bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin‐induced migration and angiogenesis in rheumatoid arthritis is mediated by reactive oxygen species
Authors: Sun Xiaotong , Wei Jing , Tang Yawei , Wang Bing , Zhang Yan , Shi Lei , Guo Jianping , Hu Fanlei , Li Xia
Published: October 2017

Rheumatoid arthritis (RA) is a progressive autoimmune disease affecting the joints. In this study, we investigated the role of the pro‐angiogenic factor leptin in regulating reactive oxygen species (ROS) to promote cell migration and angiogenesis in RA. We showed that leptin triggered RA fibroblast‐like synoviocyte (FLS) migration by increased ROS expression. Additionally, leptin enhanced human umbilical vein endothelial cell (HUVEC) tube formation in a ROS/hypoxia‐inducible factor‐1α‐dependent manner, accompanied by increased production of vascular endothelial growth factor and interleukin (IL)‐6. We also revealed that antagonists of tumor necrosis factor, IL‐6 and IL‐1β down‐regulated ROS production of RA FLS induced by leptin, which subsequently attenuated RA FLS migration and HUVEC tube formation. These findings demonstrated that leptin might play an important role in RA FLS migration and HUVEC angiogenesis.
Accelerated neuroadaptive tracking control of strict‐feedback nonlinear systems without precise knowledge of target trajectory
Authors: Zhou Shuyan , Song Yongduan , Zhao Kai
Published: October 2017

The problem of tracking control under uncertain desired trajectory is interesting but nontrivial. The problem is even more challenging if the system under consideration involves modeling uncertainties. This paper investigates such problem for strict‐feedback nonlinear systems. By combining Fourier series with radial basis function neural networks (NNs), an analytical model is developed to reconstruct the unknown desired trajectory. Based on which, 2 neural adaptive control schemes are developed to maintain target tracking closely. The first control strategy is based on direct tuning of the NN weights, and the second strategy is built upon the concept of a virtual parameter related to NN weights, which substantially reduces the number of parameters to be online updated, rendering the strategy structurally simpler and computationally less expensive. The effectiveness of the proposed control strategy is confirmed by systematic stability analysis and numerical simulation.
Combined Microwave and Laser Heating for Glazing of 8Y–ZrO2 and 8Y–ZrO2/ZrSiO4–Composites
Authors: Lehmann Sebastian , Böckler Jens , Willert‐Porada Monika , Rosin Andreas , Richter Christian
Published: October 2017

Sintered porous yttria‐stabilized zirconia and zirconia composite ceramics with zirconium silicate are surface glazed by Laser‐Assisted Microwave Plasma Processing (LAMPP). Suitable process parameters for surface glazing are determined for those ceramics. The plasma process is monitored by means of pyrometry and optical emission spectroscopy. In order to prove the quality of the surface glazing and to characterize hot corrosion resistance, tests with molten vanadium pentoxide are performed. After 4 h of exposure, the penetration depth of the molten salt is investigated as a function of ceramic composition and pre‐treatment by glazing. Upon hot corrosion testing of glazed and non‐glazed ceramics, the molten vanadium pentoxide reacts selectively with yttrium oxide, forming yttrium vanadate, and causes crack formation in the zirconia ceramics due to transition to monoclinic zirconia. The results for LAMPP‐glazed ceramics show, that a surficial melting phase is achieved because process temperatures exceed 3000 °C. Hence, a dense, crack‐free and hardness‐enhanced surface layer achieves a better resistance to hot corrosion as compared to non‐glazed ceramics. Due to LAMPP‐glazing, the vanadium ingress is reduced from 33 to 7 μm for yttria‐stabilized zirconia and from 104 to 17 μm for zirconia composite ceramic. Reactions and microstructural changes taking place upon LAMP‐Processing are discussed.
Supertough Hybrid Hydrogels Consisting of a Polymer Double‐Network and Mesoporous Silica Microrods for Mechanically Stimulated On‐Demand Drug Delivery
Authors: Choi Suji , Choi Young jin , Jang Moon‐Sun , Lee Jung Hee , Jeong Ji Hoon , Kim Jaeyun
Published: October 2017

Despite their potential in various fields of bioapplications, such as drug/cell delivery, tissue engineering, and regenerative medicine, hydrogels have often suffered from their weak mechanical properties, which are attributed to their single network of polymers. Here, supertough composite hydrogels are proposed consisting of alginate/polyacrylamide double‐network hydrogels embedded with mesoporous silica particles (SBA‐15). The supertoughness is derived from efficient energy dissipation through the multiple bondings, such as ionic crosslinking of alginate, covalent crosslinking of polyacrylamide, and van der Waals interactions and hydrogen bondings between SBA‐15 and the polymers. The superior mechanical properties of these hybrid hydrogels make it possible to maintain the hydrogel structure for a long period of time in a physiological solution. Based on their high mechanical stability, these hybrid hydrogels are demonstrated to exhibit on‐demand drug release, which is controlled by an external mechanical stimulation (both in vitro and in vivo). Moreover, different types of drugs can be separately loaded into the hydrogel network and mesopores of SBA‐15 and can be released with different speeds, suggesting that these hydrogels can also be used for multiple drug release.
Efficient Semitransparent Organic Solar Cells with Tunable Color enabled by an Ultralow‐Bandgap Nonfullerene Acceptor
Authors: Cui Yong , Yang Chenyi , Yao Huifeng , Zhu Jie , Wang Yuming , Jia Guoxiao , Gao Feng , Hou Jianhui
Published: October 2017

