bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Sensitivity Analysis and Adaptive Stochastic Sampling of a Subsurface-Flow Model Using Active Subspaces
Authors: Erdal Daniel , Cirpka Olaf A.
Published: April 2019

Abstract. Integrated hydrological modelling of domains with complex subsurface features requires many highly uncertain parameters. Performing a global uncertainty analysis using an ensemble of model runs can help bring clarity which of these parameters really influence system behavior, and for which high parameter uncertainty does not result in similarly high uncertainty of model predictions. However, already creating a sufficiently large ensemble of model simulation for the global sensitivity analysis can be challenging, as many combinations of model parameters can lead to unrealistic model behavior. In this work we use the method of active subspaces to perform a global sensitivity analysis. While building-up the ensemble, we use the already existing ensemble members to construct low-order meta-models based on the first two active subspace dimensions. The meta-models are used to pre-determine whether a random parameter combination in the stochastic sampling is likely to result in unrealistic behavior, so that such a parameter combination is excluded without running the computationally expensive full model. An important reason for choosing the active subspace method is that both the activity score of the global sensitivity analysis and the meta-models can easily be understood and visualized. We test the approach on a subsurface flow model including uncertain hydraulic parameter, uncertain boundary conditions, and uncertain geological structure. We show that sufficiently detailed active subspaces exist for most observations of interest. The pre-selection by the meta-model significantly reduces the number of full model runs that must be rejected due to unrealistic behavior. An essential but difficult part in active subspace sampling using complex models is approximating the gradient of the simulated observation with respect to all parameters. We show that this can effectively and meaningful be done with second-order polynomials.
Clock Ticks “Are We Moving Towards the Right Global Cooling”
Authors: Verma Rinku , - Sivappa
Published: April 2019

Climate change happenings over the few decades have altered the global precipitation. Increase in temperature due to land form change, deforestation, moving towards agriculture, uncontrolled urbanization and development etc., leads to decrease in precipitation. Various case studies referring to the above and the measures to restore the climate change with right global cooling has been addressed. Clear variation needs to be drawn in relation to increasing precipitation due to rising concentration of anthropogenic greenhouse gases in the atmosphere, to that by checking precipitation by increasing the tree cover. Which precipitation would really bring about a balance in the disturbed environment and which precipitation would be useful /beneficial to mankind in the long run is the real question?
Leren en werken voor vluchtelingen: beleid en interventies in drie grote gemeenten.
Authors: Klaver Jeanine , Dagevos Jaco , Dekker Rianne , Geuijen Karin , Odé Arend
Published: April 2019

Education and work for refugees. Policies and interventions in three major cities in the Netherlands.

Municipalities have increasingly adjusted their policies in order to better respond to the problematic social and economic participation of permit holders. The core elements within the chosen policies seem to consist of an early activation, combining language and professional training, and providing customization in the support of these newcomers. In this article, this policy change has been studied in the municipalities of Amsterdam, Rotterdam and Utrecht. It becomes clear that a more successful approach only succeeds when permit holders are offered additional and tailored support. For all three municipalities, this means that more permit holders are reached by the available support measures and that local policy makers can better respond to individual needs and possibilities. In addition, these municipalities pay more attention for sustainable labour market participation. At the same time, it is evident that no rapid successes are being made with this new course. In particular, more vulnerable permit holders, including those with low levels of education and women, are not always reached by municipalities. We also see that many of these newcomers must be supported for a long time, even if after have found a place on the labour market. Therefore, evidence suggests that without additional measures there is a good chance that the perspective on social and economic participation for many permit holders in the Netherlands will be extremely limited.
De zin en onzin van opkomst(bevordering)
Authors: van Ostaaijen Julien , Jacobs Daan , van Zuydam Sabine
Published: April 2019

Sense and nonsense of voter mobilization

Reflection and debate initiates academically inspired discussions on issues that are on the current policy agenda.
DENK. Factoren voor het succes, de kenmerken van de achterban en het bereiken van nieuwe stemmers
Authors: Vermeulen Floris , Kranendonk Maria
Published: April 2019

DENK. Factors for succes, characteristics of the supporters and how to reach new voters

Reflection and debate initiates academically inspired discussions on issues that are on the current policy agenda.
Restorative justice capacities in Middle Eastern culture and society: towards a hybrid model of juvenile justice in Palestine
Authors: Qafisheh Mutaz , Wardak Ali
Published: April 2019

Restorative justice capacities in Middle Eastern culture and society: towards a hybrid model of juvenile justice in Palestine

Alongside the state juvenile justice system, various forms of non-state justice providers are strongly prevalent in Palestine. Although the state juvenile justice has evolved into a modern system, it lacks adequate human, professional and infrastructural capacities to provide effective justice to all children. This field research has identified key non-state justice providers in Palestine and reveals that they are more accessible and speedy and also place more emphasis on peacemaking and reconciliation than the state justice system. It also reveals that in the processes of justice dispensation, occasional violation of children’s rights takes place within some of the male-dominated non-state justice providers. In order to minimise rights violation, while capitalising on the restorative capacities of non-state justice providers, a ‘hybrid model of juvenile justice in Palestine’ has been developed and is proposed. It is argued in this article that the ‘hybrid model’ not only promises to provide a coherent framework of links between Palestinian state juvenile justice and non-state justice providers, but also has the capacity to minimise rights violation through proposed internal and external oversight mechanisms. It is further maintained that translating the hybrid model into practice may result in the provision of more accessible, inclusive and restorative juvenile justice to all children in Palestine.
Photometric Properties of Retroreflective Materials in Dependence on their Structure and Angle of Illumination
Authors: Pościk Adam , Szkudlarek Joanna , Owczarek Grzegorz
Published: April 2019

