bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, anticancer activity, and molecular modeling of etodolac‐thioether derivatives as potent methionine aminopeptidase (type II) inhibitors
Authors: Çoruh Işıl , Çevik Özge , Yelekçi Kemal , Djikic Teodora , Küçükgüzel Ş. Güniz 
Published: March 2018

AbstractA series of (R,S)‐1‐{[5‐(substituted)sulfanyl‐4‐substituted‐4H‐1,2,4‐triazole‐3‐yl]methyl}‐1,8‐diethyl‐1,3,4,9‐tetrahydropyrano[3,4‐b]indoles (5a–v) were designed and synthesized using a five‐step synthetic protocol that involves substituted benzyl chlorides and (R,S)‐5‐[(1,8‐diethyl‐1,3,4,9‐tetrahydropyrano[3,4‐b]indole‐1‐yl)methyl]‐4‐substituted‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones in the final step. The synthesized derivatives were evaluated for cytotoxicity and anticancer activity in vitro using the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) colorimetric method against VERO, HEPG2 (human hepatocellular liver carcinoma), SKOV3 (ovarian carcinoma), MCF7 (human breast adenocarcinoma), PC3 and DU145 (prostate carcinoma) cells at 10−5 M (10 μM) for 24 h. Compounds 5d and 5h showed the best biological potency against the SKOV3 cancer cell line (IC50 = 7.22 and 5.10 μM, respectively) and did not display cytotoxicity toward VERO cells compared to etodolac. Compounds 5k, 5s, and 5v showed the most potent biological activity against the PC3 cancer cell line (IC50 = 8.18, 3.10, and 4.00 μM, respectively) and did not display cytotoxicity. Moreover, these compounds were evaluated for caspase‐3, ‐9, and ‐8 protein expression and activation in the apoptosis pathway for 6, 12, and 24 h, which play a key role in the treatment of cancer. In this study, we also investigated the apoptotic mechanism and molecular modeling of compounds 5k and 5v on the methionine aminopeptidase (type II) enzyme active site in order to get insights into the binding mode and energy.
Sustained Response Following Discontinuation of Methotrexate in Patients With Rheumatoid Arthritis Treated With Subcutaneous Tocilizumab
Authors: Kremer Joel M. , Rigby William , Singer Nora G. , Birchwood Christine , Gill Darcy , Reiss William , Pei Jinglan , Michalska Margaret 
Published: March 2018

ObjectiveTo evaluate whether tocilizumab (TCZ) monotherapy is noninferior to treatment with TCZ plus methotrexate (MTX) for maintaining clinical responses in patients with rheumatoid arthritis (RA) in whom low disease activity is achieved with TCZ plus MTX.MethodsPatients with RA who experienced an inadequate response to MTX received MTX plus TCZ 162 mg subcutaneously. At 24 weeks, patients who achieved a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) of ≤3.2 were randomized to receive TCZ monotherapy or to continue treatment with TCZ plus MTX until week 52. The primary outcome measure was the comparison of the mean change in the DAS28‐ESR from week 24 to week 40 between the TCZ monotherapy and TCZ plus MTX arms (noninferiority margin of 0.6). Secondary outcome measures included worsening of the DAS28‐ESR by ≥1.2, achievement of a DAS28‐ESR of <2.6 and ≤3.2, and safety and immunogenicity.ResultsAmong the 718 patients enrolled, 296 were randomized at week 24 to receive TCZ monotherapy (n = 147) or TCZ plus MTX (n = 147). The mean changes in the DAS28‐ESR from week 24 to week 40 were 0.46 and 0.14 in the TCZ monotherapy arm and the TCZ plus MTX arm, respectively (weighted difference between the groups, 0.318 [95% confidence interval 0.045, 0.592]); discontinuing MTX in TCZ responders was noninferior to continuing MTX. Safety events were broadly similar between the randomized treatment groups; the most common serious adverse event was infection, which occurred in 2.1% of patients in the TCZ monotherapy group and 2.2% of patients receiving TCZ plus MTX.ConclusionPatients with RA receiving TCZ plus MTX who achieve low disease activity can discontinue MTX without significant worsening of disease activity during the 16 weeks following MTX discontinuation.
Rituximab May Cause Increased Hepatitis C Virus Viremia in Rheumatoid Arthritis Patients Through Declining Exosomal MicroRNA‐155
Authors: Liao Tsai‐Ling , Hsieh Shie‐Liang , Chen Yi‐Ming , Chen Hsin‐Hua , Liu Hung‐Jen , Lee Hsiu‐Chin , Chen Der‐Yuan 
Published: March 2018

