bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA-damaging molecules and its impact on DNA repair activity
Authors: Leonova Elina , Rostoka Evita , Sauvaigo Sylvie , Baumane Larisa , Selga Turs , Sjakste Nikolajs 
Published: April 2018

Background1,4-dihydropyridines (1,4-DHP) possesses important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. It was shown that the antimutagenic 1,4-dihydropyridine AV-153-Na interacts with DNA. The aim of the current study was to test the capability of the compound to scavenge peroxynitrite and hydroxyl radical, to test intracellular distribution of the compound, and to assess the ability of the compound to modify the activity of DNA repair enzymes and to protect the DNA in living cells against peroxynitrite-induced damage.MethodsPeroxynitrite decomposition was assayed by UV spectroscopy, hydroxyl radical scavenging—by EPR spectroscopy. DNA breakage was determined by the “comet method”, activity of DNA repair enzymes—using Glyco-SPOT and ExSy-SPOT assays. Intracellular distribution of the compound was studied by laser confocal scanning fluorescence microscopy. Fluorescence spectroscopy titration and circular dichroism spectroscopy were used to study interactions of the compound with human serum albumin.ResultsSome ability to scavenge hydroxyl radical by AV-153-Na was detected by the EPR method, but it turned out to be incapable of reacting chemically with peroxynitrite. However, AV-153-Na effectively decreased DNA damage produced by peroxynitrite in cultured HeLa cells. The Glyco-SPOT test essentially revealed an inhibition by AV-153-Na of the enzymes involved thymine glycol repair. Results with ExSy-SPOT chip indicate that AV-153-Na significantly stimulates excision/synthesis repair of 8-oxoguanine (8-oxoG), abasic sites (AP sites) and alkylated bases. Laser confocal scanning fluorescence microscopy demonstrated that within the cells AV-153-Na was found mostly in the cytoplasm; however, a stain in nucleolus was also detected. Binding to cytoplasmic structures might occur due to high affinity of the compound to proteins revealed by spectroscopical methods.DiscussionActivation of DNA repair enzymes after binding to DNA appears to be the basis for the antimutagenic effects of AV-153-Na.
1‐Ethoxy‐2‐propanol [MAK Value Documentation in German language, 2018]
Authors: Hartwig A. ,   MAK Commission
Published: April 2018

Abstract

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated the maximum concentration at the work place (MAK value), the Pregnancy Risk Group and absorption through the skin of 1‐ethoxy‐2‐propanol [
1569‐02‐4
].

1‐Ethoxy‐2‐propanol is irritating to the eyes of rabbits and can damage the cornea. The critical systemic effects are pale foci in the lung and increased urine volume in rats after 13 weeks inhalation. The NAEC of these effects is estimated at 250 ml/m
3
, which results in a decreased MAK value of 20 ml/m
3
(86 mg/m
3
). This value also protects against possible irritation, as local effects are not observed up to 2000 ml/m
3
in the 13‐week rat inhalation study.

Since the critical effect of 1‐ethoxy‐2‐propanol is systemic, Peak Limitation Category II is retained. There is no specific toxicokinetic data available, so that the default excursion factor of 2 is confirmed.
New data on reproduction toxicity with 1‐ethoxy‐2‐propanol are not available. 1‐Ethoxy‐2‐propanol remains assigned to Pregnancy Risk Group C.
Skin contact is expected to contribute significantly to systemic toxicity and 1‐ethoxy‐2‐propanol remains designated with “H”.
Methylarsenic compounds [MAK Value Documentation, 2014]
Authors: Hartwig A. ,   MAK Commission
Published: April 2018

AbstractThe German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated methylarsenic compounds considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.Methylarsenic compounds are the carcinogenic metabolites of arsenic and its inorganic compounds, which are proven human carcinogens. Methylated arsenic compounds are able to interfere with all important cellular processes. In mice and rats, dimethylarsinic acid was clearly carcinogenic. Trimethylarsine oxide caused liver adenomas in F344 rats and with methylarsenic acid, preneoplastic liver effects were found. If all aspects are considered, methylarsenic compounds are classified in Carcinogen Category 1. Methylarsenic compounds are genotoxic in vitro and in vivo. As they are bioavailable and can reach the germ cells, they are classified in Category 3 A for Germ Cell Mutagens. Methylarsenic compounds are genotoxic carcinogens, for which no safe systemic exposure can be estimated. It must be assumed that even small amounts absorbed percutaneously increase the carcinogenic risk. Therefore, methylarsenic compounds are designated with an “H” (for substances that can be absorbed through the skin in toxicologically relevant amounts). Dimethylarsinic acid induced developmental toxicity in rats. Apart from a well‐documented case report, there are no clear findings available to conclude a skin‐sensitizing potential in humans.
Extension Study of PF‐05280586, a Potential Rituximab Biosimilar, Versus Rituximab in Subjects With Active Rheumatoid Arthritis
Authors: Cohen Stanley B. , Burgos‐Vargas Rubén , Emery Paul , Jin Bo , Cronenberger Carol , Vázquez‐Abad María‐Dolores 
Published: April 2018