The purpose of high visibility products is to reflect light at a low angle towards the source, such as vehicle headlights. The article presents measurements of the photometric properties of selected retroreflective materials made either of microlenses on a textile base or microprisms on a polymer base. The effects of the structure of the textile and polymer layers on the photometric properties of high visibility materials is analysed and the test methods applied are described.
Influence of the Spatial Structure of Carbon Fibres on the Strength Properties of a Carbon Composite
Authors: Juraszek Janusz
Published: April 2019

Advanced lightweight materials such as laminated composites with carbon fibres, cylindrical shells and laminated plates are used in modern civil engineering structures, such as wind power stations, as well as in the defence and automotive industries. This encourages the search for new composite structures characterised by adequately high durability and lightness. This paper determined the strains and displacements of composite specimens reinforced with carbon fibre using an innovative strain measurement method based on the fibre Bragg grating. The results of theoretical analyses were also compared using classical laminating theory and the FEM numerical method with the results of practical tests, which were carried out using the 4-point bending test, characterised by a constant bending moment between the supports and the considerable impact of shearing forces. The actual, highest values of normal stresses that the carbon fibre reinforced sample could transfer were determined. The results obtained may be useful in the design of critically stressed engineering elements, for example, civil structures.
The Relation Between Parents’ Physical Activity and Their Interest in Physical Culture of Their Early School Children
Authors: Madejski Eligiusz , Giża Edyta , Madejski Przemysław
Published: April 2019

Introduction: Active and systematic participation of parents in physical activity may have a direct impact on instilling such behaviors in their children. The aim of research was to assess parents’ physical activity and their interest in physical culture of their early school children.
Material and methods: The survey was carried out in the school year 2014/2015. 374 families from Mielec County, representing the rural environment, were randomly selected for the survey. Among the sent questionnaires 356 returned, however 54 of them were completed incorrectly. Eventually, 302 questionnaires were qualified for further analysis. The method of diagnostic survey was applied in the research, which takes advantage of survey as the basic technique.
Results: The detailed analysis of the results showed that physical activity among the majority of mothers and fathers was at a very low level. Both education and socioeconomic status have a significant influence on the level of parents’ physical activity. The empirical research also revealed a very low level of most parents’ (68.5%) interest in physical culture of their children.
Conclusions: On the basis of the research results it can be found that the participation of children in physical culture depends on their parents’ physical activity, education and socioeconomic status.
Um estudo de caso da mediação proposta para a exposição “Anos 60-70 Um Panorama – Mostra do Acervo” do Museu de Arte Contemporânea do Paraná - MACPR
Authors: Souza Leonardo De , Almeida Leonelo Dell Anhol , Silveira Luciana Martha
Published: April 2019

O objetivo dos museus de arte contemporânea, mais do que proporcionar um ambiente para a apreciação estética das peças, é o de propiciar uma reflexão crítica em seus visitantes. Porém, a informação necessária para se posicionar perante às questões propostas pela arte contemporânea não é proporcionada pela educação escolar. Este projeto visa compreender, por meio de um estudo de caso, o modo como ocorre o planejamento e a realização de visitas mediadas que visem trocas de informação no Museu de Arte Contemporânea do Paraná, objetivando identificar pontos que permitam expandir o acesso a essas informações. Ao compreender como se dão essas trocas de informação, espera-se que seja possível pensar em programas de mediação que incentivem o diálogo entre visitantes e arte.
Formação do educador musical: contribuições de uma abordagem (auto)biográfica
Authors: Almeida Jéssica De
Published: April 2019

Ao pensar as possibilidades de atuação do professor de música, a educação básica apresenta-se como um caminho de desafios e de amplos horizontes para a formação docente. Diante das novas políticas públicas e diretrizes curriculares, torna-se urgente promover o debate sobre a formação do educador musical no que se refere à sua própria trajetória educativa com a música que, na maioria dos casos, não ocorreu na educação básica. Assim, o artigo tem o objetivo de problematizar resultados de uma pesquisa apontando as possibilidades da abordagem teórico-metodológica (auto)biográfica para a formação de professores de música conscientes das implicações de suas experiências com a música e seu ensino na prática pedagógica no ensino regular.
Historia de la arquitectura y el urbanismo en bicicleta. Ibagué, Colombia 2015-2017
Authors: Francel Delgado Andrés Ernesto
Published: April 2019

Los modelos contemporáneos de educación implican la conjunción de varios factores como el aprendizaje simbólico, los hábitos saludables, la disminución de los niveles de contaminación y la transformación de las instituciones educativas para aproximar la academia a las realidades, de modo que se concreten en la transformación de la sociedad y las ciudades. Para este propósito, se presenta el caso de las clases de historia de la arquitectura y urbanismo en bicicleta, desarrolladas en una ciudad colombiana intermedia, con las limitantes de ausencia de infraestructura y cultura ciclista. Se presentan reflexiones sobre la implementación de esta metodología de aprendizaje que permite motivación, recuerdo, impacto urbano y activismo sobre las políticas públicas, con lo cual se generan espacios replicables en otras ciudades con estas mismas condiciones. Palabras clave: Bicieducación. Bicinfraestructura. Historia del Urbanismo. Historia de la Arquitectura. Pedagogía.
Vinhos de Altitude no Estado de Santa Catarina: a firmação de uma identidade
Authors: Nodari Eunice Sueli , Frank Zephyr
Published: April 2019