Semitransparent organic solar cells (OSCs) show attractive potential in power‐generating windows. However, the development of semitransparent OSCs is lagging behind opaque OSCs. Here, an ultralow‐bandgap nonfullerene acceptor, “IEICO‐4Cl”, is designed and synthesized, whose absorption spectrum is mainly located in the near‐infrared region. When IEICO‐4Cl is blended with different polymer donors (J52, PBDB‐T, and PTB7‐Th), the colors of the blend films can be tuned from purple to blue to cyan, respectively. Traditional OSCs with a nontransparent Al electrode fabricated by J52:IEICO‐4Cl, PBDB‐T:IEICO‐4Cl, and PTB7‐Th:IEICO‐4Cl yield power conversion efficiencies (PCE) of 9.65 ± 0.33%, 9.43 ± 0.13%, and 10.0 ± 0.2%, respectively. By using 15 nm Au as the electrode, semitransparent OSCs based on these three blends also show PCEs of 6.37%, 6.24%, and 6.97% with high average visible transmittance (AVT) of 35.1%, 35.7%, and 33.5%, respectively. Furthermore, via changing the thickness of Au in the OSCs, the relationship between the transmittance and efficiency is studied in detail, and an impressive PCE of 8.38% with an AVT of 25.7% is obtained, which is an outstanding value in the semitransparent OSCs.
Triggering and Tracing Electro‐Hydrodynamic Liquid‐Metal Surface Convection with a Particle Raft
Authors: Tang Jianbo , Zhao Xi , Zhou Yuan , Liu Jing
Published: October 2017

Microcopper particles are introduced to trigger and trace persistent surface convection of eutectic gallium indium (eGaIn) when the liquid‐metal is partially immersed in shallow alkaline solution. It is found that the surface convection, which further induces large‐scale shape transformation of the liquid‐metal body, is driven by the surface‐tension imbalance originated from the numerous tiny copper–eGaIn galvanic couples through the electrocapillary mechanism. Meanwhile, the particular configuration of particles binding to the liquid‐metal surface and surfing with the flow also enables one to capture the flow patterns and visualize the flow field with the assistance of particle imaging velocimetry technology. This overcomes the difficulties in directly observing and quantifying the dynamic surface‐flow behaviors of such nontransparent yet highly reflective liquid‐metals. Characteristic flow regimes of the liquid–metal surface convection are revealed and their indications regarding the flow beneath the surface are also made.
2D TiS2 Layers: A Superior Nonlinear Optical Limiting Material
Authors: Varma Sreekanth J. , Kumar Jitesh , Liu Yang , Layne Katherine , Wu Jingjie , Liang Chenglu , Nakanishi Yusuke , Aliyan Amir , Yang Wei , Ajayan Pulickel M. , Thomas Jayan
Published: October 2017

The advancement in high power lasers has urged the requisite of efficient optical limiting materials for both eye and sensor protection. The discovery of atomically thin 2D transition metal dichacogenides with distinctive properties has paved the way for a variety of applications including optical limiting. Until recently, the optical limiting effect exhibited by 2D materials is inferior to the benchmark materials fullerene (C60) and graphene. This article reports the optical limiting activity of the 2D transition metal dichalcogenide, titanium disulfide (TiS2) nanosheets, using optical and photoacoustic z‐scan techniques. The 77% nonlinear optical limiting exhibited by the TiS2 sheets with 73% linear‐transmittance is superior to that of any other existing 2D dichalcogenide sheets, graphene, and the benchmark optical limiting material, C60. The enhanced nonlinear response is attributed to the concerted effect of 2‐photon and the induced excited state absorptions. By using photoacoustic z‐scan, a unique tool developed to determine the nonlinear optical limiting mechanism in materials, it is found that the optical limiting exhibited by TiS2 2D sheets and graphene are mainly due to nonlinear absorption rather than scattering effects. These results have opened the door for 2D‐dichalcogenide‐materials‐based highly efficient optical limiters, especially at low fluences.
New Insight into Ni‐Rich Layered Structure for Next‐Generation Li Rechargeable Batteries
Authors: Lee Wontae , Muhammad Shoaib , Kim Taewhan , Kim Hyunchul , Lee Eunkang , Jeong Mihee , Son Suhan , Ryou Jae‐Hyun , Yoon Won‐Sub
Published: October 2017

An increase in the amount of nickel in LiMO2 (M = Ni, Co, Mn) layered system is actively pursued in lithium‐ion batteries to achieve higher capacity. Nevertheless, fundamental effects of Ni element in the three‐component layered system are not systematically studied. Therefore, to unravel the role of Ni as a major contributor to the structural and electrochemical properties of Ni‐rich materials, Co‐fixed LiNi0.5+xCo0.2Mn0.3–xO2 (x = 0, 0.1, and 0.2) layered materials are investigated. The results, on the basis of synchrotron‐based characterization techniques, present a decreasing trend of Ni2+ content in Li layer with increasing total Ni contents. Moreover, it is discovered that the chex.‐lattice parameter of layered system is not in close connection with the interslab thickness related to actual Li ion pathway. The interslab thickness increases with increasing Ni concentration even though the chex.‐lattice parameter decreases. Furthermore, the lithium ion pathway is preserved in spite of the fact that the c‐axis is collapsed at highly deintercalated states. Also, a higher Ni content material shows better structural properties such as larger interslab thickness, lower cation disorder, and smoother phase transition, resulting in better electrochemical properties including higher Li diffusivity and lower overpotential when comparing materials with lower Ni content.
The association of air pollution with height: Evidence from Hong Kong's “Children of 1997” birth cohort
Authors: Huang Jian V. , Leung Gabriel M. , Schooling C. Mary
Published: September 2017

Objectives

Within populations, height is positively associated with economic success and in economically developed populations inversely associated with health. Recent studies also suggest air pollution may result in higher bone turnover markers among children, which may affect growth. However, few studies have investigated the effect of air pollution on height or growth rate. We therefore assessed the associations of several air pollutants with height at different ages.

