bluuebunny/crossref_metadata_2025 huggingface dataset:
Doping and Switchable Photovoltaic Effect in Lead‐Free Perovskites Enabled by Metal Cation Transmutation
Authors: Harikesh Padinhare Cholakkal , Wu Bo , Ghosh Biplab , John Rohit Abraham , Lie Stener , Thirumal Krishnamoorthy , Wong Lydia Helena , Sum Tze Chien , Mhaisalkar Subodh , Mathews Nripan
Published: July 2018

Creating defect tolerant lead‐free halide perovskites is the major challenge for development of high‐performance photovoltaics with nontoxic absorbers. Few compounds of Sn, Sb, or Bi possess ns2 electronic configuration similar to lead, but their poor photovoltaic performances inspire us to evaluate other factors influencing defect tolerance properties. The effect of heavy metal cation (Bi) transmutation and ionic migration on the defects and carrier properties in a 2D layered perovskite (NH4)3(Sb(1−x)Bix)2I9 system is investigated. It is shown, for the first time, the possibility of engineering the carriers in halide perovskites via metal cation transmutation to successfully form intrinsic p‐ and n‐type materials. It is also shown that this material possesses a direct–indirect bandgap enabling high absorption coefficient, extended carrier lifetimes >100 ns, and low trap densities similar to lead halide perovskites. This study also demonstrates the possibility of electrical poling to induce switchable photovoltaic effect without additional electron and hole transport layers.
Discovery of a Highly Potent and Broadly Effective Epidermal Growth Factor Receptor and HER2 Exon 20 Insertion Mutant Inhibitor
Authors: Jang Jaebong , Son Jieun , Park Eunyoung , Kosaka Takayuki , Saxon Jamie A. , De Clercq Dries J. H. , Choi Hwan Geun , Tanizaki Junko , Eck Michael J. , Jänne Pasi A. , Gray Nathanael S.
Published: July 2018

Exon 20 insertion (Ex20Ins) mutations are the third most prevalent epidermal growth factor receptor (EGFR) activating mutation and the most prevalent HER2 mutation in non‐small cell lung cancer (NSCLC). Novel therapeutics for the patients with Ex20Ins mutations are urgently needed, due to their poor responses to the currently approved EGFR and HER2 inhibitors. Here we report the discovery of highly potent and broadly effective EGFR and HER2 Ex20Ins mutant inhibitors. The co‐crystal structure of compound 1 b in complex with wild type EGFR clearly revealed an additional hydrophobic interaction of 4‐fluorobenzene ring within a deep hydrophobic pocket, which has not been widely exploited in the development of EGFR and HER2 inhibitors. As compared with afatinib, compound 1 a exhibited superior inhibition of proliferation and signaling pathways in Ba/F3 cells harboring either EGFR or HER2 Ex20Ins mutations, and in the EGFR P772_H773insPNP patient‐derived lung cancer cell line DFCI127. Our study identifies promising strategies for development of EGFR and HER2 Ex20Ins mutant inhibitors.
Supramolekulare Schalter auf der Basis von Cucurbit[8]uril (CB[8])
Authors: Pazos Elena , Novo Paula , Peinador Carlos , Kaifer Angel E. , García Marcos D.
Published: July 2018

Der molekulare Wirt Cucurbit[8]uril kann in wässrigen Medien homo‐ und heteroternäre Komplexe mit molekularen Schaltern als Gastspezies bilden und gilt in der chemischen Literatur zunehmend als zuverlässiges System zum Erzeugen dynamischer chemischer Systeme. Durch Auswählen geeigneter Gastspezies kann das Redox‐, photochemische oder pH‐ausgelöste Verhalten von Mehrkomponentensystemen konditioniert werden, so dass supramolekulare Schalter auf CB[8]‐Basis vorhersehbar und modular entworfen werden können. Zudem können mit CB[8] durch sorgfältige Auswahl der Gastspezies dual/dreifach und linear/orthogonal stimuliabhängige Eigenschaften für diese molekularen Funktionseinheiten verwirklicht werden. Die vielseitigen Designmöglichkeiten verleihen diesen supramolekularen Schaltern ein enormes Potential für die rationale Entwicklung neuer Materialien, bei denen die Funktion nicht nur durch die maßgeschneiderte Ansprechbarkeit durch Reize bestimmt wird, sondern auch durch die vorübergehende Aggregation/Disaggregation homo‐ oder heteromerer Baueinheiten.
Solid‐Phase Thiol–Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist
Authors: Williams Elyse T. , Harris Paul W. R. , Jamaluddin Muhammad A. , Loomes Kerry M. , Hay Debbie L. , Brimble Margaret A.
Published: July 2018

We report a new method herein coined SP‐CLipPA (solid‐phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono‐S‐lipidated peptides. This technique utilizes thiol–ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin‐bound peptide. Advantages of SP‐CLipPA include: ease of handling, conversions of up to 91 %, by‐product removal by simple filtration, and a single purification step. Additionally, the desired lipidated products show high chromatographic separation from impurities, thus facilitating RP‐HPLC purification. To showcase the utility of SP‐CLipPA, we synthesized a potent calcitonin gene‐related peptide (CGRP) receptor antagonist peptide in excellent yield and purity. This peptide, selected from a series of lipidated analogues of CGRP8–37 and CGRP7–37, has potential for the treatment of migraine.
Fast Gas–Solid Reaction Kinetics of Nanoparticles Unveiled by Millisecond In Situ Electron Diffraction at Ambient Pressure
Authors: Yu Jian , Yuan Wentao , Yang Hangsheng , Xu Qiang , Wang Yong , Zhang Ze
Published: July 2018

