bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronically Double‐Layered Metal Boride Hollow Nanoprism as an Excellent and Robust Water Oxidation Electrocatalysts
Authors: Han HyukSu , Hong Yu‐Rim , Woo Jungwook , Mhin Sungwook , Kim Kang Min , Kwon Jiseok , Choi Heechae , Chung Yong‐Chae , Song Taeseup
Published: February 2019

Metal–metalloid compounds have been paid much attention as new high‐performance water oxidation catalysts due to their exceptional durability for water oxidation in alkaline media originating from the multi‐dimensional covalent bonding of the metalloid with the surrounding metal atoms. However, compared to the excellent stability, a relatively low catalytic activity of metal‐metalloids often limits their practical application as high‐performance water oxidation catalysts. Here, for the first time, disclosed is a novel self‐templating strategy combined with atomic layer deposition (ALD) to design the electrochemically active and stable quaternary metal boride (vanadium‐doped cobalt nickel boride, VCNB), hollow nanoprism by inducing electronic double layers on the surface. The incorporation of V in a double‐layered structure can substantially increase the number of surface active sites with unsaturated electronic structure. Furthermore, the induced electronic double layers of V can effectively protect the dissolution of the surface active sites. In addition, density functional theory (DFT) calculations reveal that the impressive water oxidation properties of VCNB originate from the synergetic physicochemical effects of the different metal elements, Co and B as active sites, Ni as a surface electronic structure modifier, and V as a charge carrier transporter and supplier.
The Turner syndrome research registry: Creating equipoise between investigators and participants
Authors: Prakash Siddharth K. , Lugo‐Ruiz Soniely , Rivera‐Dávila Michelle , Rubio Nunilo , Shah Avni N. , Knickmeyer Rebecca C. , Scurlock Cindy , Crenshaw Melissa , Davis Shanlee M. , Lorigan Gary A. , Dorfman Aaron T. , Rubin Karen , Maslen Cheryl , Bamba Vaneeta , Kruszka Paul , Silberbach Michael ,   Scientific Advisory Board of the TSRR
Published: February 2019

To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.
A Green Synthetic Approach towards Polyarylated Oxazoles via Iodine‐Catalyzed One‐Pot sp3 C−H Functionalization in Water: From Natural Product Synthesis To Photophysical Studies
Authors: Banerji Biswadip , Adhikary Saswati , Majumder Leena , Ghosh Saswati
Published: February 2019

A ‘green’ methodology for the convenient synthesis of specific regioisomers of polysubstituted oxazoles through iodine catalyzed, water‐mediated, aerobic oxidative C(sp3)−H functionalization of primary amines has been developed. This mild and regioselective domino procedure does not require toxic peroxides, transition metals and organic solvents. The versatility of this methodology was demonstrated by preparing a natural product, texaline. It is also scalable and has a wide substrate scope. This methodology opens up a simple avenue for the synthesis of polyarylated oxazoles from various readily available amines as well as 1,2‐diketones and acyloins (α‐hydroxyl ketones) in moderate to excellent yields. Furthermore, these highly substituted oxazole molecules showed excellent fluorescence properties and thus have enormous potential to be a new type of fluorescent probe for use in medicinal applications and materials science.
Zn(L‐proline)2 as an efficient and reusable catalyst for the multi‐component synthesis of pyran‐annulated heterocyclic compounds
Authors: Tahmassebi Daryoush , Blevins John E. , Gerardot Shori S.
Published: February 2019

We have developed a simple, straightforward and highly efficient multi‐component one‐pot synthesis of 2‐amino‐3‐cyano‐4H‐pyrans and pyran‐annulated heterocyclic compounds. Zn(L‐proline)2 has been utilized as a mild and efficient Lewis acid catalyst for the three‐component reaction of aromatic aldehydes, malononitrile and enolizable C‐H acids or activated phenols to synthesize pyran‐annulated scaffolds. 3‐Methyl‐1‐phenyl‐2‐pyrazolin‐5‐one, 4‐hydroxycoumarine, dimedone, 4‐hydroxy‐6‐methyl‐2‐pyrone, resorcinol, 1‐naphthol and 2‐naphthol were used as activated C‐H acids. The products were isolated in high yields via vacuum filtration and without using any chromatography. The Zn(L‐proline)2 was recovered and reused in another reaction (three times) without significant loss of activity.
Enhanced room temperature phosphorescence of palladium‐porphyrin by dual‐ordered structure of micelle‐hybridized supramolecular gels
Authors: Xue Ruru , Wei Saisai , Dong Xuelin , Zhu Tingyu , Yuan Jianhui , Feng Lu , Wang Qin , Yang Yajiang , Wang Hong
Published: February 2019

