bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiroptical study of cryptophanes subjected to self‐encapsulation
Authors: Baydoun Orsola , Buffeteau Thierry , Daugey Nicolas , Jean Marion , Vanthuyne Nicolas , Chapellet Laure‐Lise , De Rycke Nicolas , Brotin Thierry
Published: May 2019

In 1,1,2,2‐tetrachloroethane‐d2, the 129Xe NMR spectrum of the Xe@cryptophane‐223 complex bearing seven acetate groups (Xe@1 complex) shows an unusually broad signal compared with that of its congeners (Chapellet, LL. et al. J. Org. Chem. 2015;80:6143–6151). To interpret this unexpected behaviour, a 1H NMR analysis and a thorough study of the chiroptical properties of 1 as a function of the nature of the solvent have been performed. The 1H NMR spectra of 1 reveal that a self‐encapsulation phenomenon takes place in DMSO‐d6 and 1,1,2,2‐tetrachloroethane‐d2 solvents. Thanks to the separation of the two enantiomers of 1 by HPLC on chiral stationary phase, the two enantiomers of 1 have been studied in detail by polarimetry, electronic (ECD), and vibrational (VCD) circular dichroism spectroscopies. Except for ECD spectroscopy, these chiroptical techniques reveal spectroscopic changes as a function of the nature of the solvent. For instance, in DMSO and 1,1,2,2‐tetrachloroethane, in which the self‐encapsulation phenomenon takes place, the sign of the specific optical rotation of [CD(−)254]‐1 and [CD(+)254]‐1 is changed. These results have then been compared with those obtained with cryptophane‐223 bearing only one acetate group on the propylenedioxy linker (compound 2) and with cryptophane‐223 bearing six acetate groups (compound 3). A self‐encapsulation phenomenon is also observed with compound 2. Finally, compounds 2 and 3 show different chiroptical properties compared with those obtained with the two enantiomers of compound 1.
Entsalzung von Umkehrosmosekonzentraten mittels elektrisch getriebenen Membranverfahren zur Maximierung der Permeatausbeute einer Prozesswasseraufbereitungsanlage
Authors: Londoño David , Cumbana Rivelino , Gilbert Eva Marianne
Published: May 2019

Weltweit größer werdende Wasserstress‐Probleme führen zu einer Verwendung von alternativen Wasserquellen wie Brack‐ oder Abwasser. Das Anschließen solcher Wasserquellen setzt die Verwendung von neuen Entsalzungstechnologien, wie die elektrisch getriebenen Membranverfahren, voraus. Hiermit wurden die Konzentrate einer Umkehrosmose so weit entsalzt, dass das Diluat erneut mittels Umkehrosmose behandelt werden konnte. Die zu entsorgende Konzentratmenge halbierte sich bei gleichzeitiger Erhöhung der Permeatausbeute. Im Fokus der Untersuchungen lag zudem der für die Behandlung notwendige Energiebedarf.
L'utilisation des forces au travail et les comportements proactifs et de citoyenneté organisationnelle: examen du rôle médiateur du bien‐être
Authors: Belleville Karel , Dubreuil Philippe , Courcy François
Published: May 2019

Positive psychology suggests relying on workers' strengths to maintain balance between personal fulfillment and organizational goals. This article assesses whether the use of strengths in the workplace are associated with proactive behaviours and organizational citizenship behaviours (OCB) through the mediating role of well‐being. Data were collected from 142 French‐speaking Canadian professionals working in various non‐profit organizations. Results show that the use of strengths can predict some OCBs (notably mutual aid and civic virtue) as well as proactivity. Only the affective dimension of well‐being shows a mediation effect for mutual aid and proactivity. Theoretical contributions, implications for practitioners, limitations, and future research directions are also discussed.
Microenvironment and tumor inflammatory features improve prognostic prediction in gastro‐entero‐pancreatic neuroendocrine neoplasms
Authors: Milione Massimo , Miceli Rosalba , Barretta Francesco , Pellegrinelli Alessio , Spaggiari Paola , Tagliabue Giovanna , Centonze Giovanni , Paolino Cinzia , Mangogna Alessandro , Kankava Ketevani , Pusceddu Sara , Giacomelli Luca , Corti Ambra , Cotsoglou Christian , Mazzaferro Vincenzo , Sozzi Gabriella , de Braud Filippo , Pruneri Giancarlo , Anichini Andrea
Published: May 2019