Acquiring the kinetics of gas–nanoparticle fast reactions under ambient pressure is a challenge owing to the lack of appropriate in situ techniques. Now an approach has been developed that integrates time‐resolved in situ electron diffraction and an atmospheric gas cell system in transmission electron microscopy, allowing quantitative structural information to be obtained under ambient pressure with millisecond time resolution. The ultrafast oxidation kinetics of Ni nanoparticles in oxygen was vividly obtained. In contrast to the well‐accepted Wagner and Mott–Cabrera models (diffusion‐dominated), the oxidation of Ni nanoparticles is linear at the initial stage (<0.5 s), and follows the Avrami–Erofeev model (n=1.12) at the following stage, which indicates the oxidation of Ni nanoparticles is a nucleation and growth dominated process. This study gives new insights into Ni oxidation and paves the way to study the fast reaction kinetics of nanoparticles using ultrafast in situ techniques.
Aluminum toxicity related to SOD and expression of presenilin and CREB in Bombyx mori
Authors: Liu Longhai , Qian Xiaoran , Chao Mengling , Zhao Yijiao , Huang Junyi , Wang Taichu , Sun Fan , Ling Erjun , Song Hongsheng
Published: July 2018

Aluminum (Al) is an important environmental metal factor that can be potentially associated with pathological changes leading to neurotoxicity. The silkworm, Bombyx mori, is an important economic insect and has also been used as a model organism in various research areas. However, the toxicity of Al on silkworm physiology has not been reported. Here, we comprehensively investigate the toxic effects of Al on the silkworm, focusing on its effects on viability and development, superoxide dismutase (SOD) activity, and the expression of presenilin and cAMP response element‐binding protein (CREB) in BmE cells and silkworm larvae. BmE cell viability decreased after treatment with aluminum chloride (AlCl3) in both dose‐ and time‐dependent manners. When AlCl3 solution was injected into newly hatched fifth instar larvae, both larval weight gain and survival rate were significantly decreased in a manner correlating with AlCl3 dose and developmental stage. Furthermore, when BmE cells and silkworm larvae were exposed to AlCl3, SOD activity decreased significantly relative to the control group, whereas presenilin expression increased more than twofold. Additionally, CREB and phosphorylated CREB (p‐CREB) expression in the heads of fifth instar larvae decreased by 28.0% and 50.0%, respectively. These results indicate that Al inhibits the growth and development of silkworms in vitro and in vivo, altering SOD activity and the expressions of presenilin, CREB, and p‐CREB. Our data suggest that B. mori can serve as a model animal for studying Al‐induced neurotoxicity or neurodegeneration.
Pharmacokinetics and metabolic elimination of tolbutamide in female rats: Comparison with male rats
Authors: Fukuno Shuhei , Nagai Katsuhito , Horii Ayano , Yamamoto Kohei , Konishi Hiroki
Published: July 2018

As there are to be known gender differences in the expression profiles of rat hepatic CYP2C, we examined the pharmacokinetic behavior of tolbutamide (TB), a typical probe for CYP2C, and hepatic enzyme activities for metabolizing TB in female rats to compare with male rats. On the pharmacokinetic analysis of TB after intravenous administration to female rats, the elimination rate constant at the terminal phase (ke), total clearance (CLtot) and the apparent volume of distribution at steady‐state (Vdss) were significantly lower than in male rats. The binding rates of TB to serum protein were similar in male and female rats, indicating that the change in unbound TB concentration in serum is not associated with the difference in the pharmacokinetic disposition of TB. On metabolic examination using hepatic microsomes, the maximum reaction velocity (Vmax) of the metabolic conversion from TB to 4‐hydroxytolbutamide (4‐OH‐TB) in female rats was lower than that in male rats, although there was no significant difference in the Michaelis constant (Km) between genders. Consistent with this, the Vmax‐to‐Km ratio (Vmax/Km) was significantly lower in female rats than in male rats. Therefore, the low in vitro CYP2C‐dependent activity for hepatic TB removal in female rats provided a clear explanation for the lower in vivo elimination clearance of TB. Our findings strongly suggest that there is a gender difference in the metabolic capacity to eliminate drugs that serve as substrates of hepatic CYP2C enzymes in rats.
Smoothed quantile regression analysis of competing risks
Authors: Choi Sangbum , Kang Sangwook , Huang Xuelin
Published: July 2018

Censored quantile regression models, which offer great flexibility in assessing covariate effects on event times, have attracted considerable research interest. In this study, we consider flexible estimation and inference procedures for competing risks quantile regression, which not only provides meaningful interpretations by using cumulative incidence quantiles but also extends the conventional accelerated failure time model by relaxing some of the stringent model assumptions, such as global linearity and unconditional independence. Current method for censored quantile regressions often involves the minimization of the L1‐type convex function or solving the nonsmoothed estimating equations. This approach could lead to multiple roots in practical settings, particularly with multiple covariates. Moreover, variance estimation involves an unknown error distribution and most methods rely on computationally intensive resampling techniques such as bootstrapping. We consider the induced smoothing procedure for censored quantile regressions to the competing risks setting. The proposed procedure permits the fast and accurate computation of quantile regression parameter estimates and standard variances by using conventional numerical methods such as the Newton–Raphson algorithm. Numerical studies show that the proposed estimators perform well and the resulting inference is reliable in practical settings. The method is finally applied to data from a soft tissue sarcoma study.
A reliable LC‐MS/MS method for the quantification of N‐acetyl‐p‐benzoquinoneimine, acetaminophen glutathione and acetaminophen glucuronide in mouse plasma, liver and kidney: Method validation and application to a pharmacokinetic study
Authors: Zhang Xiqian , Li Ruina , Hu Wenya , Zeng Jin , Jiang Xuehua , Wang Ling
Published: July 2018