Meso‐tetra (carbonyl phenyl) porphyrin palladium (denoted as Pd‐TCPP), a typical organometallic compound, was used as phosphor and entrapped in micelle‐hybridized supramolecular hydrogels. As a novel matrix material of phosphors, the hybrid system was comprised of two ordered structures: a supramolecular 3D network structure formed by the self‐assembly of the gelator and the micelles formed from a Gemini surfactant. The dual‐ordered structure of the system was verified by SEM, TEM and fluorescent optical microscopy. By contrast with corresponding mono‐ordered structure, the room temperature phosphorescence (RTP) of Pd‐TCPP was greatly enhanced by the dual‐ordered structure of the system. The enhancement mechanism of RTP was studied by hydrophobicity of the system, RTP quenching and disassembly of supramolecular aggregates. Enhanced RTP could be attributed to the efficient inhibition of the non‐radiative transition of Pd‐TCPP by dual‐ordered structures. Significantly, the RTP intensity of Pd‐TCPP can be adjusted by changing the concentration of Gemini surfactants. Furthermore, deoxygenation was not required in this hybrid system in comparison with corresponding mono‐component systems.
Cage–ladder‐structure, phosphorus‐containing polyhedral oligomeric silsesquinoxanes as promising reactive‐type flame retardants for epoxy resin
Authors: Li Shengnan , Zhao Xiaojuan , Liu Xinghua , Yang Xin , Yu Ran , Zhang Ying , Huang Wei , Deng Kuilin
Published: February 2019

We synthesized a novel cage–ladder‐structure, phosphorus‐containing polyhedral oligomeric silsesquinoxane (CLEP–DOPO–POSS) via the hydrolytic condensation of 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO)–vinyl trimethoxysilane (VTMS) with 2‐(3,4‐epoxycyclohexyl) ethyl trimethoxysilane and then incorporated it into epoxy resins (EPs) in different ratios with thermal curing technology. The structure of CLEP–DOPO–POSS was confirmed by Fourier transform infrared spectroscopy, NMR spectroscopy (1H‐NMR and 29Si‐NMR), matrix‐assisted laser desorption ionization time‐of‐flight, and X‐ray diffraction. The thermal stability, mechanical properties and flame retardancy effect of CLEP–DOPO–POSS on EP were comprehensively evaluated via thermogravimetric analysis (TGA), dynamic mechanical analysis, universal tensile testing, limiting oxygen index (LOI) measurement, UL‐94 testing, and cone calorimetry. The flame‐retardant mechanism of the EP modified with CLEP–DOPO–POSS was investigated by TGA–IR, TGA–mass spectrometry, and scanning electron microscopy. The experimental results show that CLEP–DOPO–POSS was homogeneously dispersed in the EP matrix. The LOI value reached 31.9, and the UL‐94 grade passed V‐0 with the presence of only 0.28% P (2.91 phr CLEP–DOPO–POSS). In addition, the EP composite containing CLEP–DOPO–POSS exhibited a better thermal stability and mechanical properties. The flame‐retardant mechanism was attributed to the quenching effect of the phosphorus‐containing free radicals and the formation of phosphorus‐ and silicon‐containing char layers in the condensed phase. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47607.
Personalization of knowledge, personal knowledge ecology, and digital nomadism
Authors: Jarrahi Mohammad Hossein , Philips Gabriela , Sutherland Will , Sawyer Steve , Erickson Ingrid
Published: February 2019

We examine the concept of personal knowledge management using data drawn from our study of digital nomads. We make two contributions: an empirical and conceptual development of knowledge management as it relates to independent workers and an advancement of social informatics that builds on Gibson's ecological perspective. Digital nomads provide an empirical basis to better understand how knowledge management is shifting from organization‐centric, with its concomitant emphasis on organizational information systems, to worker‐centric, which relies on personal knowledge ecologies. We advance this concept as a combination of personal knowledge management activities and the digital technologies that support them. Our data make clear that individuals are the locus of personal knowledge ecologies, but these ecologies are embedded in a larger community of collaborators, clients, and peers who are often extensively mediated by digital technologies. This embedding and mediation are at the core of the sociotechnical arrangements that define the personal knowledge ecologies that we document.
Cu‐Catalyzed [4+1] Annulation toward Indolo[2,1‐a]isoquinolines through Oxidative C(sp3)/C(sp2)−H Bond Bifunctionalization
Authors: Zhang Tian‐Shu , Zhao Qi , Hao Wen‐Juan , Tu Shu‐Jiang , Jiang Bo
Published: February 2019

A Cu‐catalyzed [4+1] annulation of N‐aryl‐1,2,3,4‐tetrahydroisoquinolines (N‐aryl THIQs) with α‐diazoketones has been established under oxidative conditions, leading to the construction of a series of indolo[2,1‐a]isoquinolines with generally good yields. The reaction enables dediazotized dicarbonylation of α‐diazoketones, creating direct C(sp3)/C(sp2)−H bond bifunctionalization to access tetracyclic aza‐heterocyclic skeletons.
Revisiting the benefits of diversity representation in window operation models for building performance simulation
Authors: Tahmasebi Farhang , Mahdavi Ardeshir
Published: February 2019

Die Vorteile der Darstellung der Vielfalt in Fensteröffnungsmodellen für die Gebäudesimulation. Um die potenziellen Vorteile der Bereitstellung von Nutzerverhaltensmodellen mit verschiedenen Nutzerinformationen zu untersuchen, wurde der Fensteröffnungsbetrieb durch Nutzer eines Großraumbüros aggregiert und auf individueller Ebene modelliert. Anschließend wurde ein Modell des Großraumbüros unter Einbeziehung der entwickelten Modelle und Ströme aufgezeichneter Daten kalibriert, um die Vorhersageleistung der Modelle und ihren Beitrag zur Verbesserung der Zuverlässigkeit von Gebäude performance‐Bewertungen zu analysieren. Den Ergebnissen zufolge übertrafen die individuellen Fensteroperationsmodelle das aggregierte Modell, indem sie den Spitzenwert und die Variation des Fensterbetriebs über alle Nutzer im freilaufenden Betrieb erfassten, was zu einer besseren Bewertung des thermischen Komforts führte. Die individuellen Modelle ergaben jedoch eine Überschätzung des Spitzenwärmebedarfs im Vergleich zum Referenzwert, der auf dem tatsächlichen Fensterbetrieb in einem einzigen Jahr basiert.
Berechnung des sommerlichen Wärmeschutzes
Authors: Ivankovic Goran , Hafellner Hans , Kautsch Peter
Published: February 2019

