bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling technology of InP heterojunction bipolar transistor for THz integrated circuit
Authors: Zhang Yong , Chen Yapei , Li Yukun , Qu Kun , Ren Tianhao
Published: February 2019

Indium phosphide (InP)‐based transistors play an important role in high‐speed circuit and high‐frequency analog circuit applications. Over the past few decades, terahertz heterojunction bipolar transistor (HBT) is increasingly developed. As a result, many reports of HBTs operating at terahertz region have flourished. Since the high‐frequency circuit design faces the challenge from the lack of precise transistor models, this paper reviews the development of high‐frequency modeling technologies of InP HBT at terahertz region. Processes in the development of small‐signal models at terahertz frequencies, precise parasitic parameters extraction method, improvements in measurement, and the de‐embedding technologies open up more opportunities for precise representation of InP HBTs. Finally, some excellent terahertz circuits based on InP HBT are reviewed.
Exploring sources of resistance to brown rot in an interspecific almond × peach population
Authors: Baró‐Montel Núria , Eduardo Iban , Usall Josep , Casals Carla , Arús Pere , Teixidó Neus , Torres Rosario
Published: February 2019

BACKGROUND

Monilinia spp. are responsible for brown rot, one of the most significant stone fruit diseases. Planting resistant cultivars seems a promising alternative, although most commercial cultivars are susceptible to brown rot. The aim of this study was to explore resistance to Monilinia fructicola over two seasons in a backcross one interspecific population between almond ‘Texas’ and peach ‘Earlygold’ (named T1E).

RESULTS

‘Texas’ almond was resistant to brown rot inoculation, whereas peach was highly susceptible. Phenotypic data from the T1E population indicated wide differences in response to M. fructicola. Additionally, several non‐wounded individuals exhibited resistance to brown rot. Quantitative trait loci (QTLs) were identified in several linkage groups, but only two proximal QTLs in G4 were detected over both seasons and accounted for 11.3–16.2% of the phenotypic variation.

CONCLUSION

Analysis of the progeny allowed the identification of resistant genotypes that could serve as a source of resistance in peach breeding programs. The finding of loci associated with brown rot resistance would shed light on implementing a strategy based on marker‐assisted selection (MAS) for introgression of this trait into elite peach materials. New peach cultivars resistant to brown rot may contribute to the implementation of more sustainable crop protection strategies. © 2019 Society of Chemical Industry
An in‐needle solid‐phase microextraction device packed with etched steel wires for polycyclic aromatic hydrocarbons enrichment in water samples
Authors: Yang Ying , Mai Weimei , Gao Jingyi , Hu Zhe , Xu Jianqiao , Zou Shichun
Published: February 2019

A novel, low‐cost and effective in‐needle solid‐phase microextraction device was developed for the enrichment of trace polycyclic aromatic hydrocarbons in water samples. The in‐needle solid‐phase microextraction device could be easily assembled by inserting hydrofluoric acid‐etched wires, which were used as adsorbent, into a 22‐gauge needle tube within spring supporters. Compared with the commercial solid‐phase microextraction fiber, the developed device has higher efficiency for the extraction of polycyclic aromatic hydrocarbons with four to six rings from water samples using the optimized extraction conditions. With gas chromatography equipped with a flame ionization detector, the limits of detection for the polycyclic aromatic hydrocarbons with four to six rings ranged from 0.0020 to 0.0067 ng/mL. The relative standard deviations for one needle and needle‐to‐needle extractions were in the range of 5.2–9.9% (n = 5) and 3.4–12.3% (n = 5), respectively. The spiked recoveries of the polycyclic aromatic hydrocarbons in tap water samples ranged from 73.2 to 95.4%. This in‐needle solid‐phase microextraction device could be a good field sampler because of the low sample loss over a long storage time.
The spectrum of genetic variants and phenotypic features of Southeast Asian patients with Noonan syndrome
Authors: Koh Ai‐Ling , Tan Ee‐Shien , Brett Maggie S. , Lai Angeline H. M. , Jamuar Saumya Shekhar , Ng Ivy , Tan Ene‐Choo
Published: February 2019

Background

Noonan syndrome (NS) is an autosomal dominant disorder that belongs to a group of developmental disorders called RASopathies with overlapping features and multiple causative genes. The aim of the study was to identify mutations underlying this disorder in patients from Southeast Asia and characterize their clinical presentations.

Methods

Patients were identified from the hospital's Genetics clinics after assessment by attending clinical geneticists. A targeted gene panel was used for next‐generation sequencing on genomic DNA extracted from the blood samples of 17 patients.

Results

Heterozygous missense variants were identified in 13 patients: eight were in PTPN11, three in SOS1, and one each in RIT1 and KRAS. All are known variants that have been reported in patients with NS. Of the 13 patients with identified variants, 10 had short stature, the most common feature for NS. Four of the eight patients with PTPN11 variants had atrial septal defect. Only two had pulmonary stenosis which is reported to be common for PTPN11 mutation carriers. Another two had hypertrophic cardiomyopathy, a feature which is negatively associated with PTPN11 mutations.

