bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilingual and Monolingual First Language Acquisition Experience Differentially Shapes Children’s Property Term Learning: Evidence from Behavioral and Neurophysiological Measures
Authors: Groba Agnes , De Houwer Annick , Obrig Hellmuth , Rossi Sonja
Published: February 2019

Studies of novel noun learning show bilingual children rely less on the Mutual Exclusivity Constraint (MEC) for word learning than monolinguals. Shifting the focus to learning novel property terms (adjectives), the present study compared 3.5- and five-year-old bilingual and monolingual preschoolers’ adherence to the MEC. We found no bilingual-monolingual differences on a behavioral forced-choice task for the 3.5-year-olds, but five-year-old monolinguals adhered more to the MEC than bilinguals did. Older bilinguals adhered less to the MEC than younger ones, while there was no difference in MEC adherence between the younger and older monolinguals. In the 5-year-olds, we additionally acquired neurophysiological data using functional near-infrared spectroscopy (fNIRS) to allow for a first explorative look at potential neuronal underpinnings. The data show that, compared to bilinguals, monolinguals reveal higher activation over three brain regions (right frontal, left temporo-parietal, and left prefrontal) that may be involved in exploiting the MEC, building on conflict detection, inhibition, solution of a disjunction, and working memory processes. Taken together, our behavioral and neurophysiological findings reveal different paths towards novel property term learning depending on children’s language acquisition context.
MicroRNAs as Potential Pharmaco-Targets in Ischemia-Reperfusion Injury Compounded by Diabetes
Authors: Dehaini Hassan , Awada Hussein , El-Yazbi Ahmed , Zouein Fouad A. , Issa Khodr , Eid Assaad A. , Ibrahim Maryam , Badran Adnan , Baydoun Elias , Pintus Gianfranco , Eid Ali H.
Published: February 2019

Background: Ischemia-Reperfusion (I/R) injury is the tissue damage that results from re-oxygenation of ischemic tissues. There are many players that contribute to I/R injury. One of these factors is the family of microRNAs (miRNAs), which are currently being heavily studied. This review aims to critically summarize the latest papers that attributed roles of certain miRNAs in I/R injury, particularly in diabetic conditions and dissect their potential as novel pharmacologic targets in the treatment and management of diabetes. Methods: PubMed was searched for publications containing microRNA and I/R, in the absence or presence of diabetes. All papers that provided sufficient evidence linking miRNA with I/R, especially in the context of diabetes, were selected. Several miRNAs are found to be either pro-apoptotic, as in the case of miR-34a, miR-144, miR-155, and miR-200, or anti-apoptotic, as in the case of miR-210, miR-21, and miR-146a. Here, we further dissect the evidence that shows diverse cell-context dependent effects of these miRNAs, particularly in cardiomyocytes, endothelial, or leukocytes. We also provide insight into cases where the possibility of having two miRNAs working together to intensify a given response is noted. Conclusions: This review arrives at the conclusion that the utilization of miRNAs as translational agents or pharmaco-targets in treating I/R injury in diabetic patients is promising and becoming increasingly clearer.
Cage Effect under Photolysis in Polymer Matrices
Authors: Khudyakov Igor , Levin Peter , Efremkin Aleksei
Published: February 2019

Photoinduced elementary reactions of low-MW compounds in polymers is an area of active research. Cured organic polymer coatings often undergo photodegradation by free-radical paths. Besides practical importance, such studies teach how the polymer environment controls elementary free-radical reactions. Presented here is a review of recent literature which reports such studies by product analysis and by a time-resolve technique of photochemical reaction inside the cage of a polymer and in the bulk of a polymer. It was established that application of moderate external magnetic field allows the control of the kinetics of free radicals in elastomers. Preheating and stretching of elastomers affect reactivity of photoproduced radicals.
Corrosion Behavior of Hydrotalcite Film on AZ31 Alloy in Simulated Body Fluid
Authors: Chen Jun , Kang Kai , Song Yingwei , Han En-Hou , Ma Sude , Ao Jinqing
Published: February 2019

The hydrotalcite (HT) film is a promising bioactive coating for magnesium alloys. In the present study, we investigate the corrosion behavior of HT film in the simulated body fluid (SBF), and compare with which in NaCl solution. The HT film can provide a very plummy initial protection to the AZ31 alloy in SBF. The corrosion behavior of the HT film in the two solutions is quite different. When in 0.1 mol·L−1 NaCl solution, the film is dissolved gradually, and filiform corrosion is predominant after 3 days immersion. While in Hank’s solution, the thickness and composition of the film are changed. A corrosion products layer mainly consisted of Mg/Ca–PO43−/HPO42−, and minor of CaCO3 is deposited on the top of HT film, which enhances the barrier effect of the HT film. As a result, except for local pit corrosion at several active places, most of the area of the coated sample still remains integral even after immersion for 15 days. It is demonstrated that the HT film has better corrosion protection effect in SBF than in NaCl solution.
Research on Configuration Methods of Battery Energy Storage System for Pure Electric Bus Fast Charging Station
Authors: Yan Yian , Wang Huang , Jiang Jiuchun , Zhang Weige , Bao Yan , Huang Mei
Published: February 2019