No presente artigo será abordada a história recente da vitivinicultura no estado de Santa Catarina - Brasil, discutindo os territórios que trabalham com os, assim denominados, “Vinhos de Altitude”. Mostraremos que a vitivinicultura não pode mais ser percebida de forma idílica, como uma empresa de pequenos agricultores rurais. Atualmente, a produção de vinhos é vista como uma importante commodity, em que a conquista de prêmios em competições nacionais e internacionais abre os mercados para consumidores nacionais e internacionais. O estabelecimento de vinícolas com alto padrão de qualidade, visando as camadas sociais mais altas, tem crescido nos últimos anos.Palavras-chave: História Ambiental. Vinhos de Altitude. Commodity.
Francisella tularensis enters a double membraned compartment following cell-cell transfer
Authors: Steele Shaun P , Chamberlain Zach , Park Jason , Kawula Thomas H
Published: April 2019

Previously, we found that phagocytic cells ingest bacteria directly from the cytosol of infected cells without killing the initially infected cell (Steele et al., 2016). Here, we explored the events immediately following bacterial transfer. Francisella tularensis bacteria acquired from infected cells were found within double-membrane vesicles partially composed from the donor cell plasma membrane. As with phagosomal escape, the F. tularensis Type VI Secretion System (T6SS) was required for vacuole escape. We constructed a T6SS inducible strain and established conditions where this strain is trapped in vacuoles of cells infected through bacterial transfer. Using this strain we identified bacterial transfer events in the lungs of infected mice, demonstrating that this process occurs in infected animals. These data and electron microscopy analysis of the transfer event revealed that macrophages acquire cytoplasm and membrane components of other cells through a process that is distinct from, but related to phagocytosis.
A fixed agreement—consequences of brood size manipulation on alternation in blue tits
Authors: Griffioen Maaike , Müller Wendt , Iserbyt Arne
Published: April 2019

Recent studies have proposed that conditional cooperation may resolve sexual conflict over the amount of care provided by each parent. Such conditional cooperation may allow parents to equalize their investment by alternating their provisioning visits. This alternated pattern of male and female visits, that is, alternation, is thought to stimulate each other’s investment leading to higher levels of provisioning and potential benefits for offspring development. However, experimental studies testing the role of alternation as an adaptive parental strategy to negotiate the level of investment are still absent. Therefore, we manipulated blue tit (Cyanistes caeruleus) parents by temporarily changing their brood sizes to induce changes in demand and thus visit rates. Parents were expected to visit more—assuming that prey sizes were constant—and alternate at higher levels when confronted with an enlarged brood given the greater potential for sexual conflict. In contrast, in reduced broods visit rates and alternation may become lower due to the smaller investment that is needed for reduced broods. We show that the level of alternation did not differ in response to the manipulated brood sizes, despite a directional change in visit rates for enlarged and reduced broods as expected. Nestlings did not benefit from high levels of alternation as no effects on nestling mass gain were present in either of the different manipulations. These findings indicate that alternation does not serve as a mechanism to motivate each other to feed at higher rates. Parents hence appeared to be inflexible in their level of alternation. We therefore suggest that the level of alternation might reflect a fixed agreement about the relative investment by each of the caring parents.
Normal spermatogenesis in Fank1 (fibronectin type 3 and ankyrin repeat domains 1) mutant mice
Authors: Zhang Jintao , Zhang Xin , Zhang Yue , Zeng Wentao , Zhao Shuqin , Liu Mingxi
Published: April 2019

Background

The fibronectin type 3 and ankyrin repeat domains 1 gene, Fank1, is an ancient, evolutionarily conserved gene present in vertebrates. Short-hairpin RNA (shRNA)-based knockdown transgenic mice have oligospermia caused by an increase in apoptotic germ cells. In this study, we investigated the in vivo function of Fank1.

Methods

In this study, we generated Fank1-knockout mice using the CRISPR/Cas9 system. We then investigated the phenotype and in vivo function of Fank1. Testes and epididymis tissues were analyzed by histological and immunofluorescence staining. Apoptotic cells were analyzed in terminal deoxynucleotidyl transferase dUTP nick end-labeling assays. Fertility and sperm counts were also evaluated. The GTEx database were used to assess gene expression quantitative trait loci and mRNA expression of candidate genes and genes neighboring single nucleotide polymorphisms was analyzed by quantitative RT-PCR.

