bluuebunny/crossref_metadata_2025 huggingface dataset:
Scan and Learn: Quick Response Code Enabled Museum for Mobile Learning of Anatomy and Pathology
Authors: Mogali Sreenivasulu Reddy , Vallabhajosyula Ranganath , Ng Chee Hon , Lim Darren , Ang Eng Tat , Abrahams Peter
Published: December 2018

In the past, medical museums played a significant role in anatomy and pathology training. The attraction of medical museums has declined recently due to the emergence of information technology and innovative medical curricula. An innovative mobile learning platform has been developed using quick response (QR) codes for the museum specimens at the Lee Kong Chain School of Medicine, Singapore. High‐quality images of the potted specimens were captured and combined into an album and a video using Adobe Acrobat Pro 9 and Windows Movie Maker, respectively. Subsequently, QR codes were generated linking to PDF documents with annotations, pathology, and clinical history concerning the specimens. Quick response codes were piloted in gastrointestinal teaching module for Year 2 medical students. Survey responses were obtained from students to verify the efficacy of QR as a learning tool. The majority of students either agreed or strongly agreed that it was easy to access the information about the specimen with QR codes (4.47 ± 0.84), while 96% of students agreed that they are able to correlate the specimen with the annotated images (4.56 ± 0.56). The majority of students (78%) agreed that QR codes are useful for their learning (4.22 ± 0.87), while 75% of students felt QR codes motivate them to visit Anatomy Resource Centre. Most of the students agreed that QR codes are useful for revision of materials (4.13 ± 1.07) and independent learning (4.38 ± 0.87). These findings suggest that QR codes are not only effective for students learning but also enhance their exploration experience with the museum specimens.
Sanierung der Hyparschale Magdeburg
Authors: Hentschel Manuel , Schumann Alexander , Ulrich Heinz , Jentzsch Stefan
Published: December 2018

Die Hyparschale in Magdeburg war jahrelang eines der prägenden Beispiele für Schalenbauten in Deutschland. Das von Ulrich Müther im Jahre 1969 errichtete Bauwerk war über Jahrzehnte eines der größten Schalenbauwerke in Deutschland und somit eines der Wahrzeichen in Magdeburg und wurde 1990 in die Denkmalliste aufgenommen. Im Laufe der Zeit traten jedoch erhebliche Mängel und Abnutzungserscheinungen auf, weshalb das Gebäude 1997 gesperrt wurde. Um einen Abriss des einzigartigen Schalentragwerks zu verhindern, wurde jahrelang nach einer geeigneten Sanierungs‐ und Instandsetzungsvariante für die filigrane Tragstruktur gesucht. Im Zuge dessen stellte sich heraus, dass lediglich eine Sanierung mit der Carbonbeton‐Technologie für diesen Anwendungsfall infrage kommen kann, um das Tragwerk vor dem Abriss zu schützen. Das Schalenbauwerk wird mit einer 10 mm dünnen Carbonbetonschicht auf der Ober‐ und Unterseite verstärkt, sodass die historische Tragstruktur nichts an ihrer Filigranität einbüßt. Die Planungen der Sanierung des Schalentragwerks sind weitgehend abgeschlossen und die Bauausführung für das Frühjahr 2019 vorgesehen.
Befestigungen jenseits von Zulassungen
Authors: Knab Franz , Antretter Franz
Published: December 2018

Der in Deutschland bauaufsichtlich geforderte Eignungsnachweis für Befestigungen und Befestigungsmittel erfolgt über nationale und europäische Zulassungs‐ und Bewertungsdokumente. Sofern diese einen geplanten Anwendungsfall nicht abdecken, muss eine Zustimmung im Einzelfall (ZiE) oder eine vorhabenbezogene Bauartgenehmigung (vBg) erwirkt werden.

Der vorliegende Aufsatz gibt einen Überblick über bauaufsichtliche Hintergründe zu den Themen „Befestigungen/Befestigungsmittel nach Zulassung/Bewertung“ und „Erfordernis und Erwirken einer ZiE oder vBg“.

Für beurteilende Ingenieure werden neben einer Zusammenstellung wesentlicher zu behandelnder Themen und dazugehöriger Informationsquellen Hinweise für die Durchführung und Auswertung von In‐situ‐Versuchen gegeben und Erfahrungen zu typischen Problemen im Projektablauf geschildert. Abschließend folgt eine kurze Zusammenstellung verschiedener Fallbeispiele.
Estimating marginal proportions and intraclass correlations with clustered binary data
Authors: Carrasco Josep L. , Pan Yi , Abellana Rosa
Published: December 2018

A logistic regression with random effects model is commonly applied to analyze clustered binary data, and every cluster is assumed to have a different proportion of success. However, it could be of interest to obtain the proportion of success over clusters (i.e. the marginal proportion of success). Furthermore, the degree of correlation among data of the same cluster (intraclass correlation) is also a relevant concept to assess, but when using logistic regression with random effects it is not possible to get an analytical expression of the estimators for marginal proportion and intraclass correlation. In our paper, we assess and compare approaches using different kinds of approximations: based on the logistic‐normal mixed effects model (LN), linear mixed model (LMM), and generalized estimating equations (GEE). The comparisons are completed by using two real data examples and a simulation study. The results show the performance of the approaches strongly depends on the magnitude of the marginal proportion, the intraclass correlation, and the sample size. In general, the reliability of the approaches get worsen with low marginal proportion and large intraclass correlation. LMM and GEE approaches arises as reliable approaches when the sample size is large.
Spectrofluorimetric determination of eptifibatide in human plasma and dosage form
Authors: Elzanfaly Eman Saad , Amer Enas Abdel Hakim , Galal Sara Abdel Basset , Zaazaa Hala Elsayed
Published: December 2018