A rapid, specific, and sensitive liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method has been developed and validated to simultaneously quantify N‐acetyl‐p‐benzoquinoneimine (NAPQI), acetaminophen‐glutathione (acetaminophen‐glut) and acetaminophen‐glucuronide (acetaminophen‐gluc) in mouse plasma, liver and kidney homogenates. Analytes were eluted by a binary gradient mobile phase composed of water (phase A) and methanol containing 0.1% formic acid (phase B) at a flow rate of 0.3 mL/min, which was performed on a CAPCELL PAK C18 MG II column. It took 3.2 min to detect three analytes in a single run. Quantification was carried out in positive mode combined with multiple reaction monitoring. The validation of the LC‐MS/MS method consisted of specificity, linearity, precision, accuracy, protein precipitation recovery, matrix effect, dilution integrity and stability. The plasma and tissue homogenate calibration curves were linear over concentration ranges of 0.050–5.00, 0.050–5.00 and 0.100–40.0 μg/mL, with a lower limit of quantification of 0.050, 0.050, and 0.100 μg/mL for NAPQI, acetaminophen‐glut and acetaminophen‐gluc, respectively. The intra‐ and inter‐run precision values were within 12.47% for NAPQI, 12.11% for acetaminophen‐glut and 11.86% for acetaminophen‐gluc at their lower limit of quantitation levels. The samples were stable under all tested conditions. This method was successfully applied to study the pharmacokinetics of NAPQI, acetaminophen‐glut and acetaminophen‐gluc in ICR mice following oral administration of 200 mg/kg of acetaminophen suspension.
A sensitive and validated HPLC‐UV method for the quantitative determination of the new antifungal drug isavuconazole in human plasma
Authors: Nannetti Giulio , Pagni Silvana , Palù Giorgio , Loregian Arianna
Published: July 2018

Isavuconazole is a broad‐spectrum triazole antifungal drug recently approved for the therapy of both invasive aspergillosis and mucormycosis. To support a widespread therapeutic drug monitoring of isavuconazole, a simple, sensitive, and precise high‐performance liquid chromatography method with UV detection was developed and fully validated for the quantification of this drug in human plasma. The method involved a combined protein precipitation−solid‐phase extraction and a chromatographic separation on a Waters XTerra RP18 (150 × 4.6 mm, 3.5 μm) column using an isocratic mobile phase of ammonium acetate buffer (pH 8.0, 10 mm) and acetonitrile (45:55, v/v). The UV detection was performed at 285 nm. This method was linear (correlation coefficients ≥0.998), specific (no interference with plasma components or various potentially co‐administrated drugs), sensitive (lower limit of quantification of 0.025 μg/mL), reproducible (coefficients of variation were ≤7.9%) and accurate (deviations ranged from −5.0 to 8.0%) over the range of 0.025–10 μg/mL. The method fulfilled all of the US Food and Drug Administration guidelines validation criteria and performed well in an international proficiency testing program. The assay was also successfully applied to routine therapeutic drug monitoring of patients and to drug stability investigations under various conditions.
A computer aided educational tool for design, modeling, and performance analysis of Brushless DC motor in post graduate degree courses
Authors: Chasiotis Ioannis D. , Karnavas Yannis L.
Published: July 2018

The design of electrical machines is gaining more popularity in the last years especially in electrical engineering courses. However, commonly‐used teaching techniques seem to limit students' understanding and prevent the attainment of the learning objectives. The competence of this subject can be significantly improved when a practical approach based on the use of computer‐aided educational tools is followed. Thus, this paper proposes an effective and user‐friendly educational tool, which has been developed and successfully implemented in post‐graduate courses in order to facilitate the conception of brushless direct current (BLDC) machines design aspect. At first, a step‐by‐step design procedure is analytically described and then the main tool's characteristics and capabilities are also presented. Finally, its impact assessment has been conducted and the derived results revealed that its application could be extended to the design of various types of electrical motors and generators.
Coproduction of Ethyl Acetate and n‐Butyl Acetate by Using a Reactive Dividing‐Wall Column
Authors: Xie Jiangwei , Peng Fei , Li Chunli , Jiang Ting , Ma Shuaiming
Published: July 2018

The performance of the reactive distillation dividing‐wall column for coproduction of ethyl acetate and butyl acetate was experimentally studied. n‐Butanol and ethanol are raw reaction materials that react with acetic acid in the reaction zone to produce n‐butyl acetate and ethyl acetate, respectively. n‐Butyl acetate is not only a product, but also acts to remove water generated by the esterification reactions. The effects of various parameters, such as catalyst loading per stage, reflux ratio, liquid split and molar feed ratios, ethyl acetate/n‐butyl acetate purity, pressure drop, and total energy consumption, are investigated. Results show that ethanol could be completely converted and the products could be easily separated, which shows great industrial application potential in the coproduction of ethyl acetate and n‐butyl acetate.
Transition‐Metal‐Free N‐Arylation of Amines by Triarylsulfonium Triflates
Authors: Tian Ze‐Yu , Ming Xiao‐Xia , Teng Han‐Bing , Hu Yu‐Tian , Zhang Cheng‐Pan
Published: July 2018