Conclusions

Our study provides the mutation and phenotypic spectrum of NS from a new population group. The molecular testing yield of 76% is similar to other studies and shows that the targeted panel approach is useful for identifying genetic mutations in NS which has multiple causative genes. The molecular basis for the phenotypes of the remaining patients remains unknown and would need to be uncovered via sequencing of additional genes or other investigative methods.
Correlation between PLCE1 rs2274223 variant and digestive tract cancer: A meta‐analysis
Authors: Chen Qingfa , Wang Yu , Xu Yan , Lin Hai , Xue Fangxi , Chen Xingtian
Published: February 2019

Background

The relationship between phospholipase C ε‐1 (PLCE1) rs2274223 variant and digestive tract cancer remains inconclusive despite extensive investigations. Therefore, we performed this meta‐analysis to obtain a more credible conclusion.

Methods

PubMed, Medline, and Embase were systematic searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

A total of 27 studies were finally included. Pooled analyses suggested that PLCE1 rs2274223 variant was significantly correlated with the likelihood of esophageal cancer (dominant model: p < 0.001, OR = 0.77, 95% CI 0.72–0.83; recessive model: p < 0.001, OR = 1.28, 95% CI 1.12–1.45; additive model: p < 0.001, OR = 1.20, 95% CI 1.11–1.29; allele model: p < 0.001, OR = 0.80, 95% CI 0.74–0.88) and gastric cancer (recessive model: p = 0.001, OR = 1.27, 95% CI 1.10–1.47; allele model: p = 0.03, OR = 0.88, 95% CI 0.78–0.98) in overall population. Further subgroup analyses showed that the positive results were mainly driven by the East Asians. However, no positive results were detected in Caucasians and West Asians.

Conclusion

Our findings indicated that the PLCE1 rs2274223 variant might serve as a promising genetic biomarker of esophageal and gastric cancer in East Asians.
Design of novel high‐efficient DPA using ACL‐loaded SIR for linearity improvement
Authors: Xia Zu‐Xue , Cao Xin
Published: February 2019

In this article, a novel high‐efficient Doherty power amplifier (DPA) is designed for linearity improvement from 2.1 to 2.4 GHz. The proposed DPA employs a pair of anti‐coupled lines loaded with a stepped impedance resonator to replace the λ/4 transmission line in the conventional DPA for harmonic suppression, phase compensation, and impedance transformation. The DPA is simulated, fabricated, and measured. As the measured results show, in the 2.1‐2.4 GHz band, the saturated output power is between 43.2 and 44.5 dBm with the saturated gain level between 10.2 and 11.5 dB. The saturated drain efficiency (DE) is between 60% and 70% with DE at 6 dB output power back‐off between 38% and 50%. Compared with the conventional DPA, the third‐order intermodulation distortion is reduced by 20 dB. The efficiency and gain have also been improved. The proposed DPA is feasible and applicable in modern wireless communication systems.
Conjoined ultra‐wideband (2,300‐6,000 MHz) dual antennas for LTE HB/WiFi/5G multi‐input multi‐output operation in the fifth‐generation tablet device
Authors: Wong Kin‐Lu , Chen Yu‐Han , Li Wei‐Yu
Published: February 2019

Conjoined dual antennas with an ultra‐wideband (UWB) of 2300‐6000 MHz for multi‐input multi‐output operation in the fifth‐generation (5G) tablet device is presented. The UWB covers not only the 5G band in 3300‐5000 MHz, but also the long term evolution high band in 2300‐2400/2500‐2690 MHz and the Wireless Fidelity band in 2400‐2500/5100‐5900 MHz. Additionally, the envelope correlation coefficient in the UWB is less than 0.1. The conjoined dual antennas have a planar printed structure and require only 32.2 mm (about 0.25‐wavelength at 2.3 GHz) along the edge of the device ground plane. The dual antennas share a conjoined section of a ring strip for bandwidth enhancement and a band‐pass resonant structure for effective decoupling. The band‐pass resonant structure is formed by a printed structure of distributed capacitor and inductor connected in series. Details of the conjoined UWB dual antennas are presented.
Max flow vitality in general and st‐planar graphs
Authors: Ausiello Giorgio , Franciosa Paolo G. , Lari Isabella , Ribichini Andrea
Published: February 2019

The vitality of an arc/node of a graph with respect to the maximum flow between two fixed nodes s and t is defined as the reduction of the maximum flow caused by the removal of that arc/node. In this paper, we address the issue of determining the vitality of arcs and/or nodes for the maximum flow problem. We show how to compute the vitality of all arcs in a general undirected graph by solving only 2(n − 1) max flow instances and, in st‐planar graphs (directed or undirected) we show how to compute the vitality of all arcs and all nodes in O(n) worst‐case time. Moreover, after determining the vitality of arcs and/or nodes, and given a planar embedding of the graph, we can determine the vitality of a “contiguous” set of arcs/nodes in time proportional to the size of the set.
A cut mark on the Mesolithic (ca. 5850 BC) cranium from Wieliszew (Poland): A revision of an analytical conclusion from previous studies
Authors: Tomczyk Jacek , Myszka Anna , Ostrowska Agnieszka , Sulgostowska Zofia , Palczewski Piotr
Published: February 2019

We present the application of computed tomography (CT) and scanning electron microscope (SEM) technologies for the analysis of the Mesolithic skull of an adult individual from Wieliszew (Poland; ca. 5850 BC). Macroscopic examinations carried out in the 1950s showed a bone defect on the skull identified as post‐mortem. On this basis, it was argued to be evidence of cannibalistic practices in the Mesolithic period. CT and SEM demonstrated that the transverse fracture in the frontal squama has regular, oblique, sloping margins. Close to the right end of the fracture, features of healing were identified. It suggests that the individual survived the insult, at least till the beginning of the early reparative phase. It is the first time a documented case of violence has been detected in the Mesolithic in Poland. The applied CT and SEM technologies showed that the previous interpretation of the wound on the skull of Wieliszew as a trace of cannibalistic practice turned out to be wrong.
Study of effective parameters on wear behavior of rubbers based on statistical methods
Authors: Hakami Ferial , Pramanik Alokesh , Islam Nazrul , Basak Animesh , Ridgway Nigel
Published: February 2019