With the pervasiveness of electric vehicles and an increased demand for fast charging, stationary high-power fast-charging is becoming more widespread, especially for the purpose of serving pure electric buses (PEBs) with large-capacity onboard batteries. This has resulted in a huge distribution capacity demand. However, the distribution capacity is limited, and in some urban areas the cost of expanding the electric network capacity is very high. In this paper, three battery energy storage system (BESS) integration methods—the AC bus, each charging pile, or DC bus—are considered for the suppression of the distribution capacity demand according to the proposed charging topologies of a PEB fast-charging station. On the basis of linear programming theory, an evaluation model was established that consider the influencing factors of the configuration: basic electricity fee, electricity cost, cost of the energy storage system, costs of transformer and converter equipment, and electric energy loss. Then, a case simulation is presented using realistic operation data, and an economic comparison of the three configurations is provided. An analysis of the impacts of each influence factor in the case study is discussed to verify the case results. The numerical results indicate that the appropriate BESS configuration can significantly reduce the distribution demand and stationary cost synchronously.
Rescue of Sly Expression Is Not Sufficient to Rescue Spermiogenic Phenotype of Mice with Deletions of Y Chromosome Long Arm
Authors: Riel Jonathan M. , Yamauchi Yasuhiro , Ruthig Victor A. , Malinta Qushay U. , Blanco Mélina , Moretti Charlotte , Cocquet Julie , Ward Monika A.
Published: February 2019

Mice with deletions of the Y-specific (non-PAR) region of the mouse Y chromosome long arm (NPYq) have sperm defects and fertility problems that increase proportionally to deletion size. Mice with abrogated function of NPYq-encoded gene Sly (sh367 Sly-KD) display a phenotype similar to that of NPYq deletion mutants but less severe. The milder phenotype can be due to insufficient Sly knockdown, involvement of another NPYq gene, or both. To address this question and to further elucidate the role of Sly in the infertile phenotype of mice with NPYq deletions, we developed an anti-SLY antibody specifically recognizing SLY1 and SLY2 protein isoforms and used it to characterize SLY expression in NPYq- and Sly-deficient mice. We also carried out transgene rescue by adding Sly1/2 transgenes to mice with NPYq deletions. We demonstrated that SLY1/2 expression in mutant mice decreased proportionally to deletion size, with ~12% of SLY1/2 retained in shSLY sh367 testes. The addition of Sly1/2 transgenes to mice with NPYq deletions rescued SLY1/2 expression but did not ameliorate fertility and testicular/spermiogenic defects. Together, the data suggest that Sly deficiency is not the sole underlying cause of the infertile phenotype of mice with NPYq deletions and imply the involvement of another NPYq gene.
How Karen Tei Yamashita Literalizes Feminist Subversion: Extreme Domesticity, Space-Off Reversals, and Virtual Resistances in Tropic of Orange
Authors: Frank Nathan Dwight
Published: February 2019

In Tropic of Orange (1997), Karen Tei Yamashita builds an expansive narrative on the premise that the Tropic of Cancer shifts mysteriously from its actual latitude, barely north of Mazatlán, México, to that of L.A.’s latitude: from 23.43692° north of the Equator to 34.0522° N. By doing so, Yamashita literally takes that which is “south of the border” and repositions it in a hub of neoliberal hegemony; that is, she takes what is below (“sub-”) and puts it on top (“-vert”). I read such a literal and magically realistic move as an allegorical template that guides the novel in its entirety, but more specifically, in its repositioning of women from their spaces of relegation to spaces animated by their resistances to such relegation; from spaces of dependency to spaces characterized by feminine influence. This essay examines three strategies through which feminist subversions may be accomplished according to Yamashita’s textual template: The first follows Susan Fraiman’s theory of Extreme Domesticity (Fraiman 2017) as it tracks how subservient spaces of home and household can become sites of nonconformity; the second takes its cue from the cinematic strategies of “space-off” and “reversal” as examples of how marginal or negative spaces can be leveraged against the male gaze (c.f. José Rodríguez Herrera’s analysis of Sarah Polley’s film adaptation of Alice Munro’s “The Bear Came Over The Mountain,” Herrera 2013); and the third engages my own notion of a spatial virtuality (“that which is present without being local,” Munro 2014) as a mode of resistance that culminates, ultimately, in “a condition of literature,” that is to say, a condition in which Tropic of Orange refers to the conditions of its own making instead of referring to the conditions that create it (ibid.). My tripartite method thus highlights and celebrates the domestic, cinematic, and technological spaces of Yamashita’s writing, respectively, just as it articulates how these spaces might also be read as subversively feminist and feminizing. But it also meditates formally and contextually, as Tropic of Orange’s condition of literature implies, a sort of ablated feminist narratology, even as it works toward feminist narratological ends.
Documenting the Heritage of Nokia—From Discussions to Catalogue
Authors: Västi Emilia
Published: February 2019