A simple and efficient method for transition‐metal‐free N‐arylation of various amines by triarylsulfonium triflates is described. Both aliphatic and aromatic amines were smoothly converted at 80 °C in the presence of tBuOK or KOH to give the corresponding mono N‐arylated products in good to high yields. The molar ratios of the reactants and the choice of bases had a big effect on the reaction. When a large excess of [Ph3S][OTf] and tBuOK were employed for primary amines under the standard conditions, the bis(N‐phenyl) products were predominantly formed. This method was also applicable to the synthesis of bioactive N‐phenyl amino acid derivatives. The control experiments, the deuterium labelling study, and the presence of regioisomers of N‐arylated products when using 4‐substituted triarylsulfonium triflates suggested that the reaction might proceed through an aryne intermediate. The present protocol demonstrated that triarylsulfonium salts are versatile arylation reagents in the construction of CAr−N bonds.
Microporous Nanotubes and Nanospheres with Iron‐Catechol Sites: Efficient Lewis Acid Catalyst and Support for Ag Nanoparticles in CO2 Fixation Reaction
Authors: Modak Arindam , Bhanja Piyali , Bhaumik Asim
Published: July 2018

FeIII‐containing hyper‐crosslinked microporous nanotubes (FeNTs) and nanospheres (FeNSs) are synthesized through the reaction of catechol and dimethoxymethane in the presence of FeCl3 or CF3SO3H. Both FeNTs and FeNSs demonstrate excellent catalytic activity in Lewis acid catalysis (hydrolysis and regioselective methanolysis of styrene oxide) and tandem catalysis involving a sequential oxidation‐cyclization process, which selectively converts benzyl alcohol to 2‐phenyl benzimidazole. Apart from Lewis acidity, the FeNTs and FeNSs also showed CO2 uptake capacities of 2.6 and 2.2 mmol g−1, respectively, at a pressure of 1 atm and temperature of 273 K. Furthermore, Ag nanoparticles are immobilized successfully on the surfaces of FeNTs and FeNSs by the liquid‐phase impregnation method to prepare Ag@FeNT and Ag@FeNS nanocomposites, which show high catalytic activity for the selective fixation of CO2 to phenylacetylene to yield phenylpropiolic acid at 60 °C and 1 atm CO2 pressure. Hence, FeIII‐catechol‐containing hyper‐crosslinked nanotubes and nanospheres have huge potential not only as Lewis acid catalysts, but also as excellent supports for immobilizing Ag nanoparticles in the design of a robust catalyst for the carboxylation of terminal alkynes, which has wide scope in catalysis and environmental research.
Expeditious Preparation of Open‐Cage Fullerenes by Rhodium(I)‐Catalyzed [2+2+2] Cycloaddition of Diynes and C60: An Experimental and Theoretical Study
Authors: Artigas Albert , Pla‐Quintana Anna , Lledó Agustí , Roglans Anna , Solà Miquel
Published: July 2018

Invited for the cover of this issue is the group of Agustí Lledó, Anna Roglans and Miquel Solà at the Universitat de Girona. The image depicts Rh as the key to unlocking the fullerene cage. Read the full text of the article at 10.1002/chem.201802298.
Aerobic Oxidation/Annulation Cascades through Synergistic Catalysis of RuCl3 and N‐Heterocyclic Carbenes
Authors: Wang Qian , Chen Jiean , Huang Yong
Published: July 2018

Cooperative catalysis combining a transition metal with an N‐heterocyclic carbene is challenging due to strong binding of NHCs towards late transition metals. We report the first example of synergistic catalysis by a chiral NHC and a coordinatively unsaturated ruthenium compound. RuCl3 was found to mediate efficient aerobic oxidation of homoenolates generated from enals and the N‐heterocyclic carbene. The resulting α,β‐unsaturated acylazolium intermediate reacts selectively with 1,3‐dicarbonyl compounds or ketones at either the β‐ or γ‐carbon, yielding polysubstituted chiral lactones in high yield and with excellent enantioselectivity (up to 98 % yield, 94 % ee). This protocol can be applied to structurally sophisticated substrates.
Gender role strain, core schemas, and psychotic experiences in ethnically diverse women: A role for sex‐ and gender‐based analysis in psychosis research?
Authors: Haarmans Maria , McKenzie Kwame , Kidd Sean A. , Bentall Richard P.
Published: July 2018

Negative ‐self and ‐others core schemas have been implicated in the development and maintenance of psychotic experiences. One component of the self‐system is gender‐role strain (GRS; perceived discrepancy between actual self and gender‐role norms). Although the role of gender in the formation of core schemas has been underscored in social and developmental psychology literatures, GRS has not been investigated in relation to psychosis. We examined whether it might be associated with negative schemas and psychotic experiences in women consistent with the trend toward sex‐ and gender‐based analysis (SGBA) in health research. Forty‐four women with a schizophrenia spectrum disorder diagnosis and 48 female nonclinical participants completed a series of questionnaires measuring GRS, femininity ideology, core schemas, childhood trauma, and implicit femininity stereotypes (The Gender Stereotype Implicit Association Test). Half the total sample comprised women with minority‐ethnic status. Women in the psychosis group reported higher levels of GRS than comparison participants. Differences in endorsement of femininity ideology between the two groups narrowly missed significance with a trend toward greater femininity ideology in the psychosis group and significantly greater endorsement of the sexual purity domain for minority‐ethnic women. There was no difference in implicit femininity stereotypes. Analyses suggested that the relationship between GRS and symptoms was mediated by negative ‐self and ‐others schemas. Childhood sexual trauma, though higher for women with psychosis, was associated with gender‐role strain in the nonclinical sample only. Findings warrant further investigation with larger samples. SGBA has the potential to fill gaps in our current knowledge with regard to psychosis theory, research, and practice.
Proteasome inhibition with bortezomib induces a therapeutically relevant depletion of plasma cells in SLE but does not target their precursors
Authors: Alexander Tobias , Cheng Qingyu , Klotsche Jens , Khodadadi Laleh , Waka Aderajew , Biesen Robert , Hoyer Bimba F. , Burmester Gerd R. , Radbruch Andreas , Hiepe Falk
Published: July 2018