A spectrofluorimetric method for the determination of eptifibatide is presented based on its native fluorescence. The type of solvent and the wavelength of maximum excitation and emission were carefully selected to optimize the experimental conditions. Under the specified experimental conditions, the linearities obtained between the emission intensity and the corresponding concentrations of eptifibatide were in the range 0.1–2.5 μg/ml for the calibration curve constructed for direct determination of eptifibatide in dosage form and 0.05–2.2 μg/ml for the calibration curve constructed in spiked human plasma with a good correlation coefficient (r > 0.99). The lower limit of quantification for the calibration curve constructed in human plasma was 0.05 μg/ml. Recovery results for eptifibatide in spiked plasma samples and in dosage form, represented as mean ± % RSD, were 95.17 ± 1.94 and 100.29 ± 1.33 respectively. The suggested procedures were validated according to the International Conference on Harmonization (ICH) guidelines for the direct determination of eptifibatide in its pure form and dosage form and United States Food and Drug Administration (US FDA) Guidance for Industry, Bioanalytical Method Validation for the assay of eptifibatide in human plasma.
Sustainable development and research and development intensity in U.S. manufacturing firms
Authors: Kabongo Jean D.
Published: December 2018

Across manufacturing sectors, mounting regulatory pressures motivate the adoption of innovative sustainable practices to help address and improve environmental performance. Sustainable practices, however, face many challenges to minimize negative environmental impacts while conserving energy and natural resources. This study seeks to understand the effect of research and development intensity on dimensions of environmental performance in manufacturing firms. Using data from U.S. corporations over the period from 1991 through 2015, we find that sustainable practices are associated with a higher level of negative environmental ratings. In addition, the level of environmental concerns tends to decrease with firm investments in research and development intensity over time. These findings suggest that bigger firms are likely to report a higher level of environmental concerns due to their experimentation with sustainable practices. These firms are also likely to reduce negative environmental ratings over time and realize economies of scale with sustainable manufacturing.
Keep your eye on…
Authors: Knopf Alison
Published: December 2018

Possible inaccuracy of ADHD diagnoses in younger children

Lack of evidence for primary care interventions to prevent child abuse

Need to report suspected abuse or neglect as required by state law
Eltrombopag in long‐term management of pediatric thrombocytopenia
Authors: Shah Sanjay J. , Etzl Michael M.
Published: December 2018

Key Clinical Message

Eltrombopag is a thrombopoietin receptor agonist that may be effective in a broad range of thrombocytopenias of distinct etiology. We have observed rapid, robust, and sustained responses to eltrombopag in two young patients with refractory thrombocytopenia, one with primary immune thrombocytopenia and the other with Evans syndrome.
Microwave Transparent Catalytic Falling‐Film Microreactor for Automated Operation
Authors: Krtschil Ulrich , Löb Patrick , Schütt Christian , Zapf Ralf , James Rachel , Bonrath Werner , Medlock Jonathan
Published: December 2018

Falling‐film microreactors at different scales were developed to study heterogeneously catalyzed gas‐liquid reactions under microwave irradiation, as part of the EU FP7 project MAPSYN. At pilot scale, this device formed the core part of a fully automated demonstration plant which was used for semi‐hydrogenation reactions at an industrial site. The microchannels of the reaction plate were coated with novel selective catalysts. A special fiber‐optical sensor applicable under microwave irradiation and needed for controlling the liquid level in the sump via the flow rate of the discharge pump was developed and electrically connected with the automation system.
Recent Advances in Radical‐Mediated C—C Bond Fragmentation of Non‐Strained Molecules
Authors: Wu Xinxin , Zhu Chen
Published: December 2018

The carbon‐carbon (C—C) σ‐bonds construct the fundamental frameworks of organic molecules. The direct functionalization of C—C bonds represents one of the most efficient and step‐economical transformations in synthetic chemistry. The past few decades have witnessed the fast development of transition‐metal mediated C—C bond activation. In contrast, the radical‐promoted C—C bond cleavage has received relatively less attention. As the occurrence of ring strain significantly facilitates the fission of cyclic C—C bonds via radical approaches, the strain relief‐driven C—C bond activation mostly relies on the three‐ and four‐membered rings. The C—C activation of non‐strained molecules such as medium‐ or large‐sized rings and linear alkanes remains challenging. In this review, we will focus on the recent advances in radical‐mediated C—C bond activation of non‐strained molecules. Herein, the alkoxy‐ and iminyl‐radical triggered scission of non‐strained C—C bonds and C—C cleavage via the strategy of remote functional group migration is summarized.
Preparation of a New Friedländer Synthon, 2,3‐Diaminobenzene‐1,4‐dicarbaldehyde, and Its Application towards Synthesis of 1,10‐Phenanthrolines and Related Cyclophane
Authors: Lu Yang , Jahng Yurngdong
Published: December 2018