In 2015, the Museum of Technology received a donation of ninety data communication devices from the 1960s to 2010s, collected and arranged by employees of the Nokia Data Communications department. The museum has been organizing (2018–2019) documentation workshops to collect information and connect individual objects with larger concepts such as company history, innovations, and technologies. The idea is to gain comprehensive contextual information about the collection by bringing together expertise and experiences of (former) Nokia employees, and documentation and interpretation skills of museum professionals. The method of the documentation workshops is a conversational interview inspired by the objects. Subsequently, workshop discussions were planned to be digested and used in cataloguing individual objects and object groups by museum professionals. Eventually significance assessment was chosen as a tool for summarizing the documentation project. The paper discusses the planning and organizing of the outcomes of the documentation workshops and asks the following questions: What is the optimal relationship between cataloguing information in the collections management system and documentation of workshop discussions preserved in the museum’s collection archive? How should the workshop be documented to trace the provenance of the information? What information should and can be collected on the workshop participants?
An Interdisciplinary Study of Early Mediaeval Churches in North-Western Spain (Galicia)
Authors: Sanjurjo-Sánchez Jorge , Blanco-Rotea Rebeca , Sánchez-Pardo José Carlos
Published: February 2019

Over the last five years, the EMCHAHE (Early Medieval Churches: History, Archaeology and Heritage) Project has analysed the architecture, archaeology and history of numerous rural churches of the High Middle Ages in Galicia (NW Spain), through its historical, stratigraphic and chronological study. As a result, the knowledge of this historical period has been broadened and even changed, as well as an interdisciplinary methodology on how to approach this type of study. According to the results obtained, the project has allowed us to reflect on two issues, the potential of a relatively low-cost type of study to understand, assess and disseminate this type of heritage and the special appreciation and ownership that local communities have towards these churches as an engine of sustainable social development.
Mini Review/Commentary: Growth Hormone Treatment in Children with Type 1 Diabetes
Authors: Bonfig Walter , Holl Reinhard W.
Published: February 2019

In the state of insulin deficiency, the growth hormone—insulin-like growth factor-I (GH–IGF-I) axis is altered due to hepatic GH resistance, which leads to GH hypersecretion and low circulating IGF-I concentration. On the other hand, both growth hormone deficiency (GHD) and GH excess have significant influence on carbohydrate metabolism. These complex interactions are challenging in diagnosing GHD in subjects with type 1 diabetes mellitus (T1DM) and in treating subjects with T1DM with GH. So far, there is only limited clinical experience in GH treatment in patients with T1DM, but recently first reports on metabolic safety and efficacy of GH treatment in subjects with T1DM have been published.
High-Throughput Sequencing to Investigate Phytopathogenic Fungal Propagules Caught in Baited Insect Traps
Authors: Tremblay Émilie D. , Kimoto Troy , Bérubé Jean A. , Bilodeau Guillaume J.
Published: February 2019

Studying the means of dispersal of plant pathogens is crucial to better understand the dynamic interactions involved in plant infections. On one hand, entomologists rely mostly on both traditional molecular methods and morphological characteristics, to identify pests. On the other hand, high-throughput sequencing (HTS) is becoming the go-to avenue for scientists studying phytopathogens. These organisms sometimes infect plants, together with insects. Considering the growing number of exotic insect introductions in Canada, forest pest-management efforts would benefit from the development of a high-throughput strategy to investigate the phytopathogenic fungal and oomycete species interacting with wood-boring insects. We recycled formerly discarded preservative fluids from the Canadian Food Inspection Agency annual survey using insect traps and analysed more than one hundred samples originating from across Canada. Using the Ion Torrent Personal Genome Machine (PGM) HTS technology and fusion primers, we performed metabarcoding to screen unwanted fungi and oomycetes species, including Phytophthora spp. Community profiling was conducted on the four different wood-boring, insect-attracting semiochemicals; although the preservative (contained ethanol) also attracted other insects. Phytopathogenic fungi (e.g., Leptographium spp. and Meria laricis in the pine sawyer semiochemical) and oomycetes (mainly Peronospora spp. and Pythium aff. hypogynum in the General Longhorn semiochemical), solely associated with one of the four types of semiochemicals, were detected. This project demonstrated that the insect traps’ semiochemical microbiome represents a new and powerful matrix for screening phytopathogens. Compared to traditional diagnostic techniques, the fluids allowed for a faster and higher throughput assessment of the biodiversity contained within. Additionally, minimal modifications to this approach would allow it to be used in other phytopathology fields.
Multilayered-Sheet Hot Stamping and Application in Electric-Power-Fitting Products
Authors: Zhu Bin , Zhu Zhoujie , Jin Yongmin , Wang Kai , Wang Yilin , Zhang Yisheng
Published: February 2019

Traditional electric transmission line fittings, which are always manufactured from thick metal slabs, possess the disadvantage of heavy weight. In this study, a new type of electrical-connection-fitting, clevis-clevis component made of high-strength steel is developed to reduce weight, and a new hot-stamping process for multilayered sheets is proposed to manufacture the component efficiently. First, the structure of the new clevis-clevis component is designed, and the corresponding tool is developed. Second, a flat-tool heat transfer experiment is conducted. The influence of the number of layers and contact pressure on the cooling rate of each sheet is investigated. The optimizing number of layers and contact pressure for the multilayered-sheet, hot-stamping process are obtained. The optimal number of layers is two, and the optimal contact pressure is more than 20 MPa. The final microstructure of each sheet is fully martensitic, and the strength is about 1500 MPa. Finally, U-shaped, double-layer-sheet hot stamping is implemented to produce a typical electrical-connection-fitting, clevis-clevis component. The bearing capacity of a four-layered clevis-clevis is tested through numerical and experimental methods. The new connection-fitting clevis-clevis component exhibits a high load capacity of 280 kN. Compared with that of the traditional component, the weight of the new component is reduced by 60%.
Modeling of Knudsen Layer Effects in the Micro-Scale Backward-Facing Step in the Slip Flow Regime
Authors: Bhagat Apurva , Gijare Harshal , Dongari Nishanth
Published: February 2019