Methods

We simultaneously assessed associations of particulate matter with a diameter of 10 micrometers or less (PM10), sulfur dioxide (SO2), nitric oxide (NO), and nitrogen dioxide (NO2) in utero, in infancy, and in childhood with height at different ages (∼9, ∼11, ∼13, and ∼15 years), in a population‐representative birth cohort “Children of 1997” (n = 8327) from the developed non‐Western setting of Hong Kong with relatively high air pollution and short children, using partial least square regression.

Results

After considering multiple comparison, higher SO2 in childhood was associated with shorter height at ∼13 years (–0.20 cm, 99% CI −0.32 to −0.06). This difference was not evident at ∼15 years.

Conclusions

These observations suggest that air pollution may affect the trajectory of growth and development rather than final height, with corresponding implications for health in later life.
Biosynthese des enterotoxischen Pyrrolobenzodiazepin‐Naturstoffs Tilivallin
Authors: Dornisch Elisabeth , Pletz Jakob , Glabonjat Ronald A. , Martin Florian , Lembacher‐Fadum Christian , Neger Margit , Högenauer Christoph , Francesconi Kevin , Kroutil Wolfgang , Zangger Klaus , Breinbauer Rolf , Zechner Ellen L.
Published: October 2017

Das nichtribosomale Enterotoxin Tilivallin war das erste natürliche Pyrrolobenzodiazepin, das als Ursache von Erkrankungen des menschlichen Darm erkannt worden ist. Der produzierende Organismus Klebsiella oxytoca ist Bestandteil des Darmmikrobioms. Da die Pathogenese der Darmcolitis durch das Pyrrolobenzodiazepin verursacht wird, ist es wichtig, die Biosynthese und Regulierung der Aktivität von Tilivallin zu verstehen. Wir berichten über die Biosynthese von Tilivallin und zeigen, dass in einem nichtribosomalem Peptidaufbauweg zunächst Tilimycin, ein einfaches Pyrrolobenzodiazepin mit zytotoxischen Eigenschaften, gebildet wird. Tilivallin entsteht durch eine nichtenzymatische spontane Reaktion von Tilimycin mit biogenetisch erzeugtem Indol. Durch chemische Totalsynthese von Tilimycin konnten wir die über die Biosynthese gemachten Vorhersagen belegen. Die Produktion von zwei zytotoxischen Pyrrolobenzodiazepinen mit unterschiedlichen Funktionen durch Klebsiella oxytoca hat Implikationen für das Verständnis von Darmkrankheiten.
Biosynthesis of the Enterotoxic Pyrrolobenzodiazepine Natural Product Tilivalline
Authors: Dornisch Elisabeth , Pletz Jakob , Glabonjat Ronald A. , Martin Florian , Lembacher‐Fadum Christian , Neger Margit , Högenauer Christoph , Francesconi Kevin , Kroutil Wolfgang , Zangger Klaus , Breinbauer Rolf , Zechner Ellen L.
Published: October 2017

The nonribosomal enterotoxin tilivalline was the first naturally occurring pyrrolobenzodiazepine to be linked to disease in the human intestine. Since the producing organism Klebsiella oxytoca is part of the intestinal microbiota and the pyrrolobenzodiazepine causes the pathogenesis of colitis it is important to understand the biosynthesis and regulation of tilivalline activity. Here we report the biosynthesis of tilivalline and show that this nonribosomal peptide assembly pathway initially generates tilimycin, a simple pyrrolobenzodiazepine with cytotoxic properties. Tilivalline results from the non‐enzymatic spontaneous reaction of tilimycin with biogenetically generated indole. Through a chemical total synthesis of tilimycin we could corroborate the predictions made about the biosynthesis. Production of two cytotoxic pyrrolobenzodiazepines with distinct functionalities by human gut resident Klebsiella oxytoca has important implications for intestinal disease.
New organotin supramolecular complexes based on copper cyanide and auxiliary N‐donor ligands as potent inhibitors of cancer cell lines: In vitro and antioxidant experiments
Authors: Etaiw Safaa Eldin H. , Abdou Safaa N.
Published: October 2017

The new synthesized supramolecular complexes (SC); [Cu2(CN)4(Et3Sn)2(tbpe)], 1 and [Cu2(CN)3(Et3Sn)(bpe)], 2 (tbpe = trans‐1,2‐bis(4‐pyridyl)ethene and bpe = 1,2‐bis(4‐pyridyl)ethane), were characterized by elemental analyses, electrical conductance, spectroscopic studies and thermal analyses. UV–Vis spectra and magnetic moment data suggested the tetrahedral geometry around Cu(I) atoms. The structures of the SC 1 and 2 were also theoretically studied using molecular mechanics (MM+). The structures were minimized with a semi‐empirical (PM3) method. The organotin compounds represent significant advances in the clinical management of some cancer cell lines. 1 and 2 were tested as inhibitors and their citotoxicities showed potent growth inhibitory activity for hepatocellular carcinoma HePG‐2, mammary gland breast cancer MCF‐7, human prostate cancer PC3 and Colorectal carcinoma HCT‐116 cell lines. The tested compounds showed high inhibitory anti‐oxidant activity either using erythrocyte hemolysis or ABTS method.
Thermodynamics and kinetics control of support layer synthesis for enhanced thin film composite membrane performance
Authors: Beh J. J. , Ng E. P. , Sum J. Y. , Ooi B. S.
Published: October 2017