Summary of main observation and conclusion

A new Friedländer synthon, 2,3‐diaminobenzene‐1,4‐dicarbaldehyde, was prepared from p‐xylene in 4 steps, of which the Friedländer reaction with acetaldehyde and acetone in a Schulenk bottle afforded 1,10‐phenathroline and neocuprine in 44% and 82% yield, respectively. The scope of the Friedländer reactions of 2,3‐diaminobenzene‐1,4‐dicarbaldehyde, including the synthesis of hexaazacyclic cyclophane with 1,10‐phenanthroline and pyridine units, was described
Predictive value of oncogenic driver subtype, programmed death‐1 ligand (PD‐L1) score, and smoking status on the efficacy of PD‐1/PD‐L1 inhibitors in patients with oncogene‐driven non–small cell lung cancer
Authors: Ng Terry L. , Liu Yiwei , Dimou Anastasios , Patil Tejas , Aisner Dara L. , Dong Zhengwei , Jiang Tao , Su Chunxia , Wu Chunyan , Ren Shengxiang , Zhou Caicun , Camidge D. Ross
Published: December 2018

Background

This multicenter, retrospective study explored the value of oncogene driver subtype, programmed death‐1 ligand (PD‐L1) status, and smoking status for predicting which patients with oncogene‐driven non–small cell lung cancer (NSCLC) would benefit from treatment with programmed death‐1 (PD‐1)/PD‐L1 inhibitors.

Methods

The clinical features, PD‐L1 tumor proportion scores, and PD‐1/PD‐L1 inhibitor (PDi) outcomes (objective response rate and progression‐free survival) of patients who had advanced NSCLC with Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations or common, actionable oncogenic drivers were captured.

Results

In total, 189 oncogene‐positive patients were analyzed. Of these, 104 received a PDi, and 108 had undergone prior PD‐L1 testing. The frequency of PD‐L1 positivity (≥1%) was higher in patients who had KRAS mutations (P = .031), smokers (P = .006), and non‐Asian patients (P = .002). Multivariable analysis indicated that smoking status (P < .001) was the only factor associated significantly with KRAS mutation. The objective response rate to PDi treatment was 16.9% (11 of 65 patients) among smokers (17.3% in the KRAS‐mutant and 15.4% in the non‐KRAS–mutant smoker subgroups), which was significantly higher than the 0% rate (0 of 26 patients; P = .019) among never‐smokers. In subgroup analyses, progression‐free survival was influenced by KRAS mutation status (median, 4.57 vs 1.63 months; P = .004), smoking status (4.07 vs 1.73 months; P = .004), PD‐L1 positivity (3.8 vs 1.2 months; P = .040), and non‐Asian race (3.0 vs 1.97 months; P = .046). In multivariable analysis, only smoking status (P = .008) remained a significant predictor when a PD‐L1 level ≥1% was used. However, both smoking status (P = .001) and PD‐L1 status (P = .028) were independent predictors when a PD‐L1 level ≥50% was used.

Conclusions

Among associated clinical features among patients who have NSCLC with oncogenic drivers, smoking status potentially was the most important, easily available predictor of single PDi efficacy.
The effect of TiO2 nanopigment on the optical properties of polyester fabric in UV–VIS–NIR regions
Authors: Piri Negin , Shams‐Nateri Ali , Mokhtari Javad
Published: December 2018

The particle size parameter is a key factor that affects radiative properties of nanopigments, and consequently, pigments of the same type but different sizes represent different spectral performance. Therefore, current study dealt with a systematic experimental investigation on the effect of TiO2 pigmented coatings on spectral reflectance and color performance of white and colored polyester fabrics in UV, VIS, and NIR region of electromagnetic spectrum, with a special emphasis on VIS region. In order to accomplish this target, polyester fabrics were coated with TiO2 nanopigment with various concentrations and different diameters, and their reflectance spectra were measured using spectrophotometric method. Two‐way analysis of variance (ANOVA) was utilized to investigate the significance of the effect of TiO2 nanopigment on the color performance of coated fabrics. According to experimental observations, an organized color shift appears in color coordinate of fabrics coated with TiO2 nanopigment of various sizes. Moreover, although TiO2 nanopigment with 35 nm diameter has the most significant impact on short wavelength region (UV region), the effect of pigment with 250 nm diameter is more noticeable on NIR region as long wavelength region.
Understanding Local‐Field Correction Factors in the Framework of the Onsager−Böttcher Model
Authors: Aubret Antoine , Orrit Michel , Kulzer Florian
Published: December 2018

The determination of the appropriate local‐field factor for quantifying the response of a molecule to an external electric field is of major importance in optical spectroscopy. Although numerous studies have dealt with the evolution of the optical properties of emitters as a function of their environment, the choice of the model used to quantify local fields is still ambiguous, and sometimes even arbitrary. In this paper, we review the Onsager–Böttcher model, which introduces the polarizability of the probe molecule as the determinant parameter for the local field factor, and we establish a simple conceptual framework encompassing all commonly used models. Finally, a discussion of published experimental research illustrates the potential of the measurement of local electric fields in dense dielectric media, as well as the subtleties involved in their interpretation.
Tuning Redox Properties and Self‐Assembly of Thienoacene‐Extended Tetrathiafulvalenes
Authors: Lindholm Andersen Cecilie , Zalibera Michal , Lušpai Karol , Christensen Mikkel A. , Darvasiová Denisa , Lukeš Vladimír , Rapta Peter , Haley Michael M. , Hammerich Ole , Brøndsted Nielsen Mogens
Published: December 2018