ObjectiveThis extension study provided continued treatment to subjects with active rheumatoid arthritis who had participated for ≥16 weeks in a pharmacokinetic similarity study of PF‐05280586 (potential rituximab biosimilar). Objectives were to evaluate overall pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of PF‐05280586 after transition from rituximab reference products to PF‐05280586, and follow‐up of biomarker and efficacy assessments.MethodsSubjects were offered ≤3 additional courses of treatment of PF‐05280586, with or without a single transition from rituximab in Europe (rituximab‐EU; MabThera) or the US (rituximab‐US; Rituxan) to PF‐05280586. Each course comprised 2 intravenous infusions (1,000 mg on days 1 and 15, separated by 24 weeks [± 8 weeks]).ResultsOf 220 subjects in the parent study, 185 were randomized and included in this study. There were no notable differences in drug concentrations between groups or across courses, with little variation in depletion of CD19+ B cells between groups, and no apparent relationship between infusion‐related reactions and antidrug antibodies with or without single transition from rituximab reference products to PF‐05280586. Long‐term safety and tolerability of PF‐05280586 was acceptable in all groups for up to 96 weeks, with a low incidence of treatment‐emergent adverse events independent of single drug transition. The percentage of subjects with a low disease activity score and disease activity score remission was similar across groups for all time points, and responses were sustained until end of study.ConclusionThis study demonstrated acceptable safety, tolerability, and immunogenicity, with or without single transition from rituximab reference products to PF‐05280586, without increased immunogenicity on single transition.
All‐Cause and Cause‐Specific Mortality in Patients With Granulomatosis With Polyangiitis: A Population‐Based Study
Authors: Tan Ju Ann , Choi Hyon K. , Xie Hui , Sayre Eric C. , Esdaile John M. , Aviña‐Zubieta J. Antonio 
Published: April 2018

ObjectiveTo investigate all‐cause and cause‐specific mortality in patients with newly diagnosed granulomatosis with polyangiitis (GPA) between 2 calendar time periods, 1997–2004 and 2005–2012.MethodsUsing an administrative health database, we compared all patients with incident GPA with non‐GPA controls matched for sex, age, and time of entry into the study. The study cohorts were divided into 2 subgroups based on the year of diagnosis (“early cohort [1997–2004] and “late cohort” [2005–2012]). The outcome was death (all‐cause, cardiovascular disease [CVD]–related cancer‐related, renal disease–related, and infection‐related) during the follow‐up period. Hazard ratios (HR) were estimated using Cox proportional hazards models, first adjusted for age, sex, and time of entry and then adjusted for selected covariates based on a purposeful selection algorithm.ResultsThree hundred seventy patients with GPA and 3,700 non‐GPA controls were included in this study, contributing 1,624.8 and 1,8671.3 person‐years of follow‐up, respectively. Sixty‐eight deaths occurred in the GPA cohort, and 310 deaths occurred in the non‐GPA cohort. Overall, the age‐, sex‐, and entry time–adjusted all‐cause mortality HR in the GPA cohort was 3.12 (95% confidence interval CI 2.35–4.14). There was excess mortality due to CVD‐related causes, but not cancer, in the GPA cohort. Reports of death due to infection or renal disease was not permitted, because the numbers of death were insufficient (<6 deaths for each outcome). All‐cause mortality significantly improved between the early cohort and late cohort time periods (HR 5.61 and 2.33, respectively; P for interaction = 0.017).ConclusionThis population‐based study showed increased all‐cause and CVD‐related mortality risks in patients with GPA. There was significant improvement in the all‐cause mortality risk over time, but the risk remained increased compared with that in the general population.
One‐pot Syntheses of 3‐Amino‐2‐pyrones and 3‐Amino‐5,6‐dihydro‐2‐pyridones from β,γ‐Unsaturated α‐Iminoesters: Application to the Synthesis of A Tricyclic Pyranoindole
Authors: Nakahama Kenta , Suzuki Misato , Ozako Mami , Mizota Isao , Shimizu Makoto 
Published: April 2018