ObjectiveSeveral studies have shown that rituximab may enhance hepatitis C virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the host immune response in HCV infection; miRNAs can be packaged into the exosomes and then shuttled by the exosomes to aid biologic functions. However, the role of exosomal miRNAs (exo‐miRNAs) in rituximab‐related HCV activity enhancement remains unclear.MethodsThe association between rituximab and increased HCV activity was examined using an in vitro cell‐based assay. Purified exosomes were confirmed using immunoblotting and flow cytometry and quantified using enzyme‐linked immunosorbent assay. Exosomal miRNA‐155 (exo‐miR‐155) levels were measured using quantitative reverse transcription–polymerase chain reaction.ResultsIn vitro data showed that B cell–derived miR‐155 could inhibit HCV replication in hepatocytes through exosome transmission. Rituximab could both induce B cell depletion and affect intracellular miR‐155 production as well as exo‐miR‐155 transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum exosome levels were increased in rheumatoid arthritis (RA) patients with HCV infection compared with the levels in RA patients without HCV infection (P < 0.01). The exo‐miR‐155 levels were significantly increased in RA patients with HCV infection compared with those without infection (P < 0.01). A significantly greater decrement of exo‐miR‐155 expression was observed after rituximab therapy compared with those observed before therapy (P < 0.01), and hepatitis C viral loads increased simultaneously (P < 0.05).ConclusionCirculating exo‐miR‐155 levels were negatively correlated with hepatitis C viral loads and subsequently associated with rituximab‐related HCV activity enhancement in RA patients. Exo‐miR‐155 may become a potential diagnostic biomarker or therapeutic target.
Selenadiazole Derivatives Inhibit Angiogenesis‐Mediated Human Breast Tumor Growth by Suppressing the VEGFR2‐Mediated ERK and AKT Signaling Pathways
Authors: Lai Haoqiang , Fu Xiaoyan , Sang Chengcheng , Hou Liyuan , Feng Pengju , Li Xiaoling , Chen Tianfeng 
Published: March 2018

AbstractSelenadiazole derivatives (SeDs) have been found to show promise in chemo‐/radiotherapy applications by activating various downstream signaling pathways. However, the functional role of SeDs on angiogenesis, which is pivotal for tumor progression and metastasis, has not yet been elucidated. In the present study, we have examined the antiangiogenic activities of SeDs and elucidated their underlying mechanisms. The results showed that the as‐synthesized SeDs not only enhanced their anticancer activities against several human cancer cells but also showed more potent inhibition on human umbilical vein endothelial cells (HUVECs). The in vitro results suggested that SeDs, especially 1 a, dose‐dependently inhibited the vascular endothelial growth factor (VEGF)‐induced cell migration, invasion, and capillary‐like structure formation of HUVECs. Compound 1 a also significantly suppressed VEGF‐induced angiogenesis in a Matrigel plug assay as part of a C57/BL6 mice assay by means of down regulation of VEGF. Furthermore, we found that 1 a significantly inhibited MCF‐7 human breast tumor growth in nude mice without severe systematic cytotoxicity. Compound 1 a was more effective in inhibiting cell proliferation and induced a much more pronounced apoptosis effect in endothelial cells than MCF‐7 cells, which implies that endothelial cells might be the primary target of 1 a. Further mechanistic studies on tumor growth inhibition effects and neovessel formation suppression demonstrated that 1 a inhibited cell viability of MCF‐7 and HUVECs by induction of cell apoptosis, accompanied by poly(adenosine diphosphate ribose)polymerase (PARP) cleavage and caspase activation. Additionally, the 1 a‐induced antiangiogenesis effect was achieved by abolishing the VEGF‐VEGFR2‐ERK/AKT (ERK=extracellular signal–regulated kinases; AKT=protein kinease B) signal axis and enhanced the apoptosis effect by triggering reactive oxygen species (ROS)‐mediated DNA damage. Taken together, these results clearly demonstrate the antiangiogenic potency of SeDs and the underlying molecular mechanisms.
Redox‐Driven Symmetry Change for Terbium(III) Bis(porphyrinato) Double‐Decker Complexes by the Azimuthal Rotation of the Porphyrin Macrocycles
Authors: Yamashita Ken‐ichi , Yamanaka Takayo , Sakata Naoya , Ogawa Takuji 
Published: March 2018