Die zeitgenössische Architektur, die zunehmend transparente Gebäudehüllen vorsieht, führt oft zu unerwünschten Effekten in Bezug auf die behagliche Raumtemperatur im Sommer und somit rückt der Schutz des Gebäudes vor Überhitzung immer stärker in den Vordergrund. Es wird die Auswirkung von unterschiedlichen Klimata auf die Berechnung der sommerlichen Überwärmung untersucht. Es wird eine Büro‐ und eine Wohnnutzung mit Bauteilaufbauten aus Massivbau‐Beton, Massivbau‐Ziegel, Holzmassivbau und Holzrahmenbau simuliert. Die Ergebnisse der Gebäudesimulation werden mit den Berechnungsergebnissen gemäß des derzeit gültigen und in der Praxis verankerten vereinfachten Nachweisverfahren gemäß ÖNORM B 8110‐3 [3] gegenübergestellt und ein Vorschlag für die Überarbeitung der Norm dargelegt.
Apprasial of the surface anatomy of the Thorax in an adolescent population
Authors: Nadesan Thiasha , Keough Natalie , Suleman Farhana E. , Lockhat Zarina , van Schoor Albert N.
Published: February 2019

Surface anatomy is considered a fundamental part of anatomy curricula and clinical practice. Recent studies have reappraised surface anatomy using CT, but the adolescent age group has yet to be appraised. Sixty adolescent thoracoabdominal CT scans (aged 12–18 years) were examined. The surface anatomy of the central veins, cardiac apex, diaphragmatic openings, and structures in relation to the sternal angle plane were analyzed. The results showed that the brachiocephalic vein (left and right) formed mostly posterior to the sternoclavicular joint. The superior vena cava formed close to the second costal cartilage, ±16.3 mm to the right of the midline. The apex of the heart was located in relation to the fifth intercostal space; ±78.6 mm to the left of the midline. The caval hiatus was in relation to T9 and T10; the esophageal hiatus was at T10; whereas the aortic hiatus was at T11. The sternal angle plane was in relation to the upper half of T5, which was also where the bifurcations of the trachea and pulmonary trunk were observed. The SVC/azygos vein junction and the concavity of the aortic arch were observed to be more than 10 mm superior to this plane. The results of this study further highlight the substantial variability of the surface anatomy between age groups. It also emphasizes the notion that surface anatomy is a dynamic variable and cannot be treated as a static observation. Clin. Anat. 32:762–769, 2019. © 2019 Wiley Periodicals, Inc.
Competency‐based education: An evolutionary higher education business model
Authors: Rivers Carlos , Gibson Shonda , Contreras Erica , Livingston Tina , Hanson Paula
Published: February 2019

As new education models emerge in the higher education landscape, constituents and stakeholders increasingly demand greater evidence of the return on investment to the institution. To date, little research has explored and reported the financial underpinnings and outcomes for new models such as Competency‐based Education (Desrochers & Staisloff, 2016, http://rpkgroup.com/wp-content/uploads/2016/10/rpkgroup_cbe_business_model_report_20161018.pdf). This case study explores and reports on potential revenues and expenses associated with launching competency‐based programs, identify break‐even points, and forecast timelines for projecting returns on investments. The analyses included in this study encompass the entirety of the program, from inception to current state. A narrative and visual description reveals that the competency‐based program has grown to be self‐sustaining within five years. In the sixth year, enrollment trends predict a new record for the program, with forecasts indicating increased return on investment for the university by year end. The results support the notion that institutions should expect a competency‐based program of this type to break‐even by the fifth year of operation (Desrochers & Staisloff, 2016, http://rpkgroup.com/wp-content/uploads/2016/10/rpkgroup_cbe_business_model_report_20161018.pdf). Additionally, this work seeks to serve as a foundation of exploration and reporting of evolutionary business models related to innovative approaches in higher education such as competency‐based education.
Full‐Loop Simulation of Gas‐Solids Flow in a Pilot‐Scale Circulating Fluidized Bed
Authors: Wang Min , Wu Yingya , Shi Xiaogang , Lan Xingying , Wang Chengxiu , Gao Jinsen
Published: February 2019