Microenvironment‐related immune and inflammatory markers, when combined with established Ki‐67 and morphology parameters, can improve prognostic prediction in gastro‐entero‐pancreatic neuroendocrine neoplasms (GEP‐NENs). Therefore, we evaluated the prognostic value of microenvironment and tumor inflammatory features (MoTIFs) in GEP‐NENs. For this purpose, formalin‐fixed paraffin‐embedded tissue sections from 350 patients were profiled by immunohistochemistry for immune, inflammatory, angiogenesis, proliferation, NEN‐, and fibroblast‐related markers. A total of 314 patients were used to generate overall survival (OS) and disease‐free survival (DFS) MoTIFs prognostic indices (PIs). PIs and additional variables were assessed using Cox models to generate nomograms for predicting 5‐year OS and DFS. A total of 36 patients were used for external validation of PIs and nomograms' prognostic segregations. From our analysis, G1/G2 versus G3 GEP‐NENs showed phenotypic divergence with immune‐inflammatory markers. HLA, CD3, CD8, and PD‐1/PD‐L1 IHC expression separated G3 into two sub‐categories with high versus low adaptive immunity‐related features. MoTIFs PI for OS based on COX‐2Tumor(T) > 4, PD‐1Stromal(S) > 0, CD8S < 1, and HLA‐IS < 1 was associated with worst survival (hazard ratio [HR] 2.50; 95% confidence interval [CI], 2.12–2.96; p < 0.0001). MoTIFs PI for DFS was based on COX‐2T > 4, PD‐1S > 4, HLA‐IS < 1, HLA‐IT < 2, HLA‐DRS < 6 (HR 1.77; 95% CI, 1.58–1.99; p < 0.0001). Two nomograms were developed including morphology (HR 4.83; 95% CI, 2.30–10.15; p < 0.001) and Ki‐67 (HR 11.32; 95% CI, 5.28–24.24; p < 0.001) for OS, and morphology (PI = 0: HR 10.23; 95% CI, 5.67–18.47; PI = 5: HR 2.87; 95% CI, 1.21–6.81; p < 0.001) and MoTIFs PI for DFS in well‐differentiated GEP‐NENs (HR 6.21; 95% CI, 2.52–13.31; p < 0.001). We conclude that G1/G2 to G3 transition is associated with immune‐inflammatory profile changes; in fact, MoTIFs combined with morphology and Ki‐67 improve 5‐year DFS prediction in GEP‐NENs. The immune context of a subset of G3 poorly differentiated tumors is consistent with activation of adaptive immunity, suggesting a potential for responsiveness to immunotherapy targeting immune checkpoints.
Bird’s eye view of modern cytopathology: Report from the seventh international Molecular Cytopathology Meeting in Naples, Italy, 2018
Authors: Pisapia Pasquale , Bellevicine Claudio , Malapelle Umberto , De Luca Caterina , Vigliar Elena , Troncone Giancarlo
Published: May 2019

In the era of personalized medicine, cytopathology reports must be standardized to provide clinicians with clear information regarding relevant diagnostic, prognostic, and predictive tumor features. Since 2010, the international Molecular Cytopathology Meeting has been held annually in Naples, Italy, to disseminate recent breakthroughs and ongoing investigations in the field of modern cytopathology. In particular, the seventh annual meeting, which took place on November 26 through 27, 2018, focused on novel cytological and molecular classifications and novel DNA sequencing techniques, as well as on the possibility of using cytological rather than tissue specimens for lung cancer biomarker testing. The present review aims to update cytopathologists on the more recent achievements in modern cytopathology and to identify key research questions that still remain unanswered.
Oxygen‐Doped Ta3N5 Nanoparticles for Enhanced Z‐Scheme Carbon Dioxide Reduction with a Binuclear Ruthenium(II) Complex under Visible Light
Authors: Muraoka Kanemichi , Vequizo Junie Jhon M. , Kuriki Ryo , Yamakata Akira , Uchiyama Tomoki , Lu Daling , Uchimoto Yoshiharu , Ishitani Osamu , Maeda Kazuhiko
Published: May 2019

Metal‐complex/semiconductor hybrids are promising photocatalysts for visible‐light CO2 reduction with high selectivity for the formation of a desired product. Herein we applied nanoparticulate Ta3N5/SiO2 as the semiconductor component of a hybrid system with the aid of a binuclear ruthenium(II) complex. The Ta3N5/SiO2 material was prepared by the nitridation of nanoparticulate Ta2O5/SiO2 (which had been previously synthesized by a sol‐gel method) under a flow of NH3 gas at 973–1223 K. The synthesized hybrid reduced CO2 into formate with very high selectivity (>99 %) under irradiation with visible light (λ>480 nm). The activity increased with nitridation temperature up to 1023 K, beyond which it began to drop. The optimized photocatalyst, which consisted of oxygen‐doped Ta3N5 as revealed by UV‐visible diffuse reflectance spectroscopy and X‐ray photoelectron spectroscopy, exhibited 6 times higher activity than that for an analogous hybrid constructed with bulk Ta3N5. Physicochemical analyses indicated that reducing the defect density by high‐temperature nitridation contributed to the suppression of charge recombination, which resulted in higher activity of Ta3N5/SiO2, while a nitridation temperature that was too high was undesirable because of a decrease in the reactivity of photogenerated holes due to a loss of the doped oxygen content in Ta3N5.
Using Density Functional Theory Based Methods to Investigate the Photophysics of Polycyclic Aromatic Hydrocarbon Radical Cations: A Benchmark Study on Naphthalene, Pyrene and Perylene Cations
Authors: Boggio‐Pasqua Martial , Bearpark Michael J.
Published: May 2019

Unrestricted DFT (UDFT), time‐dependent DFT (TDDFT) and spin‐flip TDDFT (SF‐TDDFT) were used to investigate the potential energy surfaces of the ground and first two electronic excited states of the naphthalene, pyrene and perylene radical cations. In particular, conical intersections (which play a central role in the photophysics of these cations) were located with these DFT‐based methods. The results are consistent with accurate multiconfigurational wavefunction‐based ab initio methods. These show that naphthalene and pyrene cations can quickly relax nonradiatively from their excited states back down to the original ground state species through easily accessible conical intersections, but the perylene cation cannot do so, due to the absence of any accessible funnels between the lowest excited state and the ground state, leaving radiative decay as the most probable photophysical pathway. This study paves the way for using computationally efficient density functional theory (DFT)‐based methods in future investigations of the photophysics of much larger polycyclic aromatic hydrocarbons, for which multiconfigurational wavefunction‐based methods become prohibitively expensive.
Developmental Changes in Task‐Induced Brain Deactivation in Humans Revealed by a Motor Task
Authors: Morita Tomoyo , Asada Minoru , Naito Eiichi
Published: May 2019