AbstractAs the α‐imino ester has an ester moiety adjacent to the imino group, it is known as a highly reactive imine, and the reaction with a nucleophile leads to the umpolung N‐addition reaction predominantly by subjecting it to appropriate reaction conditions, while the general C‐addition reaction is suppressed. Utilizing N‐addition makes it possible the synthesis of α‐amino acids incorporating various kinds of nucleophiles on the nitrogen atom. Herein, an efficient method for the one‐pot synthesis of 3‐amino‐2‐pyrones utilizing tandem N‐alkylation/vinylogous aldol reaction/cyclization of β,γ‐unsaturated α‐iminoester was described, and it was found that BF3⋅OEt2 promoted the elimination of an alkylthio group to give 2‐pyrones in good yields. The synthesis of 3‐amino‐5,6‐dihydro‐2‐pyridones was also developed using a vinylogous Mannich‐type reaction in good yields. These reactions exhibit broad generality for electrophiles and Grignard reagents. Further functionalization to the tricyclic pyranoindole derivative was achieved in 4 steps by using this tandem reaction as a key step.
Biosynthese und heterologe Expression der Vioprolide: rationale gentechnische Eingriffe in die Biosynthese und 4‐Methylazetidincarbonsäure‐Bildung
Authors: Yan Fu , Auerbach David , Chai Yi , Keller Lena , Tu Qiang , Hüttel Stephan , Glemser Amelie , Grab Hanusch A. , Bach Thorsten , Zhang Youming , Müller Rolf 
Published: April 2018

AbstractDie Vioprolide sind eine vielversprechende Klasse von Leitverbindungen gegen Krebserkrankungen und Pilzinfektionen, die vom Myxobakterium Cystobacter violaceus Cb vi35 produziert werden. Bislang weiß man nichts über ihre Biosynthese, einschließlich des Ursprungs der ungewöhnlichen 4‐Methylazetidincarbonsäure (MAZ). Hier wird der Biosynthese‐Gencluster der Vioprolide beschrieben und die Produktionsproblematik durch Expression in drei heterologen Wirten gelöst. Ausgehend von der instabilen Produktion im einstelligen mg/L‐Maßstab im Wildtyp wurde ein stabiler Wirtstamm entwickelt, der in Fermentern Ausbeuten von bis zu einem halben Gramm pro Liter erzielt. Gen‐Inaktivierungen in Verbindung mit Isotopen‐Fütterungsstudien identifizierten ein S‐Adenosylmethionin(SAM)‐abhängiges Enzym und eine Methyltransferase, die für die Bildung des MAZ‐Bausteins über einen bei Bakterien bisher unbekannten Mechanismus verantwortlich sind. Darüber hinaus wurden nichtnatürliche Vioprolid‐Derivate durch den Einsatz rationaler Genmanipulationen erzeugt.
A Hybrid Co Quaterpyridine Complex/Carbon Nanotube Catalytic Material for CO2 Reduction in Water
Authors: Wang Min , Chen Lingjing , Lau Tai‐Chu , Robert Marc 
Published: April 2018

AbstractAssociating a metal‐based catalyst to a carbon‐based nanomaterial is a promising approach for the production of solar fuels from CO2. Upon appending a CoII quaterpyridine complex [Co(qpy)]2+ at the surface of multi‐walled carbon nanotubes, CO2 conversion into CO was realized in water at pH 7.3 with 100 % catalytic selectivity and 100 % Faradaic efficiency, at low catalyst loading and reduced overpotential. A current density of 0.94 mA cm−2 was reached at −0.35 V vs. RHE (240 mV overpotential), and 9.3 mA cm−2 could be sustained for hours at only 340 mV overpotential with excellent catalyst stability (89 095 catalytic cycles in 4.5 h), while 19.9 mA cm−2 was met at 440 mV overpotential. Such a hybrid material combines the high selectivity of a homogeneous molecular catalyst to the robustness of a heterogeneous material. Catalytic performances compare well with those of noble‐metal‐based nano‐electrocatalysts and atomically dispersed metal atoms in carbon matrices.
Modeling the Evolution of Crosslinked and Extractable Material in an Oil‐Based Paint Model System
Authors: Oakley Lindsay H. , Casadio Francesca , Shull Professor Kenneth R. , Broadbelt Professor Linda J. 
Published: April 2018