In order to study the system hydrodynamics in a circulating fluidized bed (CFB), a 3D full‐loop simulation was conducted for a pilot‐scale CFB. The Eulerian‐Eulerian two‐fluid model with the kinetic theory of granular theory helped to simulate the gas‐solids flow in the CFB. The system hydrodynamics including pressure balance, vectors of gas and solids, distribution of solids holdup, and instantaneous circulating rates were obtained to get a comprehensive understanding of the system. It was predicted that the main driving force was the pressure drop of the storage tank. The storage height and valve opening were critical operating factors to control the riser operation. The effects of operating conditions including solids circulating rates and superficial gas velocity on the hydrodynamics were investigated to provide guidance for the stable operation of the CFB system.
Cover Picture: Collective Synthesis of Schilancidilactones A, B and Schilancitrilactones A, B, C, 20‐epi‐Schilancitrilactone A (Chin. J. Chem. 3/2019)
Authors: Wang Hengtao , Wang Liang , Li Yihang , Zhang Xiunan , Tang Pingping
Published: February 2019

The cover picture shows Schilancidilactones A, B and Schilancitrilactones A, B, C all belong to schinortriterpenoid. Preliminary bioassay shows some of them possess fascinating bioactivities, such as antitumor, antihepatitis, and anti‐HIV‐1 activities. The total synthesis of Schilancidilactones A, B and Schilancitrilactones A, B, C has been accomplished from the common intermediates for the first time by Tang group. An intramolecular radical cyclization, late‐stage halogenation and AIBN‐mediated or Ni‐catalyzed intermolecular radical cross coupling reaction were employed as the key steps. More details are discussed in the article by Tang et al. on page 255–268.

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Evaluating functional covariate‐environment interactions in the Cox regression model
Authors: Zhou Ling , Li Haoqi , Lin Huazhen , Song Peter X.‐K.
Published: February 2019

Children exposed to mixtures of endocrine disrupting compounds such as phthalates are at high risk of experiencing significant friction in their growth and sexual maturation. This article is primarily motivated by a study that aims to assess the toxicants‐modified effects of risk factors related to the hazards of early or delayed onset of puberty among children living in Mexico City. To address the hypothesis of potential nonlinear modification of covariate effects, we propose a new Cox regression model with multiple functional covariate‐environment interactions, which allows covariate effects to be altered nonlinearly by mixtures of exposed toxicants. This new class of models is rather flexible and includes many existing semiparametric Cox models as special cases. To achieve efficient estimation, we develop the global partial likelihood method of inference, in which we establish key large‐sample results, including estimation consistency, asymptotic normality, semiparametric efficiency and the generalized likelihood ratio test for both parameters and nonparametric functions. The proposed methodology is examined via simulation studies and applied to the analysis of the motivating data, where maternal exposures to phthalates during the third trimester of pregnancy are found to be important risk modifiers for the age of attaining the first stage of puberty. The Canadian Journal of Statistics 47: 204–221; 2019 © 2019 Statistical Society of Canada
Meta‐analysis on the association between the frequency of tooth brushing and diabetes mellitus risk
Authors: Fu Wenning , Lv Chuanzhu , Zou Li , Song Fujian , Zeng Xiantao , Wang Chao , Yan Shijiao , Gan Yong , Chen Fan , Lu Zuxun , Cao Shiyi
Published: February 2019

Background and Objective

Epidemiological studies suggested that the frequency of tooth brushing might be associated with the risk of diabetes mellitus (DM), but the results were inconsistent, and no systematic review was conducted to focus on this topic. In this meta‐analysis, we synthesized available observational epidemiological evidences to identify the association between tooth brushing and DM risk and investigate the potential dose‐response relationship of them.

Methods

We searched PubMed and Embase from their inception through December 2017 to identify observational studies examining the association between tooth brushing and the risk of DM. Reference lists from retrieved articles were also reviewed. We quantitatively combined results of the included studies using a random‐effects model. Dose‐response meta‐analysis was conducted to further examine the effect of tooth brushing frequency on DM risk.

Results

We identified 20 relevant studies (one cohort study, 14 case‐control studies, and 5 cross‐sectional studies) involving 161 189 participants and 10 884 patients with DM. Compared with the highest tooth brushing frequency, the lowest level was significantly associated with an increased risk of DM (OR 1.32; 95% CI, 1.19‐1.47), and there was no significant heterogeneity across the included studies (p = 0.119, I2 = 28.1%).

Exclusion of any single study did not materially alter the combined risk estimate. The dose‐response analysis indicated that the summary odds of DM for an increment of one time of tooth brushing per day was 1.20 (95% CI, 1.16‐1.24).

Conclusions

Integrated epidemiological evidence supports the hypothesis that low frequency of tooth brushing may be a risk factor of DM, and lower frequencies of tooth brushing were significantly associated with higher risk of DM.
Correlation of creatinine‐ and specific gravity‐normalized free and glucuronidated urine cannabinoid concentrations following smoked, vaporized, and oral cannabis in frequent and occasional cannabis users
Authors: Huestis Marilyn A. , Blount Benjamin C. , Milan Daniel F. , Newmeyer Matthew N. , Schroeder Jennifer , Smith Michael L.
Published: February 2019

