent extraction and separation of Co (0.8 g/L), Ni (0.3 g/L), and Mg (0.5 g/L) with various cationic extractants (D2EHPA, PC88A, Cyanex 272, Versatic 10, and Cyanex 301) from chloride solutions are investigated. The effects of initial pH, extractant concentration, and saponification degree on the extraction and separation of metals are also studied. Co was preferentially extracted over Mg and Ni by saponified PC88A and Cyanex 272. On the other hand, Cyanex 301 and Versatic 10 exhibited selectivity on the extraction of both Co and Ni over Mg. HCl solution selectively stripped Co over Ni from the loaded Cyanex 301, which made it possible to separate the two metals during the stripping process.
Structure and Performances of xLiFePO4/C·(1 − x)Li3V2(PO4)3/C Cathode for Lithium‐Ion Batteries by Using Poly(vinyl alcohol) as Carbon Source
Authors: Fan Chang‐ling , Zhang Wei‐hua , Zeng Tao‐tao , Li Ling‐fang , Zhang Xiang , Han Shao‐chang
Published: September 2015

Poly(vinyl alcohol), whose pyrolysis carbon possesses high conductivity of 8.88 × 10−1 S/cm, was used to synthesize xLiFePO4/C·(1 − x)Li3V2(PO4)3/C cathode. It was characterized by X‐ray diffraction, scanning electron microscopy, conductivity, cyclic voltammetry, and galvanostatic charge and discharge experiments. Results show that LiFePO4/C and Li3V2(PO4)3/C coexists in the cathode. The particles sizes of 0.75LiFePO4/C·0.25Li3V2(PO4)3/C (x = 0.75) are much smaller than 100 nm due to the role of poly(vinyl alcohol). Its conductivity is 8.79 × 10−2 S/cm. The oxidative and reductive peaks in cyclic voltammetry are sharp and symmetrical. Their low potential gaps indicate that the extractions and insertions of lithium ion possess excellent reversibility. Its discharge capacities at 1 and 5 C are 141.1 and 100.1 mAh/g. The more Li3V2(PO4)3/C in cathode results in the deterioration of electrochemical performances due to its low theoretical capacity. It is concluded that poly(vinyl alcohol) is an effective carbon source in the preparation of xLiFePO4/C·(1 − x)Li3V2(PO4)3/C composite cathode with excellent performances.
Chiral Ammonium Aryloxides: Efficient Multipurpose Basic Organocatalysts
Authors: Godemert Jérémy , Oudeyer Sylvain , Levacher Vincent
Published: September 2015

This review summarizes the recent developments in chiral quaternary ammonium aryloxides as flexible organocatalysts that are able to act as both a Brønsted and Lewis base. A particular class of ammonium aryloxides, namely betaines, has emerged as an efficient class of catalysts. The performance of betaines stems mainly from the intramolecular nature of these ammonium ion pairs, leading to highly reactive catalytic species with a high level of organization. The above‐mentioned catalysts have been successfully applied to a wide range of asymmetric chemical transformations, including Mukaiyama aldol reactions, tandem Michael addition/lactonization sequences, trifluoromethylation reactions, aza‐Henry reactions, silyl enolates protonation reactions, and Steglich‐type rearrangements, with a high level of enantioselectivity.
Exploration of the Chiral Recognition of Sugar‐Based Diindolylmethane Receptors: Anion and Receptor Structures
Authors: Granda Jarosław M. , Jurczak Janusz
Published: September 2015

In this study, we have conducted a systematic investigation of the chiral recognition of carboxylic anions by D‐glucuronic acid/diindolylmethane receptors. We investigate the influence of the anion structure on chiral recognition in the diindolylmethane/glucuronic acid‐based receptor 1 a. We found that presence of an additional hydrogen‐bond donor at the α position to the carboxylic function is essential for effective chiral differentiation in these systems. Furthermore, we present a synthetic procedure that allows for the synthesis of sugar‐decorated receptors that possess a modified substituent at the anomeric position. Four new receptors 1 b–e have been synthesized, and their chiral‐discrimination ability toward model carboxylates is studied. The obtained results show that the chiral recognition of these receptors can be fine‐tuned by incorporation of a proper substituent into the receptor structure.
Multiple‐Stimuli Responsive Luminescent Gels Based on Cholesterol Containing Benzothiadiazole Fluorophores
Authors: Sun Huibin , Liu Shujuan , Zhao Qiang , Huang Wei
Published: September 2015

Two new fluorescent organogelators based on cholesterol containing benzothiadiazole group have been designed and synthesized. Three methods for gels preparation have been presented, such as heating‐cooling process, ultrasonic treatment and mixed solvents under room temperature. For both of the gels, their states and emission colors exhibit striking changes upon addition of Hg2+. The gelation properties, structural characteristics and fluorescence of the gels were studied by FT‐IR, UV‐Vis absorption and PL spectra. The underlying mechanism of gelation property was studied by X‐ray diffraction combined with theoretical calculation, and the important role of π‐ π interactions in forming the gels has been proved.
Bromine/para‐Toluenesulfonic Acid‐Catalyzed Synthesis of 3,3‐Bis(indole‐3‐yl)indoline‐2‐(1H)‐ones by Condensing Indoles with Isatins
Authors: Huang Wenzhong , Nang Lingli , Li Xiangguang , Yuan Lin , Ma Yinhai , Liang Deqiang
Published: September 2015