Results

In contrast to the Fank1-knockdown model, no significant changes in epididymal sperm content and the number of apoptotic cells were observed in Fank1−/− homozygotes. In addition, a different pattern of Dusp1, Klk1b21 and Klk1b27 mRNA expression was detected in Fank1-knockout testis. These results reveal differences in the molecular changes between Fank1-knockdown mice and Fank1-knockout mice and provide a basic resource for population genetics studies.
Laser‐Associated Selective Metallization of Ceramic Surface with Infrared Nanosecond Laser Technology
Authors: Wang Li , Fu Zongwen , Suess‐Wolf Robert , Travitzky Nahum , Greil Peter , Franke Joerg
Published: April 2019

A new approach for the metallization of ceramic substrate by Infrared Nanosecond Laser Technology (INLT) is developed in the present work. The activation of ceramic surface by INLT with a wavelength of 1064 nm promotes the chemical electroless copper plating. The laser associated modification of ceramics in terms of laser ablation is also determined. The ablation threshold for the Al2O3‐Cu2O ceramic used in this study is identified at 3.82 and 1.86 J cm−2 with respect to single pulse irradiation and multiple pulses irradiation, respectively. The thickness of plated copper layer on the activated ceramic surface is strongly dependent on the laser fluence and can reach the maximum thickness at the fluence nearby the ablation threshold.
Rational Design of Carbon Nanomaterials for Electrochemical Sodium Storage and Capture
Authors: Kim Jiyoung , Choi Min Sung , Shin Kang Ho , Kota Manikantan , Kang Yingbo , Lee Soojung , Lee Jun Young , Park Ho Seok
Published: April 2019

Electrochemical sodium storage and capture are considered an attractive technology owing to the natural abundance, low cost, safety, and cleanness of sodium, and the higher efficiency of the electrochemical system compared to fossil‐fuel‐based counterparts. Considering that the sodium‐ion chemistry often largely deviates from the lithium‐based one despite the physical and chemical similarities, the architecture and chemical structure of electrode materials should be designed for highly efficient sodium storage and capture technologies. Here, the rational design in the structure and chemistry of carbon materials for sodium‐ion batteries (SIBs), sodium‐ion capacitors (SICs), and capacitive deionization (CDI) applications is comprehensively reviewed. Types and features of carbon materials are classified into ordered and disordered carbons as well as nanodimensional and nanoporous carbons, covering the effect of synthesis parameters on the carbon structure and chemistry. The sodium storage mechanism and performance of these carbon materials are correlated with the key structural/chemical factors, including the interlayer spacing, crystallite size, porous characteristics, micro/nanostructure, morphology, surface chemistry, heteroatom incorporation, and hybridization. Finally, perspectives on current impediment and future research directions into the development of practical SIBs, SICs, and CDI are also provided.
Gate‐Tunable Graphene–WSe2 Heterojunctions at the Schottky–Mott Limit
Authors: LaGasse Samuel W. , Dhakras Prathamesh , Watanabe Kenji , Taniguchi Takashi , Lee Ji Ung
Published: April 2019

Metal–semiconductor interfaces, known as Schottky junctions, have long been hindered by defects and impurities. Such imperfections dominate the electrical characteristics of the junction by pinning the metal Fermi energy. Here, a graphene–WSe2 p‐type Schottky junction, which exhibits a lack of Fermi level pinning, is studied. The Schottky junction displays near‐ideal diode characteristics with large gate tunability and small leakage currents. Using a gate electrostatically coupled to the WSe2 channel to tune the Schottky barrier height, the Schottky–Mott limit is probed in a single device. As a special manifestation of the tunable Schottky barrier, a diode with a dynamically controlled ideality factor is demonstrated.
Surgical quality improvement programs in Japan and USA: Report from the collaborative projects between Japanese Society of Gastroenterological Surgery and American College of Surgeons National Surgical Quality Improvement Program
Authors: Marubashi Shigeru , Liu Jessica Y. , Miyata Hiroaki , Cohen Mark E. , Ko Clifford Y. , Seto Yasuyuki , Gotoh Mitsukazu
Published: April 2019

The Japanese Society of Gastroenterological Surgery (JSGS) and the American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP) have collaboratively developed several clinical projects since 2011 using two nationwide clinical registries with the goal of achieving further improvement of surgical quality in both countries. In this review, the historical viewpoints and the collaboration between JSGS and ACS and their use of nationwide registries [National Clinical Database (NCD) and NSQIP] for research are reviewed. We have carried out a joint project, the 30‐day Mortality Risk Model Study and, currently, we are working on several joint projects such as the Morbidity‐Mortality Study, Japan‐USA Calibration Study, Geriatric Study, and Safety Culture Study as well as Auditing in JSGS/NCD with reference to the NSQIP method. These joint projects will continue to provide us with important information and data to drive improvements in surgical care in both countries. This will also help us to identify any unknown weaknesses in the health‐care systems of the USA and Japan.
Effect of particle orientation on the drag force in random arrays of prolate ellipsoids in low‐Reynolds‐number flows
Authors: Li Xinyang , Jiang Ming , Huang Zheqing , Zhou Qiang
Published: April 2019