The desalination performance of a thin film composite (TFC) membrane hinges highly on the surface characteristics of support membrane. In this study, good wettability, regular pore size, and moderate roughness were identified as the critical surface properties of support membrane in forming a defect‐free, uniform, and structurally stable polyamide film. These features were tailored by adjusting the thermodynamics and kinetics properties of the polymer solution via polysulfone (PSf)/polyvinylpyrrolidone (PVP) ratio as well as using N,N‐dimethylacetamide (DMAc) and N,N‐dimethylformamide as co‐solvent. It was found that the membrane formation was controlled kinetically by altering the PSf/PVP ratio but thermodynamically by using co‐solvent. The TFC membrane with better desalination performance was achieved with the support membrane prepared at PSf/PVP ratio of 0.941 without any co‐solvent. The resulting TFC membrane attained the highest permeability ratio of 0.691 bar−1 for water/NaCl filtration in this study. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45802.
Simultaneous determination and pharmacokinetic study of three flavonoid glycosides in rat plasma by LC–MS/MS after oral administration of Rubus chingii Hu extract
Authors: Zan Tao , Piao Li , Wei Yuntao , Gu Yue , Liu Baohua , Jiang Daqing
Published: October 2017

A simple and sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of isoquercitrin, kaempferol‐3‐O‐rutinoside and tiliroside in rat plasma. Plasma samples were deproteinized with methanol and separated on a Hypersil Gold C18 column (2.1 × 50 mm, i.d., 3.0 μm) using gradient elution with the mobile phase of water and methanol at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed with negative ion electrospray ionization in selected reaction monitoring mode. All analytes showed good linearity over their investigated concentration ranges (r2 > 0.99). The lower limit of quantification was 1.0 ng/mL for isoquercitrin and 2.0 ng/mL for kaempferol‐3‐O‐rutinoside and tiliroside, respectively. Intra‐ and inter‐day precisions were <8.2% and accuracy ranged from −11.5 to 9.7%. The mean extraction recoveries of analytes and IS from rat plasma were >80.4%. The assay was successfully applied to investigate the pharmacokinetic study of the three ingredients after oral administration of Rubus chingii Hu to rats.
Quantification and application of a liquid chromatography–tandem mass spectrometric method for the determination of WKYMVm peptide in rat using solid‐phase extraction
Authors: Lee Byeong ill , Park Min‐Ho , Heo Soon Chul , Park Yuri , Shin Seok‐Ho , Byeon Jin‐Ju , Kim Jae Ho , Shin Young G.
Published: October 2017

A liquid chromatographic–electrospray ionization–time‐of‐flight/mass spectrometric (LC‐ESI‐TOF/MS) method was developed and applied for the determination of WKYMVm peptide in rat plasma to support preclinical pharmacokinetics studies. The method consisted of micro‐elution solid‐phase extraction (SPE) for sample preparation and LC‐ESI‐TOF/MS in the positive ion mode for analysis. Phenanthroline (10 mg/mL) was added to rat blood immediately for plasma preparation followed by addition of trace amount of 2 m hydrogen chloride to plasma before SPE for stability of WKYMVm peptide. Then sample preparation using micro‐elution SPE was performed with verapamil as an internal standard. A quadratic regression (weighted 1/concentration2), with the equation y = ax2 + bx + c was used to fit calibration curves over the concentration range of 3.02–2200 ng/mL for WKYMVm peptide. The quantification run met the acceptance criteria of ±25% accuracy and precision values. For quality control samples at 15, 165 and 1820 ng/mL from the quantification experiment, the within‐run and the between‐run accuracy ranged from 92.5 to 123.4% with precision values ≤15.1% for WKYMVm peptide from the nominal values. This novel LC‐ESI‐TOF/MS method was successfully applied to evaluate the pharmacokinetics of WKYMVm peptide in rat plasma.
The prognostic significance of incomplete revascularization and untreated coronary anatomy following percutaneous coronary intervention: An analysis of 6,755 patients with multivessel disease
Authors: Iqbal M. Bilal , Smith Robert D. , Lane Rebecca , Patel Niket , Mattar Wala , Kabir Tito , Panoulas Vasileios , Mason Mark , Dalby Miles C. , Grocott‐Mason Richard , Ilsley Charles D. ,   on behalf of the Harefield Cardiac Outcomes Group Investigators
Published: September 2017

Background

More than half of the patients undergoing percutaneous coronary intervention (PCI) have multivessel disease. Whether complete revascularization impacts long‐term mortality or whether selected patients or those with specific coronary anatomy benefit from complete revascularization is unclear.

Methods

A total of 14,452 patients underwent PCI between 2004 and 2015 at Harefield Hospital, UK. Of these, 7,076 patients had multivessel disease. We excluded 321 patients with left main‐stem stenosis ≥50%, with 6,755 patients included in the analysis (936 patients had complete revascularization).