AbstractThe construction of mechanistic models for the autoxidation of fatty acid or ester substrates found in oil paint binders is a challenging undertaking due to the complexity of the large crosslinked species that form, and the small molecules that volatilize. Building models that capture this product diversity are made possible by automating the process of network generation. This work presents a microkinetic model for the autoxidation of ethyl linoleate catalyzed by cobalt(II) 2‐ethyl hexanoate. The mechanism size was controlled by using a rate‐based criterion to include the most kinetically relevant reactions from among the millions of possible reactions generated. The resulting model was solved and compared to experimental metrics. Quantities such as hexanal production and the consumption of unsaturated moieties were in good agreement with experiment. Finally, the model was used to explore the effect of the catalyst concentration and temperature on key measurables.
Transformation of Sugars into Chiral Polyols over a Heterogeneous Catalyst
Authors: Tamura Masazumi , Yuasa Naoto , Cao Ji , Nakagawa Yoshinao , Tomishige Keiichi 
Published: April 2018

AbstractTransformation of sugars, while maintaining the intrinsic stereochemical structure, is desirable. However, such a transformation requires multistep synthesis with protection and deprotection of the OH groups. Herein, a new method for selective transformation of sugar derivatives into chiral building blocks and a diol synthon, with retention of the intrinsic configuration (stereo‐ and regioselectively), is demonstrated. The method is based on the selective recognition of cis‐vicinal OH groups in sugars and leads to the one‐pot removal of the cis‐vicinal OH groups, without protection of OH groups (except the OH group of the hemiacetal group), over a heterogeneous CeO2‐supported ReOx and Pd (ReOx‐Pd/CeO2) catalyst by using H2 as a reducing agent.
Influence of aminergic and peptidergic substances on heart beat frequency in the stick insect Carausius morosus (Insecta, Phasmatodea)
Authors: Marco Heather G. , Katali Ottilie K. H. , Gäde Gerd 
Published: April 2018

AbstractThe dorsal heart of the Indian stick insect, Carausius morosus, is responsible for the anterograde flow of hemolymph to the aorta and into the body cavity. The contraction frequency of the insect heart is known to be influenced by several substances of neural source. Here, a semi‐exposed heart assay was employed to study the effect of an aminergic substance (octopamine) and three neuropeptides (C. morosus hypertrehalosemic hormone [Carmo‐HrTH], crustacean cardioactive peptide [CCAP], and proctolin) on heart contraction. The contraction frequency was measured as beats per minute in adults ligated between the head and the prothorax. All three investigated neuropeptides had a stimulatory effect on heart contraction that lasted approximately 6 min, after which the normal heart beat rate was restored. Proctolin and CCAP stimulated the rate of heart beat also in unligated stick insects, whereas Carmo‐HrTH was active only in ligated insects. The latter could suggest that when the stick insect is not ligated, a competing substance may be released from the head of C. morosus; the competing substance is, apparently, not physiologically active but it binds or blocks access to the receptor of Carmo‐HrTH‐II, thereby rendering the HrTH peptide “not active.” In ligated stick insects, 6.7 × 10−8 M Carmo‐HrTH‐II significantly increased the heart beat rate; higher doses resulted in no further increase, suggesting the saturation of the HrTH receptor. Octopamine inhibited the rate at which the heart contracted in a dose‐dependent manner; inhibition was achieved with 10−4 M of octopamine.
Plug‐In Hybrid Vehicle and Second‐Life Applications of Lithium‐Ion Batteries at Elevated Temperature
Authors: Vaidya Rutvik , Selvan Vishnu , Badami Pavan , Knoop Kathy , Kannan Arunachala M. 
Published: April 2018