Direct numerical simulations are performed to study the effect of particle orientation on flows through fixed random arrays of prolate ellipsoids at low Reynolds numbers. The Hermans orientation factor and Beta distribution are introduced to quantify the mean orientation and orientation deviation of the particles. The simulation results show that the effect of particle orientation is profound especially when the solid volume fraction and the aspect ratio are large. With the increase of Hermans orientation factors, the drag force decreases when the flow follows a reference direction defined by the average direction of all particles' semi‐major axes, while increases when the flow is perpendicular to the reference direction. Comparisons show that the traditional drag force correlations for ellipsoidal particles significantly under‐predict the drag force. Based on current simulation results, new drag relations are proposed for prolate ellipsoidal particles at arbitrary aspect ratios, Hermans orientation factors and solid volume fractions.
Severe digital malformations in a rare variant of fibrodysplasia ossificans progressiva
Authors: Gucev Zoran , Tasic Velibor , Plaseska‐Karanfilska Dijana , Dimishkovska Marija , Laban Nevenka , Bozinovski Zoran , Kostovski Marko , Saveski Alek , Polenakovic Momir , Towler O. Will , Shore Eileen M. , Kaplan Frederick S.
Published: April 2019

A 16‐year‐old girl with a history of nontraumatic swelling of both forearms, osteochondromas of the knees, heterotopic ossification of the neck and back, severe malformations of all digits with hypoplastic or absent nails, alopecia partialis of the scalp, and moderate cognitive impairment was seen for diagnostic evaluation. Whole exome sequencing identified an activating mutation of ACVR1 (c.983G > A; p.Gly328Glu) which confirmed a suspected FOP variant. The delayed diagnosis of an FOP variant in this patient could have been avoided if the significance of severe digital malformations had been recognized, especially in the setting of progressive heterotopic ossification.
Structure and Bonding in [Sb@In8Sb12]3− and [Sb@In8Sb12]5−
Authors: Liu Chao , Tkachenko Nikolay V. , Popov Ivan A. , Fedik Nikita , Min Xue , Xu Cong‐Qiao , Li Jun , McGrady John E. , Boldyrev Alexander I. , Sun Zhong‐Ming
Published: April 2019

We report the characterization of the compound [K([2.2.2]crypt)]4[In8Sb13], which proves to contain a 1:1 mixture of [Sb@In8Sb12]3− and [Sb@In8Sb12]5−. The tri‐anion displays perfect Th symmetry, the first completely inorganic molecule to do so, and contains eight equivalent In3+ centers in a cube. The gas‐phase potential energy surface of the penta‐anion has eight equivalent minima where the extra pair of electrons is localized on one In+ center, and these minima are linked by low‐lying transition states where the electron pair is delocalized over two adjacent centers. The best fit to the electron density is obtained from a model where the structure of the 5− cluster lies close to the gas‐phase transition state.
Organocatalytic, Enantioselective Dichlorination of Unfunctionalized Alkenes
Authors: Wedek Volker , Van Lommel Ruben , Daniliuc Constantin G. , De Proft Frank , Hennecke Ulrich
Published: April 2019

The use of a new class of unsymmetrical cinchona‐alkaloid‐based, phthalazine‐bridged organocatalysts enabled the highly enantioselective dichlorination of unfunctionalized alkenes. In combination with the electrophilic chlorinating agent 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH) and triethylsilyl chloride (TES‐Cl) as the source of nucleophilic chloride, 1‐aryl‐2‐alkyl alkenes were dichlorinated with enantioselectivities of up to 94:6 er. Initial mechanistic investigations suggest that no free chlorine is formed, and by replacement of the chloride by fluoride, enantioselective chlorofluorinations of alkenes are possible.
Synthesis, structural studies and antimicrobial evaluation of nickel (II) complexes of NNS tridentate thiosemicarbazone based ligands
Authors: Ibrahim Ahmed B.M. , Farh Micheal K. , Mayer Peter
Published: April 2019

Synthesis and characterization of three nickel complexes [NiCl(L1)] 1, [NiCl(L2)] 2 and [NiCl(L3)] 3 are described {HL1 = 4‐(2,5‐dimethoxyphenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide, HL2 = 4‐(3‐nitrophenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide and HL3 = 4‐(2,4‐dimethoxyphenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide} and among the tridentate ligands HL3 is reported for the first time. The structures of the complexes were assigned based on CHNS microanalysis, spectroscopic (IR & UV–Vis.) data and solution conductivity studies. The absence of any magnetism for the complexes proved their square planar geometry. Single crystals of complex 1 were grown and analyzed by XRD analysis which confirmed the complex planarity as each Ni atom connects to three (two nitrogen and one sulfur) atoms from the thiosemicarbazone ligand and an additional chlorine atom. Packing of the complex 1 in the crystal lattice was proved to stabilize via intermolecular hydrogen bonds. Antimicrobial activities of 1–3 were studied in vitro against fungal and bacterial species and, in several instances, the complexes possessed improved antibacterial behavior in comparison to chloramphenicol.
Peroxidase activity of new mixed‐valence cobalt complexes with ligands derived from pyridoxal
Authors: Fontana Liniquer André , Siqueira Josiéli Demetrio , Ceolin Joice , Iglesias Bernardo Almeida , Piquini Paulo Cesar , Neves Ademir , Back Davi Fernando
Published: April 2019