Results

The unadjusted 3‐year mortality rates were lower with complete revascularization (10.8% vs 13.1%, P = 0.047). However, multivariable‐adjusted analyses indicated that complete revascularization was not independently associated with mortality (HR = 1.01, 95% CI: 0.78–1.31, P = 0.939). These findings were unchanged when addressing measured confounding using propensity‐matched analyses (HR = 1.16, 95% CI: 0.81–1.65, P = 0.417) and inverse probability treatment weighted analyses (HR = 1.01, 95% CI: 0.77–1.33, P = 0.950); and unmeasured confounding using instrumental variable analyses (Δ = 0.9%, 95% CI: −2.5%, 4.3%, P = 0.958). There was no association with mortality and untreated LAD disease (HR = 0.92, 95% CI: 0.72–1.17, P = 0.482) and LCx disease (HR = 0.90, 95% CI: 0.74–1.10, P = 0.999). However, untreated proximal LAD disease (HR = 1.23, 95% CI: 1.06–1.51, P = 0.045) and RCA disease (HR = 1.36, 95% CI: 1.08–1.65, P = 0.007) was associated with increased mortality, particularly in patients with ST‐elevation acute coronary syndrome (STEACS).

Conclusions

In this study of unselected patients undergoing PCI, complete revascularization did not confer a mortality benefit. However, the presence of untreated proximal LAD and RCA disease was prognostic in patients with STEACS. Thus, complete revascularization may be considered in select patient groups with anatomical subsets of coronary disease.
Catalytic N−H Bond Activation and Breaking by a Well‐Defined CoII1O4 Site of a Heterogeneous Catalyst
Authors: Khivantsev Konstantin , Biancardi Alessandro , Fathizadeh Mahdi , Almalki Fahad , Grant Job L. , Tien Huynh Ngoc , Shakouri Abolfazl , Blom Douglas A. , Makris Thomas M. , Regalbuto John R. , Caricato Marco , Yu Miao
Published: October 2017

Catalytic N−H bond activation and breaking by well‐defined molecular complexes or their heterogeneous analogues is considered to be a challenge in chemical science. Metal(0) nanoparticles catalytically decompose NH3; they are, however, ill defined and contain a range of contiguous metal sites with varying coordination numbers and catalytic properties. So far, no well‐defined/molecular Mn+‐containing materials have been demonstrated to break strong N−H bonds catalytically, especially in NH3, the molecule with the strongest N−H bonds. Recently, noncatalytic activation of NH3 with the liberation of molecular H2 on an organometallic molybdenum complex was demonstrated. Herein, we show the catalytic activation and breaking of N−H bonds on a singly dispersed, well‐defined, and highly thermally resistant (even under reducing environments) CoII1O4 site of a heterogeneous catalyst for organic (ethylamine) and inorganic (NH3, with the formation of N2 and H2) molecules. The single‐site material serves as a viable precursor to ultrasmall (2.7 nm and less) silica‐supported cobalt nanoparticles; thus, we directly compare the activity of isolated cationic cobalt sites with small cobalt nanoparticles. Density functional theory (DFT) calculations suggest a unique mechanism involving breaking of the N−H bonds in NH3 and N−N coupling steps taking place on a Co1O4 site with the formation of N2H4, which then decomposes to H2 and N2H2; N2H2 subsequently decomposes to H2 and N2. In contrast, Co1N4 sites are not catalytically active, which implies that the ligand environment around a single atom of a heterogeneous catalyst largely controls reactivity. This may open a new chapter for the design of well‐defined heterogeneous materials for N−H bond‐activation reactions.
Rhodococcus erythropolis Oleate Hydratase: a New Member in the Oleate Hydratase Family Tree—Biochemical and Structural Studies
Authors: Lorenzen Jan , Driller Ronja , Waldow Ayk , Qoura Farah , Loll Bernhard , Brück Thomas
Published: October 2017

Recently, the enzyme family of oleate hydratases (OHs: EC 4.2.1.53) has gained increasing scientific and economic interest, as these FAD‐binding bacterial enzymes do not require cofactor recycling and possess high thermal and pH stability. Their products, hydroxy fatty acids, are used in specialty chemical applications including surfactant and lubricant formulations. The “oleate hydratase engineering database”, established by Schmid et al. (2017), divides all OHs into 11 families (HFam1 to 11). To date, only two crystal structures of homodimeric OHs from the families HFam2 and HFam11 have been reported. In this study, we biophysically characterized an OH belonging to the HFam3 family, originating from the marine bacterium Rhodococcus erythropolis, for the first time. The crystal structure revealed that this new OH (OhyRe) surprisingly is a monomer in its active form. This particular feature provides new avenues for enzyme engineering and recycling through immobilization.
Development of a Dynamic Process Model for the Mechanical Fluid Separation in Decanter Centrifuges
Authors: Gleiss Marco , Hammerich Simon , Kespe Michael , Nirschl Hermann
Published: October 2017

A dynamic process model for the simulation of the separation process in countercurrent decanter centrifuges is presented. The numerical approach uses an interconnection of compartments to characterize the residence time distribution of the particles within the centrifuge. First, the theoretical basis of the numerical approach is described. Compared to the state‐of‐the‐art modeling of decanter centrifuges, the proposed approach allows the simulation of the temporal filling process. The short computing time results in further advantages of the dynamic process model. The so‐called real‐time simulation is an opportunity for a model‐based control of the separation process. An exemplary simulation with the product limestone demonstrates the main features of the numerical approach.
Sensing site‐specific structural characteristics and chirality using vibrational circular dichroism of isotope labeled peptides
Authors: Keiderling Timothy A.
Published: October 2017