Long‐lived plasma cells (PCs) not only provide protective humoral immunity, they are also an essential component of the autoreactive immunologic memory that may drive chronic immune responses in systemic autoimmunity, such as systemic lupus erythematosus (SLE). The therapeutic relevance of their targeting has been demonstrated in preclinical models and severe, treatment‐refractory cases of autoimmune diseases using the proteasome inhibitor bortezomib. Herein, we describe in detail the dynamic serologic changes and effects on immune effector cells in eight SLE patients receiving a median two cycles of 1.3 mg/m2 intravenous bortezomib. Upon proteasome inhibition, immunoglobulin levels gradually declined by ∼30%, associated with a significant reduction of autoantibodies, and serum complement whereas B‐cell activation factor levels increased. While proteasome inhibition was associated with a significant depletion of short‐ and long‐lived PCs in peripheral blood and bone marrow by ∼50%, including those with a distinctly mature CD19− phenotype, their precursor B cells and T cells largely remained unaffected, resulting in a rapid repopulation of short‐lived PCs after bortezomib withdrawal, accompanied by increasing autoantibody levels. Collectively, these findings identify proteasome inhibitors as a promising treatment option for refractory SLE, but also indicate that PC depletion needs to be combined with targeted B‐cell therapies for sustained responses in systemic autoimmunity.
Functionalization, Modification, and Transformation of Platinum Chini Clusters
Authors: Berti Beatrice , Femoni Cristina , Iapalucci Maria Carmela , Ruggieri Silvia , Zacchini Stefano
Published: July 2018

In this microreview, the authors summarize the reactions of [Pt3n(CO)6n]2–(n= 1–10) Chini clusters aimed at their functionalization, modification and transformation. The results are organized on the basis of the fact that the final products do or do not retain the structure of the parent Chini clusters. The first category comprises the redox reactions of homoleptic Chini clusters, CO/phosphine substitution affording heteroleptic Chini‐type clusters and the formation of Lewis acid‐base adducts by capping the external Pt3‐triangular faces with Lewis acids. The second category consists of globular molecular platinum nanoclusters (platinum browns) obtained by thermal decomposition of Chini clusters, as well as surface decorated platinum carbonyl clusters, composed of a low valent Pt‐CO core decorated by cationic metal fragments. The relevance of such species to molecular cluster chemistry and metal nanoclusters is outlined.
Luminescent Silver–Copper “Hourglass” Hepta‐ and Decanuclear Alkynyl‐Phosphine Clusters
Authors: Kritchenkov Ilya S. , Gitlina Anastasia Yu. , Koshevoy Igor O. , Melnikov Alexey S. , Tunik Sergey P.
Published: July 2018

The heterometallic Ag–Cu compounds easily assemble from the corresponding metal triflates and alkynes in the presence of tris(diphenylphosphanyl)methane (tppm) under basic conditions. The formation of two types of cluster skeletons – heptanuclear [Ag6Cu(C2R)3{HC(PPh2)3}2(CF3SO3)3](CF3SO3) {R = C6H4‐4‐X (X = CF3, 1A; OMe, 2A; NMe2, 3A; NC10H20O4, 4A); CPh2OH, 5A} and decanuclear [Ag6Cu4(C2C6H4‐4‐X)8{HC(PPh2)3}2](CF3SO3)2 (X = CF3, 1B; H, 6B) species is governed by the electronic properties of the alkynyl ligands and the ratio of the starting components. All of the complexes, except 4A, were structurally characterized by single‐crystal XRD analysis. The solid‐state photophysical studies reveal room‐temperature phosphorescence (Φem = 0.3–42.5 %, λem = 556–756 nm), which is dependent on the electron‐donating ability of the alkynyl fragments and the nature of the metal core. Moreover, the geometry of the cluster framework is substantially influenced by the bridging counterions that, together with electronic modulation of organic blocks, allow near‐IR emission.
Synergistic antinociception between ZC88, an N‐type voltage‐dependent calcium channel blocker, and ibuprofen in mouse models of visceral and somatic inflammatory pain
Authors: Zhou W.‐Z. , Zhao T.‐Y. , Wang Z.‐Y. , Lu G.‐Y. , Zhang S.‐Z. , Zhang C. , Wu N. , Li J.
Published: July 2018

Background

A combination of analgesic agents with different mechanisms can induce additive or synergistic analgesia. The N‐type voltage‐dependent calcium channel (N‐VDCC) is a novel therapeutic target for pain control. In addition to providing effective pain relief when used alone, N‐VDCC blockers produce synergistic analgesia when used in combination with opiates. However, the interaction between N‐VDCC blockers and nonsteroidal anti‐inflammatory drugs (NSAIDs) remains unclear.

Methods

Using isobolographic analysis and composite additive curve analysis, the antinociceptive interaction between ZC88, a selective N‐VDCC blocker and ibuprofen, a classical NSAID, was investigated in two mouse models of visceral and somatic inflammatory pain.