This study investigates the wear, surface roughness, and temperature buildup (TBU) of styrene butadiene rubber (SBR), natural rubber (NR), and nitrile butadiene rubber (NBR) while sliding over abrasives of different sizes with the variation of normal load. Rubber properties such as tensile strength (s) and elongation at break (e) were considered as input parameters. Individual, as well as interacting effects of different parameters, were analyzed in‐depth by using statistical methods. Overall wear of rubber depends not only on the tribological system but also on mechanical properties that contribute different wear mechanisms in addition to abrasion. The abrasive particle size and1/(se)are the first and second most significant contributing factors, respectively, to all output parameters except the wear rate where the second contributing factor is the applied load and abrasive size is the highest contributor. Larger abrasive particles deepen ploughing marks, which is enhanced by the higher load, and lead to higher surface roughness. The effect of load on TBU is negligible because of the soft nature of the rubber material.
Design and fabrication of poly (glycerol sebacate)‐based fibers for neural tissue engineering: Synthesis, electrospinning, and characterization
Authors: Saudi Ahmad , Rafienia Mohammad , Zargar Kharazi Anousheh , Salehi Hossein , Zarrabi Ali , Karevan Mehdi
Published: February 2019

Poly (glycerol sebacate) (PGS) is a thermoset biodegradable elastomer considered as a promising candidate material for nerve applications. However, PGS synthesis is very time and energy consuming. In this study, the PGS pre‐polymer (pPGS) was synthesized using three synthesis times of 3, 5, and 7 hours at 170°C. Fourier transform infrared (FTIR), nuclear magnetic resonance spectroscopy, X‐ray diffraction analysis, and differential scanning calorimetry thermogram were utilized to study the pPGS behavior. Poly (vinyl alcohol) was used as a carrier to fabricate aligned poly (vinyl alcohol)‐poly (glycerol sebacate) (PVA‐PGS) fibers with various ratios (60:40, 50:50, and 40:60) using electrospinning and crosslinked through the thermal crosslinking method. Morphology of the fibers was studied before and after crosslinking using scanning electron microscopy (SEM). FTIR, mechanical properties in the dry and wet state, water contact angle, in vitro degradation, and water uptake behavior of crosslinked scaffolds were also investigated. 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, SEM analysis, and 4′, 6‐diamidino‐2‐phenylindole (DAPI) staining were utilized to determine the biocompatibility of scaffolds. The results show the synthesized pPGS in 3 hours at 170°C is the optimized sample in the terms of chemical reaction. All scaffolds have bead‐free and a uniform fiber diameter. The Young's modulus of crosslinked PVA‐PGS (50:50 and 40:60) fibers is shown to be in the expected range for nerve applications. The cell culture studies reveal PVA‐PGS (50:50 and 40:60) fibers could lead to better cell adhesion and proliferation. The results suggest that PVA‐PGS (50:50 and 40:60) is a suitable and promising biodegradable material in the fabrication of scaffolds for nerve regeneration.
Biodegradable polyester/modified mesoporous silica composites for effective bone repair with self‐reinforced properties
Authors: Wang Jielin , Yu Jianshu , Yan Yinan , Yang Dicheng , Wang Ping , Xu Yan , Zhu Jun , Xu Guohua , He Dannong , Huang Gang
Published: February 2019

A series novel composites based on poly(L‐lactide) (PLLA) oligomer modified mesoporous silica (MCM41) homogeneous dispersed into poly(L‐lactide‐co‐trimethylene carbonate‐co‐glycolide) (PLTG) terpolymer has been successfully prepared. The structure of PLTG terpolymer was characterized by 1H NMR. The structure and properties of modified and unmodified MCM41 were attested by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analyzer (TGA), X‐ray diffraction (XRD), N2 adsorption–desorption, scanning electron microscope (SEM), and transmission electron microscope (TEM), which demonstrated that the MCM41 was successfully grafted by the PLLA oligomer. The effect of different concentration of modified MCM41 in PLTG matrix on thermal properties, mechanical properties, and hydrophilicity was investigated by TGA, differential scanning calorimetry (DSC), mechanical testing, contact angle measurement, and SEM. The results of mechanical tests showed that 5 wt% of modified MCM41 nanoparticles gave rise to optimal reinforcing effect. The tensile strength, Young's modulus, and elongation at break of the PLTG/PLLA‐MCM41 (5%) composites were 33.2 Mpa, 1.58 Gpa, and 268.7%, respectively, which were all higher than the PLTG/MCM41 (5%) composites and pristine PLTG matrix, which were due to good interfacial adhesion between the PLTG matrix and MCM41 nanoparticles. TGA and DSC have shown that 5% modified MCM41 in the PLTG increased the temperature of composite degradation and Tg. Water contact angle measurement showed the hydrophilicity of the composites increases with the increase of modified MCM41 content. The live/dead assay showed that the modified MCM41 existing on the PLTG matrix presents very excellent cytocompatibility. Therefore, the novel composite material represents promising way for bone tissue engineering application.
Prenatal imaging throughout gestation in Beckwith‐Wiedemann syndrome
Authors: Shieh Hester F. , Estroff Judy A. , Barnewolt Carol E. , Zurakowski David , Tan Wen‐Hann , Buchmiller Terry L.
Published: February 2019

Purpose

Prenatal occurrence and timing of appearance of associated features in Beckwith‐Wiedemann syndrome (BWS) are unknown. We reviewed our BWS patients with serial fetal imaging and correlated these with postnatal findings.