Isotope labeling has a long history in chemistry as a tool for probing structure, offering enhanced sensitivity, or enabling site selection with a wide range of spectroscopic tools. Chirality sensitive methods such as electronic circular dichroism are global structural tools and have intrinsically low resolution. Consequently, they are generally insensitive to modifications to enhance site selectivity. The use of isotope labeling to modify vibrational spectra with unique resolvable frequency shifts can provide useful site‐specific sensitivity, and these methods have been recently more widely expanded in biopolymer studies. While the spectral shifts resulting from changes in isotopic mass can provide resolution of modes from specific parts of the molecule and can allow detection of local change in structure with perturbation, these shifts alone do not directly indicate structure or chirality. With vibrational circular dichroism (VCD), the shifted bands and their resultant sign patterns can be used to indicate local conformations in labeled biopolymers, particularly if multiple labels are used and if their coupling is theoretically modeled. This mini‐review discusses selected examples of the use of labeling specific amides in peptides to develop local structural insight with VCD spectra.
Fast liquid chromatography for racemic atenolol acetate separation—The analytical protocol
Authors: Agustian Joni , Kamaruddin Azlina Harun , Aboul‐Enein Hassan Y.
Published: September 2017

Kinetic resolution of (R,S)‐atenolol is a faster strategy to produce (S)‐atenolol. Since this racemate is a less soluble compound, resolution of its ester offers high concentrations in the process. A good analytical method is required to observe the enantiomer concentrations. This paper described application of ultra‐fast liquid chromatography on the atenolol ester separation using different resolution media and analytical procedures. Chiralcel OD column resolved the ester. The chromatograms indicated different characteristics of the process. The enantiomers could be recognized by the column in less than 1 (one) hour. Symmetrical peaks were obtained, but several procedures produced peaks with wide bases and slanted baselines. Efficient enantioresolution was obtained at high mobile phase flow rate, decreased concentration of amine‐type modifier, but increased alcohol content in the mobile phase. High UV detection wavelength was required. At 1.0 mL/min, the (90/10/0.5) composition resulted α = 1.46 and RS = 0.9998 that were good separation.
Early detection versus primary prevention in the PLCO flexible sigmoidoscopy screening trial: Which has the greatest impact on mortality?
Authors: Doroudi Maryam , Schoen Robert E. , Pinsky Paul F.
Published: October 2017

BACKGROUND

Screening for colorectal cancer (CRC) with flexible sigmoidoscopy (FS) has been shown to reduce CRC mortality. The current study examined whether the observed mortality reduction was due primarily to the prevention of incident CRC via removal of adenomatous polyps or to the early detection of cancer and improved survival.

METHODS

The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial randomized 154,900 men and women aged 55 to 74 years. Individuals underwent FS screening at baseline and at 3 or 5 years versus usual care. CRC‐specific survival was analyzed using Kaplan‐Meier curves and proportional hazards modeling. The authors estimated the percentage of CRC deaths averted by early detection versus primary prevention using a model that applied intervention arm survival rates to CRC cases in the usual‐care arm and vice versa.

RESULTS

A total of 1008 cases of CRC in the intervention arm and 1291 cases of CRC in the usual‐care arm were observed. Through 13 years of follow‐up, there was no significant difference noted between the trial arms with regard to CRC‐specific survival for all CRC (68% in the intervention arm vs 65% in the usual‐care arm; P =.16) or proximal CRC (68% vs 62%, respectively; P = .11) cases; however, survival in distal CRC cases was found to be higher in the intervention arm compared with the usual‐care arm (77% vs 66%; P<.0001). Within each arm, symptom‐detected cases had significantly worse survival compared with screen‐detected cases. Overall, approximately 29% to 35% of averted CRC deaths were estimated to be due to early detection and 65% to 71% were estimated to be due to primary prevention.

CONCLUSIONS

CRC‐specific survival was similar across arms in the PLCO trial, suggesting a limited role for early detection in preventing CRC deaths. Modeling suggested that approximately two‐thirds of avoided deaths were due to primary prevention. Future CRC screening guidelines should emphasize primary prevention via the identification and removal of precursor lesions. Cancer 2017;123:4815‐22. © 2017 American Cancer Society.
First‐in‐human trial of the PI3Kβ‐selective inhibitor SAR260301 in patients with advanced solid tumors
Authors: Bédard Philippe L. , Davies Michael A. , Kopetz Scott , Juric Dejan , Shapiro Geoffrey I. , Luke Jason J. , Spreafico Anna , Wu Bin , Castell Christelle , Gomez Corinne , Cartot‐Cotton Sylvaine , Mazuir Florent , Dubar Michel , Micallef Sandrine , Demers Brigitte , Flaherty Keith T.
Published: October 2017

BACKGROUND

Phosphoinositide 3‐kinase (PI3K) β is the dominant isoform for PI3K activity in many phosphatase and tensin homolog (PTEN)‐deficient tumor models. This was a first‐in‐human study to determine the maximum tolerated dose, safety, pharmacokinetics (PK), pharmacodynamics, and preliminary activity of SAR260301, a potent PI3Kβ‐selective inhibitor (clinicaltrials.gov identifier NCT01673737).

METHODS

Successive cohorts of patients with advanced solid tumors received increasing doses of oral SAR260301 according to a Bayesian escalation with an overdose‐control process based on the occurrence of dose‐limiting toxicity in the first 28‐day cycle. Adverse events, tumor response, PK, and the effect of food on PK were evaluated. Target engagement was assessed in platelets. Physiologically‐based PK modeling was used for exposure predictions.

RESULTS

Twenty‐one patients received treatment at doses ranging from 100 mg once daily to 440 mg/m2 twice daily. Dose‐limiting toxicities included 1 episode of grade 3 pneumonitis (400 mg twice daily) and 1 grade 3 γ‐glutamyltransferase increase (600 mg twice daily). The maximum tolerated dose was not reached. The most frequently occurring treatment‐related adverse events were nausea, vomiting, and diarrhea (14% each). Pharmacologically active concentrations were reached, but SAR260301 was rapidly cleared, and exposures associated with antitumor activity in preclinical models were not maintained at the highest dose tested. Food further decreased SAR260301 exposure.