The effect of the Knudsen layer in the thermal micro-scale gas flows has been investigated. The effective mean free path model has been implemented in the open source computational fluid dynamics (CFD) code, to extend its applicability up to slip and early transition flow regime. The conventional Navier-Stokes constitutive relations and the first-order non-equilibrium boundary conditions are modified based on the effective mean free path, which depends on the distance from the solid surface. The predictive capability of the standard ‘Maxwell velocity slip—Smoluchwoski temperature jump’ and hybrid boundary conditions ‘Langmuir Maxwell velocity slip—Langmuir Smoluchwoski temperature jump’ in conjunction with the Knudsen layer formulation has been evaluated in the present work. Simulations are carried out over a nano-/micro-scale backward facing step geometry in which flow experiences adverse pressure gradient, separation and re-attachment. Results are validated against the direct simulation Monte Carlo (DSMC) data, and have shown significant improvement over the existing CFD solvers. Non-equilibrium effects on the velocity and temperature of gas on the surface of the backward facing step channel are studied by varying the flow Knudsen number, inlet flow temperature, and wall temperature. Results show that the modified solver with hybrid Langmuir based boundary conditions gives the best predictions when the Knudsen layer is incorporated, and the standard Maxwell-Smoluchowski can accurately capture momentum and the thermal Knudsen layer when the temperature of the wall is higher than the fluid flow.
PES Pathogens in Severe Community-Acquired Pneumonia
Authors: Cillóniz Catia , Dominedò Cristina , Nicolini Antonello , Torres Antoni
Published: February 2019

Worldwide, there is growing concern about the burden of pneumonia. Severe community-acquired pneumonia (CAP) is frequently complicated by pulmonary and extra-pulmonary complications, including sepsis, septic shock, acute respiratory distress syndrome, and acute cardiac events, resulting in significantly increased intensive care admission rates and mortality rates. Streptococcus pneumoniae (Pneumococcus) remains the most common causative pathogen in CAP. However, several bacteria and respiratory viruses are responsible, and approximately 6% of cases are due to the so-called PES (Pseudomonas aeruginosa, extended-spectrum β-lactamase Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus) pathogens. Of these, P. aeruginosa and methicillin-resistant Staphylococcus aureus are the most frequently reported and require different antibiotic therapy to that for typical CAP. It is therefore important to recognize the risk factors for these pathogens to improve the outcomes in patients with CAP.
Geology, Geochronology and Geochemistry of Weilasituo Sn-Polymetallic Deposit in Inner Mongolia, China
Authors: Yang Fan , Sun Jinggui , Wang Yan , Fu Junyu , Na Fuchao , Fan Zhiyong , Hu Zhizhong
Published: February 2019

The recently discovered Weilasituo Sn-polymetallic deposit in the Great Xing’an Range is an ultralarge porphyry-type deposit. The mineralization is closely associated with an Early Cretaceous quartz porphyry. Analysis of quartz porphyry samples, including zircon U-Pb dating and Hf isotopies, geochemical and molybdenite Re-Os isotopic testing, reveals a zircon U-Pb age of 138.6 ± 1.1 Ma and a molybdenite Re-Os isotopic age of 135 ± 7 Ma, suggesting the concurrence of the petrogenetic and metallogenic processes. The quartz porphyry has high concentrations of SiO2 (71.57 wt %–78.60 wt %), Al2O3 (12.69 wt %–16.32 wt %), and K2O + Na2O (8.85 wt %–10.44 wt %) and A/CNK ratios from 0.94–1.21, is mainly peraluminous, high-K calc-alkaline I-type granite and is relatively rich in LILEs (large ion lithophile elements, e.g., Th, Rb, U and K) and HFSEs (high field strength elements, e.g., Hf and Zr) and relatively poor in Sr, Ba, P, Ti and Nb. The zircon εHf(t) values range from 1.90 to 6.90, indicating that the magma source materials were mainly derived from the juvenile lower crust and experienced mixing with mantle materials. Given the regional structural evolution history, we conclude that the ore-forming magma originated from lower crust that had thickened and delaminated is the result of the subduction of the Paleo–Pacific Ocean. Following delamination, the lower crustal material entered the underlying mantle, where it was partially melted and reacted with mantle during ascent. The deposit formed at a time of transition from post-orogenic compression to extension following the subduction of the Paleo–Pacific Ocean.
Sonication of Yeast Biomasses to Improve the Ageing on Lees Technique in Red Wines
Authors: del Fresno Juan Manuel , Morata Antonio , Escott Carlos , Loira Iris , Cuerda Rafael , Suárez-Lepe José Antonio
Published: February 2019