Methods

All BWS patients with fetal ultrasound (US) or magnetic resonance imaging (MRI) from 2000 to 2016 were reviewed to determine the presence of polyhydramnios, placentamegaly, macrosomia, macroglossia, retrognathia, omphalocele, visceromegaly, and hemihypertrophy. These observations were correlated with postnatal findings. Data were analyzed by Mann–Whitney U test.

Results

Nine BWS patients underwent 42 fetal imaging studies with median of five (range of two to six) studies per patient between 13 and 35 weeks gestation. All prenatal findings were confirmed postnatally with complete concordance. All patients with omphalocele were detected early in gestation but other postnatal findings less predictably so. All omphaloceles were small, and were found significantly earlier in gestation than macrosomia (P = 0.004) and macroglossia (P = 0.012). Visceromegaly and retrognathia were less frequent, with no significant differences in median gestational age from omphalocele when prenatally identified.

Conclusions

In BWS, omphalocele is the most common prenatal finding and routinely observed in early gestation with 100% accuracy. Associated findings of macrosomia, macroglossia, visceromegaly, and retrognathia, when present, are detected later in gestation. Imaging in later gestation may reveal additional abnormalities that support a BWS diagnosis.
Effect of drug loading on the properties of temperature‐responsive polyester–poly(ethylene glycol)–polyester hydrogels
Authors: Prince David Andrew , Villamagna Ian J , Hopkins Cameron C , de Bruyn John R , Gillies Elizabeth R
Published: February 2019

Hydrogels that can undergo gelation upon injection in vivo are promising systems for the site‐specific delivery of drugs. In particular, some thermo‐responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo‐responsive hydrogels based on poly(ϵ‐caprolactone‐co‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(ϵ‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti‐inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol−1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol−1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo‐responsive hydrogels can be substantial and depend on the drug. For applications such as intra‐articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case‐by‐case basis. © 2019 Society of Chemical Industry
A Dual‐Purpose Bromocoumarin Tag Enables Deep Profiling of the Cellular Cysteinome
Authors: Rabalski Adam J. , Williams Jon D. , McClure Ryan A. , Vasudevan Anil , Baranczak Aleksandra
Published: February 2019

Chemical proteomics enables comprehensive profiling of small molecules in complex proteomes. A critical component to understand the interactome of a small molecule is the precise location on a protein where the interaction takes place. Several approaches have been developed that take advantage of bio‐orthogonal chemistry and subsequent enrichment steps to isolate peptides modified by small molecules. These methods rely on target identification at the level of mass spectrometry making it difficult to interpret an experiment when modified peptides are not identified. Herein, an approach in which fluorescence‐triggered two‐dimensional chromatography enables the isolation of small molecule‐conjugated peptides prior to mass spectrometry analysis is described. In this study, a bromocoumarin moiety has been utilized that fluoresces and generates a distinct isotopic signature to locate and identify modified peptides. Profiling of a cellular cysteinome with the use of a bromocoumarin tag demonstrates that two‐dimensional fluorescence‐based chromatography separation can enable the identification of proteins containing reactive cysteine residues. Moreover, the method facilitates the interrogation of low abundance proteins with greater depth and sensitivity than a previously reported isotope‐targeted approach. Lastly, this workflow enables the identification of small‐molecule modified peptides from a protein‐of‐interest.
Cannabinoid hyperemesis syndrome – recognition, diagnosis and treatment
Authors: Rehman Ajaz‐Ur , Pervaiz Amjadali , Narayan Manoj , Saqib Sarah
Published: February 2019

There is limited awareness of cannabinoid hyperemesis syndrome among psychiatrists and physicians, which results in diagnostic failure and inadequate treatment. In this article, Dr Rehman and colleagues discuss the successful management of such a case, including recognition of the condition, diagnostic measures, treatment and long‐term follow‐up.
Above genes: epigenetics and psychiatry
Authors: Greener Mark
Published: February 2019

Epigenetics could provide some insights into the risk of developing psychiatric disease and uncover a potential therapeutic target if researchers can discover enough about the role of this intriguing biological mechanism. Mark Greener reports.
Counter‐ion and solvent effects in the C‐ and O‐alkylation of the phenoxide ion with allyl chloride
Authors: Nogueira Isac C. , Pliego Josefredo R.
Published: February 2019

The alkylation reaction of the phenoxide ion with allyl chloride can take place in the oxygen atom or in the carbons of the aromatic ring in the ortho position. Experimental studies have suggested that solvent effects and ion pairing are important for the regioselectivity. In this work, this reaction has been studied by means of theoretical methods using density functional theory, continuum solvation models, and inclusion of some explicit water molecules. It was found that O‐alkylation is the only product in the reaction of free phenoxide ion in the gas phase. Inclusion of the solvent effect induces an activation barrier, and although the effect is more important for O‐alkylation, it is not enough to reverse the major O‐alkylation reaction path. When the reaction via the ion pair was considered, it was found that attack in the C3 carbon of the allyl chloride in the syn orientation of the leaving chloride ion leads to a stable transition state, with close activation barriers for both O‐ and C‐alkylations. Inclusion of the solvent effect to the ion pair reaction makes both the reaction barriers closer (difference of 0.2 kcal mol−1), in excellent agreement with the experimental data. The absolute theoretical free energy barriers also reproduce the experimental barriers with a deviation of 3.5 kcal mol−1. Thus, theoretical calculations point out that both ion pairing and solvation are critical for controlling reactivity and regioselectivity of this reaction.
From Embassy Ties to Twitter Links: Comparing Offline and Online Diplomatic Networks
Authors: Sevin Efe , Manor Ilan
Published: February 2019