Turning on and off associations between molecules by a reversible change in their redox states is a convenient way of controlling self‐assembly and hence for advancing supramolecular chemistry. Here we present systematic studies on a selection of extended tetrathiafulvalenes with thienoacene spacers. By cyclic and differential pulse voltammetry and in situ EPR/UV‐Vis‐NIR spectroelectrochemistry, in combination with computations, we have elucidated how the number and orientations of thiophene rings in the spacer between the two dithiafulvene rings influence both the donor strength and association properties. The radical cations and their associates were found to cover a remarkable large region of the UV‐Vis‐NIR spectrum, but the appearance of the absorption spectrum of the radical cations as well as of the unassociated dications also depended strongly on the exact molecular structure.
An international approach of the relationship between board attributes and the disclosure of corporate social responsibility issues
Authors: Pucheta‐Martínez María Consuelo , Gallego‐Álvarez Isabel
Published: December 2018

Firms interested in being perceived by all stakeholders and society as drivers of corporate social responsibility (CSR) activities, especially regarding CSR reporting, should have boards of directors that defend not only shareholder interests but also all stakeholders' needs. Thus, we expect that efficient boards, particularly if well‐structured, will impact on CSR disclosure. As a result, in this paper, we examine the effect of board composition, particularly board size, board independence, board gender diversity, chief executive officer (CEO) duality, and CSR board committee, on CSR reporting. Using a sample of international firms, concretely 13,178 observations belonging to 39 countries, we hypothesize that all these attributes positively affect CSR disclosure, except board independence and CEO duality, which are expected to impact negatively. These hypotheses are theoretically supported by the agency and stakeholder perspectives. Our findings support all the hypotheses, except that of CEO duality, and therefore, we conclude that board characteristics such as board size, board gender diversity, and CSR board committees encourage the disclosure of CSR matters, whereas board independence discourages this reporting. Contrary to our predictions, CEO duality has a positive effect on CSR reporting.
Label‐Free Metabolic Classification of Single Cells in Droplets Using the Phasor Approach to Fluorescence Lifetime Imaging Microscopy
Authors: Ma Ning , Kamalakshakurup Gopakumar , Aghaamoo Mohammad , Lee Abraham P. , Digman Michelle A.
Published: December 2018

Characterization of single cell metabolism is imperative for understanding subcellular functional and biochemical changes associated with healthy tissue development and the progression of numerous diseases. However, single‐cell analysis often requires the use of fluorescent tags and cell lysis followed by genomic profiling to identify the cellular heterogeneity. Identifying individual cells in a noninvasive and label‐free manner is crucial for the detection of energy metabolism which will discriminate cell types and most importantly critical for maintaining cell viability for further analysis. Here, we have developed a robust assay using the droplet microfluidic technology together with the phasor approach to fluorescence lifetime imaging microscopy to study cell heterogeneity within and among the leukemia cell lines (K‐562 and Jurkat). We have extended these techniques to characterize metabolic differences between proliferating and quiescent cells—a critical step toward label‐free single cancer cell dormancy research. The result suggests a droplet‐based noninvasive and label‐free method to distinguish individual cells based on their metabolic states, which could be used as an upstream phenotypic platform to correlate with genomic statistics. © 2018 International Society for Advancement of Cytometry
The Synaptic and Neuronal Functions of the X‐Linked Intellectual Disability Protein Interleukin‐1 Receptor Accessory Protein Like 1 (IL1RAPL1)
Authors: Montani Caterina , Gritti Laura , Beretta Stefania , Verpelli Chiara , Sala Carlo
Published: December 2018

Since the first observation that described a patient with a mutation in IL1RAPL1 gene associated with intellectual disability in 1999, the function of IL1RAPL1 has been extensively studied by a number of laboratories. In this review, we summarize all the major data describing the synaptic and neuronal functions of IL1RAPL1 and recapitulate most of the genetic deletion identified in humans and associated to intellectual disability (ID) and autism spectrum disorders (ASD). All the data clearly demonstrate that IL1RAPL1 is a synaptic adhesion molecule localized at the postsynaptic membrane. Mutations in IL1RAPL1 gene cause either the absence of the protein or the production of a dysfunctional protein. More recently it has been demonstrated that IL1RAPL1 regulated dendrite formation and mediates the activity of IL‐1β on dendrite morphology. All these data will possibly contribute to identifying therapies for patients carrying mutations in IL1RAPL1 gene.
Maternal size and body condition predict the amount of post‐fertilization maternal provisioning in matrotrophic fish
Authors: Hagmayer Andres , Furness Andrew I. , Reznick David N. , Pollux Bart J. A.
Published: December 2018