Performing tasks activates relevant brain regions in adults while deactivating task‐irrelevant regions. Here, using a well‐controlled motor task, we explored how deactivation is shaped during typical human development and whether deactivation is related to task performance. Healthy right‐handed children (8–11 years), adolescents (12–15 years), and young adults (20–24 years; 20 per group) underwent functional magnetic resonance imaging with their eyes closed while performing a repetitive button‐press task with their right index finger in synchronization with a 1‐Hz sound. Deactivation in the ipsilateral sensorimotor cortex (SM1), bilateral visual and auditory (cross‐modal) areas, and bilateral default mode network (DMN) progressed with development. Specifically, ipsilateral SM1 and lateral occipital deactivation progressed prominently between childhood and adolescence, while medial occipital (including primary visual) and DMN deactivation progressed from adolescence to adulthood. In adults, greater cross‐modal deactivation in the bilateral primary visual cortices was associated with higher button‐press timing accuracy relative to the sound. The region‐specific deactivation progression in a developmental period may underlie the gradual promotion of sensorimotor function segregation required in the task. Task‐induced deactivation might have physiological significance regarding suppressed activity in task‐irrelevant regions. Furthermore, cross‐modal deactivation develops to benefit some aspects of task performance in adults.
Divergent selection along elevational gradients promotes genetic and phenotypic disparities among small mammal populations
Authors: Feijó Anderson , Wen Zhixin , Cheng Jilong , Ge Deyan , Xia Lin , Yang Qisen
Published: May 2019

Species distributed along mountain slopes, facing contrasting habitats in short geographic scale, are of particular interest to test how ecologically based divergent selection promotes phenotypic and genetic disparities as well as to assess isolation‐by‐environment mechanisms. Here, we conduct the first broad comparative study of phenotypic variation along elevational gradients, integrating a large array of ecological predictors and disentangling population genetic driver processes. The skull form of nine ecologically distinct species distributed over a large altitudinal range (100–4200 m) was compared to assess whether phenotypic divergence is a common phenomenon in small mammals and whether it shows parallel patterns. We also investigated the relative contribution of biotic (competition and predation) and abiotic parameters on phenotypic divergence via mixed models. Finally, we assessed the population genetic structure of a rodent species (Niviventer confucianus) via analysis of molecular variance and FST along three mountain slopes and tested the isolation‐by‐environment hypothesis using Mantel test and redundancy analysis. We found a consistent phenotypic divergence and marked genetic structure along elevational gradients; however, the species showed mixed patterns of size and skull shape trends across mountain zones. Individuals living at lower altitudes differed greatly in both phenotype and genotype from those living at high elevations, while middle‐elevation individuals showed more intermediate forms. The ecological parameters associated with phenotypic divergence along elevation gradients are partly related to species' ecological and evolutionary constraints. Fossorial and solitary animals are mainly affected by climatic factors, while terrestrial and more gregarious species are influenced by biotic and abiotic parameters. A novel finding of our study is that predator richness emerged as an important factor associated with the intraspecific diversification of the mammalian skull along elevational gradients, a previously overlooked parameter. Population genetic structure was mainly driven by environmental heterogeneity along mountain slopes, with no or a week spatial effect, fitting the isolation‐by‐environment scenario. Our study highlights the strong and multifaceted effects of heterogeneous steep habitats and ecologically based divergent selective forces in small mammal populations.
MHC‐restricted Ag85B‐specific CD8+ T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice
Authors: Komine‐Aizawa Shihoko , Jiang Jiansheng , Mizuno Satoru , Hayakawa Satoshi , Matsuo Kazuhiro , Boyd Lisa F. , Margulies David H. , Honda Mitsuo
Published: May 2019

Despite efforts to develop effective treatments and vaccines, Mycobacterium tuberculosis (Mtb), particularly pulmonary Mtb, continues to provide major health challenges worldwide. To improve immunization against the persistent health challenge of Mtb infection, we have studied the CD8+ T cell response to Bacillus Calmette‐Guérin (BCG) and recombinant BCG (rBCG) in mice. Here, we generated CD8+ T cells with an rBCG‐based vaccine encoding the Ag85B protein of M. kansasii, termed rBCG‐Mkan85B, followed by boosting with plasmid DNA expressing the Ag85B gene (DNA‐Mkan85B). We identified two MHC‐I (H2‐Kd)‐restricted epitopes that induce cross‐reactive responses to Mtb and other related mycobacteria in both BALB/c (H2d) and CB6F1 (H2b/d) mice. The H2‐Kd‐restricted peptide epitopes elicited polyfunctional CD8+ T cell responses that were also highly cross‐reactive with those of other proteins of the Ag85 complex. Tetramer staining indicated that the two H2‐Kd‐restricted epitopes elicit distinct CD8+ T cell populations, a result explained by the X‐ray structure of the two peptide/H2‐Kd complexes. These results suggest that rBCG‐Mkan85B vector‐based immunization and DNA‐Mkan85B boost may enhance CD8+ T cell response to Mtb, and might help to overcome the limited effectiveness of the current BCG in eliciting tuberculosis immunity.
Synthesis of 4‐C‐β‐D‐Glucosylated Isoliquiritigenin and Analogues for Aldose Reductase Inhibition Studies
Authors: Reddy Mannem Rajeswara , Aidhen Indrapal Singh , Reddy Utkarsh A. , Reddy Geereddy Bhanuprakash , Ingle Kundane , Mukhopadhyay Sami
Published: May 2019