This article investigates how diplomatic networks move into a new digital media platform, namely Twitter, through the analytical lenses of networked diplomacy studies and mediatization. We employ the studies in the former field to argue for the need to study the entire network to evaluate diplomatic relations, rather than relying on bilateral relations alone. Mediatization is then introduced to argue that moving to a digital platform (i.e., digitization) is a process in which countries might end up enjoying different levels of technology adoption. We first use social network analysis to compare the sizes and structures of brick and mortar embassy networks and Twitter following–follower relationship networks among ministries and ministers of foreign affairs of 130 countries. We then present a theoretical explanation of digitization of diplomatic networks. Our findings suggest that the majority of countries still have a larger diplomatic presence offline compared to their Twitter network. However, the structures of offline and online networks are similar, showing that countries have diplomatic relations (whether brick and mortar embassies or Twitter links) with the same groups of countries. We conclude by presenting the variance of the digitization process among countries.
q‐Deformed Quantum Mechanics Based on the q‐Addition
Authors: Chung Won Sang , Hassanabadi Hassan
Published: February 2019

In this paper we consider the q‐derivative appearing in the non‐extensive thermodynamics to formulate the q‐deformed quantum mechanics. From the q‐addition we discuss the q‐deformed calculus and q‐deformed elementary functions. We use these to construct the q‐deformed quantum mechanics. As examples we discuss momentum eigenfunction, one dimensional box problem and quantum harmonic potential problem.
Cardosin A endocytosis mediated by integrin leads to lysosome leakage and apoptosis of epithelial cells
Authors: Wu Hao , Castanheira Pedro , Faro Carlos , Tang Jordan
Published: February 2019

Cardosin A is an aspartic protease present in large amount in the pistils of cardoon flowers. This protease is known to contain an ‐Arg‐Gly‐Asp‐ (RGD) motif located on the molecular surface. In this study, we found that isolated recombinant cardosin A attached to human epithelial cells A549, mediated by the binding of its RGD motif to cell surface integrins. The cell bound cardosin A was internalized to endosomes and lysosomes and triggered the permeability of lysosomal membrane leading to apoptosis of the epithelial cells. These events are identical to those observed for three RGD‐containing aspartic proteases, Saps 4‐6, secreted by Candida albicans. Such a process, which has been called the Trojan Horse mechanism, is believed to benefit the invasion of C. albican into the epithelium of the host. The location of the RGD motifs of cardosin A and Saps 4‐6 are on the opposite ends of the homologous three‐dimensional structures, suggesting that the Trojan Horse mechanism is insensitive to the RGD position. Current finding also suggests that cardosin A may have a defensive function against the ingestion of cardoon flowers by human, insects, and other herbivores.
Binding characterization of N‐(2‐chloro‐5‐thiomethylphenyl)‐N′‐(3‐[3H]3methoxy phenyl)‐N′‐methylguanidine ([3H]GMOM), a non‐competitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist
Authors: Metaxas Athanasios , van Berckel Bart N. M. , Klein Pieter J. , Verbeek Joost , Nash Emily C. , Kooijman Esther J. M. , Renjaän Véronique A. , Golla Sandeep S. V. , Boellaard Ronald , Christiaans Johannes A. M. , Windhorst Albert D. , Leysen Josée E.
Published: February 2019

Labeled with carbon‐11, N‐(2‐chloro‐5‐thiomethylphenyl)‐N′‐(3‐methoxyphenyl)‐N′‐methylguanidine ([11C]GMOM) is currently the only positron emission tomography (PET) tracer that has shown selectivity for the ion‐channel site of N‐methyl‐D‐aspartate (NMDA) receptors in human imaging studies. The present study reports on the selectivity profile and in vitro binding properties of GMOM. The compound was screened on a panel of 80 targets, and labeled with tritium ([3H]GMOM). The binding properties of [3H]GMOM were compared to those of the reference ion‐channel ligand [3H](+)‐dizocilpine maleate ([3H]MK‐801), in a set of concentration‐response, homologous and heterologous inhibition, and association kinetics assays, performed with repeatedly washed rat forebrain preparations. GMOM was at least 70‐fold more selective for NMDA receptors compared to all other targets examined. In homologous inhibition and concentration‐response assays, the binding of [3H]GMOM was regulated by NMDA receptor agonists, albeit in a less prominent manner compared to [3H]MK‐801. Scatchard transformation of homologous inhibition data produced concave upward curves for [3H]GMOM and [3H]MK‐801. The radioligands showed bi‐exponential association kinetics in the presence of 100 μmol L−1 l‐glutamate/30 μmol L−1 glycine. [3H]GMOM (3 nmol L−1 and 10 nmol L−1) was inhibited with dual affinity by (+)‐MK‐801, (R,S)‐ketamine and memantine, in both presence and absence of agonists. [3H]MK‐801 (2 nmol L−1) was inhibited in a monophasic manner by GMOM under baseline and combined agonist conditions, with an IC50 value of ~19 nmol L−1. The non‐linear Scatchard plots, biphasic inhibition by open channel blockers, and bi‐exponential kinetics of [3H]GMOM indicate a complex mechanism of interaction with the NMDA receptor ionophore. The implications for quantifying the PET signal of [11C]GMOM are discussed.
Selectivity of novel and traditional insecticides used for management of whiteflies on the parasitoid Encarsia formosa
Authors: Wang Zhuo , Dai Peng , Yang Xiangbing , Ruan Chang‐Chun , Biondi Antonio , Desneux Nicolas , Zang Lian‐Sheng
Published: February 2019