Ageing on Lees (AOL) is a technique to improve the aromatic and gustatory complexity of wine, mainly by improving its body and reducing its astringency. However, the autolytic process is slow, resulting in high production costs. This work evaluated the effect of adding sonicated lees and combining it with oak chips, as a new technique to accelerate the AOL process and improve the aromatic quality of aged red wine. Cell disruption due to sonication was verified by optical microscopy. Volatile acidity, total polyphenol index, color intensity, tonality, dissolved oxygen, anthocyanins, and fermentative volatiles were monitored throughout the ageing of the wines. Sensory analysis was performed at the end of the ageing process. Polysaccharides released from the cell walls and the oxygen consumption, was quantified using a hydroalcoholic solution. The results indicated a 20% increase of the polysaccharide content and suggested an increase in the antioxidant capacity of the lees. No significant changes were observed in the fermentative volatile compounds and the total polyphenol index (TPI), except for those wines in contact with wood. The sonication of lees had some protective effect on the total anthocyanins content, however, color intensity was significantly lower in the sonicated treatments. The sonication of the lees did not cause any defect at the sensory level. Therefore, sonication could allow a reduction in the SO2 addition to wine, as well as a shortening of the ageing times.
Computational Structural Biology: Successes, Future Directions, and Challenges
Authors: Nussinov Ruth , Tsai Chung-Jung , Shehu Amarda , Jang Hyunbum
Published: February 2019

Computational biology has made powerful advances. Among these, trends in human health have been uncovered through heterogeneous ‘big data’ integration, and disease-associated genes were identified and classified. Along a different front, the dynamic organization of chromatin is being elucidated to gain insight into the fundamental question of genome regulation. Powerful conformational sampling methods have also been developed to yield a detailed molecular view of cellular processes. when combining these methods with the advancements in the modeling of supramolecular assemblies, including those at the membrane, we are finally able to get a glimpse into how cells’ actions are regulated. Perhaps most intriguingly, a major thrust is on to decipher the mystery of how the brain is coded. Here, we aim to provide a broad, yet concise, sketch of modern aspects of computational biology, with a special focus on computational structural biology. We attempt to forecast the areas that computational structural biology will embrace in the future and the challenges that it may face. We skirt details, highlight successes, note failures, and map directions.
Experimental Evaluation of the Thermal Polarization in Direct Contact Membrane Distillation Using Electrospun Nanofiber Membranes Doped With Molecular Probes
Authors: Santoro Sergio , Vidorreta Ivan , Coelhoso Isabel , Lima Joao Carlos , Desiderio Giovanni , Lombardo Giuseppe , Drioli Enrico , Mallada Reyes , Crespo Joao , Criscuoli Alessandra , Figoli Alberto
Published: February 2019

Membrane distillation (MD) has recently gained considerable attention as a valid process for the production of fresh-water due to its ability to exploit low grade waste heat for operation and to ensure a nearly feed concentration-independent production of high-purity distillate. Limitations have been related to polarization phenomena negatively affecting the thermal efficiency of the process and, as a consequence, its productivity. Several theoretical models have been developed to predict the impact of the operating conditions of the process on the thermal polarization, but there is a lack of experimental validation. In this study, electrospun nanofiber membranes (ENMs) made of Poly(vinylidene fluoride) (PVDF) and doped with (1, 10-phenanthroline) ruthenium (II) Ru(phen)3 were tested at different operating conditions (i.e., temperature and velocity of the feed) in direct contact membrane distillation (DCMD). The temperature sensitive luminophore, Ru(phen)3, allowed the on-line and non-invasive mapping of the temperature at the membrane surface during the process and the experimental evaluation of the effect of the temperature and velocity of the feed on the thermal polarization.
Synthesis of Meso-Diarylaminocorroles via SNAr Reactions
Authors: Ueta Kento , Tanaka Takayuki , Osuka Atsuhiro
Published: February 2019

A corrole is a tetrapyrrolic macrocycle known as a ring-contracted porphyrinoid. Despite the progress of the synthetic chemistry of meso-aryl-substituted corroles since the early 2000s, meso-heteroatom-substituted corroles have been scarcely reported. Herein we report that the SNAr-type substitution reaction of a meso-chlorocorrole silver complex with diphenylamine or carbazole in the presence of NaH as a base produced meso-aminocorroles. The structures, ultraviolet–visible spectroscopy (UV/Vis), and emission spectra of these meso-aminocorroles were discussed. Furthermore, the oxidation reaction of a meso-diphenylaminocorrole was examined, which resulted in the formation of 10,10-diethoxyisocorrole.
Development of a Potential Gallium-68-Labelled Radiotracer Based on DOTA-Curcumin for Colon-Rectal Carcinoma: From Synthesis to In Vivo Studies
Authors: Orteca Giulia , Pisaneschi Federica , Rubagotti Sara , Liu Tracy W. , Biagiotti Giacomo , Piwnica-Worms David , Iori Michele , Capponi Pier Cesare , Ferrari Erika , Asti Mattia
Published: February 2019