Variability in urine dilution complicates urine cannabinoid test interpretation. Normalizing urine cannabinoid concentrations to specific gravity (SG) or creatinine was proposed to account for donors' hydration states. In this study, all urine voids were individually collected from eight frequent and eight occasional cannabis users for up to 85 hours after each received on separate occasions 50.6 mg Δ9‐tetrahydrocannabinol (THC) by smoking, vaporization, and oral ingestion in a randomized, within‐subject, double‐blind, double‐dummy, placebo‐controlled protocol. Each urine void was analyzed for 11 cannabinoids and phase I and II metabolites by liquid chromatography−tandem mass spectrometry (LC–MS/MS), SG, and creatinine. Normalized urine concentrations were log10 transformed to create normal distributions, and Pearson correlation coefficients determined the degree of association between the two normalization methods. Repeated‐measures linear regression determined if the degree of association differed by frequent or occasional cannabis use, or route of administration after adjusting for gender and time since dosing. Of 1880 urine samples examined, only 11‐nor‐9‐carboxy‐THC (THCCOOH), THCCOOH‐glucuronide, THC‐glucuronide, and 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabivarin (THCVCOOH) were greater than the method's limits of quantification (LOQs). Associations between SG‐ and creatinine‐normalized concentrations exceeded 0.90. Repeated‐measures regression analysis found small but statistically significant differences in the degree of association between normalization methods for THCCOOH and THCCOOH‐glucuronide in frequent vs occasional smokers, and in THCVCOOH and THC‐glucuronide by route of administration. For the first time, SG‐ and creatinine‐normalized urine cannabinoid concentrations were evaluated in frequent and occasional cannabis users and following oral, smoked, and inhaled cannabis. Both normalization methods reduced variability, improving the interpretation of urine cannabinoid concentrations and methods were strongly correlated.
Contrasting patterns of divergence at the regulatory and sequence level in European Daphnia galeata natural populations
Authors: Ravindran Suda Parimala , Herrmann Maike , Cordellier Mathilde
Published: February 2019

Understanding the genetic basis of local adaptation has long been a focus of evolutionary biology. Recently, there has been increased interest in deciphering the evolutionary role of Daphnia's plasticity and the molecular mechanisms of local adaptation. Using transcriptome data, we assessed the differences in gene expression profiles and sequences in four European Daphnia galeata populations. In total, ~33% of 32,903 transcripts were differentially expressed between populations. Among 10,280 differentially expressed transcripts, 5,209 transcripts deviated from neutral expectations and their population‐specific expression pattern is likely the result of local adaptation processes. Furthermore, a SNP analysis allowed inferring population structure and distribution of genetic variation. The population divergence at the sequence level was comparatively higher than the gene expression level by several orders of magnitude consistent with strong founder effects and lack of gene flow between populations. Using sequence homology, the candidate transcripts were annotated using a comparative genomics approach. Additionally, we also performed a weighted gene co‐expression analysis to identify population‐specific regulatory patterns of transcripts in D. galeata. Thus, we identified candidate transcriptomic regions for local adaptation in this key species of aquatic ecosystems in the absence of any laboratory‐induced stressor.
FinFET 4T‐SRAM operable at near‐threshold region
Authors: Wakemoto Ryota , Takahashi Yasuhiro , Sekine Toshikazu
Published: February 2019

This paper presents a new FinFET 4T‐SRAM that is operated with differential write and single‐end read mode, in the near‐threshold region. To improve the read margin and the write stability, a 3T read/write assist circuit is added to the proposed SRAM. From the HSPICE simulation results in 20‐nm predictive technology model (PTM), the proposed circuit has the same static noise margin (SNM), a shorter read/write time and smaller energy dissipation compared to conventional circuits.
Dendritic cells modulate c‐kit expression on the edge between activation and death
Authors: Simonetti Sonia , Seijas Amairelys B. Barroeta , Natalini Ambra , Vitale Sara , Runci Daniele , Soriani Alessandra , Di Virgilio Antonio , Aricò Eleonora , Gabriele Lucia , Santoni Angela , Di Rosa Francesca
Published: February 2019

Dendritic cells (DCs) are key players in immunity and tolerance. Some DCs express c‐kit, the receptor for stem cell factor (SCF), nevertheless c‐kit functional role and the regulation of its expression in DCs are incompletely defined. We recently demonstrated that autocrine SCF sustains a pro‐survival circuit, and that SCF increases phospho‐AKT in c‐kit+ mouse bone marrow‐derived DCs (BMdDCs).

Herein we observed that CpG and PolyI:C, two stimuli mimicking bacterial and viral nucleic acids respectively, strongly inhibited c‐kit expression by BMdDCs and spleen DCs in vitro and in vivo. Experiments in IFNARI−/− mice showed that IFN‐I pathway was required for c‐kit down‐regulation in cDC1s, but only partially supported it in cDC2s. Furthermore, CpG and PolyI:C strongly inhibited c‐kit mRNA expression. In agreement with the reduced c‐kit levels, SCF pro‐survival activity was impaired. Thus in the presence of exogenously provided SCF, either PolyI:C or CpG induced spleen DC death in 2 days, while at earlier times IL‐6 and IL‐12 production were slightly increased. In contrast, SCF improved survival of unstimulated spleen DCs expressing high c‐kit levels.