BACKGROUND

Encarsia formosa Gahan is the most important parasitoid exploited for the control of whitefly pests of vegetable crops. However, the non‐target effects of recently developed insecticides for controlling whiteflies toward this biocontrol agent is little documented. Here we evaluated the susceptibility of E. formosa adults and juveniles to eight commonly used insecticides against whiteflies.

RESULTS

Residual toxicity tests on glass showed that E. formosa adults were susceptible (over 98% mortality after 6 h treated) to field concentrations of the tested neonicotinoids (imidacloprid, acetamiprid, nitenpyram and thiamethoxam), abamectin, cyantraniliprole, and sulfoxaflor at their field concentrations. Pyriproxyfen was harmless to both adult and pupae of E. formosa. A risk quotient analysis showed that toxicity of pyriproxyfen to E. formosa adults was the lowest, followed by acetamiprid and cyantraniliprole. In the leaf residues test, mortality of E. formosa adults under all insecticides decreased when the residue age increased. Interestingly, E. formosa experiencing contact with the residues of most insecticides, except pyriproxyfen and abamectin, parasitized significantly more hosts 5‐days after treatment, suggesting a hormetic effect on parasitism.

CONCLUSION

The risk assessment of insecticides indicated that pyriproxyfen and cyantraniliprole were the least toxic to E. formosa. Our results suggest that the inclusion of the insecticides in sustainable integrated pest management programs of whiteflies should be carefully evaluated on a case‐by‐case basis. © 2019 Society of Chemical Industry
Assessment of potential effects and detection efficacy of a fluorescent marking system on a medically important hard tick,Haemaphysalis longicornis(Acari: Ixodidae)
Authors: Kim Joo‐Young , Kho Jung‐Wook , Jung Minhyung , Lee Doo‐Hyung
Published: February 2019

BACKGROUND

AlthoughHaemaphysalis longicornis(Acari: Ixodidae) is an important disease vector, its small size restricts the tracking methods applicable. Recently, fluorescent marking as a conventional detection method for small arthropods has been improved by combining it with an ultraviolet laser. We examined the application potential of this new fluorescent marking system (FMS) for trackingH. longicornisby evaluating the effect of fluorescent marking on the ticks and detection efficacy.

RESULTS

Under laboratory conditions, fluorescent marking did not significantly affect the survivorship, movement patterns, and CO2response ofH. longicornisat all three developmental stages. Fluorescent‐marked individuals could be detected at distances ranging from 12 to 29 m under dark, increasing with the body size. Finally, in grassland, >90% of fluorescent‐marked individuals were retrieved at night regardless of developmental stage. However, the overall detection rate (<42%) was substantially reduced during the day.

CONCLUSIOIN

Our results show that FMS can reliably detectH. longicornisat night. Nevertheless, fluorescent‐marked individuals are not as conspicuous under sunlight when they are illuminated with ultraviolet lasers, limiting the use of FMS during the day. Therefore, the development of an alternative tracking method is warranted for an effective detection of ticks during the day. © 2019 Society of Chemical Industry
Novel therapeutic targets in inflammatory bowel disease
Authors: Chaplin Steve
Published: February 2019

SMAD7 antisense oligonucleotides and sphingosine‐1‐phosphate receptor modulators are new oral agents that are being investigated as potential treatments for inflammatory bowel disease (Crohn's disease and ulcerative colitis). This article reports on some of the clinical trial outcomes so far.
Developing new medicines for the treatment of pain
Authors: Houlton Sarah
Published: February 2019

Because of the many problems with existing treatments, there is an urgent need for new pain medications, but the journey from drug development to the clinic is notoriously challenging, reports Sarah Houlton.
Prescribing for patients with chronic fatigue syndrome
Authors: Bhatti Shabir , Bhatti Qasid Ahmad
Published: February 2019

Chronic fatigue syndrome, also known as myalgic encephalomyelitis, can be difficult to both diagnose and treat, but there are many prescribed medications that can help with specific symptoms and co‐morbidities. This article provides a guide to treatment in primary care.
Benefits of a comprehensive COPD inhaler identification aid
Authors: Lee Karen , Ibrahim Kamal
Published: February 2019

A vast number of inhalers are available to treat COPD, and it is extremely difficult for both healthcare professionals and patients to keep track of them all. Karen Lee and Kamal Ibrahim from Bolton Hospital NHS Foundation Trust have therefore helped to develop a comprehensive COPD inhaler identification poster and here they discuss its usefulness in a range of clinical settings.
The mechanism of phosphatidylcholine‐induced interference of PAP (248‐286) aggregation
Authors: Kumar Vijay , Gour Shalini , Verma Nidhi , Kumar Suman , Gadhave Kundlik , Mishra Pushpendra Mani , Goyal Pankaj , Pandey Janmejay , Giri Rajanish , Yadav Jay Kant
Published: February 2019