AbstractMolecular structures for three oxidation forms (anion, radical, and cation) of terbium(III) bis(porphyrinato) double‐decker complexes have been systematically studied. We found that the redox state controls the azimuthal rotation angle (φ) between the two porphyrin macrocycles. For [TbIII(tpp)2]n (tpp: tetraphenylporphyrinato, n=−1, 0, and +1), φ decreases at each stage of the oxidation process. The decrease in φ is due to the higher steric repulsion between the phenyl rings on the porphyrin macrocycle and the β hydrogen atoms on the other porphyrin macrocycle, which results from the shorter interfacial distance between the two porphyrin macrocycles. Conversely, φ=45° for both [TbIII(oep)2]−1 and [TbIII(oep)2]0 (oep: octaethylporphyrinato), but φ=36° for [TbIII(oep)2]+1. Theoretical calculations suggest that the smaller azimuthal rotation angle of the cation form is due to the electronic interaction in the doubly oxidized ligand system.
Symbolic Geometric Modelling of Tree‐Structure Robotic Mechanisms Using Lie Groups and Graph Theory
Authors: Escalera Juan A. , Abu‐Dakka Fares J. , Abderrahim Mohamed 
Published: March 2018

AbstractThe present work describes a symbolic formulation based on Lie groups and graph theory to obtain the dynamic equations of tree‐structure robotic mechanisms (TRM)s. The resulting equation is the equivalent geometric form of the classical Newton‐Euler's equation of motion. Such formulation is valid for any TRM without closed kinematic chains and whose joints have one degree of freedom (revolute and/or prismatic). For instance, open chain manipulator, robotic hands or humanoids are included within TRM. The structure of the proposed formulation allows analytic differentiation, which is required for techniques such as optimal control or robust control. Moreover, the assembly parameters are explicitly held in matrices, so that they can be mathematically manipulated in order to be adapted for simulation, analysis or identification algorithms. Finally, the formulation is applied to a 7DOF manipulator and to a two arm torso of 16 degrees of freedom. The results are compared with the multi‐body simulation software package MSC/ADAMS© proving the correctness of the formulation.
Synchronization and Tracking Control for Dual‐motor Driving Servo Systems with Friction Compensation
Authors: Zhao Wei , Ren Xuemei , Li Linwei 
Published: March 2018