Results

In the acetic acid writhing test, both ZC88 (10.5–42 mg/kg, intraperitoneally) and ibuprofen (50–200 mg/kg, orally) produced dose‐dependent antinociception, with ED50 values of 27.2 and 100.5 mg/kg, respectively. ZC88 in combination with ibuprofen (ZC88 + ibuprofen) also induced significant antinociception, and isobolographic analysis revealed a synergistic interaction at 50% effect level. The experimental ED50 (ED50 mix) of this combination (34.5 mg/kg) was significantly lower than the theoretical ED50 (ED50 add; 63.8 mg/kg). Additionally, composite additive curve analysis displayed synergistic interaction at other effect levels. In the formalin test, ZC88 or ibuprofen alone significantly reduced late‐phase rather than early‐phase pain, with ED50 values of 31.3 and 123.9 mg/kg, respectively. Similarly, both isobolographic analysis and composite additive curve analysis revealed synergistic antinociception of ZC88 + ibuprofen (40.6 mg/kg of ED50 mix vs. 77.6 mg/kg of ED50 add).

Conclusion

ZC88 in combination with ibuprofen produces synergistic antinociception in mouse models of somatic and visceral inflammatory pain.

Significance

Because ZC88 + ibuprofen achieves the same antinociceptive effect at lower doses, the use of this combination could result in fewer dose‐related untoward effects. The potentiation of ZC88 on ibuprofen‐induced antinociception indicates that N‐VDCC blocker has potential benefit to treat severe inflammatory pain.
Assessment of the dynamic response of unreinforced masonry structures using a macroelement modeling approach
Authors: Chácara César , Cannizzaro Francesco , Pantò Bartolomeo , Caliò Ivo , Lourenço Paulo B.
Published: July 2018

The seismic performance of unreinforced masonry structures is strongly associated with the interaction between in‐plane and out‐of‐plane mechanisms. The seismic response of these structures has been thoroughly investigated by means of experimental testing, analytical procedures, and computational approaches. Within the framework of the numerical simulations, models based on the finite element method provide a good prediction of the seismic performance of unreinforced masonry structures. However, they usually require a high computational cost and advanced user expertise to define appropriate mechanical properties and to interpret the numerical results. Because of these limitations, simplified models for practical applications have been developed during the last decades. Despite this, a great number of these models focus mostly on the evaluation of the in‐plane response, assuming box (or integral) behavior of the structure. In this paper, a simplified macroelement modeling approach is used to simulate the seismic response of 2 masonry prototypes taking into consideration the combined in‐plane and out‐of‐plane action. The numerical investigations were performed in the static and dynamic fields by using pushover analyses and nonlinear dynamic analyses respectively. The latter is a novel implementation of a model previously developed for static analysis. The results obtained from this study are in good agreement with those provided by a detailed nonlinear continuum FE approach, demonstrating the applicability of this macroelement model with a significant reduction of the computational cost.
Preparation of phosphorus‐containing and nitrogen‐containing durable flame retardant polyacrylonitrile fabric via surface chemical modification
Authors: Ren Yuanlin , Huo Tongguo , Qin Yiwen
Published: July 2018

Ultraviolet‐induced photografting polymerization combined with surface modification was developed to prepare durable flame retardant polyacrylonitrile (PAN) fabric. First, acrylic acid (AA) was grafted onto PAN fabric (PAN‐g‐PAA) through ultraviolet‐induced photograft polymerization. Then, PAN‐g‐PAA was modified sequentially by acylation, ammonization, and phosphorylation to obtain acylated PAN‐g‐PAA, ammoniated Cl‐PAN‐g‐PAA, and fire retardant PAN fabric, respectively. The influence of grafting time, concentration of acrylic acid, and initiator on the grafting percentage was studied in detail. Fourier transform infrared spectrometer, X‐ray diffraction, and scanning electron microscopy confirm the successful grafting of AA. The thermal properties of the fabrics were investigated by thermogravimetric analysis and differential scanning calorimetry. Thermal analysis indicates that FR‐PAN has good thermal stability at higher temperature and the char residue is about 41 wt% at 800°C. The limiting oxygen index value of the fire retardant fabrics can achieve 28.1 vol% and is still 27.3 vol% after 20 cycles washing, showing good durability.
The effect of sex work regulation on health and well‐being of sex workers: Evidence from Senegal
Authors: Ito Seiro , Lépine Aurélia , Treibich Carole
Published: July 2018

Senegal is the only African country where sex work is legal and regulated by a health policy. Senegalese female sex workers (FSWs) are required to register with a health facility and to attend monthly routine health checks aimed at testing and treating sexually transmitted infections (STIs). Compliance to those routine visits is recorded on a registration card that must be carried by FSWs in order to avoid sanctions in case of police arrests. Although this policy was first introduced in 1969 to limit the spread of STIs, there is no evidence so far of its impact on FSWs' health and well‐being. The paper aims to fill this gap by exploiting a unique data set of registered and unregistered Senegalese FSWs. Using propensity score matching, we find that registration has a positive effect on FSWs' health. However, we find that registration reduces FSWs' subjective well‐being. This finding is explained by the fact that registered FSWs are found to engage in more sex acts, in riskier sex acts, have less social support from their peers, and are more likely to experience violence from clients and police officers. We prove that those results are robust to the violation of the conditional independence assumption, to misspecification of the propensity score model, and that covariate balance is achieved. The results suggest that more efforts should be deployed to reduce the stigma associated with registration and to address the poor well‐being of FSWs, which is counterproductive to HIV prevention efforts.
Evaluation of snow water equivalent datasets over the Saint‐Maurice river basin region of southern Québec
Authors: Brown Ross , Tapsoba Dominique , Derksen Chris
Published: July 2018