New mixed‐valence cobalt complexes with ligands derived from pyridoxal were synthesized and characterized, and their application as mimetics of the peroxidase enzyme was investigated. Single‐crystal X‐ray diffraction was used to analyze all complex structures in the solid state and their electrochemical behavior was investigated. A reactivity pattern was observed in the complex synthesis regarding the cobalt compounds from which analogous zwitterionic derivatives were obtained. The importance of these compounds lies in understanding their behavior in an oxidizing environment and evaluating whether they can activate hydrogen peroxide to oxidize phenolic compounds. In nature, enzymes called peroxidases, which efficiently oxidize phenolic compounds, trigger many reactions involving the activation of hydrogen peroxide to oxidize organic substrates. However, these enzymes present several disadvantages, including denaturation and elevated costs. Therefore, these limitations can be overcome by expanding research into the study of synthetic catalysts for the oxidation of phenolic compounds using hydrogen peroxide, which is a highly relevant field of bioinorganic chemistry.
Synthesis and Evaluation of Ruthenium 2‐Alkyl‐6‐mercaptophenolate Catalysts for Olefin Metathesis
Authors: Wang Tao , Yu Xiaobo , Zhang Huiqing , Wu Shutao , Guo Weijie , Wang Jianhui
Published: April 2019

A series of ruthenium carbene catalysts containing 2‐sulfidophenolate bidentate ligand with an ortho‐substituent next to the oxygen atom were synthesized. The molecular structure of ruthenium carbene complex containing 2‐isopropyl‐6‐sulfidophenolate ligand was confirmed through single crystal X‐ray diffraction. An oxygen atom can be found in the opposite position of the N‐heterocyclic carbene (NHC) based on the steric hindrance and strong trans‐effects of the NHC ligand. The ruthenium carbene catalyst can catalyze ring‐opening metathesis polymerization (ROMP) reaction of norbornene with high activity and Z‐selectivity and cross metathesis (CM) reactions of terminal alkenes with (Z)‐but‐2‐ene‐1,4‐diol to give Z‐olefin products (Z/E ratios, 70:30–89:11) in low yields (13%–38%). When AlCl3 was added into the CM reactions, yields (51%–88%) were considerably improved and process becomes highly selective for E‐olefin products (E/Z ratios, 79:21–96:4). Similar to other ruthenium carbene catalysts, these new complexes can tolerate different functional groups.
Densities and Viscosities of Oleic Acid at Atmospheric Pressure
Authors: Sagdeev Damir , Gabitov Il'giz , Isyanov Chingiz , Khairutdinov Vener , Farakhov Mansur , Zaripov Zufar , Abdulagatov Ilmutdin
Published: April 2019

The densities of oleic acid were measured over the temperature range from (293 to 459) K at atmospheric pressure using a densimeter based on the modified hydrostatic weighing method. The dynamic viscosities of the same oleic acid sample were measured using a capillary viscometer (VPZ‐2 m) in the range from (293 to 363) K at atmospheric pressure. The combined expanded uncertainty of the density, atmospheric pressure, viscosity, and temperature measurements at the 95% confidence level with a coverage factor of k = 2 is estimated to be 0.15%, 1.0%, 3.5%, and 15 mK, respectively. The values of uncertainty for density and viscosity include the effects of purity and calibration (total expanded uncertainty). These experimental data were used to develop wide‐range correlations for the density and viscosity based on theoretically confirmed Arrhenius–Andrade and Vogel‐Tamman‐Fulcher (VTF) models. The value of the glass temperature (
T
g=179.78 K.) for the oleic acid was estimated using the VTF parameters derived from the present viscosity measurements. To additionally validate the reliability of the measured density data, the same oleic acid samples were measured using the pycnometric method. The present study showed that the densities measured using the modified hydrostatic weighing densimeter (HWD) agree with the values obtained using the pycnometric method within 0.09% for Sample 1 and 0.25% for Sample 2.
Chemical and mechanical degradation of silicone rubber under two compression loads in simulated proton‐exchange membrane fuel‐cell environments
Authors: Wang Zhiqiang , Tan Jinzhu , Wang Yankang , Liu Zenghui , Feng Qiuyue
Published: April 2019

Long‐term chemical and mechanical stability of gaskets in proton‐exchange membrane (PEM) fuel cells is critical to the sealing and normal operation of these fuel cells. In this study, the chemical and mechanical degradation of a silicone rubber was investigated. Two compression loads and two simulated environments were used. The weight change of sample was monitored. Optical microscopy was applied to observe the morphological changes on the specimen surface. Attenuated total reflection (ATR)–Fourier transform infrared (FTIR) spectroscopy and X‐ray photoelectron spectroscopy (XPS) were used to investigate the chemical changes on the surface of specimens after exposure to the simulated solutions and subjection to compression loads over time. A compression stress‐relaxation test was used to elucidate the stress‐relaxation property changes of the specimens after exposure to the simulated fuel‐cell environments and the compression loads. Optical microscopy showed that the surface morphology of the specimens changed from initially smooth to slightly rough followed by crack initiation and finally propagation. The ATR–FTIR and XPS results indicate that the surface chemistry of the specimens significantly changed via decrosslinking and chain scission after exposure to the simulated environments and compression loads over time. The compression stress‐relaxation test results indicate that the mechanical properties of the silicone rubber specimens changed significantly. We found that both the acid concentration of the test solution and the compression load significantly affected the degradation of the silicone rubber material. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47855.
Synthesis of novel gefitinib‐based derivatives and their anticancer activity
Authors: Sharma Mrunal J. , Kumar Maushmi S. , Murahari Manikanta , Mayur Y. C.
Published: April 2019