Colorectal cancer is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women worldwide. We have recently reported that curcuminoid complexes labelled with gallium-68 have demonstrated preferential uptake in HT29 colorectal cancer and K562 lymphoma cell lines compared to normal human lymphocytes. In the present study, we report a new gallium-68-labelled curcumin derivative (68Ga-DOTA-C21) and its initial validation as marker for early detection of colorectal cancer. The precursor and non-radioactive complexes were synthesized and deeply characterized by analytical methods then the curcuminoid was radiolabelled with gallium-68. The in vitro stability, cell uptake, internalization and efflux properties of the probe were studied in HT29 cells, and the in vivo targeting ability and biodistribution were investigated in mice bearing HT29 subcutaneous tumour model. 68Ga-DOTA-C21 exhibits decent stability (57 ± 3% after 120 min of incubation) in physiological media and a curcumin-mediated cellular accumulation in colorectal cancer cell line (121 ± 4 KBq of radiotracer per mg of protein within 60 min of incubation). In HT29 tumour-bearing mice, the tumour uptake of 68Ga-DOTA-C21 is 3.57 ± 0.3% of the injected dose per gram of tissue after 90 min post injection with a tumour to muscle ratio of 2.2 ± 0.2. High amount of activity (12.73 ± 1.9% ID/g) is recorded in blood and significant uptake of the radiotracer occurs in the intestine (13.56 ± 3.3% ID/g), lungs (8.42 ± 0.8% ID/g), liver (5.81 ± 0.5% ID/g) and heart (4.70 ± 0.4% ID/g). Further studies are needed to understand the mechanism of accumulation and clearance; however, 68Ga-DOTA-C21 provides a productive base-structure to develop further radiotracers for imaging of colorectal cancer.
Cucurbitacin B Induces the Lysosomal Degradation of EGFR and Suppresses the CIP2A/PP2A/Akt Signaling Axis in Gefitinib-Resistant Non-Small Cell Lung Cancer
Authors: Liu Pengfei , Xiang Yuchen , Liu Xuewen , Zhang Te , Yang Rui , Chen Sen , Xu Li , Yu Qingqing , Zhao Huzi , Zhang Liang , Liu Ying , Si Yuan
Published: February 2019

Non-small cell lung cancer (NSCLC) patients carrying an epidermal growth factor receptor (EGFR) mutation are initially sensitive to EGFR-tyrosine kinase inhibitors (TKIs) treatment, but soon develop an acquired resistance. The treatment effect of EGFR-TKIs-resistant NSCLC patients still faces challenges. Cucurbitacin B (CuB), a triterpene hydrocarbon compound isolated from plants of various families and genera, elicits anticancer effects in a variety of cancer types. However, whether CuB is a viable treatment option for gefitinib-resistant (GR) NSCLC remains unclear. Here, we investigated the anticancer effects and underlying mechanisms of CuB. We report that CuB inhibited the growth and invasion of GR NSCLC cells and induced apoptosis. The inhibitory effect of CuB occurred through its promotion of the lysosomal degradation of EGFR and the downregulation of the cancerous inhibitor of protein phosphatase 2A/protein phosphatase 2A/Akt (CIP2A/PP2A/Akt) signaling axis. CuB and cisplatin synergistically inhibited tumor growth. A xenograft tumor model indicated that CuB inhibited tumor growth in vivo. Immunohistochemistry results further demonstrated that CuB decreased EGFR and CIP2A levels in vivo. These findings suggested that CuB could suppress the growth and invasion of GR NSCLC cells by inducing the lysosomal degradation of EGFR and by downregulating the CIP2A/PP2A/Akt signaling axis. Thus, CuB may be a new drug candidate for the treatment of GR NSCLC.
Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence
Authors: Hajialyani Marziyeh , Hosein Farzaei Mohammad , Echeverría Javier , Nabavi Seyed Mohammad , Uriarte Eugenio , Sobarzo-Sánchez Eduardo
Published: February 2019

Neuroprotection is the preservation of function and networks of neural tissues from damages caused by various agents, as well as neurodegenerative diseases such as Parkinson’s, Alzheimer’s, Huntington’s diseases, and multiple sclerosis. Hesperidin, a flavanone glycoside, is a natural phenolic compound with a wide range of biological effects. Mounting evidence has demonstrated that hesperidin possesses inhibitory effect against development of neurodegenerative diseases. Our review discusses neuropharmacological mechanisms for preventive and therapeutic effects of hesperidin in neurodegenerative diseases. In addition, the review examines clinical evidence confirming its neuroprotective function. Various cellular and animal models specific to neurodegenerative diseases have been conducted to evaluate the underlying neuropharmacological mechanisms of hesperidin. Neuroprotective potential of this flavonoid is mediated by improvement of neural growth factors and endogenous antioxidant defense functions, diminishing neuro-inflammatory and apoptotic pathways. Despite the various preclinical studies on the role of hesperidin in the neurodegenerative diseases, less is known about its definite effect on humans. A limited number of clinical trials showed that hesperidin-enriched dietary supplements can significantly improve cerebral blood flow, cognition, and memory performance. Further clinical trials are also required for confirming neuroprotective efficacy of this natural flavonoid and evaluating its safety profile.
Synthesis of 4-Alkyl-4H-1,2,4-triazole Derivatives by Suzuki Cross-Coupling Reactions and Their Luminescence Properties
Authors: Olesiejuk Monika , Kudelko Agnieszka , Swiatkowski Marcin , Kruszynski Rafal
Published: February 2019

New derivatives of 4-alkyl-3,5-diaryl-4H-1,2,4-triazole were synthesized utilizing the Suzuki cross-coupling reaction. The presented methodology comprises of the preparation of bromine-containing 4-alkyl-4H-1,2,4-triazoles and their coupling with different commercially available boronic acids in the presence of ionic liquids or in conventional solvents. The obtained compounds were tested for their luminescence properties.
Molecular Mechanisms of Colistin-Induced Nephrotoxicity
Authors: Gai Zhibo , Samodelov Sophia L. , Kullak-Ublick Gerd A. , Visentin Michele
Published: February 2019