AbstractA nonsingular fast terminal sliding mode (NFTSM) controller is designed by incorporating the variable gain neural network (NN) observer, which is utilized to guarantee motor speed synchronization and load position tracking of dual‐motor driving servo systems. By designing the variable gain NN observer, the states and uncertain nonlinearities of servo systems are estimated with fast convergence rate and small steady‐state error, where the effects from external disturbance are suppressed as well. Based on the estimated states, the cross‐coupling synchronization strategy and NFTSM tracking scheme are designed to achieve the rapid speed synchronization and precise load tracking, where the NNs are introduced to approximate and compensate friction nonlinearities. In particular, a novel nonlinear synchronization factor characterizing the degree of speed synchronization is proposed to achieve switching between synchronization control and tracking control, which is proven to deal with the coupling problem of synchronization and tracking. Finally, the comparative simulations and experiments are included to verify the reliability and effectiveness.
Gemcitabine induces apoptosis and autophagy via the AMPK/mTOR signaling pathway in pancreatic cancer cells
Authors: Zhu Jinhui , Chen Yan , Ji Yun , Yu Yuanquan , Jin Yun , Zhang Xiaoxiao , Zhou Jiale 
Published: March 2018

AbstractGemcitabine (GEM)‐based chemotherapy is a commonly used treatment for pancreatic cancer. However, acquired drug resistance, a major problem in pancreatic cancer treatment, causes a reduction in the survival rate of patients with cancer. In this study, we attempted to reveal the molecular mechanism of GEM resistance. Our data showed that GEM treatment inhibits cell growth, induces apoptosis, and activates autophagy via the AMP‐activated protein kinase (AMPK) pathway. The combination of GEM treatment and AMPK knockdown resulted in a dramatic increase of apoptosis and inhibition of autophagy. Additionally, inhibition of mammalian target of Rapamycin induced autophagy. Our findings show the potential therapeutic implications of the combined treatment with GEM and AMPK inhibitors for pancreatic cancer.
Mischungsstabilität fließfähiger Betone
Authors: Begemann Christoph , Cotardo Dario , Lohaus Ludger 
Published: March 2018

AbstractInsbesondere unter schwierigen Verarbeitungsbedingungen ist es erforderlich, weiche bis fließfähige Betone einzusetzen. Mit zunehmender Fließfähigkeit der Betone geht allerdings gleichzeitig ein erhöhtes Risiko der Entmischung einher. Insbesondere unter dem Einfluss einer Verdichtung gewinnt die Mischungsstabilität als maßgebliche Frischbetoneigenschaft an Bedeutung. Sie ist im Entwurf neben der hohen Fließfähigkeit gleichbedeutend zu berücksichtigen. Im Gegensatz zu selbstverdichtenden Betonen (SVB) existieren jedoch für fließfähige Rüttelbetone weder Modelle noch Strategien zur Beschreibung und Sicherstellung der Mischungsstabilität. Es sind noch nicht einmal geeignete Prüfverfahren etabliert, die zur Beurteilung der Mischungsstabilität im Labor und auf der Baustelle herangezogen werden könnten. Der vorliegende Beitrag beschreibt zunächst Konzepte, wie Mischungsstabilität im Entwurf berücksichtigt werden kann. Dabei wird zum einen auf die Anteile der granularen Partikel (Gesteinskörnung), der fließfähigen Komponente (Bindemittelleim), ihre jeweiligen Eigenschaften sowie deren gegenseitige Beeinflussung bei Rütteleinwirkung eingegangen. Zum anderen werden weiterentwickelte Prüfmethoden zur Beurteilung der Mischungsstabilität (insbesondere die Sedimentationsstabilität) näher beschrieben.
Postfolate spina bifida lesion level change
Authors: Eldridge Carin , Bandlamuri Sruti , Andrews Jennifer G. , Galindo Maureen Kelly , Contreras Dianna , Flood Timothy J. , Rice Sydney 
Published: March 2018