Inspired from natural product isoliquiritine, an O‐glucoside and the corresponding aglycon chalcone, isoliquiritigenin (ISL), several C‐glucosylated chalcones and dihydrochalcones have been synthesized and evaluated for aldose reductase (AR) inhibition activity, for the first time. The initial inputs from molecular docking studies were also encouraging. Claisen‐Schmidt condensation reaction between 4‐C‐glucosylated benzaldehyde, a key building block developed during the synthetic efforts and acetophenones enabled convenient access to the targeted compounds in good yields. Excellent AR inhibition has been observed with C‐glucosylated ISL with IC50 value of 21 µM. This is similar to the chalcone ISL, displaying IC50 of 19 µM. In the light of limited aqueous solubility of ISL, the observed AR inhibition with C‐glucosylated ISL, gains importance. Additionally, the studies have revealed significance of the oxygenation pattern on the aromatic residue and paved way for the identification of few more new compounds with equally promising AR inhibition.
Smooth Metal‐Free Photoinduced Preparation of Valuable 8‐Arylxanthines
Authors: Abdulla Havall Othman , Amin Ahmed A. , Raviola Carlotta , Opatz Till , Protti Stefano , Fagnoni Maurizio
Published: May 2019

A set of 8‐arylxanthines was prepared under metal‐free conditions and in aqueous solvents from arylazo sulfones and caffeine or theophylline. Notably, the process took place by simply exposing the reaction vessel to visible or solar light, and unreacted xanthine could be easily recovered during the purification step.
Copper‐Catalyzed One‐Pot Synthesis of Dibenzofurans, Xanthenes, and Xanthones from Cyclic Diphenyl Iodoniums
Authors: Zhu Daqian , Li Min , Wu Zhouming , Du Yongliang , Luo Bingling , Huang Peng , Wen Shijun
Published: May 2019

Oxygenation of cyclic diphenyl iodoniums (CDPIs) with varied medium‐ring sizes has been fully investigated. This practical copper‐catalyzed tandem reaction of CDPIs with water as the oxygen source enables the construction of derivatised dibenzofurans and xanthenes at moderate to good yields. Moreover, structurally important xanthones are also successfully accessed under the oxygenation conditions with additional TEMPO.
A pragmatic effectiveness study of 10‐session cognitive behavioural therapy (CBT‐T) for eating disorders: Targeting barriers to treatment provision
Authors: Pellizzer Mia L. , Waller Glenn , Wade Tracey D.
Published: May 2019

Objective

Ten‐session cognitive behavioural therapy (CBT‐T) for transdiagnostic eating disorders targets several barriers to treatment, including cost, therapist expertise, and lengthy wait lists.

Method

We used a case series design to investigate the effectiveness of CBT‐T delivered by trainee psychologists in a postgraduate training clinic. Participants were randomly allocated to commence treatment either immediately or after a 4‐week waitlist period. CBT‐T was delivered to 52 patients, by six different trainees under supervision. Measures of eating disorder cognitions and behaviours, quality of life, and general psychopathology were examined in completer and intention‐to‐treat analyses using multilevel modelling. Last observation carried forward was applied for abstinence, remission, and good outcome analyses to aid comparison with prior studies.

Results

Significant improvements, associated with medium to large effect sizes, were found for eating disorder cognitions, behaviours quality of life, and negative affect from baseline to posttreatment, and at 1‐ and 3‐month follow‐up. Attrition (38.5%) was comparable with other treatment studies.

Conclusion

Results provide evidence for the effectiveness of CBT‐T delivered by trainee psychologists for transdiagnostic eating disorder patients, thus tackling some important barriers for treatment. Longer follow‐up, randomised controlled trial designs, and moderator analyses will provide more robust evidence about which patients do best with a shorter therapy.
On the incipient formation of bars and channels on alluvial fans
Authors: Tambroni Nicoletta , Seminara Giovanni , Paola Chris
Published: May 2019

The morphodynamics of topographic expansion has been recently investigated both experimentally, by Sittoni et al., (2014) Shaw et al., (2018), and numerically Sittoni et al., 2014. Here, we study the basic mechanism that governs the evolution of topographic and expansions and explore the instability of the bottom topography under conditions of steady but spatially expanding flow. We model the expanding flow via a by configuration where water and sediments are supplied from a central hole and flow on a cone shaped surface confined by lateral walls. The governing equations are the shallow‐water equations coupled with the Exner equation, written in cylindrical coordinates. We initially approach the problem analytically by considering the conditions required for the basic state, consisting of a pure radial flow and bottom profile, to lose stability to small amplitude perturbations. This analysis suggests that more than one mode may be unstable, encouraging us to extend the analysis to the nonlinear regime. We do this through numerical modeling of the full governing equations, which allows us to predict the establishment of a bar pattern whose features are similar to those experimentally observed. Two prominent features of the finite‐amplitude bar pattern are (1) bar apices are distributed at a radial distance from the inflow consistent with work of Shaw et al. (2018); and (2) that the flow aspect ratio of the interbar areas remain high without provoking further instability. Both features imply that in general expansion acts to reduce bar development relative to an equivalent rectilinear flow. © 2019 John Wiley & Sons,  Ltd.
Context‐aware cognitive disaster management using fog‐based Internet of Things
Authors: Butt Talal Ashraf
Published: May 2019