CONCLUSIONS

SAR260301 had an acceptable safety profile, but exposure sufficient to inhibit the PI3K pathway was unachievable because of rapid clearance, and clinical development was terminated. These results demonstrate the importance of PK and pharmacodynamic assessments in early drug development. Cancer 2018;124:315‐24. © 2017 American Cancer Society.
Adherence to tyrosine kinase inhibitors among Medicare Part D beneficiaries with chronic myeloid leukemia
Authors: Shen Chan , Zhao Bo , Liu Lei , Shih Ya‐Chen Tina
Published: October 2017

BACKGROUND

Tyrosine kinase inhibitors (TKIs) improve the survival of patients with chronic myeloid leukemia (CML) dramatically; however, nonadherence to TKI therapy may lead to resistance to the therapy. TKIs are very expensive and are covered under Part D insurance for Medicare patients. To the authors' knowledge, the impact of low‐income subsidy status and cost sharing on adherence among this group has not been well studied in the literature.

METHODS

Surveillance, Epidemiology, and End Results (SEER) registry data linked with Medicare Part D data from the years 2007 through 2012 were used in the current study. The authors identified 836 patients with CML with Medicare Part D insurance coverage who were new TKI users. Treatment nonadherence was defined as a binary variable indicating the percentage of days covered was <80% during the 180‐day period after the initiation of TKI therapy. Logistic regression was used to examine the relationship between out‐of‐pocket costs per 30‐day drug supply, Medicare Part D plan characteristics, and treatment adherence while controlling for other patient characteristics.

RESULTS

Overall, 244 of the 836 patients with CML (29%) were nonadherent to targeted oral therapy during the 180 days after the initiation of treatment with TKIs. The multivariable logistic regression demonstrated that patients with heavily subsidized (odds ratio, 6.7; 95% confidence interval, 2.8‐15.9) and moderately subsidized (odds ratio, 3.0; 95% confidence interval, 1.4‐6.5) Medicare Part D plans were much more likely to demonstrate nonadherence compared with patients without a subsidy.

CONCLUSIONS

The current population‐based study found a significantly higher rate of nonadherence among heavily subsidized patients with substantially lower out‐of‐pocket costs, which suggests that future research is needed to help lower the nonadherence rate among these individuals. Cancer 2018;124:364‐73. © 2017 American Cancer Society.
Treatment seeking for eating disorders: Results from a nationally representative study
Authors: Bohrer Brittany K. , Carroll Ian A. , Forbush Kelsie T. , Chen Po‐Yi
Published: September 2017

Objective

Eating disorders (EDs) are associated with substantial morbidity and mortality, yet up to 45% of individuals with EDs never receive treatment for their eating‐related problems. This study sought to identify whether comorbidity, suicidality, discrimination, family cohesion, employment status, income, sex, age, marital status, religious belongingness, and ED‐specific variables (body mass index and past‐year ED diagnoses) were associated with treatment seeking in a nationally representative sample of individuals with EDs (N = 595; 77.8% women; 72.4% ethnic minority).

Method

Structural equation modeling was used to identify significant predictors of treatment seeking.

Results

In the full sample, age was associated with a greater probability of treatment seeking, and men had a lower probability of seeking treatment. No variables were significant predictors of treatment seeking among individuals in Hispanic or Caucasian subgroups.

Discussion

To our knowledge, this was the largest study to characterize predictors of treatment seeking in adults with EDs. Results from this study were consistent with existing literature documenting age and sex differences in treatment seeking among adolescents with an ED. Findings suggest a need for improved ED education and outreach—including greater mental health/ED literacy and decreased stigmatization for patients, providers, and the general public—and additional persuasive public‐health messages to change community knowledge about treatment options for younger persons and men with EDs.
Environmental correlates of internal coloration in frogs vary throughout space and lineages
Authors: Franco‐Belussi Lilian , Provete Diogo Borges , De Oliveira Classius
Published: October 2017

Internal organs of ectotherms have melanin‐containing cells that confer different degrees of coloration to them. Previous experimental studies analyzed their developmental origin, role in immunity, and hormonal regulation. For example, melanin increases with ultraviolet radiation (UV) and temperature in frogs and fish. However, little is known about how environmental variables influence the amount of coloration on organs among amphibian species over a large spatial extent. Here, we tested how climatic variables (temperature, UV, and photoperiod) influence the coloration of internal organs of anurans. We recorded the level of melanin pigmentation using four categories on 12 internal organs and structures of 388 specimens from 43 species belonging to six anuran families. Then, we tested which climatic variables had the highest covariation with the pigmentation on each organ after controlling for spatial autocorrelation in climatic variables and phylogenetic signal in organ coloration using the extended version of the RLQ ordination. Coloration in all organs was correlated with the phylogeny. However, the coloration of different organs was affected by different variables. Specifically, the coloration of the heart, kidneys, and rectum of hylids, Rhinella schneideri, some Leptodactylus, and Proceratophrys strongly covaried with temperature and photoperiod, whereas that of the testicle, lumbar parietal peritoneum, lungs, and mesenterium of Leiuperinae, Hylodidae, Adenomera, and most Leptodactylus had highest covariation with UV‐B and temperature. Our results support the notion that melanin pigmentation on the surface of organs of amphibians has an adaptive function conferred by the protective functions of the pigment. But most importantly, internal melanin seems to respond differently to climatic variables depending on the lineage and locality in which species occur.
Syntopic frogs reveal different patterns of interaction with the landscape: A comparative landscape genetic study of Pelophylax nigromaculatus and Fejervarya limnocharis from central China
Authors: Garcia Vhon Oliver S. , Ivy Catherine , Fu Jinzhong
Published: October 2017