Seminal amyloids are well known for their role in enhancing HIV infection. Among all the amyloidogenic peptides identified in human semen, PAP248‐286 was found to be the most active and was termed as semen‐derived enhancer of viral infection (SEVI). Although amyloidogenic nature of the peptide is mainly linked with enhancement of the viral infection, the most active physiological conformation of the aggregated peptide remains inconclusive. Lipids are known to modulate aggregation pathway of a variety of proteins and peptides and constitute one of the most abundant biomolecules in human semen. PAP248‐286 significantly differs from the other known amyloidogenic peptides, including Aβ and IAPP, in terms of critical concentration, surface charge, fibril morphology, and structural transition during aggregation. Hence, in the present study, we aimed to assess the effect of a lipid, 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC), on PAP248‐286 aggregation and the consequent conformational outcomes. Our initial observation suggested that the presence of the lipid considerably influenced the aggregation of PAP248‐286. Further, ZDOCK and MD simulation studies of peptide multimerization have suggested that the hydrophobic residues at C‐terminus are crucial for PAP248‐286 aggregation and are anticipated to be major DOPC‐interacting partners. Therefore, we further assessed the aggregation behaviour of C‐terminal (PAP273‐286) fragment of PAP248‐286 and observed that DOPC possesses the ability to interfere with the aggregation behaviour of both the peptides used in the current study. Mechanistically, we propose that the presence of DOPC causes considerable inhibition of the peptide aggregation by interfering with the peptide's disordered state to β‐sheet transition.
Disorder and Weak Localization near Charge Neutral Point in Ti‐cleaned Single‐Layer Graphene
Authors: Fujimoto Akira , Perini Christopher J. , Terasawa Daiju , Fukuda Akira , Harada Yoshiyuki , Sasa Shigehiko , Yano Mitsuaki , Vogel Eric M.
Published: February 2019

The charge neutral point (CNP) for chemical‐vapor‐deposited (CVD) graphene appears at relatively high back‐gate voltages (VG) because of molecular adsorption and impurities on the graphene surface. Potential fluctuations due to these disorders strongly affect transport properties when the Fermi level approaches the Dirac point. In this work, a Ti‐cleaning process is used to shift the CNP of the transferred graphene surface to a lower VG. The effectiveness of charge doping due to Ti‐cleaning is also investigated through Raman scattering measurements. From the temperature dependence of the carrier concentration, the strength of the disorder potential for the CVD single‐layer graphene is estimated. The quadratic increase in the carrier concentration with temperature agrees with the theoretical prediction, which considers intrinsic thermal excitation combined with electron–hole puddles. Furthermore, based on weak localization (WL) analysis, the inelastic scattering length (Lϕ) decreases with temperature because of electron–electron interactions. The Lϕ also decreases near the CNP because of inhomogeneous charge distributions such as electron–hole puddles.
Structural and Electronic Properties of Cu2MnSnS4 from Experiment and First‐Principles Calculations
Authors: Rudisch Katharina , Espinosa‐García William F. , Osorio‐Guillén Jorge M. , Araujo Carlos M. , Platzer‐Björkman Charlotte , Scragg Jonathan J. S.
Published: February 2019

Cu2MnSnS4 shares several promising properties with the widely investigated Cu2ZnSnS4 for photovoltaic applications such as containing only earth abundant and non‐toxic elements, and suitable absorption characteristics for absorber materials. Thin film Cu2MnSnS4 samples with various cation compositions are co‐sputtered reactively followed by a high temperature anneal. Formation of Cu2MnSnS4 and co‐existence of several secondary phases is verified by XRD and Raman. Our investigation of the crystal structure based on first‐principles DFT confirms that stannite crystal structure is preferred over kesterite, although, further verification considering cation disorder is needed. The direct band gap of Cu2MnSnS4 is calculated as 1.52 eV (1.62 eV) for stannite (kesterite), which coincides with the range of the measured band gaps from spectrophotometry of 1.42–1.59 eV. After further annealing treatments below 240 °C, the absorption shows reversible changes: the band gap blue‐shifts and the Urbach tail energy is reduced. It is concluded that, just like Cu2ZnSnS4, disorder also occurs in Cu2MnSnS4. The implications of our findings are discussed and related to the current understanding of cation disorder in Cu2ZnSnS4 and related compounds. Furthermore, for the first time first‐principles DFT investigations are presented for the thiospinel Cu2MnSn3S8 which is observed experimentally as a secondary phase in Sn‐rich Cu2MnSnS4 thin films.
Classifying the nocturnal atmospheric boundary layer into temperature and flow regimes
Authors: Pfister Lena , Lapo Karl , Sayde Chadi , Selker John , Mahrt Larry , Thomas Christoph K.
Published: February 2019

We propose a classification scheme for nocturnal atmospheric boundary layers and apply it to investigate the spatio‐temporal structure of air temperature and wind speed in a shallow valley during the Shallow Cold Pool Experiment. This field campaign was the first to collect spatially continuous temperature and wind information at high resolution (1 s, 0.25 m) using the distributed temperature sensing technique across a 220 m long transect at three heights (0.5, 1.0, 2.0 m). The night‐time classification scheme was motivated by a surface energy balance and used a combination of static stability, wind regime and longwave radiative forcing as quantities to determine physically meaningful boundary‐layer regimes. Out of all potential combinations of these three quantities, 14 night‐time classes contained observations, of which we selected three for detailed analysis and comparison.