The natural and man‐made disasters are inevitable in many circumstances. Thus, an effective disaster management system (DMS) is vital for any community that can use state‐of‐the‐art technologies to deal with such cataclysmic events. There is plethora of latest technologies such as Internet of Things (IoT) and cloud and fog Computing that have provided the required infrastructure and connectivity to collect and analyze data from users and physical environment for cognitive decision‐making. This article analyzes different stages of DMSs, and existing IoT solutions are also discussed that are focused on prevention, preparation, response, and recovery from disasters. It also proposes a context‐aware fog‐based IoT architecture to realize a cognitive DMS that can learn from the collected and synthesized data to reduce the impact of catastrophic events by taking immediate actions. Furthermore, the significance of the architecture is validated in different scenarios and inherent open research challenges are emphasized.
Methodology for material property determination
Authors: Yang Fengchang , Rippe Christian , Hodges Jonathan , Lattimer Brian
Published: May 2019

Predicting solid material pyrolysis requires numerous parameters/properties that are time consuming and difficult to measure. Multiobjective optimization techniques have been used to determine these parameters; however, a methodology for the types of tests needed for the optimization and parameters that should be optimized versus measured has not been fully established. This study investigated combinations of testing protocols and parameters for optimization to determine a testing and optimization methodology that results in the accurate parameters. A Shuffled Complex Evolution (SCE) optimization routine was used to determine parameters based on some parameters being known (ie, measured) and others being determined through optimization and different combinations of types of input data. The results indicate that material testing should be done at three different heating rates in a thermogravimetric analyzer (TGA) and at three different heat fluxes in the cone calorimeter. The TGA tests and two cone calorimeter tests are input into the SCE optimization routine to determine the remaining parameters. The third cone calorimeter test is used to validate the parameters determined using the methodology. The method provides parameters within 20% of the actual parameters input into the Fire Dynamics Simulator (FDS) virtual experiment models. This method is applied to Polymethyl methacrylate (PMMA) experimental data to prove effectiveness.
Variable spaced particle in mesh‐free method to handle wave‐floating body interactions
Authors: Rijas A.S. , Sriram V. , Yan S.
Published: May 2019

In this work, the motion of a two‐dimensional rectangular freely floating body under waves is simulated using Improved Meshless Local Petrov‐Galerkin method with Rankine Source function (IMLPG_R) with variable spacing resolutions. The IMLPG_R method is a particle method that solves Navier–Stokes equations using the fractional step method to capture the wave properties. However, many existing particle methods are computationally intensive to model the wave‐floating body due to the requirement of fine particles, needing uniform distribution throughout the domain. To improve the computational efficiency and capture the body response properly, variable spaced particle distribution with fine resolution near the floating body and coarse resolution far from the body is implemented. Numerical schemes to handle variable resolutions are reported. An iterative scheme to handle the wave‐floating body is implemented in the particle method. Two test cases, one with small wave and another with steep waves, are simulated for uniform particle distribution and the result shows good agreement with literature. Based on this, the performance of the variable spaced particle distribution is tested in coupling with floating body solver. The application of the method for wave impact load from the green water loading of the floating structure is also simulated.
The role of culture in appraisals, emotions and helplessness in response to threats
Authors: Günsoy Ceren , Cross Susan E. , Uskul Ayse K. , Gercek‐Swing Berna
Published: May 2019

In honour cultures, such as Turkey, reputation management is emphasised, whereas in dignity cultures such as northern US, self‐respect and personal achievements are central. Turkey is also a collectivistic culture, where relationship harmony is as important as reputation management. When Turkish people's reputation is threatened, they may experience an internal conflict between these two motives and display helplessness. The purpose of the present study was to examine how people from Turkey (an honour culture; n = 52) and northern US (a dignity culture; n = 48) would perceive and respond to reputation threats as opposed to self‐respect threats. As predicted, Turkish participants anticipated stronger anger, shame, and helplessness in response to reputation threats than self‐respect threats, whereas differences were smaller or non‐existent in northern US. Moreover, shame was a mediator between appraisal and helplessness for reputation threats in Turkey (shame positively predicted helplessness); anger was a mediator between appraisal and helplessness for self‐respect threats in northern US (anger negatively predicted helplessness). These results are novel in their inclusion of helplessness and appraisal theory of emotions when examining responses to threats in honour and dignity cultures.
Liver safety evaluation of endothelin receptor antagonists using HepatoPac®: A single model impact assessment on hepatocellular health, function and bile acid disposition
Authors: Aleo Michael D. , Ukairo Okechukwu , Moore Amanda , Irrechukwu Onyi , Potter David M. , Schneider Richard P.
Published: May 2019

Marketed (bosentan, ambrisentan) and discontinued (sitaxsentan, CI‐1034) endothelin receptor antagonists were examined in the human micropatterned hepatocyte co‐culture (MPCC) model HepatoPac®. Differences across hepatocellular health (cellular adenosine triphosphate/glutathione content), function (urea production/albumin secretion) and taurocholic acid transport (biliary clearance/excretion index) were compared using amiodarone and ciclosporin A as positive controls. Ambrisentan had the weakest potency in all six endpoints, while sitaxsentan, bosentan and CI‐1034 had more potent effects on hepatobiliary transport than health/function endpoints. Normalization to clinical Cmax gave the following relative rank order of safety based on margins for each endpoint: ambrisentan ≥ CI‐1034 ~ bosentan > sitaxsentan. These data suggested impaired hepatobiliary disposition might contribute to a more prominent role in liver injury associated within sensitive human populations exposed to these compounds than direct hepatocellular toxicity. Rat, dog and monkey MPCCs also showed greater sensitivity potential to disrupted hepatobiliary disposition compared with hepatocellular health/functional endpoints. Drug metabolism competency was exhibited across all species. In vivo, rats and dogs appear more resistant to transaminase elevations and/or histological evidence of liver injury caused by these mechanisms even at exceedingly high systemic exposures relative to sensitive humans. Rats and dogs are resistant to hepatobiliary toxicants due to physiological differences in bile composition/handling. Although traditional animal testing provides adequate safety coverage for advancement of novel pharmaceuticals into clinical trials, supplemental assays employing human MPCCs may strengthen weight‐of‐evidence predictions for sensitive human populations. Proving the predictive value of this single impact assessment model in advance of clinical trial information for human liver injury risk is needed across more pharmaceuticals.
MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease
Authors: Zhao Xiao‐Hui , Wang Yong‐Bing , Yang Juan , Liu Hui‐Qin , Wang Ling‐Ling
Published: May 2019