The emergence of multidrug resistant (MDR) infections and the shortage of new therapeutic options have made colistin, a polymyxin antibiotic, the main option for the treatment of MDR Gram-negative bacterial infections in the last decade. However, the rapid onset of renal damage often prevents the achievement of optimal therapeutic doses and/or forces the physicians to interrupt the therapy, increasing the risk of drug resistance. The proper management of colistin-induced nephrotoxicity remains challenging, mostly because the investigation of the cellular and molecular pharmacology of this drug, off the market for decades, has been largely neglected. For years, the renal damage induced by colistin was considered a mere consequence of the detergent activity of this drug on the cell membrane of proximal tubule cells. Lately, it has been proposed that the intracellular accumulation is a precondition for colistin-mediated renal damage, and that mitochondria might be a primary site of damage. Antioxidant approaches (e.g., ascorbic acid) have shown promising results in protecting the kidney of rodents exposed to colistin, yet none of these strategies have yet reached the bedside. Here we provide a critical overview of the possible mechanisms that may contribute to colistin-induced renal damage and the potential protective strategies under investigation.
Strain-Tunable Visible-Light-Responsive Photocatalytic Properties of Two-Dimensional CdS/g-C3N4: A Hybrid Density Functional Study
Authors: Wang Guangzhao , Zhou Feng , Yuan Binfang , Xiao Shuyuan , Kuang Anlong , Zhong Mingmin , Dang Suihu , Long Xiaojiang , Zhang Wanli
Published: February 2019

By means of a hybrid density functional, we comprehensively investigate the energetic, electronic, optical properties, and band edge alignments of two-dimensional (2D) CdS/g-C 3 N 4 heterostructures by considering the effect of biaxial strain and pH value, so as to improve the photocatalytic activity. The results reveal that a CdS monolayer weakly contacts with g-C 3 N 4 , forming a type II van der Waals (vdW) heterostructure. The narrow bandgap makes CdS/g-C 3 N 4 suitable for absorbing visible light and the induced built-in electric field between the interface promotes the effective separation of photogenerated carriers. Through applying the biaxial strain, the interface adhesion energy, bandgap, and band edge positions, in contrast with water, redox levels of CdS/g-C 3 N 4 can be obviously adjusted. Especially, the pH of electrolyte also significantly influences the photocatalytic performance of CdS/g-C 3 N 4 . When pH is smaller than 6.5, the band edge alignments of CdS/g-C 3 N 4 are thermodynamically beneficial for oxygen and hydrogen generation. Our findings offer a theoretical basis to develop g-C 3 N 4 -based water-splitting photocatalysts.
Functionalized Porous Silica-Based Nano/Micro Particles for Environmental Remediation of Hazard Ions
Authors: Li Chun Min , Wang Xin Peng , Jiao Zi Hao , Zhang Yu Sheng , Yin Xiang Biao , Cui Xue Min , Wei Yue Zhou
Published: February 2019

The adsorption and separation of hazard metal ions, radioactive nuclides, or minor actinides from wastewater and high-level radioactive waste liquids using functional silica-based nano/micro-particles modified with various inorganic materials or organic groups, has attracted significant attention since the discovery of ordered mesoporous silica-based substrates. Focusing on inorganic and organic modified materials, the synthesis methods and sorption performances for specific ions in aqueous solutions are summarized in this review. Three modification methods for silica-based particles, the direct synthesis method, wetness impregnation method, and layer-by-layer (LBL) deposition, are usually adopted to load inorganic material onto silica-based particles, while the wetness impregnation method is currently used for the preparation of functional silica-based particles modified with organic groups. Generally, the specific synthesis method is employed based on the properties of the loading materials and the silicon-based substrate. Adsorption of specific toxic ions onto modified silica-based particles depends on the properties of the loaded material. The silicon matrix only changes the thermodynamic and mechanical properties of the material, such as the abrasive resistance, dispersibility, and radiation resistance. In this paper, inorganic loads, such as metal phosphates, molybdophosphate, titanate-based materials, and hydrotalcite, in addition to organic loads, such as 1,3-[(2,4-diethylheptylethoxy)oxy]-2,4-crown-6-Calix{4}arene (Calix {4}) arene-R14 and functional 2,6-bis-(5,6-dialkyl-1,2,4-triazin-3-yl)-pyridines(BTP) are reviewed. More specifically, we emphasize on the synthesis methods of such materials, their structures in relation to their capacities, their selectivities for trapping specific ions from either single or multi-component aqueous solutions, and the possible retention mechanisms. Potential candidates for remediation uses are selected based on their sorption capacities and distribution coefficients for target cations and the pH window for an optimum cation capture.
Tuning Localized Surface Plasmon Resonance of Nanoporous Gold with a Silica Shell for Surface Enhanced Raman Scattering
Authors: Li Wei , Ma Chao , Zhang Ling , Chen Bin , Chen Luyang , Zeng Heping
Published: February 2019

We report the tuning of localized surface plasmon resonance (LSPR) of nanoporous gold (NPG) by silica coating, which also affects the surface enhanced Raman scattering (SERS) of NPG. In this study, controllable silica shell is assembled on the NPG surface, and a fully silica thin layer causes more than 50 nm red-shift of LSPR band due to dielectric medium dependence. Additionally, ~1 nm silica coated NPG film shows excellent SERS enhancement, which is due to electromagnetic coupling between ligaments and local surface plasmon field enhancement within pores, and theoretical analysis indicates that silica coating further improves the coupling effect, which demonstrates the electromagnetic origin of the tuning of SERS effect.
Chitosan-Modified PLGA Nanoparticles for Control-Released Drug Delivery
Authors: Lu Boting , Lv Xikun , Le Yuan
Published: February 2019

Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) are well recognized as an ideal drug delivery carrier for their biocompatibility and biodegradability. In order to overcome the disadvantage of drug burst release, chitosan (CS) was used to modify the PLGA nanoparticles. In this work, CS-PLGA nanoparticles with different ratio of CS to PLGA were prepared using high-gravity rotating packed bed (RPB). With the increase of amount of CS, the particle size increased from 132.8 ± 1.5 nm to 172.7 ± 3.2 nm, zeta potential increased from −20.8 ± 1.1 mV to 25.6 ± 0.6 mV, and drug encapsulation efficiency increased from 65.8% to 87.1%. The initial burst release of PLGA NPs reduced after being modified by CS, and the cumulative release was 66.9%, 41.9%, 23.8%, and 14.3%, after 2 h, respectively. The drug release of CS-modified PLGA NPs was faster at pH5.5 than that at pH 7.4. The cellular uptake of CS-modified PLGA NPs increased compared with PLGA NPs, while cell viability was reduced. In conclusion, these results indicated that CS-modified, PTX-loaded PLGA NPs have the advantages of sustained drug release and enhanced drug toxicity, suggesting that CS-modified NPs can be used as carriers of anticancer drugs.
Believing in the Church: Why Ecumenism Needs the Invisibility of the Church
Authors: Littlejohn Bradford
Published: February 2019

Amidst the plethora of approaches to ecumenical dialogue and church reunion over the last century, a common theme has been the depreciation of the classic Protestant distinction between the “visible” and “invisible” church. Often seen as privileging an abstract predestinarianism over the concrete lives and structures of church communities and underwriting a complacency about division that deprives Christians of any motive to ecumenical endeavor, the concept of the “invisible” church has been widely marginalized in favor of a renewed focus on the “visible” church as the true church. However, I argue that this stress on visible unity creates a pressure toward institutional forms of unity that ultimately privilege Roman Catholic ecclesiologies at the expense of Protestant ones, and thus fails of its ecumenical promise. Renewed attention to Reformational understandings of the relationship between divine grace and human action and the centrality and uniqueness of Christ as the foundation of the church, I argue, dispels some misunderstandings of the church’s “invisibility” and demonstrates the indispensability of the concept. I argue that this Reformational framework, which refuses to accept the empirical divisions of the Church as definitive and summons us to an ecumenism that belongs to the church’s sanctification, provides the best theological ground for ecumenical endeavor.
The Politics of Christian Love: Shaping Everyday Social Interaction and Political Sensibilities among Coptic Egyptians
Authors: Van Raemdonck An
Published: February 2019

Christian love has historically been subject of extensive theological study but has rarely been studied within anthropology. Contemporary Coptic society receives growing attention over the last two decades as a minority in Egyptian Muslim majority society. An important bulk of this scholarship involves a discussion of the community’s sometimes self-defined and sometimes ascribed characterization as a persecuted minority. Particular attention has gone to how social and political dimensions of minority life lead to changes in Christian theological understandings. This paper builds on these insights and examines how Christian love is experienced, and shapes feelings of belonging, everyday morality and political sensibilities vis-à-vis Muslim majority society. It draws from ethnographic observations and meetings with Copts living in Egypt between 2014–2017. It focuses on three personal narratives that reveal the complex ways in which a theology of love affects social and political stances. An anthropological focus reveals the fluid boundaries between secular and religious expressions of Christian love. Love for God and for humans are seen as partaking in one divine love. Practicing this love, however, shapes very different responses and can lead to what has been described as Coptic ‘passive victim behaviour’, but also to political activity against the status-quo.
3D SSY Estimate of EPFM Constraint Parameter under Biaxial Loading for Sensor Structure Design
Authors: Ding Ping , Wang Xin
Published: February 2019

Conventional sensor structure design and related fracture mechanics analysis are based on the single J-integral parameter approach of elastic-plastic fracture mechanics (EPFM). Under low crack constraint cases, the EPFM one-parameter approach generally gives a stress overestimate, which results in a great cost waste of labor and sensor components. The J-A two-parameter approach overcomes this limitation. To enable the extensive application of the J-A approach on theoretical research and sensor engineering problem, under small scale yielding (SSY) conditions, the authors developed an estimate method to conveniently and quickly obtain the constraint (second) parameter A values directly from T-stress. Practical engineering application of sensor structure analysis and design focuses on three-dimensional (3D) structures with biaxial external loading, while the estimate method was developed based on two-dimensional (2D) plain strain condition with uniaxial loading. In the current work, the estimate method was successfully extended to a 3D structure with biaxial loading cases, which is appropriate for practical sensor design. The estimate method extension and validation process was implemented through a thin 3D single edge cracked plate (SECP) specimen. The process implementation was completed in two specified planes of 3D SECP along model thickness. A wide range of material and geometrical properties were applied for the extension and validation process, with material hardening exponent value 3, 5 and 10, and crack length ratio 0.1, 0.3 and 0.7.