AbstractIn improving fuel economy and reducing carbon footprint, hybrid, plug‐in hybrid and all‐electric vehicles are considered as sustainable modes of transportation in the automotive industry. Here, commercial Li‐ion cells (26650 and 18650 with lithium iron phosphate (LFP) and nickel manganese cobalt (NMC) cathodes) were subjected to simulated plug‐in hybrid electric vehicle (PHEV) conditions, using the Federal Urban Driving Schedule (FUDS) under charge‐depleting mode at elevated temperature (50 °C and <10 % RH). The capacity degradation (16 % over 800 cycles) under the PHEV test protocol for Li‐ion batteries with 26650 NMC cathodes was twice of that using LFP cathodes (8 % over 800 cycles) under identical conditions. The Li‐ion batteries were also subjected to second‐life charge–discharge cycling at C/5 rate after evaluating them under the PHEV protocol (800 cycles for 26650 cells and 1200 cycles for 18650 cells). In addition, the high‐frequency resistance measured by electrochemical impedance spectroscopy was found to increase significantly with cycling for both the NMC‐ as well as LFP‐based batteries, leading to power fading. XRD analysis of the 18650 LFP‐based battery showed change of phase from LiFePO4 to FePO4, indicating Li+‐ion loss. However, the cathode active materials of the Li‐ion cells (26650 with LFP and NMC cathodes), examined using XRD, showed no significant phase change in the materials after 800 PHEV cycles and around 200 second‐life charge–discharge cycles.
A New Rechargeable Seawater Desalination Battery System
Authors: Zhang Yanjun , Senthilkumar Sirugaloor Thangavel , Park Jeongsun , Park Jehee , Kim Youngsik 
Published: April 2018

AbstractThe exploitation and utilization of seawater resources has become a significant research topic nowadays. In this communication, we report a rechargeable desalination battery system for the first time. This design can integrate the electrochemical battery, seawater desalination, and acid‐alkali production in one system. The basic working principle of the designed system was illustrated, and further proved by the results of the experiments. Furthermore, future research directions and outlooks of this system are proposed. This conceptual work provides a promising technology for utilization of natural seawater resources.
Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases
Authors: Margonis G A , Sasaki K , Gholami S , Kim Y , Andreatos N , Rezaee N , Deshwar A , Buettner S , Allen P J , Kingham T P , Pawlik T M , He J , Cameron J L , Jarnagin W R , Wolfgang C L , D'Angelica M I , Weiss M J 
Published: April 2018

Abstract

Background
This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS.

Methods
A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predictors of overall survival (OS) that can be assessed before operation; these factors were combined into the Genetic And Morphological Evaluation (GAME) score. The score was compared with the current standard (Fong score) and validated in an external cohort of patients from the Memorial Sloan Kettering Cancer Center (MSKCC).

Results
Six preoperative predictors of worse OS were identified on multivariable Cox regression analysis in the JHH cohort (502 patients). The GAME score was calculated by allocating points to each patient according to the presence of these predictive factors: KRAS-mutated tumours (1 point); carcinoembryonic antigen level 20 ng/ml or more (1 point), primary tumour lymph node metastasis (1 point); Tumour Burden Score between 3 and 8 (1 point) or 9 and over (2 points); and extrahepatic disease (2 points). The high-risk group in the JHH cohort (GAME score at least 4 points) had a 5-year OS rate of 11 per cent, compared with 73·4 per cent for those in the low-risk group (score 0–1 point). Importantly, in cohorts from both the JHH and MSKCC (747 patients), the discriminatory capacity of the GAME score was superior to that of the Fong score, as demonstrated by the C-index and the Akaike information criterion.

Conclusion
The GAME score is a preoperative prognostic tool that can be used to inform treatment selection.
PBL in the teaching of computer networks: The role of LMS PBL‐Maestro in the management and authenticity of the learning environment
Authors: de Oliveira Felipe Soares , Santos Simone C. dos 
Published: April 2018

ABSTRACTThe area of Computer Networks requires an educational model based on real market practices that can provide students with consistent technological training. However, it should be noted that a Network Project is subject to a wide range of restrictions (such as time constraints, budgeting, and the use of other necessary resources) which means there is a need to work with real cases and in the presence of a client. The purpose of this paper is to describe the effects of the application of PBL‐Maestro in the area of Network Design. PBL‐Maestro consists of a LMS (Learning Management System) that has been designed to underpin a methodological workflow for implementing PBL (Problem‐Based Learning) in the teaching of Computing, called xPBL, which provides support for Authentic Assessment. By taking xPBL as a benchmark, the course management can be carried out by following the dynamics of the cycle and stages. The topics was taught in an entirely ̈hands‐on̈ format with the use of real equipment installed inside the classroom, and it included situations and problems arising from real circumstances. Clients took part in the whole process and took on the responsibility of making requests, monitoring, guiding, and evaluating the development of the problem solution, together with the teacher. In addition, the fact that they were immersed in a practical environment and could make use of the devices employed in companies enabled them to solve problems when requested, with more facility and assertiveness. Semi‐structured interviews were conducted with the users who used the LMS.