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR‐326 in PD through the JNK signaling pathway by targeting X‐box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR‐326 and XBP1 was confirmed. The expression of miR‐326 and XBP1 was measured in PD mice, and gain‐ and loss‐function assay was conducted to examine the regulatory effect of miR‐326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR‐326 mimic and siRNA‐XBP1 showed increased traction test scores, activation of autophagy, expression of LC3‐II, c‐Jun, and p‐α‐Syn, but diminished climbing time and expressions of iNOS, α‐Syn, and p‐c‐Jun. The siRNA‐XBP1 treatment could reverse the effect of miR‐326 inhibitor on PD mice. Overexpression of miR‐326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.
Overexpression of miR‐224‐3p alleviates apoptosis from cerebral ischemia reperfusion injury by targeting FIP200
Authors: Deng Yiming , Ma Gaoting , Dong Qihao , Sun Xuan , Liu Lian , Miao Zhongrong , Gao Feng
Published: May 2019

Aims

In previous studies, numerous differential microRNAs (miRNAs) in cerebral ischemic/reperfusion (I/R) injury were identified using the miRNA microarray analysis. However, the relationship between miRNA and cerebral I/R injury remains largely unknown. In this study, we investigated the function and explored the possible mechanism of miR‐224‐3p in cerebral I/R injury.

Methods

Oxygen glucose deprivation model in N2a cells were used to perform the cerebral I/R injury in vitro. Trypan blue staining, reactive oxygen species (ROS) production, and caspase‐3 were measured to evaluate the function of miR‐224‐3p.

Results

Overexpression of miR‐224‐3p alleviated the apoptosis induced by oxygen glucose deprivation (OGD) and cleaved caspase‐3 was significantly reduced. We further provided the possible mechanism that miR‐224‐3p may protect cells from cerebral I/R injury by targeting FAK family‐interacting protein (FIP200). Further rescue experiment proved that overexpression of FIP200 partially blocked the effect of miR‐224‐3p.

Conclusions

We evaluated the function and mechanism of miR‐224‐3p in ischemic brain injury. miR‐224‐3p may serve as a potential target for new therapeutic intervention.
Transcriptomic analysis reveals the molecular mechanism of Alzheimer‐related neuropathology induced by sevoflurane in mice
Authors: Ge Xing , Zhang Ying , Zuo Yong , Israr Muhammad , Li Bowen , Yu Peng , Gao Guofen , Chang Yan‐Zhong , Shi Zhenhua
Published: May 2019

Anesthetics could induce cognitive dysfunctions, such as Alzheimer's disease in humans or mice. However, the precise molecular mechanism is unclear. Sevoflurane is a common anesthetic widely used in clinical practice. Here, we demonstrated the induction of cognitive dysfunction induced by Sev in mice to corroborate the signaling pathway and the differentially expressed genes (DEGs) followed by analyzing their functions. The cognitive function of mice was measured by the Morris water maze test. Transcriptomic data were annotated with Illumina HiSeq. 2000. Further, the changes in related proteins or genes were analyzed by western blotting and real‐time quantitative polymerase chain reaction. Our results showed that Sev could cause a decline in cognitive competence in mice. The transcriptomic data indicated that adding up to 566 genes were upregulated and 1073 genes were downregulated. The genes of Plin4, Lcn2, Lrg1, Foxf1, and Ctla2a were significantly upregulated, while the genes of Arc, Npas4, Egr2, Hes5, and Cdh9 were downregulated dramatically. The Gene Ontology term with the highest enrichment of DEGs are involved in the regulation of cellular and macromolecule metabolism and cation and nucleic acid binding, respectively. The Kyoto encyclopedia of genes and genomes analysis indicated that the mitogen‐activated protein kinases (MAPK) pathway was one of the most important metabolic pathways. In addition, the metabolic pathways related to cognitive function, such as the nervous system and neurodegenerative disease showed significant changes. Furthermore, we found that p38, c‐Jun N‐terminal kinase, and extracellular signal‐regulated kinase of the MAPK signaling pathway played important roles in this process. In conclusion, these results provide the first important clues for identifying the DEGs and signaling pathways in the hippocampus due to a Sev‐induced cognitive deficiency in mice.
SOD1 in amyotrophic lateral sclerosis development – in silico analysis and molecular dynamics of A4F and A4V variants
Authors: Da Silva Aloma Nogueira Rebello , Pereira Gabriel Rodrigues Coutinho , Moreira Lorena Giannini Alves , Rocha Catielly Ferreira , De Mesquita Joelma Freire
Published: May 2019