Drug latentiation is a process of modifying a drug molecule structurally to improve its binding affinity as well as increasing the drug–receptor interactions and potentiate its therapeutic potential. In the quest for discovering more potent epidermal growth factor receptor (EGFR) inhibitors, gefitinib‐based derivatives were designed by simple structural modification at the secondary amine of gefitinib by N‐alkylation. Three gefitinib derivatives (gefitinib‐NB, ‐NP, and ‐NIP) were synthesized by N‐alkylation and phase transfer catalysis. Structural characterization, physicochemical parameters such as solubility, log
P, and p
K
a were determined. Molecular docking studies were carried out to investigate the binding interactions at the active site. Further drug‐bovine serum albumin (BSA) protein and drug‐calf thymus (CT) DNA interactions were performed to understand the pharmacokinetics of the synthesized derivatives. All the compounds were screened for preliminary in vitro cytotoxic activity against A549, A431 lung, and MDA‐MB‐231 breast cancer cell lines by MTT assay. The gefitinib‐NP and gefitinib‐NB derivatives exhibited strong cytotoxic activity compared with gefitinib. They also showed higher drug‐BSA and drug‐DNA interactions. Molecular docking studies showed the orientation and binding interactions with the EGFR as well as with BSA and CT DNA. The results establish a strong correlation between the experimental and molecular docking studies. EGFR inhibition studies were also carried out for the derivatives and we identified the NP derivative of gefitinib as a potential lead compound. The gefitinib‐based derivatives reported herein are cytotoxic agents and can be tested for further pharmacokinetic profiles and toxicity studies which might be helpful for designing more potent gefitinib‐based derivatives in the future.
Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis
Authors: Carvalheiro Tiago , Affandi Alsya J. , Malvar‐Fernández Beatriz , Dullemond Ilse , Cossu Marta , Ottria Andrea , Mertens Jorre S. , Giovannone Barbara , Bonte‐Mineur Femke , Kok Marc R. , Marut Wioleta , Reedquist Kris A. , Radstake Timothy R. , García Samuel
Published: April 2019

Objective

To analyze the potential role of semaphorin 4A (Sema4A) in inflammatory and fibrotic processes involved in the pathology of systemic sclerosis (SSc).

Methods

Sema4A levels in the plasma of healthy controls (n = 11) and SSc patients (n = 20) were determined by enzyme‐linked immunosorbent assay (ELISA). The expression of Sema4A and its receptors in monocytes and CD4+ T cells from healthy controls and SSc patients (n = 6–7 per group) was determined by ELISA and flow cytometry. Th17 cytokine production by CD4+ T cells (n = 5–7) was analyzed by ELISA and flow cytometry. The production of inflammatory mediators and extracellular matrix (ECM) components by dermal fibroblast cells (n = 6) was analyzed by quantitative polymerase chain reaction, ELISA, Western blotting, confocal microscopy, and ECM deposition assay.

Results

Plasma levels of Sema4A, and Sema4A expression by circulating monocytes and CD4+ T cells, were significantly higher in SSc patients than in healthy controls (P < 0.05). Inflammatory mediators significantly up‐regulated the secretion of Sema4A by monocytes and CD4+ T cells from SSc patients (P < 0.05 versus unstimulated SSc cells). Functional assays showed that Sema4A significantly enhanced the expression of Th17 cytokines induced by CD3/CD28 in total CD4+ T cells as well in different CD4+ T cell subsets (P < 0.05 versus unstimulated SSc cells). Finally, Sema4A induced a profibrotic phenotype in dermal fibroblasts from both healthy controls and SSc patients, which was abrogated by blocking or silencing the expression of Sema4A receptors.

Conclusion

Our findings indicate that Sema4A plays direct and dual roles in promoting inflammation and fibrosis, 2 main features of SSc, suggesting that Sema4A might be a novel therapeutic target in SSc.
Incidence and lifetime risk of hospitalization and surgery for diverticular disease
Authors: Sköldberg F , Granlund J , Discacciati A , Hjern F , Schmidt P T , Olén O
Published: April 2019

Background

Studies on incidence rates of first-time colonic diverticular disease are few, and population-based estimates of lifetime risk are lacking. In this observational study, the incidence, admission rates and lifetime risks of hospitalization and surgery for diverticular disease were investigated.

Methods

Considering the entire Swedish population as an open cohort, incidence and admission rates, and lifetime risk estimates (considering death as a competing risk) of hospitalization and surgery for diverticular disease were calculated using data from cross-linked national registers and population statistics from 1987 to 2010.

Results

In total, there were 144 107 hospital admissions for diverticular disease in 95 049 individual patients. Of these, 17 599 were admissions with bowel resection or stoma formation in 16 824 patients. The total number of person-years in the population during the study period was 213 949 897. Age-standardized incidence rates were 47·4 (95 per cent c.i. 47·1 to 47·7) for first-time hospitalization with diverticular disease and 8·4 (8·2 to 8·5) per 100 000 person-years for diverticular disease surgery. The corresponding admission rates (including readmissions) were 70·8 (70·4 to 71·2) and 8·7 (8·6 to 8·9) per 100 000 person-years. Following an increase in 1990–1994, rates stabilized. Based on incidence and mortality rates from 2000 to 2010, the estimated remaining lifetime risk of hospitalization from 30 years of age was 3·1 per cent in men and 5·0 per cent in women. The corresponding risk of surgery was 0·5 per cent in men and 0·8 per cent in women.