Our studies suggest that c‐kit down‐modulation is a previously neglected component of DC response to CpG and PolyI:C, regulating DC survival and ultimately tuning immune response.
Styk1 is specifically expressed in NK1.1+ lymphocytes including NK, γδ T, and iNKT cells in mice, but is dispensable for their ontogeny and function
Authors: Wilharm Anneke , Sandrock Inga , Marotel Marie , Demera Abdi , Naumann Ronald , Walzer Thierry , Prinz Immo
Published: February 2019

Innate T cells, NK cells, and innate‐like lymphocytes (ILCs) share transcriptional signatures that translate into overlapping developmental and functional programs. A prominent example for genes that are highly expressed in NK cells but not in ILCs is serine‐threonine‐tyrosine kinase 1 (Styk1 encoded by Styk1). We found Styk1 to be specifically expressed in lymphocytes positive for Killer cell lectin‐like receptor subfamily B, member 1, also known as CD161 or NK1.1, i.e. in NK cell, αβ iNKT, and γδ NKT cell lineages. To investigate the role of Styk1 in the development and function of NK1.1+ innate T‐cell subsets, we generated and analyzed a novel Styk1null mutant mouse line. Furthermore, we validated Styk1 expression in γδ NKT cells and in thymic, but not in peripheral invariant αβ iNKT cells through ex vivo analysis of a concomitantly generated transgenic Styk1 reporter mouse line. Despite the very specific expression of Styk1 in NK cells, γδ NKT cells, and thymic αβ iNKT, its absence did not alter homeostasis and function of these lineages. Thus, Styk1 expression is specific for NK cells and selected NK‐like innate T‐cell subsets, but dispensable for their development and function.
A Petri Net Approach to Physiologically Based Toxicokinetic Modeling
Authors: Edhlund Ian , Lee Cindy
Published: February 2019

Physiologically based toxicokinetic (PBTK) modeling enables researchers to predict internal tissue concentrations for various species exposed to exogenous compounds through different routes at varying concentrations without having to run in vivo experiments for each scenario. Parameters for the models may be gathered from in vivo or in vitro measurements, cross-species or cross-chemical extrapolations, literature reviews, or other models. The PBTK models, described using ordinary differential equations (ODEs), are then simulated using these parameters for a given compound/exposure/species scenario. Although they are potentially useful for regulatory toxicology, the complexity of ODE programming and simulation remains a barrier for many would-be researchers. Petri nets, a graphical modeling framework, offers a more intuitive approach to PBTK modeling. To demonstrate their utility and ease of use, we present a model of waterborne fluoranthene exposure to rainbow trout (Oncorhynchus mykiss) written and simulated in Snoopy, a graphical Petri net development and simulation software package. We converted an existing ODE PBTK model and evaluated the Petri net model against the ODE model results. The simulated tissue concentrations of the Petri net model closely mirrored the simulated concentrations of the ODE model. To convert the ODE model to a Petri net model, we introduced a new parameter, blood volume (V  BLOOD). Sensitivity analysis found V  BLOOD to be very robust when varied over an order of magnitude. The resulting Petri net PBTK model has a number of advantages over ODE models, while maintaining equivalent predictive functionality. Environ Toxicol Chem 2019;00:1–10. © 2019 SETAC
Understanding the Time‐Dependent Mechanical Behavior of Bimodal Nanoporous Si–Mg Films via Nanoindentation
Authors: Maxwell Tyler L. , Balk Thomas John
Published: February 2019

This study addresses the mechanical response of nanoporous Si–Mg films, which are fabricated using free‐corrosion dealloying and which represent an intriguing form of silicon that may find use as an anode material in lithium‐ion batteries. The porous thin‐film samples, in both the as‐dealloyed and annealed states, are designed to have a final thickness of ≈1 µm so that substrate effects can be avoided during mechanical characterization in both the time and frequency domains. The as‐dealloyed and annealed samples are investigated using a modified continuous stiffness measurement (CSM) technique that optimizes the ability to achieve steady‐state harmonic motion, such that accurate phase angle measurements can be obtained; the as‐dealloyed and annealed samples exhibit distinct phase angles of 1.9° and 2.6°, respectively. Observations made in the time domain suggest that the time dependence of nanoporous Si–Mg stems largely from plasticity. The reduced modulus values of as‐dealloyed and annealed samples are investigated using the CSM technique and have corresponding values of 5.78 and 11.9 GPa, respectively. Similarly, the hardness of as‐dealloyed and annealed samples are 167 and 250 MPa, respectively.
Unique mutation patterns in anaplastic thyroid cancer identified by comprehensive genomic profiling
Authors: Khan Saad A. , Ci Bo , Xie Yang , Gerber David E. , Beg Muhammad S. , Sherman Steven I. , Cabanillas Maria E. , Busaidy Naifa L. , Burtness Barbara A. , Heilmann Andreas M. , Bailey Mark , Ross Jeffrey S. , Sher David J. , Ali Siraj M.
Published: February 2019

Introduction

Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer. Those ATC with genomic alterations (GAs) in TSC2, ALK, and BRAF may respond to targeted therapies.

Methods

Comprehensive genomic profiling on 90 ATC specimens identified base substitutions, short insertions and deletions, amplifications, copy number alterations, and genomic rearrangements in up to 315 cancer‐related genes and 28 genes commonly rearranged in cancer.

Results

Median patient age was 65 (range, 33‐86) years, 50 patients were male. There was a mean of 4.2 GA per case, range 1‐11. The most common GA were TP53 (66%), BRAF (34%), TERT (32%), CDKN2A (32%), and NRAS (26%). BRAF V600E and NRAS/HRAS/KRAS alteration were mutually exclusive. BRAF, CDKN2A, PIK3CA, and JAK2 were more frequent in patients >70 years of age; while myc, PTEN, and NRAS were more common in those ≤50 years.