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized by the selective loss of motor neurons. Approximately 5% to 10% of patients with ALS have a family history of the disease, and approximately 20% of familial amyotrophic lateral sclerosis (fALS) cases are associated with mutations in Cu/Zn superoxide dismutase (SOD1). In this study, we evaluated the structural and functional effects of human A4F and A4V SOD1 protein mutations. We performed an in silico analysis using prediction algorithms of nonsynonymous single‐nucleotide polymorphisms (nsSNPs) associated with the fALS development. Our structural conservation results show that the mutations analyzed (A4V and A4F) were in a highly conserved region. Molecular dynamics simulations using the Linux GROMACS package revealed how these mutations affect protein structure, protein stability, and aggregation. These results suggest that there might be an effect on the SOD1 function. Understanding the molecular basis of disease provides new insights useful for rational drug design and advancing our understanding of the ALS development.
Effects of Pro1266Leu mutation on structure and function of glycoprotein Ib binding domain of von Willebrand factor
Authors: Naqvi Ahmad Abu Turab , Alajmi Mohamed F. , Rehman Tabish , Hussain Afzal , Hassan Imtaiyaz
Published: May 2019

Glycoprotein Ibα (GpIbα) binding ability of A1 domain of von Willebrand factor (vWF) facilitates platelet adhesion that plays a crucial role in maintaining hemostasis and thrombosis at the site of vascular damage. There are both “loss as well as gain of function” mutations observed in this domain. Naturally occurring “gain of function” mutations leave self‐activating impacts on the A1 domain which turns the normal binding to characteristic constitutive binding with GPIbα. These “gain of function” mutations are associated with the von Willebrand disease type 2B. In recent years, studies focused on understanding the mechanism and conformational patterns attached to these phenomena have been conducted, but the conformational pathways leading to such binding patterns are poorly understood as of now. To obtain a microscopic picture of such events for the better understanding of pathways, we used molecular dynamics (MD) simulations along with principal component analysis and normal mode analysis to study the effects of Pro1266Leu (Pro503Leu in structural context) mutation on the structure and function of A1 domain of vWF. MD simulations have provided atomic‐level details of intermolecular motions as a function of time to understand the dynamic behavior of A1 domain of vWF. Comparative analysis of the trajectories obtained from MD simulations of both the wild type and Pro503Leu mutant suggesting appreciable conformational changes in the structure of mutant which might provide a basis for assuming the “gain of function” effects of these mutations on the A1 domain of vWF, resulting in the constitutive binding with GpIbα.
Upregulation of microRNA‐27a inhibits synovial angiogenesis and chondrocyte apoptosis in knee osteoarthritis rats through the inhibition of PLK2
Authors: Liu Wenjing , Zha Zhuqing , Wang Haitao
Published: May 2019

The function of microRNA‐27a (miR‐27a) on synovial angiogenesis and chondrocyte apoptosis in rats with knee osteoarthritis (KOA) by targeting PLK2 is explored in this present study.

The rat model of KOA was conducted by anterior cruciate ligament transection. Rats were injected with miR‐27a mimics, mimics NC, pcDNA3.1‐PLK2 pcDNA3.1, or RLK2 RNAi plasmid via tail vein. A series of assays were used to figure out the functions of miR‐27a and PLK2 in synovial angiogenesis and chondrocyte apoptosis in rats with KOA. Furthermore, the putative binding site between miR‐27a and PLK2 was determined. Downregulated miR‐27a was found in synovial tissues and cartilage tissues of KOA rats. Upregulated miR‐27a and downregulated PLK2 inhibited synovial injury and promoted apoptosis of synovial cells, inhibited synovial angiogenesis, inhibited cartilage injury and chondrocyte apoptosis, inhibited cartilage collagen destruction, and alleviates inflammatory injury of synovial tissue and cartilage tissue in KOA rats. Overexpression of PLK2 reverses the effect of upregulation of miR‐27a on synovial angiogenesis and chondrocyte injury in KOA rats. Our study suggests that upregulation of miR‐27a inhibits synovial angiogenesis and chondrocyte apoptosis in KOA rats through the inhibition of PLK2.
CT‐measured skeletal muscle mass used to assess frailty in patients with head and neck cancer
Authors: Zwart Aniek T. , van der Hoorn Anouk , van Ooijen Peter M.A. , Steenbakkers Roel J.H.M. , de Bock Geertruida H. , Halmos Gyorgy B.
Published: May 2019

Background

Skeletal muscle depletion or sarcopenia is related to multiple adverse clinical outcome. However, frailty questionnaires are currently applied in the daily practice to identify patients who are potentially (un)suitable for treatment but are time consuming and straining for patients and the clinician. Screening for sarcopenia in patients with head and neck cancer (HNC) could be a promising fast biomarker for frailty. Our objective was to quantify sarcopenia with pre‐treatment low skeletal muscle mass from routinely obtained neck computed tomography scans at level of third cervical vertebra in patients diagnosed with HNC and evaluate its association with frailty.

Methods

A total of 112 HNC patients with Stages III and IV disease were included from a prospective databiobank. The amount of skeletal muscle mass was retrospectively defined using the skeletal muscle index (SMI). Correlation analysis between SMI and continuous frailty data and the observer agreement were analysed with Pearson's r correlation coefficients. Sarcopenia was present when SMI felt below previously published non‐gender specific thresholds (<43.2 cm2/m2). Frailty was evaluated by Geriatrics 8 (G8), Groningen Frailty Indicator, Timed Up and Go test, and Malnutrition Universal Screening Tool. A univariate and multivariate logistic regression analysis was performed for all patients and men separately to obtain odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results

The cohort included 82 men (73%) and 30 women (27%), with a total mean age of 63 (±9) years. The observer agreement for cross‐sectional measurements was excellent for both intra‐observer variability (r = 0.99, P < 0.001) and inter‐observer variability (r = 0.98, P < 0.001). SMI correlated best with G8 frailty score (r = 0.38, P < 0.001) and did not differ per gender. Sarcopenia was present in 54 (48%) patients, whereof 25 (46%) men and 29 (54%) women. Prevalence of frailty was between 5% and 54% depending on the used screening tool. The multivariate regression analysis for all patients and men separately isolated the G8 questionnaire as the only independent variable associated with sarcopenia (OR 0.76, 95% CI 0.66–0.89, P < 0.001 and OR 0.76, 95% CI 0.66–0.88, P < 0.001, respectively).