Maternal effects often provide a mechanism for adaptive transgenerational phenotypic plasticity. The maternal phenotype can profoundly influence the potential for such environmentally induced adjustments of the offspring phenotype, causing correlations between offspring and maternal traits. Here, we study potential effects of the maternal phenotype on offspring provisioning prior to and during gestation in the matrotrophic live‐bearing fish speciesPoeciliopsis retropinna. Specifically, we examine how maternal traits such as body fat, lean mass, and length relate to pre‐ (i.e., allocation to the egg prior to fertilization) and post‐fertilization (i.e., allocation to the embryo during pregnancy) maternal provisioning and how this ultimately affects offspring size and body composition at birth. We show that pre‐ and post‐fertilization maternal provisioning is associated with maternal length and body fat, but not with maternal lean mass. Maternal length is proportionally associated with egg mass at fertilization and offspring mass at birth, notably without changing the ratio of pre‐ to post‐fertilization maternal provisioning. This ratio, referred to as the matrotrophy index (MI), is often used to quantify the level of matrotrophy. By contrast, the proportion of maternal body fat is positively associated with post‐fertilization, but not pre‐fertilization, maternal provisioning and consequently is strongly positively correlated with the MI. We furthermore found that the composition of embryos changes throughout pregnancy. Females invest first in embryo lean mass, and then allocate fat reserves to embryos very late in pregnancy. We argue that this delay in fat allocation may be adaptive, because it delays an unnecessary high reproductive burden to the mother during earlier stages of pregnancy, potentially leading to a more slender body shape and improved locomotor performance. In conclusion, our study suggests that (a) offspring size at birth is a plastic trait that is predicted by both maternal length and body fat, and (b) the MI is a plastic trait that is predicted solely by the proportion of maternal body fat. It herewith provides new insights into the potential maternal causes and consequences of embryo provisioning during pregnancy in matrotrophic live‐bearing species.
Seasonal drought in North America’s sagebrush biome structures dynamic mesic resources for sage‐grouse
Authors: Donnelly J. Patrick , Allred Brady W. , Perret Daniel , Silverman Nicholas L. , Tack Jason D. , Dreitz Victoria J. , Maestas Jeremy D. , Naugle David E.
Published: December 2018

The North American semi‐arid sagebrush, Artemisia spp., biome exhibits considerable climatic complexity driving dynamic spatiotemporal shifts in primary productivity. Greater and Gunnison sage‐grouse, Centrocercus urophasianus and C. minimus, are adapted to patterns of resource intermittence and rely on stable adult survival supplemented by occasional recruitment pulses when climatic conditions are favorable. Predictions of intensifying water scarcity raise concerns over new demographic bottlenecks impacting sage‐grouse populations in drought‐sensitive landscapes. We estimate biome‐wide mesic resource productivity from 1984 to 2016 using remote sensing to identify patterns of food availability influencing selective pressures on sage‐grouse. We linked productivity to abiotic factors to examine effects of seasonal drought across time, space, and land tenure, with findings partitioned along gradients of ecosystem water balance within Great Basin, Rocky Mountains and Great Plains regions. Precipitation was the driver of mesic resource abundance explaining ≥70% of variance in drought‐limited vegetative productivity. Spatiotemporal shifts in mesic abundance were apparent given biome‐wide climatic trends that reduced precipitation below three‐quarters of normal in 20% of years. Drought sensitivity structured grouse populations wherein landscapes with the greatest uncertainty in mesic abundance and distribution supported the fewest grouse. Privately owned lands encompassed 40% of sage‐grouse range, but contained a disproportional 68% of mesic resources. Regional drought sensitivity identified herein acted as ecological minimums to influence differences in landscape carrying capacity across sage‐grouse range. Our model depictions likely reflect a new normal in water scarcity that could compound impacts of demographic bottlenecks in Great Basin and Great Plains. We conclude that long‐term population maintenance depends on a diversity of drought resistant mesic resources that offset climate driven variability in vegetative productivity. We recommend a holistic public–private lands approach to mesic restoration to offset a deepening risk of water scarcity.
The Gambian epauletted fruit bat shows increased genetic divergence in the Ethiopian highlands and in an area of rapid urbanization
Authors: Riesle‐Sbarbaro Silke A. , Amponsah‐Mensah Kofi , de Vries Stefan , Nicolas Violaine , Lalis Aude , Suu‐Ire Richard , Cunningham Andrew A. , Wood James L. N. , Sargan David R.
Published: December 2018

The Gambian epauletted fruit bat (Epomophorus gambianus) is an abundant species that roosts in both urban and rural settings. The possible role of E. gambianus as a reservoir host of zoonotic diseases underlines the need to better understand the species movement patterns. So far, neither observational nor phylogenetic studies have identified the dispersal range or behavior of this species. Comparative analyses of mitochondrial and nuclear markers from 20 localities across the known distribution of E. gambianus showed population panmixia, except for the populations in Ethiopia and southern Ghana (Accra and Ve‐Golokwati). The Ethiopian population may be ancestral and is highly divergent to the species across the rest of its range, possibly reflecting isolation of an ancient colonization along an east–west axis. Mitochondrial haplotypes in the Accra population display a strong signature of a past bottleneck event; evidence of either an ancient or recent bottleneck using microsatellite data, however, was not detected. Demographic analyses identified population expansion in most of the colonies, except in the female line of descent in the Accra population. The molecular analyses of the colonies from Ethiopia and southern Ghana show gender dispersal bias, with the mitochondrial DNA fixation values over ten times those of the nuclear markers. These findings indicate free mixing of the species across great distances, which should inform future epidemiological studies.
Defensive chemicals of neighboring plants limit visits of herbivorous insects: Associational resistance within a plant population
Authors: Ida Takashi Y. , Takanashi Kojiro , Tamura Momoka , Ozawa Rika , Nakashima Yoshitaka , Ohgushi Takayuki
Published: December 2018