Amphibians are often considered excellent environmental indicator species. Natural and man‐made landscape features are known to form effective genetic barriers to amphibian populations; however, amphibians with different characteristics may have different species–landscape interaction patterns. We conducted a comparative landscape genetic analysis of two closely related syntopic frog species from central China, Pelophylax nigromaculatus (PN) and Fejervarya limnocharis (FL). These two species differ in several key life history traits; PN has a larger body size and larger clutch size, and reaches sexual maturity later than FL. Microsatellite DNA data were collected and analyzed using conventional (FST, isolation by distance (IBD), AMOVA) and recently developed (Bayesian assignment test, isolation by resistance) landscape genetic methods. As predicted, a higher level of population structure in FL (FST′ = 0.401) than in PN (FST′ = 0.354) was detected, in addition to FL displaying strong IBD patterns (r = .861) unlike PN (r = .073). A general north–south break in FL populations was detected, consistent with the IBD pattern, while PN exhibited clustering of northern‐ and southern‐most populations, suggestive of altered dispersal patterns. Species‐specific resistant landscape features were also identified, with roads and land cover the main cause of resistance to FL, and elevation the main influence on PN. These different species–landscape interactions can be explained mostly by their life history traits, revealing that closely related and ecologically similar species have different responses to the same landscape features. Comparative landscape genetic studies are important in detecting such differences and refining generalizations about amphibians in monitoring environmental changes.
T cell receptor alpha variable 12‐2 bias in the immunodominant response to Yellow fever virus
Authors: Bovay Amandine , Zoete Vincent , Dolton Garry , Bulek Anna M. , Cole David K. , Rizkallah Pierre J. , Fuller Anna , Beck Konrad , Michielin Olivier , Speiser Daniel E. , Sewell Andrew K. , Fuertes Marraco Silvia A.
Published: October 2017

The repertoire of human αβ T‐cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen‐specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA‐A*0201‐restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8+ T cell response to the highly effective YF‐17D vaccine. We discover that these A2/LLW‐specific CD8+ T cells are highly biased for the TCR α chain TRAV12‐2. This bias is already present in A2/LLW‐specific naïve T cells before vaccination with YF‐17D. Using CD8+ T cell clones, we show that TRAV12‐2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline‐encoded complementarity determining region (CDR) 1α loop of TRAV12‐2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T‐cell responses specific for the A2/LLW epitope.
An experimental study of a damage‐controllable plastic‐hinge‐supported wall structure
Authors: Wang Xiaoting , Wang Tao , Qu Zhe
Published: October 2017

The reinforced concrete (RC) shear wall serves as one of the most important components sustaining lateral seismic forces. Although they allow advanced seismic performance to be achieved, RC shear walls are rather difficult to repair once the physical plastic hinge at the bottom part has been formed. To overcome this, a damage‐controllable plastic hinge with a large energy dissipation capacity is developed herein, in which the sectional forces are decoupled and sustained separately by different components. The components sustaining the axial and the shear forces all remain elastic even under a rarely occurred earthquake, while the bending components yield and dissipate seismic energy during a design‐level earthquake. This design makes the behavior of the system more predictable and thus more easily customizable to different performance demands. Moreover, the energy dissipation components can be conveniently replaced to fully restore the occupancy function of a building. To examine the seismic behavior of the newly developed component, 3 one third‐scale specimens were tested quasi‐statically, including 1 RC wall complying with the current design codes of China and 2 installed with the damage‐controllable plastic hinges. Each wall was designed to have the same strength. The experimental results demonstrated that the plastic‐hinge‐supported walls had a better energy dissipation capacity and damage controllability than the RC specimen. Both achieved drift ratios greater than 3% under a steadily increasing lateral force.
Application of natural deep eutectic solvents for the “green”extraction of vanillin from vanilla pods
Authors: González Cecilia Guízar , Mustafa Natali Rianika , Wilson Erica Georgina , Verpoorte Robert , Choi Young Hae
Published: October 2017

In recent years, a new type of solvents, natural deep eutectic solvents (NADES), have been developed and are gaining popularity as an alternative “green solvent” to conventional organic solvents. The traditional extraction of flavor or fragrance from plant materials such as vanillin is a tedious procedure that involves the use of organic solvents. In this case the solubility of vanillin and its extractability from vanilla pods in 14 NADES was evaluated. The solubility in some NADES such as lactic acid: propanediol (620 mg/mL) and lactic acid: fructose (320 mg/mL) was found to be almost similar to that of organic solvents e.g. methanol (632.94 mg/mL) or ethanol (375.81 mg/mL). Interestingly, the extractability of vanillin from vanilla pods did not reflect the results observed for the solubility tests. Some NADES with constituents that are suitable as food ingredients such as citric acid‐fructose‐glucose (CAFG), fructose‐glucose (FG), malic acid‐glucose (MAG), and malic acid‐fructose‐glucose (MAFG), showed a higher extraction power (7.6, 10.1, 16.7, and 16.3 mg/g DW, respectively) than ethanol (4.4 mg/g DW). The discrepancy between solubility and extractability might be due to differences in the interaction with the matrix depending on the NADES. The effect of water content in some NADES on the extractability of vanillin was also studied. With the high extraction capacity and the absence of toxicity of their components, NADES are very suitable for extraction of flavours and fragrances used in food and cosmetics.