Conclusions

This is the first study that demonstrates that sarcopenia is independently associated with frailty based on the G8 questionnaire in HNC patients. These results suggest that in the future, screening for sarcopenia on routinely obtained neck computed tomography scans may replace time consuming frailty questionnaires and help to select the (un)suitable patients for therapy, which is highly clinically relevant.
Synthesis and Antibacterial Evaluation of Some New Thiazole‐Based Polyheterocyclic Ring Systems
Authors: Abdel‐Latif Ehab , Almatari Altaf S. , Abd‐ElGhani Ghada E.
Published: May 2019

2‐Cyanoacetamido‐thiazole (1) was employed as a key for the construction of 6‐cyano‐7‐oxo‐7H‐thiazolo[3,2‐a]pyrimidine (4) which underwent reaction with hydrazine, malononitrile, ethyl cyanoacetate, and/or various 1,3‐bi‐nuclophilic reagents furnished the corresponding tri‐heterocyclic and tetra‐heterocyclic ring systems 5–12. In addition, the reactions of 1 with various types of arylidene‐malononitriles and/or ethyl 3‐aryl‐2‐cyanoacrylates yielded the corresponding 1‐thiazolyl‐pyridine derivatives 16 and 20, respectively. Furthermore, treatment of the precursor 1 with carbon disulfide and methyl iodide afforded the ketene dithioacetal derivative 21 which cyclized upon heating with hydrazine and/or 2‐aminobenzimidazole into the corresponding derivatives of N‐(thiazol‐2‐yl)‐1H‐pyrazole‐4‐carboxamide 22 and N‐(thiazol‐2‐yl)benzimidazo[1,2‐a]‐pyrimidine‐3‐carboxamide 23. The antibacterial properties of these thiazole‐based heterocycles were examined against panel of two bacterial strains.
Sitosterolemia—10 years observation in two sisters
Authors: Veit Lara , Allegri Machado Gabriella , Bürer Céline , Speer Oliver , Häberle Johannes
Published: May 2019

Familial hypercholesterolemia due to heterozygous low‐density lipoprotein‐receptor mutations is a common inborn errors of metabolism. Secondary hypercholesterolemia due to a defect in phytosterol metabolism is far less common and may escape diagnosis during the work‐up of patients with dyslipidemias. Here we report on two sisters with the rare, autosomal recessive condition, sitosterolemia. This disease is caused by mutations in a defective adenosine triphosphate‐binding cassette sterol excretion transporter, leading to highly elevated plant sterol concentrations in tissues and to a wide range of symptoms. After a delayed diagnosis, treatment with a diet low in plant lipids plus ezetimibe to block the absorption of sterols corrected most of the clinical and biochemical signs of the disease. We followed the two patients for over 10 years and report their initial presentation and long‐term response to treatment.
Genetic defect of the sodium‐dependent multivitamin transporter: A treatable disease, mimicking biotinidase deficiency
Authors: Schwantje Marit , de Sain‐van der Velden Monique , Jans Judith , van Gassen Koen , Dorrepaal Charlotte , Koop Klaas , Visser Gepke
Published: May 2019

The sodium‐dependent multivitamin transporter that facilitates the uptake of the water‐soluble vitamins biotin, pantothenic acid, and the vitamin‐like substance lipoate is coded by the SLC5A6 gene. Variants in this gene cause a relatively novel treatable metabolic disorder. Here we describe the second case. A 17‐month‐old girl presented with hypoglycemia (2.0 mmol/L) and severe metabolic acidosis (pH 6.87), leading to resuscitation. Her history revealed feeding problems from birth and poor weight gain. Metabolic investigation showed elevated plasma C3‐carnitine and C5‐OH‐carnitine. Urine analysis showed persistently elevated excretion of 3‐OH‐isovaleric acid. Biochemically, the combination of elevated C5‐OH‐carnitine and increased excretion of 3‐OH‐isovaleric acid seemed compatible with biotinidase deficiency. Supplementation with biotin was started. Biotinidase activity in plasma showed only marginally decreased activity, which was considered insufficient explanation for her clinical symptoms. Subsequent trio‐based whole exome sequencing revealed compound heterozygosity for variants in the SLC5A6 gene. Upon increasing the dosage of biotin supplementation and introduction of pantothenic acid supplementation, a striking clinical improvement was seen.
Physical layer authentication of off‐body channels by probabilistic neural networks
Authors: Raida Zbynek
Published: May 2019

A probabilistic neural network (PNN) for the authentication of an off‐body channel of a wireless body area network is discussed in this paper. The off‐body channel is authenticated by radio‐frequency fingerprints of on‐body channels. Thanks to a relatively high stationarity of on‐body channels, a reasonable probability of radio‐frequency fingerprinting identification is reached. Radio‐frequency fingerprints are used to train a probabilistic neural network playing the role of an authentication key. The authentication process can be efficiently controlled by setting tolerance zones of the network. Functionality of the concept was proven by computer simulations.