Despite our understanding of chemical defenses and their consequences for plant performance and herbivores, we know little about whether defensive chemicals in plant tissues, such as alkaloids, and their spatial variation within a population play unappreciated and critical roles in plant‐herbivore interactions. Neighboring plants can decrease or increase attractiveness of a plant to herbivores, an example of a neighborhood effect. Chemical defensive traits may contribute to neighborhood effects in plant‐herbivore interactions. We examined the effects of nicotine in leaves (a non‐emitted defense chemical) on plant‐herbivore interactions in a spatial context, using two varieties of Nicotiana tabacum with different nicotine levels. A common garden experiment demonstrated that visits by grasshoppers decreased with increasing density of neighboring plants with a greater nicotine level. In contrast, visits of leaf caterpillars were not affected by neighbors, irrespective of nicotine levels. Thus, our results clearly highlighted that the neighborhood effect caused by the nicotine in leaves depended on the insect identity, and it was mediated by plant‐herbivore interactions, rather than plant‐plant interactions. This study demonstrates that understanding of effects of plant defensive traits on plant‐herbivore interactions requires careful consideration of the spatial distribution of plant defenses, and provides support for the importance of spatial context to accurately capture the ecological and evolutionary consequences of plant‐herbivore interactions.
Structure and function of the bacterial and fungal gut microbiota of Neotropical butterflies
Authors: Ravenscraft Alison , Berry Michelle , Hammer Tobin , Peay Kabir , Boggs Carol
Published: December 2018

The relationship between animals and their gut flora is simultaneously one of the most common and most complex symbioses on Earth. Despite its ubiquity, our understanding of this invisible but often critical relationship is still in its infancy. We employed adult Neotropical butterflies as a study system to ask three questions: First, how does gut microbial community composition vary across host individuals, species and dietary guilds? Second, how do gut microbiota compare to food microbial communities? Finally, are gut flora functionally adapted to the chemical makeup of host foods? To answer these questions we captured nearly 300 Costa Rican butterflies representing over 50 species, six families, and two feeding guilds: frugivores and nectivores. We characterized bacteria and fungi in guts, wild fruits, and wild nectars via amplicon sequencing and assessed the catabolic abilities of the gut microbiota via culture‐based assays. Gut communities were distinct from food communities, suggesting that the gut environment acts as a filter on potential colonists. Nevertheless, gut flora varied widely among individuals and species. On average, a pair of butterflies shared 21% of their bacterial species and 6% of their fungi. Host species explained 25–30% of variation in microbial communities while host diet explained 4%, suggesting that non‐dietary aspects of host biology play a large role in structuring the butterfly gut flora. Much of the variation between species correlated with host phylogeny. Host diet was related to gut microbial function: compared to frugivores, nectivores’ gut flora exhibited increased catabolism of sugars and sugar alcohols and decreased catabolism of amino acids, carboxylic acids, and dicarboxylic acids. Since fermented juice contains more amino acids and less sugar than nectar, it appears that host diet filters the gut flora by favoring microbes that digest compounds abundant in foods. By quantifying the degree to which gut communities vary among host individuals, species and dietary guilds and evaluating how gut microbial composition and catabolic potential are related to host diet, this study highlights the linkages between structure and function in one of the most complex and ubiquitous symbioses in the animal kingdom.
Substitution Effect on Near Infrared Absorbance Based Selective Fluoride Sensing of Indole Functionalized Thiourea Molecules
Authors: Chowdhury Bijit , Sinha Sanghamitra , Ghosh Pradyut
Published: December 2018

A series of six new symmetrically functionalized thiourea based indole conjugated ligands (S1–S6) are synthesized in good yields and their anion recognition/sensing ability in the solution as well as in solid state is explored. Chemosensors S1–S6 show selective colorimetric sensing of fluoride by stable NIR signatures at 942 nm, 956 nm, 825 nm, 890 nm, 948 nm, and 1160 nm with corresponding spectral shifts (Δλ) of 592 nm, 588 nm, 603 nm, 485 nm, 610 nm, and 800 nm by virtue of position, conjugation and electronic effect of different functional groups attached to indole unit. To the best of our knowledge the peak shift of a chemosensor by magnitude of 800 nm (from UV to NIR region) in the presence of fluoride represents the highest of its kind. The changes in absorption spectra in the presence of various anions follow the Hofmeister series of anions. All the chemosensors show a bathochromic shift in the absorption spectra of the ligands in the presence of acetate, benzoate, dihydrogen phosphate and hydrogen pyrophosphate due to hydrogen bonding interactions with the indole and thiourea‐NH groups. The single‐crystal X‐ray structures evidence in favour of planar structures of the free sensors (S1, S4, and S5) and strong hydrogen bonding interactions between phosphate anion and indole–thiourea NH groups.
3‐Aryl Substituted 1‐Methylquinolinium Salts as Carbene Precursors
Authors: Batsyts Sviatoslav , Vedmid Roman , Namyslo Jan C. , Nieger Martin , Schmidt Andreas
Published: December 2018