BackgroundSpina bifida accounts for a large proportion of birth defects in the United States. Studies have evaluated the decrease in prevalence at birth after folate fortification of food grains, but little is known about neurologic functional changes related to fortification. This study assesses the functional level of lesions in the prefortification and postfortification eras.MethodsData were collected through retrospective review of medical records from a regional multispecialty clinic in Arizona. This study included individuals born between 1981–1995 (prefortification) and 1999–2013 (postfortification). Patients were included if they had a primary diagnosis of spina bifida with or without hydrocephalus.ResultsThere was a significant difference in functional lesion level with an 85% reduction in thoracic level lesions in the postfortification era (p < .005). There were no differences in gender or ethnicity across eras; however, Hispanic ethnicity had a higher number of cases overall (51.7%). The most common lesion level in both eras was mid‐lumbar, accounting for 35.7 and 34.4% of cases in the prefolate and postfolate eras, respectively.ConclusionsThis study demonstrates a significant difference in the distribution of lesion level of spina bifida patients born in the postfortification era, based on neurologic function. Further research with a larger sample size is needed to determine if this observation holds true nationally.
Abdichten von Fugen in Beton mit Fugenbändern – die neue Anwendungsnorm DIN 18197
Authors: Hohmann Rainer 
Published: March 2018

AbstractMit der DIN 18197 „Abdichten von Fugen in Beton mit Fugenbändern“ wird dem Planer sowie dem Bauausführenden ein Regelwerk zur Verfügung gestellt, in dem neben relevanten Hinweisen für die Planung und Handhabung von Fugenbändern auch Auswahldiagramme zu finden sind, mit denen der Planer in Abhängigkeit von der Beanspruchung auf einfache Art Fugenbänder auswählen kann. Dieser Beitrag geht auf die wesentlichen, die Fugenabdichtung mit Fugenbändern betreffenden Regeln ein und zeigt an ausgewählten Beispielen, wie der Planer das auf seine Belastungen abgestimmte Fugenband mithilfe der Auswahldiagramme der DIN 18197 auswählen kann. Den Bauausführenden wird ausführlich erläutert, was beim Umgang mit Fugenbändern auf der Baustelle zu beachten ist.
Improvement of mimetic peroxidase activity of gold nanoclusters on the luminol chemiluminescence reaction by surface modification with ethanediamine
Authors: Han Lu , Li Ying , Fan Aiping 
Published: March 2018

AbstractPeroxidase is a commonly used catalyst in luminol–H2O2 chemiluminescence (CL) reactions. Natural peroxidase has a sophisticated separation process, short shelf life and unstable activity, therefore it is important to develop peroxidases that have both high catalytic activity and good stability as alternatives to the natural enzyme. Gold nanoclusters (Au NCs) are an alternative peroxidase with catalytic activity in the luminol–H2O2 CL reaction. In the present study, ethanediamine was modified on the surface of Au NCs forming cationic Au NCs. The zeta potential of the cationic Au NCs maintained its positive charge when the pH of the solution was between 4 and 9. The cationic Au NCs showed higher catalytic activity in the luminol–H2O2 CL reaction than did unmodified Au NCs. A mechanism study showed that the better performance of cationic Au NCs may be attributed to the generation of 1O2 on the surface of cationic Au NCs and a positive surface charge, for better affinity to luminol. Cationic Au NC, acting as a peroxidase mimic, has much better stability than horseradish peroxidase over a wide range of temperatures. We believe that cationic Au NCs may be useful as an artificial peroxidase for a wide range of potential applications in CL and bioanalysis.
Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide‐cofactor specificity for increasing l‐lysine production
Authors: Xu Jian‐Zhong , Yang Han‐Kun , Liu Li‐Ming , Wang Ying‐Yu , Zhang Wei‐Guo 
Published: March 2018