Conclusion

ATC shows many GA with potential therapeutic significance and suggesting different molecular pathways can lead to ATC.
Resected specimen size: A reliable predictor of severe Frey syndrome after parotidectomy
Authors: Lin Hung‐Ju , Hsiao Jenn‐Ren , Chang Jeffrey S. , Hu Chi‐Lun , Chen Ting‐Rong , Lee Wei‐Ting , Huang Cheng‐Chih , Ou Chun‐Yen , Tsai Shu‐Wei , Lu Yu‐Cheng , Tsai Sen‐Tien , Chao Wen‐Yuan , Chang Chan‐Chi
Published: February 2019

Background

Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers.

Methods

A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome.

Results

A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01‐1.68; P = 0.04).

Conclusions

Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high‐risk patients whose resected specimen size (in largest dimension) is greater than 40 mm.
Low‐dose fludarabine and cyclophosphamide combined with standard dose rituximab (LD‐FCR) is an effective and safe regimen for elderly untreated patients with chronic lymphocytic leukemia: The Israeli CLL study group experience
Authors: Herishanu Yair , Tadmor Tamar , Braester Andrei , Bairey Osnat , Aviv Ariel , Rahimi‐Levene Naomi , Fineman Riva , Levi Itai , Yuklea Mona , Ruchlemer Rosa , Shvidel Lev , Polliack Aaron
Published: February 2019

Chronic lymphocytic leukemia (CLL) is a disease of elderly patients. The fludarabine, cyclophosphamide, and rituximab (FCR) regimen is considered the treatment of choice for young fit patients with CLL; however, this combination is toxic for older patients. At the time this study was first planned and initiated, there was no standard chemo‐immunotherapy regimen regarded as standard therapy for the less fit elderly patient with CLL. Here, we conducted a single‐arm, phase II trial to examine the efficacy and safety of lower‐dose fludarabine and cyclophosphamide combined with a standard dose of rituximab (LD‐FCR) in elderly patients with previously untreated CLL. Forty patients received LD‐FCR and were included in the efficacy analysis. Two patients treated with FC alone were only included in the safety analysis. The median age was 72.7 years (range, 65.0 to 85.0). The overall response and complete response rates were 67.5% and 42.5%, respectively. Median progression‐free survival (PFS) was 35.5 months (95% CI, 29.27‐41.67). Two patients (4.8%) died during the study period. Hematological toxicities and infections were the most common complications encountered; grade 3 to 4 treatment‐related neutropenia occurred in 20 (47.6%) patients. During the entire study follow‐up, 26 patients (61.9%) had all grades of infection including six (14.3%) with neutropenic fever and eight (19%) with grade 3 to 4 non‐neutropenic infections. In conclusion, LD‐FCR is an effective and relatively safe regimen for previously untreated patients with CLL. It has the advantage of being both “time and cost limited” and, even in the era of novel agents, can still be considered when planning treatment for elderly patients without high‐risk biomarkers. However, recent results in fit elderly patients using the combination of bendamustine and rituximab which have achieved longer PFS with good safety profile must be taken into consideration in this regard.
Popular Psychology Myths as a Frame for Character Analysis in High School English
Authors: Heron‐Hruby Alison , Johnson Lindsay Ellis
Published: February 2019

In this classroom study, the authors examine the use of popular psychology myths as a frame for literary analysis in high school English. The study reflects a cultural studies approach to teaching that attends to students’ cultural awareness in interpreting what they read. Previous research has demonstrated that students’ cultural awareness, in general, offers a rich framework for literary interpretation. Students in an Advanced Placement junior English class wrote analytic essays in which they used popular psychology myths, pervasive cultural tropes about human behavior, to evaluate whether characters in F. Scott Fitzgerald ‘s novel The Great Gatsby perpetuate or challenge the myths. Analysis of the essays demonstrated that the myths provided a compelling frame for character analysis, prompting students to consider nuances in character behavior. Moreover, the analysis indicated that the myths offer a way for teachers to prompt students’ understanding of how readers and fiction authors can perpetuate or challenge simplistic notions of human behavior.
EGFR Signaling: Friend or Foe for Cartilage?
Authors: Qin Ling , Beier Frank
Published: February 2019

Recent studies using genetically modified mice, pharmacological approaches, and human samples have highlighted an important role for the epidermal growth factor receptor (EGFR), selected ligands, and downstream components in endochondral bone formation and joint homeostasis. Although most data demonstrate an important function of this pathway in endochondral ossification and articular cartilage growth, conflicting results on its role in osteoarthritis have been reported. In some contexts, inactivation of EGFR signaling has been shown to protect joints from surgically induced osteoarthritis, whereas in others, similar manipulations worsened joint pathology. The current review summarizes recent studies of cartilage EGFR signaling in long bone development and diseases, provides potential explanations for the reported discrepancies, and suggests directions for future work to clarify the potential of this pathway as target for osteoarthritis treatment. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Longitudinal Evaluation of Pain, Flare‐Up, and Emotional Health in Fibrodysplasia Ossificans Progressiva: Analyses of the International FOP Registry
Authors: Peng Ke , Cheung Kin , Lee Arielle , Sieberg Christine , Borsook David , Upadhyay Jaymin
Published: February 2019