1‐Methylquinolinium salts substituted at the C3 position with phenyl, naphthalen‐1‐yl, phenanthren‐9‐yl, and pentaphenyl phenyl as well as aryl ethynyl substituents were prepared. The phenyl, naphthalen‐1‐yl, and phenanthren‐9‐yl substituents are in conjugation with the quinolinium ring, and the sterically crowded pentaphenyl phenyl residue causes a propeller‐type molecule possessing a calculated dihedral angle between aryl substituent and the quinolinium ring of approximately 54°. The different influences of the substituents including the aryl ethynyl residues on the π‐architecture is well reflected in their frontier orbital profiles, their spectroscopic properties, and in their ability to form N‐heterocyclic carbenes. The latter were generated from the C3‐aryl substituted quinolinium salts and trapped as sulfur and selenium adducts, whereas the aryl ethynyl substituted derivatives failed to undergo the NHC generation under the conditions applied. 77Se NMR measurements of the corresponding selenones reveal that quinolin‐2‐ylidenes are electron poor carbenes with strong π‐acceptor character.
The 1800‐year variation of the lower Yellow River bank breachings in relation to the drainage basin vegetation reconstructed using cave stalagmite records
Authors: Xu Jiongxin
Published: December 2018

Rivers are closely related to climate, and the hydrogeomorphic features and stability of river channels respond sensitively to climatic change. However, the history of instrumental observations of climatic, hydrological and channel changes is short, notably limiting our ability to understand the complex river responses to long‐term climate change and human activity. In this study, we show that cave stalagmite records reflected the variations in precipitation and temperature in the Yellow River basin, and the net primary productivity (NPP) of vegetation over the past 1800 years can therefore be reconstructed. We found that the reconstructed annual mean precipitation (Pm) and NPP closely related to the 1800‐year variation of the lower Yellow River (LYR) channel instability indexed by the frequency of the LYR levee breaching events (LBEs) (Fb) derived from historical documents. The temporal variations inPm, NPP andFbexhibited an anti‐phase relationship (negative correlation) and in‐phase relationship (positive correlation), referred to as Type I and Type II relationships, respectively. The two types alternately appeared, dividing the studied period into several sub‐periods. Type I occurred when the vegetation remained in a quasi‐natural condition, and Type II occurred when the vegetation had been altered by humans to some degree. These features reflect complex river behaviours in response to climate change and human activity and may be explained by the interaction between climate, vegetation and human activity on the millennial timescale. © 2018 John Wiley & Sons, Ltd.
Meteorological measurements at Auchencorth Moss from 1995 to 2016
Authors: Coyle Mhairi , Cape John N. , Flechard Chris , Fowler David , Helfter Carole , Jones Mathew , Kentisbeer John , Leeson Sarah R. , Leith Ian D. , Mullinger Neil , Nemitz Eiko , Roberts Elin , Simmons Ivan , Storeton‐West Robert , Twigg Marsailidh , Van Dijk Netty
Published: December 2018

The Auchencorth Moss atmospheric observatory has being measuring meteorological parameters since 1995. The site was originally set‐up to measure the deposition of sulphur dioxide at a site that represented the vegetation and climate typical of NW Europe, in relatively clean background air. It is one of the longest running flux monitoring sites in the region, over semi‐natural vegetation, providing infrastructure and support for many measurement campaigns and continuous monitoring of air pollutants and greenhouse gases. The meteorological sensors that are used, data processing and quality reviewing procedures are described for a set of core measurements up to 2016. These core measurements are essential for the interpretation of the other atmospheric variables.

Open Practices

This article has earned an Open Data badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at http://catalogue.ceda.ac.uk/uuid/8e6cbb111cfd41a19c92aadcb2d040fd. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
Feasibility of indocyanine green fluorescence imaging for intraoperative identification of parathyroid glands during thyroid surgery
Authors: van den Bos Jacqueline , van Kooten Lottie , Engelen Sanne M. E. , Lubbers Tim , Stassen Laurents P. S. , Bouvy Nicole D.
Published: December 2018

Background

This study assessed the feasibility of near‐infrared fluorescence imaging with indocyanine green (ICG) to identify the parathyroid glands (PGs) intraoperatively and to assess their perfusion after thyroid resection.

Methods

Patients undergoing elective thyroidectomy were enrolled in this prospective study. An intravenous bolus of 7.5 mg ICG was administered twice: the first bolus to identify the PGs before resection of the thyroid and the second to assess vascularization of the PGs after resection.

Results

A total of 30 operations in 26 patients were included. In 17 surgeries (56.7%), fluorescence imaging was of added value, especially to confirm the presence of a suspected PG. No intraoperative or postoperative complications occurred because of the use of ICG.

Conclusion

Near‐infrared fluorescence imaging with the use of ICG for intraoperative identification of the PGs and the assessment of its vascularization is feasible and safe and can provide more certainty about the location of the PGs.
Orographic distillation and spatio‐temporal variations of stable isotopes in precipitation in the North Atlantic
Authors: Antunes Paulo , Boutt David F. , Rodrigues Francisco C.
Published: December 2018