Abstractl‐lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l‐lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H‐dependent enzyme, shows a variance in nucleotide‐cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide‐cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L−1), carbon yield (from 0.35 to 0.44 g [g glucose]−1) and productivity (from 2.07 to 2.93 g L−1 hr−1) of l‐lysine in JL‐6 ΔdapB::Ec‐dapBC115G,G116C in fed‐batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero‐expression of NADH‐dependent EcDHDPR increased l‐lysine production. Subsequently, we rationally modified the conserved structure of cofactor‐binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide‐cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l‐lysine production were investigated. The highest increase (26.2%) in l‐lysine production was observed for JL‐6 ΔdapB::Ec‐dapBC115G,G116C, followed by JL‐6 Cg‐dapBC37G,G38C (21.4%) and JL‐6 ΔdapB::Ec‐dapBC46G,G47C (15.2%). This is the first report of a rational modification of DHDPR that enhances the l‐lysine production and yield through the modulation of nucleotide‐cofactor specificity.
Direct solid‐state evidence of H2‐induced partial U(VI) reduction concomitant with adsorption by extracellular polymeric substances (EPS)
Authors: Li Ang , Zhou Chen , Liu Zhuolin , Xu Xiaoyin , Zhou Yun , Zhou Dandan , Tang Youneng , Ma Fang , Rittmann Bruce E. 
Published: March 2018

AbstractAdsorption of hexavalent uranium (U(VI)) by extracellular polymeric substances (EPS) has been studied, but the possibility of simultaneous U(VI) reduction mediated by EPS has not had experimental confirmation, as the reduction products have not yet been directly proven. Here, we reported the first direct evidence of lower‐valent products of U(VI) immobilization by loosely associated EPS (laEPS) isolated from a fermenter strain of Klebsiella sp. J1 when the laEPS was exposed to H2. During the 120‐min tests for similarly 86% adsorption under O2, N2, and H2, 8% more U was immobilized through a non‐adsorptive pathway by the EPS for H2 than for N2 and O2. A set of solid‐state characterization tools (FT‐IR, XPS, EELS, and TEM‐EDX) confirmed partial reduction of U(VI) to lower‐valence U, with the main reduced form being uraninite (UIVO2) nanoparticles, and the results reinforced the role of the reduction in accelerating U immobilization and shaping the characteristics of immobilized U in terms of valency, size, and crystallization. The laEPS, mostly comprised of carbohydrate and protein, contained non‐cytochrome enzymes and electron carriers that could be responsible for electron transfer to U(VI). Taken together, our results directly confirm that EPS was able to mediate partial U(VI) reduction in the presence of H2 through non‐cytochrome catalysis and that reduction enhanced overall U immobilization. Our study fills in some gaps of the microbe‐mediated U cycle and will be useful to understand and control U removal in engineered reactors and in‐situ bioremediation.
Parallel fabrication of macroporous scaffolds
Authors: Dobos Andrew , Grandhi Taraka Sai Pavan , Godeshala Sudhakar , Meldrum Deirdre R. , Rege Kaushal 
Published: March 2018

AbstractScaffolds generated from naturally occurring and synthetic polymers have been investigated in several applications because of their biocompatibility and tunable chemo‐mechanical properties. Existing methods for generation of 3D polymeric scaffolds typically cannot be parallelized, suffer from low throughputs, and do not allow for quick and easy removal of the fragile structures that are formed. Current molds used in hydrogel and scaffold fabrication using solvent casting and porogen leaching are often single‐use and do not facilitate 3D scaffold formation in parallel. Here, we describe a simple device and related approaches for the parallel fabrication of macroporous scaffolds. This approach was employed for the generation of macroporous and non‐macroporous materials in parallel, in higher throughput and allowed for easy retrieval of these 3D scaffolds once formed. In addition, macroporous scaffolds with interconnected as well as non‐interconnected pores were generated, and the versatility of this approach was employed for the generation of 3D scaffolds from diverse materials including an aminoglycoside‐derived cationic hydrogel (“Amikagel”), poly(lactic‐co‐glycolic acid) or PLGA, and collagen. Macroporous scaffolds generated using the device were investigated for plasmid DNA binding and cell loading, indicating the use of this approach for developing materials for different applications in biotechnology. Our results demonstrate that the device‐based approach is a simple technology for generating scaffolds in parallel, which can enhance the toolbox of current fabrication techniques.