Fibrodysplasia ossificans progressiva (FOP) is an ultra‐rare, inherited, connective tissue disease with ∼800 documented cases worldwide. The principal pathological feature of FOP is the transition of skeletal muscle, tendons, ligaments, and fascia into cartilage and bone. This heterotopic ossification (HO) is often preceded by painful soft tissue swellings or flare‐ups that may last several months. For many individuals, experiencing a flare‐up may represent a worsening of their condition and contribute to feelings of anxiety or suppressed affect, both of which are well‐recognized to exacerbate pain perception. To date, much remains unknown regarding the dynamics of pain and emotional health in FOP during flare‐up and also quiescent, non–flare‐up disease phases. In order to elucidate the occurrence and effect of pain in FOP, this study analyzed Patient‐Reported Outcomes Measurement Information System–based questionnaires completed by 99 patients participating in the international FOP Registry over a 30‐month period. We observed that although moderate to severe pain (≥4, 0 to 10 pain scale) was commonly associated with flare‐ups (56% to 67%), surprisingly, 30% to 55% of patients experienced similar pain levels during non–flare‐up states. In those patients reporting pain levels of ≥4, 45% to 74% of patients report experiencing anxiety, depression, or irritability, with 36% to 48% reporting emotional problems during no to mild pain states. Furthermore, independent of the flare‐up status, the severity of pain in FOP patients was found to be significantly anti‐correlated with emotional health, physical health, and overall quality‐of‐life. These findings strongly suggest the need for an improved understanding of pain and emotional health in FOP during flare‐up and quiescent periods. © 2019 The Authors.JBMR Pluspublished by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Hyperphosphatemic Familial Tumoral Calcinosis With Galnt3 Mutation: Transient Response to Anti‐Interleukin‐1 Treatments
Authors: Dauchez Astrid , Souffir Camille , Quartier Pierre , Baujat Geneviève , Briot Karine , Roux Christian
Published: February 2019

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disease caused by mutations in genes involved in phosphate homeostasis and characterized by high serum phosphate concentration and occurrence of ectopic calcifications. Management of the disease includes lowering of phosphate concentration and, when clinically necessary, debulking surgery of calcifications. In addition, high inflammatory disease flares can occur. Our case is about a patient with GALNT3 mutation and several localizations of refractory calcinosis. Assuming HFTC acts like an auto‐inflammatory syndrome, we report the effect of anti‐interleukine‐1 therapies on the evolution of the disease. Anakinra (100 mg, then 200 mg subcutaneous daily) and canakinumab (300 mg every 4 weeks) were sequentially given to the patient. Anti‐IL‐1 therapy was effective in controlling inflammatory flares; however, it did not prevent extension of calcinosis. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Ga2O3/TiO2 semiconductors free of noble metals for the photocatalytic hydrogen production in a water/methanol mixture
Authors: Navarrete Michelle , Cipagauta‐Díaz Sandra , Gómez Ricardo
Published: February 2019

Background

Hydrogen gas (H2) has been identified as a potential energy source to reduce the dependence on fossil fuels. Titanium dioxide (TiO2) semiconductor has been widely used in photocatalysis. Doping of different semiconductor oxides into TiO2 has been documented to enhance its photocatalytic activity. In the present work, β‐Ga2O3/TiO2 (TG) photocatalysts for H2 production by water/methanol mixture decomposition have been synthesized by the sol–gel method varying the β‐Ga2O3 content (3%, 5% and 10% w/w). The catalysts were characterized by X‐ray diffraction, nitrogen adsorption, ultraviolet (UV)‐visible diffuse reflectance, Fourier‐transform infrared spectroscopy, scanning electron microscopy and photoluminescence analysis.

Results

An excellent activity for H2 production under UV light (I0 = 2.0 mW cm–2, λ = 254 nm) was detected in TG composites. Experimental results indicated that the maximum H2 production rate was 1217 µmol g−1 during 5 h of reaction and the TG5 photocatalyst was observed to have a higher activity for photocatalytic H2 evolution than pure Ga2O3 and Pt/TiO2 (TPt) test material. Moreover, a possible mechanism of charge separation in the composite under UV light irradiation was proposed.

Conclusions

The H2 improved activity of TG5 can be attributed to low charge recombination of the e−‐h+ pairs that improves the interfacial charge transfer, which is in agreement with the photoluminescence study. © 2019 Society of Chemical Industry
Dynamical prediction of Indian monsoon: Past and present skill
Authors: Köhn‐Reich Lisei , Bürger Gerd
Published: February 2019

Ongoing development of dynamical atmosphere–ocean general circulation models keep expectations high regarding seasonal predictions of Indian monsoon rainfall. This study compares past and present skill of four currently operating forecasting systems, CFSv2 from NCEP, ENSEMBLES, System 4 and the newest SEAS5 from ECMWF, by analysing correlations of respective hindcasts with observed all‐India summer rainfall. For the common time period 1982–2005, only ENSEMBLES and CFSv2 give significantly skilful forecasts. It is shown that skill is highly dependent on the chosen time period. Especially the intense El Niño of 1997 seems to degrade the predictions, most notably for SEAS4 and SEAS5 which seem to be linked to El Niño too strongly. We show that by discarding that year, a regime shift in the 1990s is no longer visible. Overall, we observe a convergence of skill towards the present with correlations of about 0.4 for CFSv2 and of 0.6 for System 4 and SEAS5.