Little is known about the spatial and temporal variability of the stable isotopic composition of precipitation in the North Atlantic and its relationship to the North Atlantic Oscillation (NAO) and anthropogenic climate change. The islands of the Azores archipelago are uniquely positioned in the middle of the North Atlantic Ocean to address this knowledge gap. A survey of spatial and temporal variability of the stable isotope composition of precipitation in Azores is discussed using newly presented analyses along with Global Network of Isotopes in Precipitation data. The collected precipitation samples yield a new local meteoric water line (δ2H = 7.1 * δ18O + 8.46) for the Azores region and the North Atlantic Ocean. The annual isotopic mean of precipitation shows a small range for the unweighted and precipitation mass‐weighted δ18O‐H2O values. Results show an inverse relation between the monthly δ18O‐H2O and the amount of precipitation, which increases in elevation and into the interior of the island. Higher amounts of precipitation (from convective storm systems) do not correspond to the most depleted values of stable isotopes in precipitation. Precipitation shows an orographic effect with depleted δ18O‐H2O values related to the Rayleigh effect. Monthly δ18O‐H2O values for individual precipitation sampling stations show little relationship to air temperature. Results show a local source of moisture during the summer with the characteristics of the first vapour condensate. The stable isotope composition of precipitation is strongly correlated to the NAO index, and δ18O‐H2O values show a statistically significantly trend towards enrichment since 1962 coincident with the increased air temperature and relative humidity due to climate change. Results are in line with observations of increasing sea surface temperature and relative humidity.
Hypermutagenesis in untreated adult gliomas due to inherited mismatch mutations
Authors: Sa Jason K. , Choi Seung Won , Zhao Junfei , Lee Yeri , Zhang Jing , Kong Doo‐Sik , Choi Jung Won , Seol Ho Jun , Lee Jung‐Il , Iavarone Antonio , Rabadan Raul , Nam Do‐Hyun
Published: December 2018

Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in the DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)‐induced mutagenesis. In our study, we have identified a rare subset of treatment‐naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment‐induced hypermutagenesis. We conducted Whole‐Exome Sequencing (WES), Whole‐Transcriptome Sequencing (WTS), and Single‐Cell Sequencing (SCS) of TMZ‐naïve and post‐TMZ‐treated hypermutated tumors to identify distinct clinical or genomic manifestations that contribute to the development of hypermutation in untreated adult gliomas. TMZ‐naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ‐induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery. The immediate family members of the TMZ‐naive hypermutated glioma patients were also previous diagnosed with cancer development history, suggesting that germline dysfunction of the MMR pathway could potentially pose hereditary risk to genetic predisposition of carcinogenesis in gliomas. Lastly, both TMZ‐naïve and post‐TMZ‐treated hypermutated tumors exhibited a significant accumulation of neoantigen loads, suggesting immunotherapeutic alternatives. Our results present new and unique understanding of hypermutagenic process in adult gliomas and an important step towards clinical implication of immunotherapy in glioma treatment.
Expression of PD‐L1 in tumor‐associated nerves correlates with reduced CD8+ tumor‐associated lymphocytes and poor prognosis in prostate cancer
Authors: Mo Ru‐Jun , Han Zhao‐Dong , Liang Ying‐Ke , Ye Jian‐Heng , Wu Shu‐Lin , Lin Sharron X. , Zhang Yan‐Qiong , Song Sheng‐Da , Jiang Fu‐Neng , Zhong Wei‐De , Wu Chin‐Lee
Published: December 2018

To investigate immune profile consisting of stromal PD‐L1 expression, inhibitory or non‐T‐cell inflamed tumor microenvironment that may predict response to anti‐PD‐L1/PD‐1 immunotherapy in prostate cancer, we validated the specificity of a PD‐L1 monoclonal antibody (E1L3N) and identified PD‐L1 specific expression in prostatic stromal nerve cells. PD‐L1 expression was analyzed in 73 primary prostate cancers and 7 castration‐resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor‐associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD‐L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD‐L1 was frequently observed in the nerve branches in the tumor‐associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3‐, CD3‐ and CD8‐positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD‐L1+ tumor‐associated nerves (TANs) was inversely correlated with that of CD8+ TALs. Higher density of PD‐L1+ TANs was significantly associated with biochemical recurrence (BCR) in Kaplan–Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD‐L1+ TANs was independently prognostic of BCR. In conclusion, PD‐L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8+ TALs. Neuro‐immunological interaction may be a contribution to immune‐suppressive microenvironment. Combinatorial treatment regimen designs to neural PD‐L1 and TALs should be warranted in future clinical application of anti‐PD‐L1/PD‐1 immunotherapy in prostate cancer.
Cyclin‐dependent kinase 9 promotes cervical cancer development via AKT2/p53 pathway
Authors: Xu Junfen , Xu Shanshan , Fang Yifeng , Chen Tingting , Xie Xing , Lu Weiguo
Published: December 2018

Aberrant activation of cyclin‐dependent kinase 9 (CDK9) is widespread in human cancers. However, the underlying mechanisms of CDK9 activation and the therapeutic potential of CDK9 inhibition in cervical cancer remain largely unknown. Here, we report that CDK9 is gradually upregulated during cervical lesion progression and regulated by HPV16 E6. CDK9 levels are highly correlated with FIGO stage, pathological grade, deep‐stromal invasion, tumor size, and lymph nodes metastasis. Knockdown of CDK9 by specific siRNA inhibits cervical cancer cell proliferation in vitro, as well as tumorigenesis in vivo. CDK9 inhibition causes a significant decreased AKT2 and increased p53 protein expression revealing novel CDK9‐regulatory mechanisms. Overexpression of AKT2 rescued the suppressive effects caused by CDK9 knockdown, suggesting that AKT2 induction is essential for CDK9‐induced transformation. Moreover, CDK9 expression was positively correlated with AKT2 and negatively correlated with p53 in cervical cancer tissues with HPV16 infection. Our findings demonstrate for the first time that CDK9 acts as a proto‐oncogene in cervical cancer, modulating cell proliferation and apoptosis through AKT2/p53 pathway. Therefore, our data provide novel mechanistic insights into the role of CDK9 in cervical cancer development. © 2018 IUBMB Life, 71(3):347–356, 2019