A 10‐km gridded snow water equivalent (SWE) dataset is developed over the Saint‐Maurice River basin region in southern Québec from kriging of observed snow survey data for evaluation of SWE products. The gridded SWE dataset covers 1980–2014 and is based on manual gravimetric snow surveys carried out on February 1, March 1, March 15, April 1, and April 15 of each snow season, which captures the annual maximum SWE (SWEM) with a mean interpolation error of ±19%. The dataset is used to evaluate SWEM from a range of sources including satellite retrievals, reanalyses, Canadian regional climate models, and the Canadian Meteorological Centre operational snow depth analysis. We also evaluate a number of solid precipitation datasets to determine their contribution to systematic errors in estimated SWEM. None of the evaluated datasets is able to provide estimates of SWEM that are within operational requirements of ±15% error, and insufficient solid precipitation is determined to be one of the main reasons. The Climate System Forecast Reanalysis is the only dataset where snowfall is sufficiently large to generate SWEM values comparable to observations. Inconsistencies in precipitation are also found to have a strong impact on year‐to‐year variability in SWEM dataset performance and spread. Version 3.6.1 of the Canadian Land Surface Scheme land surface scheme driven with ERA‐Interim output downscaled by Version 5.0.1 of the Canadian Regional Climate Model was the best physically based model at explaining the observed spatial and temporal variability in SWEM (root‐mean‐square error [RMSE] = 33%) and has potential for lower error with adjusted precipitation. Operational snow products relying on the real‐time snow depth observing network performed poorly due to a lack of real‐time data and the strong local scale variability of point snow depth observations. The results underscore the need for more effort to be invested in improving solid precipitation estimates for use in snow hydrology applications.
Comparison of automatic procedures for selecting flood peaks over threshold based on goodness‐of‐fit tests
Authors: Durocher Martin , Mostofi Zadeh Shabnam , Burn Donald H. , Ashkar Fahim
Published: July 2018

In comparison with the traditional analysis of annual maximums, the peaks over threshold method provides many advantages when performing flood frequency analysis and trend analysis. However, the choice of the threshold remains an important question without definite answers and common visual diagnostic tools are difficult to reproduce on a large scale. This study investigates the behaviour of some automatic methods for threshold selection based on the generalized Pareto model for flood peak exceedances of the threshold and the Anderson–Darling test for fitting this model. In particular, the choice of a critical significance level to define an interval of acceptable values is addressed. First, automatic methods are investigated using a simulation study to assess fitting and prediction performance in a controlled environment. It is shown that P values approximated by an existing table of critical values can speed up computation without affecting the quality of the outcomes. Second, a case study compares automatically and manually selected thresholds for 285 sites across Canada by flood regime and super regions based on site characteristics. Correspondences are examined in terms of prediction of flood quantiles and trend analysis. Results show that trend detection is sensitive to the threshold selection method when studying the evolution of the number of peaks per year. Finally, a hybrid method is developed to combine automatic methods and is calibrated on the basis of super regions. The outcomes of the hybrid method are shown to more closely reproduce the estimates of the manually selected thresholds while reducing the model uncertainty.
The importance of incorporating diurnally fluctuating stream discharge in stream temperature energy balance models
Authors: Baker Emily A. , Lautz Laura K. , Kelleher Christa A. , McKenzie Jeffrey M.
Published: July 2018

Although stream temperature energy balance models are useful to predict temperature through time and space, a major unresolved question is whether fluctuations in stream discharge reduce model accuracy when not exactly represented. However, high‐frequency (e.g., subdaily) discharge observations are often unavailable for such simulations, and therefore, diurnal streamflow fluctuations are not typically represented in energy balance models. These fluctuations are common due to evapotranspiration, snow pack or glacial melt, tidal influences within estuaries, and regulated river flows. In this work, we show when to account for diurnally fluctuating streamflow. To investigate how diurnal streamflow fluctuations affect predicted stream temperatures, we used a deterministic stream temperature model to simulate stream temperature along a reach in the Quilcayhuanca Valley, Peru, where discharge varies diurnally due to glacial melt. Diurnally fluctuating streamflow was varied alongside groundwater contributions via a series of computational experiments to assess how uncertainty in reach hydrology may impact simulated stream temperature. Results indicated that stream temperatures were more sensitive to the rate of groundwater inflow to the reach compared with the timing and amplitude of diurnal fluctuations in streamflow. Although incorporating observed diurnal fluctuations in discharge resulted in a small improvement in model RMSE, we also assessed other diurnal discharge signals and found that high amplitude signals were more influential on modelled stream temperatures when the discharge peaked at specific times. Results also showed that regardless of the diurnal discharge signal, the estimated groundwater flux to the reach only varied from 1.7% to 11.7% of the upstream discharge. However, diurnal discharge fluctuations likely have a stronger influence over longer reaches and in streams where the daily range in discharge is larger, indicating that diurnal fluctuations in stream discharge should be considered in certain settings.
Oral contraceptive use and cutaneous melanoma risk: a French prospective cohort study
Authors: Cervenka I. , Mahamat‐Saleh Y. , Savoye I. , Dartois L. , Boutron‐Ruault M.C. , Fournier A. , Kvaskoff M.
Published: July 2018