The three classes represent a transition from mechanical to radiative forcing. The first night class represents conditions with strong dynamic forcing caused by locally induced lee turbulence dominating near‐surface temperatures across the shallow valley. The second night class was a concurrence of enhanced dynamic mixing due to significant winds at the valley shoulders and cold‐air pooling at the bottom of the shallow valley as a result of strong radiative cooling. The third night class was characteristic of weak winds eliminating the impact of mechanical mixing but emphasizing the formation and pooling of cold air at the valley bottom.

The proposed night‐time classification scheme was found to sort the experimental data into physically meaningful regimes of surface flow and transport. It is suitable to stratify short‐ and long‐term experimental data for ensemble averaging and to identify case studies.
Re‐weighted random series path integral simulations of molecular clusters: Applications to lithium solvated by a mixed Stockmayer cluster
Authors: Hyers Matthew J. , Fodor Alex M. , Bierwisch Dominic K. , Curotto Emanuele
Published: February 2019

Nuclear quantum effects in finite temperature simulations of molecular clusters are determined by taking advantage of a recently developed method based on the Feynman Path Integral. The structural and thermodynamic properties, including the nuclear quantum effects are determined for three Stockmayer clusters. The ionic system contain a lithium ion solvated by six strong dipoles and 12 weaker ones. The presence of the ion in the mixed Stockmayer cluster drastically enhances the fluxional nature of the less polar components which occupy the second solvation layer, whereas the neutral counterpart has the effect of reducing it. The nuclear quantum effects are significant at room temperature and above for the solvated ionic system. These are attributable to two factors: (a) the lightness of the lithium ion and (b) the stiffness of the ion‐dipole interactions. At 300 K, the difference between the fully converged quantum and the classical heat capacities is about 1.3 KB for the ionic cluster. This difference is about 10 SDs obtained from 95% confidence estimates of the statistical fluctuations. Cubic convergence is confirmed for temperatures as low as 50 K by regression analysis. The nuclear quantum effects do not change the peak melting temperature of the cluster.
Multiple isotope tracers in fur keratin discriminate between mothers and offspring
Authors: Kravchenko Kseniia A. , Lehnert Linn S. , Vlaschenko Anton S. , Voigt Christian C.
Published: February 2019

Rationale

Isoscape origin models for mammals may be impaired by fractionation and routing of isotopes during lactation. Here, we tested if the stable carbon, nitrogen and hydrogen ratios of juvenile bats differ from those of their mothers and if derived isotopic dietary niches and geographical assignments vary accordingly between mothers and juveniles.

Methods

During the post‐lactation period, we collected fur of juvenile and female common noctule bats (Nyctalus noctula) from the same maternity roost. Using a combination of elemental analysis and stable isotope ratio mass spectrometry, we measured the hydrogen, carbon and nitrogen isotope ratios in fur keratin. The hydrogen isotope ratios were measured for the non‐exchangeable portion of hydrogen in keratin. The derived isotopic niches and isoscape origin models were compared between mothers and juveniles.

Results

The fur keratin of juveniles was enriched by 1.6‰ in 15N and depleted by 2.9‰ in 13C compared with that of the mothers. In addition, the hydrogen isotope ratios were 13.4‰ lower in the fur keratin of juveniles than in that of mothers. The estimated isotopic niches of nursing females and juveniles were not overlapping and differed in size. Overall, the isoscape origin models projected juveniles as being from a more northern origin than the mothers; yet both models suggested the study site as a likely place of origin.

Conclusions

Our results suggest that isotope ratio data of juvenile bats should not be used for transfer functions in isoscape origin models because of isotopic routing and discrimination during lactation. Not accounting for age effects may increase the inaccuracy of geographical assignments in mammals when based on stable hydrogen isotopes.
Bone Morphogenetic Protein-6 Attenuates Type 1 Diabetes Mellitus-Associated Bone Loss
Authors: Wang Jesse F. , Lee Ming-Song , Tsai Tsung-Lin , Leiferman Ellen M. , Trask Darrin J. , Squire Matthew W. , Li Wan-Ju
Published: February 2019

Patients with type 1 diabetes mellitus (T1DM) often suffer from osteopenia or osteoporosis. Although most agree that T1DM-induced hyperglycemia is a risk factor for progressive bone loss, the mechanisms for the link between T1DM and bone loss still remain elusive. In this study, we found that bone marrow-derived mesenchymal stem cells (BMSCs) isolated from T1DM donors were less inducible for osteogenesis than those from non-T1DM donors and further identified a mechanism involving bone morphogenetic protein-6 (BMP6) that was produced significantly less in BMSCs derived from T1DM donors than that in control cells. With addition of exogenous BMP6 in culture, osteogenesis of BMSCs from T1DM donors was restored whereas the treatment of BMP6 seemed not to affect non-T1DM control cells. We also demonstrated that bone mineral density (BMD) was reduced in streptozotocin-induced diabetic mice compared with that in control animals, and intraperitoneal injection of BMP6 mitigated bone loss and increased BMD in diabetic mice. Our results suggest that bone formation in T1DM patients is impaired by reduction of endogenous BMP6, and supplementation of BMP6 enhances osteogenesis of BMSCs to restore BMD in a mouse model of T1DM, which provides insight into the development of clinical treatments for T1DM-assocaited bone loss. Stem Cells Translational Medicine  2019;8:522–534