Conclusion

Diverticular disease is a common reason for hospital admission, particularly in women, but rates are stable and the lifetime risk of surgery is low.
Simultaneous quantitative analysis of phosphocreatine, creatine and creatinine in plasma of children by HPLC–MS/MS method: Application to a pharmacokinetic study in children with viral myocarditis
Authors: Sun Ning , Li Qirui , Zhao Libo , He Huan , Zhang Meng , Wang Xiaoling
Published: April 2019

A simple and rapid HPLC–MS/MS method was developed and validated for simultaneous measurement of phosphocreatine and its metabolites creatine and creatinine in children's plasma. A 50 μL aliquot of plasma was prepared by protein precipitation with acetonitrile–water (1000 μL, 1:1, v/v) followed by separation on a Hypersil Gold C18 column (35°C) with gradient mobile phase consisting of 2 mm ammonium acetate aqueous solution (pH 10) and methanol at a flow rate of 0.3 mL/min and analyzed by mass spectrometry in both positive (phosphocreatine) and negative (creatine and creatinine) ion multiple reaction monitoring mode. Good linearity (r > 0.99) was obtained for the three analytes. The intra‐day and inter‐day values of CV were <5.46% (−13.09% ≤ RE ≤ 2.57%). The average recoveries of the three analytes were 70.9–97.5%. No obvious impact was found for the quantitation of three analytes in normal, hemolyzed and hyperlipemic plasma. In the end, this method was successfully applied to a pharmacokinetic study of phosphocreatine in children (six cases) with viral myocarditis of children after intravenous infusion of 2 g of the test drug. The pharmacokinetc parameters of phosphocreatine/creatine were as follows: t1/2 0.24/0.83 h, Tmax 0.49/0.55 h, Cmax 47.34/59.29 μg/mL, AUClast 17.07/59.63 h μg/mL, AUCinf 17.16/79.01 h μg/mL and MRT 0.29/0.67 h.
The association of cancer‐related fatigue with all‐cause mortality of colorectal and endometrial cancer survivors: Results from the population‐based PROFILES registry
Authors: Adam Salome , van de Poll‐Franse Lonneke V. , Mols Floortje , Ezendam Nicole P. M. , de Hingh Ignace H. J. T. , Arndt Volker , Thong Melissa S. Y.
Published: April 2019

Purpose

Cancer‐related fatigue (CRF) is one of the most prevalent symptoms experienced by cancer survivors. However, researchers are only beginning to elucidate the risk factors, underlying mechanism(s), and its association with other outcomes. Research on the association between CRF and mortality is limited.

Methods

The study sample comprised 2059 short‐term (<5 years postdiagnosis) cancer survivors from four PROFILES registry studies. Survivors diagnosed with stage I‐III colorectal cancer (CRC) or stage I‐III endometrial cancer (EC), with no evidence of disease, were identified and followed‐up by the Netherlands Cancer Registry. Fatigue was assessed with the Fatigue Assessment Scale. Cox proportional hazards models adjusted for demographic, clinical, and lifestyle characteristics were performed to assess the association of CRF with all‐cause mortality. Date of censoring was February 1, 2017.

Results

Prevalence of CRF varied between 35.8% (male CRC) and 43.6% (female CRC). After a median follow‐up period of 9.0 years, a total of 408 survivors (20%) had died. CRF was associated with increased all‐cause mortality in male CRC survivors (HRadj = 1.75, 95% CI [1.31‐2.33]). This association remained statistically significant after excluding survivors experiencing anhedonia. For female CRC (HRadj = 1.32, 95% CI [0.90‐1.97]) and EC (HRadj = 1.27, 95% CI [0.84‐1.90]) survivors, there was no significant association with all‐cause mortality for the fatigued group in multivariable analyses.

Conclusion

Our study found that CRF is significantly associated with all‐cause mortality in male CRC survivors, irrespective of potential confounders. This result suggests that clinicians should increase their attention towards the recognition and treatment of CRF.
Generating Cyan Fluorescence with De Novo Tripeptides: An In Vitro Mutation Study on the Role of Single Amino Acid Residues and Their Sequence
Authors: Guo Jun , Ramachandran Srinivasan , Zhong Ruibo , Lal Ratnesh , Zhang Feng
Published: April 2019

Amino acids are natural choices as building blocks when developing biofunctional entities owing to their superior diversity and versatile physicochemical properties compared to nucleotide bases. A simple permutation of the amino acids creates a broad palette of proteins and these have been successfully engineered into useful biofunctional agents. For example, the intrinsic ultraviolet fluorescence of phenylalanine and tryptophan has been engineered to emit in the visible spectrum, which has broad applications for imaging/sensing probes, photothermal therapy agents, optogenetic switches, etc. Nature produces more colorful coats/furs, feathers/hairs, and eyes through various biochemical modifications of tyrosine‐based pigmentation. However, it is challenging to modulate the fluorescence wavelength from the UV to the visible region through oligopeptides. Herein, we report an innovative approach to obtain cyan fluorescence by using de novo tripeptides containing glycine, tyrosine, and lysine, which form robust dimer structures under moderate oxidizing conditions. Through an in vitro mutation approach, we deduce that both the amino acids and their sequence play significant roles in modulating the fluorescence. We believe this work holds great promise for developing novel cell imaging and resonance energy‐transfer‐based fluorescent probes.