Under the catalysis of only 3 mol% of Br2 at room temperature, indoles reacted
rapidly with isatins to form biologically important 3,3‐bis(indole‐3‐yl)indoline‐2‐(1H)‐ones with high efficiency and
wide substrate scope. Moreover, we demonstrated that p‐toluenesulfonic acid (TsOH) could serve as a surrogate to
catalyze this transformation.
N‐Heterocyclic Carbene‐Catalysed Direct Synthesis of Cyano Esters via Cyanation‐Esterification Reaction of α‐Keto Esters
Authors: Zhang Jie , Wang Ying , Du Guangfen , Gu Cheng‐Zhi , Dai Bin
Published: September 2015

The cyanation‐esterification reaction of α‐keto esters catalysed by N‐heterocyclic carbenes (NHCs) is developed. Under the catalysis of 10 mol% 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene, aromatic and aliphatic α‐keto esters reacted with ethyl cyanoformate or acetyl cyanide to produce the corresponding cyano esters with a tetrasubstituted carbon center in high yields.
Synthesis and Biological Activity of Novel Furan/Thiophene and Piperazine‐Containing (Bis)1,2,4‐triazole Mannich Bases
Authors: Wang Baolei , Shi Yanxia , Zhan Yizhou , Zhang Liyuan , Zhang Yan , Wang Lizhong , Zhang Xiao , Li Yonghong , Li Zhengming , Li Baoju
Published: September 2015

Series of novel furan/thiophene and piperazine‐containing 1,2,4‐triazole Mannich bases and bis(1,2,4‐triazole) Mannich bases have been conveniently synthesizedviaMannich reaction with triazole Schiff bases, various piperazine derivatives, and formaldehyde as intermediates in good yields. Their structures were characterized by melting points,1H NMR,13C NMR, IR and elemental analysis. The preliminary bioassay showed that most compounds exhibited significantin vitroandin vivofungicidal activity against several test plant fungi. Among 32 new compounds, the trifluoromethyl‐containing compounds showed superior activity than the methyl‐containing ones. Several compounds, such asF8,F9,F10,G5,H7,H8,I3andI4, were comparable with some commercial fungicides against different fungi during the present study and could be further structurally optimized. Meanwhile, several compounds showed good herbicidal activity againstBrassica campestrisat 100 µg/mL and KARI inhibitory activity at 200 µg/mL. However, compounds exhibited poor insecticidal activity against oriental armyworm at 200 µg/mL in the preliminary studies. The research results will provide useful information for the design and discovery of new agrochemicals with novel heterocyclic structures.
Sulfonated Graphene Synthesizedviaa Green Route and Its Capacitive Properties
Authors: Zhou Wen , Han Gaoyi , Xiao Yaoming , Chang Yunzhen , Li Miaoyu , Zhang Yuyu
Published: September 2015

An environmentally friendly approach is presented to synthesize sulfonated reduced graphene oxide (S‐rGO) by usingL‐ascorbic acid (L‐AA) and aryl diazonium salt of sulfanilic acid. The preparation conditions have been optimized in order to obtain isolated and conductive S‐rGO, and the products have been characterized by Ultraviolet‐Visible spectroscopy, Fourier transformed infrared spectroscopy, Raman, X‐ray photoelectron spectroscopy and X‐ray powder diffraction and electrochemical methods. The results show that the S‐rGO sheets possess excellent water‐solubility and high electrical conductivity, which implies that the oxygen‐containing functional groups have been removed and conjugated sp2network has been restored. What's more, the electrochemical measurements reveal that the capacitive performance of the S‐rGO has been improved compared with the graphene oxide (GO) and the reduced graphene oxide (rGO, reduced byL‐AA). The optimum S‐rGO exhibits a specific capacitance of 205 F·g−1and good cycling stability (3.9% decreasing after 10000 cycles), which are better than those for graphene oxide (109 F·g−1and decreasing 6.6% after 10000 cycles) and rGO (139 F·g−1and decreasing 11.3% after 10000 cycling). This approach proves a new route to improve the capacitive properties of rGO.
DBU‐Promoted Trifluoromethylation of Aryl Iodides with Difluoromethyltriphenylphosphonium Bromide
Authors: Wei Yun , Yu Liuying , Lin Jinhong , Zheng Xing , Xiao Jichang
Published: September 2015

DBU‐promoted trifluoromethylation of aryl iodides with difluoromethyltriphenylphosphonium bromide (DFPB) in the presence of copper source is described. In this transformation, DBU not only acts as base to deprotonate the difluoromethyl group in DFPB to generate difluoromethylene phosphonium ylide Ph3P+CF2−, but also converts the difluorocarbene generated from ylide Ph3P+CF2− into trifluoromethyl anion, finally resulting in the trifluoromethylation of aryl iodides. The reactions proceeded smoothly to afford expected products in moderate to good yields.