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between oral contraceptive (OC) use and melanoma risk. However, findings were conflicting and data from large prospective studies are lacking. E3N is a prospective cohort of 98,995 French women aged 40–65 years at inclusion in 1990. Exposure to lifetime OC use was assessed in 1992 and through biennial questionnaire updates. To assess the association between OC use and melanoma risk, we used Cox models adjusted for age, pigmentary traits, residential ultraviolet (UV) exposure in county of birth and at inclusion and family history of skin cancer. Over 1992–2008, 539 melanoma cases were ascertained among 79,365 women. In age‐adjusted models, we found a modest positive association between ever use of OCs and melanoma risk (hazard ratio (HR) = 1.18, 95% confidence intervals (CIs) = 0.98–1.42), which was reduced after adjustment (HR = 1.14, 95% CI = 0.95–1.38). The association was stronger in long‐term users (duration ≥10 years: HR = 1.33, 95% CI = 1.00–1.75) and in women who used high‐estrogen OCs (HR = 1.27, 95% CI = 1.04–1.56). Among users, there was an inverse association with age at first use (ptrend < 0.01), but no evidence of an association with age at last use or time since last use. OC use was positively associated with tanning bed use (OR = 1.14, CI = 1.01–1.29), sunburns (ptrend = 0.5) and sunscreen use (OR = 1.13, CI = 1.00–1.28) since age 25. Overall, our findings do not support a strong association between OC use and melanoma risk and suggest intentional UV exposure in OC users, which supports a potential confusion by UV exposure in this relationship.
The prognostic value of tumor–stroma ratio in tumor‐positive axillary lymph nodes of breast cancer patients
Authors: Vangangelt Kiki M.H. , Tollenaar Lisanne S.A. , van Pelt Gabi W. , de Kruijf Esther M. , Dekker Tim J.A. , Kuppen Peter J.K. , Tollenaar Rob A.E.M. , Mesker Wilma E.
Published: July 2018

The tumor–stroma ratio (TSR) has previously been found to be a strong prognostic parameter in primary breast cancer tumors. Since the presence of tumor cells in lymph nodes is important for clinical decision making, the influence of TSR in the primary breast tumor combined with the TSR in tumor‐positive lymph nodes on prognosis was evaluated. Women with invasive breast cancer without distant metastasis who underwent an axillary lymph node dissection between 1985 and 1994 at the Leiden University Medical Center were retrospectively analyzed. TSR assessment was performed on hematoxylin and eosin stained tissue slides. In total, 87 (45.5%) primary tumors were scored as stroma‐low and 104 (54.5%) as stroma‐high. Patients with a high stromal percentage in the primary tumors had a statistically significant worse relapse free period (RFP) compared to stroma‐low tumors (HR 1.97, 95% CI 1.37–2.82, p < 0.001). A total number of 915 lymph nodes were assessed for TSR. In 101 (52.9%) patients, heterogeneity was observed between stroma percentage category in primary tumor and lymph nodes. The combination of TSR of the primary tumor combined with TSR of tumor‐positive lymph nodes strengthened each other as independent prognostic parameter for RFP (p = 0.019). Patients with primary tumor stroma‐low/lymph nodes stroma‐low tumors showed strongly improved RFP rates compared to patients with primary tumor stroma‐high/lymph node stroma‐high tumors with 10‐year percentages of 58 versus 8%, respectively. Assessing the TSR on tumor‐positive lymph nodes can provide additional prognostic information. Stromal activation strongly differs between primary tumors and lymph node metastasis.
How long does it take until the effects of endoscopic screening on colorectal cancer mortality are fully disclosed?: a Markov model study
Authors: Chen Chen , Stock Christian , Hoffmeister Michael , Brenner Hermann
Published: July 2018

A recent randomized trial has suggested persisting protection from colorectal cancer (CRC) incidence and mortality of a single flexible sigmoidoscopy for up to 17 years and possibly beyond. We performed a simulation study to explore the time course and magnitude of protection provided by screening colonoscopy against CRC death over 25 years. Using data from the German national screening colonoscopy registry, a multistate Markov model was set up based on the adenoma–carcinoma pathway to estimate cumulative CRC mortality when different proportions of the population have a single screening colonoscopy at age 55, or two screening colonoscopies at ages 55 and 65. Cumulative CRC mortality continuously increased with age and reached 2.6 and 1.7% at age 80 in the absence of screening for men and women, respectively. A single colonoscopy at age 55, even with limited uptake, would lead to much lower cumulative mortality (0.7% for men and 0.5% for women at age 80 under 100% uptake). Relative mortality reduction continued to increase over more than 10 years and reached the maximum around 12–13 years after screening. Absolute risk reduction steadily increased throughout follow‐up and more than half of the total risk reduction would occur between 15–25 years. A repeat colonoscopy 10 years later further enhanced the effects and cumulative mortality remained at 0.1–0.2% under 100% uptake. Even a single (once‐only) screening colonoscopy has the potential to prevent most of CRC mortalities. Protective effects are expected to be long‐lasting and to become fully manifest after more than two decades from screening.
A New Muscle Memory: Training Systems Engineers in the Agile Culture of Trust
Authors: Fairbairn Sharon Torres
Published: July 2018

The transition to an agile team often causes culture shock for systems engineers who spent their early careers following a waterfall development process. Even agile mindset enthusiasts can experience friction while retraining their “muscle memory” from a waterfall upbringing. One disadvantage is that the prevailing training model for systems engineers still consists more of systematic control than of systemic trust, where trust relates to the quality of the relationships within and among the disciplines involved in an agile engineering effort. The engineering of complex systems involves capricious, uncertain, risky, variable, and evolving (CURVE) problems, so are we adding to the burden by not transforming the way we cultivate systems thinkers? This paper explores agile systems engineering training, behaviors, and a culture of trust as critical enablers to thriving in the CURVE domain.