bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmid transfection influences the readout of nonsense-mediated mRNA decay reporter assays in human cells
Authors: Gerbracht Jennifer V. , Boehm Volker , Gehring Niels H.
Published: August 2017

Messenger RNA (mRNA) turnover is a crucial and highly regulated step of gene expression in mammalian cells. This includes mRNA surveillance pathways such as nonsense-mediated mRNA decay (NMD), which assesses the fidelity of transcripts and eliminates mRNAs containing a premature translation termination codon (PTC). When studying mRNA degradation pathways, reporter mRNAs are commonly expressed in cultivated cells. Traditionally, the molecular mechanism of NMD has been characterized using pairs of reporter constructs that express the same mRNA with (“PTC-containing mRNA”) or without (“wild-type mRNA”) a PTC. Cell lines stably expressing an NMD reporter have been reported to yield very robust and highly reproducible results, but establishing the cell lines can be very time-consuming. Therefore, transient transfection of such reporter constructs is frequently used and allows analysis of many samples within a short period of time. However, the behavior of transiently and stably transfected NMD constructs has not been systematically compared so far. Here, we report that not all commonly used human cell lines degrade NMD targets following transient transfection. Furthermore, the degradation efficiency of NMD substrates can depend on the manner of transfection within the same cell line. This has substantial implications for the interpretation of NMD assays based on transient transfections.
A Novel Benzocoumarin-Stilbene Hybrid as a DNA ligase I inhibitor with in vitro and in vivo anti-tumor activity in breast cancer models
Authors: Hussain Mohd. Kamil , Singh Deependra Kumar , Singh Akhilesh , Asad Mohd. , Ansari Mohd. Imran , Shameem Mohammad , Krishna Shagun , Valicherla Guru R. , Makadia Vishal , Meena Sanjeev , Deshmukh Amit Laxmikant , Gayen Jiaur R. , Imran Siddiqi Mohammad , Datta Dipak , Hajela Kanchan , Banerjee Dibyendu
Published: August 2017

Existing cancer therapies are often associated with drug resistance and toxicity, which results in poor prognosis and recurrence of cancer. This necessitates the identification and development of novel therapeutics against existing as well as novel cellular targets. In this study, a novel class of Benzocoumarin-Stilbene hybrid molecules were synthesized and evaluated for their antiproliferative activity against various cancer cell lines followed by in vivo antitumor activity in a mouse model of cancer. The most promising molecule among the series, i.e. compound (E)-4-(3,5-dimethoxystyryl)-2H-benzo[h]chromen-2-one (19) showed maximum antiproliferative activity in breast cancer cell lines (MDA-MB-231 and 4T1) and decreased the tumor size in the in-vivo 4T1 cell-induced orthotopic syngeneic mouse breast cancer model. The mechanistic studies of compound 19 by various biochemical, cell biology and biophysical approaches suggest that the compound binds to and inhibits the human DNA ligase I enzyme activity that might be the cause for significant reduction in tumor growth and may constitute a promising next-generation therapy against breast cancers.
Some sustained improvements in pneumonia case management four and five years following implementation of paediatric hospital guidelines in Lao PDR
Authors: Gray Amy , Chhor Louis , Sanyalack Saysanasongkham , Lim Ruth , Lai Jana , Vilivong Keo , Morpeth Melinda , Soukaloun Douangdao , Russell Fiona
Published: August 2017

In 2010, WHO paediatric hospital guidelines were implemented in Lao PDR, along with training workshops and feedback audits, achieving significant improvements in pneumonia case management when assessed one-year post-intervention. The sustainability of these improvements is hereby assessed, four and five years post-intervention. Medical records of children aged 1–59 months, diagnosed with pneumonia in 2010, 2011, 2014 and 2015 from a central Lao hospital were reviewed. Information relating to clinical steps in pneumonia case management was extracted and a scoring system applied based on the documentation of each clinical step, producing a pneumonia assessment score for each case. Comparisons of clinical steps and mean assessment score across study years were performed using Pearson’s chi-squared and t-tests, respectively. Of 231 pneumonia cases, the mean assessment scores in 2010, 2011, 2014 and 2015 were 57%, 96%, 69% and 69% respectively, showing a significant reduction from the immediate post-intervention period (2011) to 2015 (p < 0.01). Mean assessment score in 2014/2015 was significantly higher than in 2010 (p < 0.01). The high standards of pneumonia case management in 2011 were not observed in 2014/2015 in the absence of ongoing intervention but overall quality of care remained higher than pre-intervention levels, suggesting some degree of sustainability in the long-term.
Halotolerant aminopeptidase M29 from Mesorhizobium SEMIA 3007 with biotechnological potential and its impact on biofilm synthesis
Authors: Sierra Elwi Machado , Pereira Mariana Rangel , Maester Thaís Carvalho , Gomes-Pepe Elisangela Soares , Mendoza Elkin Rodas , Lemos Eliana G. de Macedo
Published: August 2017

The aminopeptidase gene from Mesorhizobium SEMIA3007 was cloned and overexpressed in Escherichia coli. The enzyme called MesoAmp exhibited optimum activity at pH 8.5 and 45 °C and was strongly activated by Co2+ and Mn2+. Under these reaction conditions, the enzyme displayed Km and kcat values of 0.2364 ± 0.018 mM and 712.1 ± 88.12 s−1, respectively. Additionally, the enzyme showed remarkable stability in organic solvents and was active at high concentrations of NaCl, suggesting that the enzyme might be suitable for use in biotechnology. MesoAmp is responsible for 40% of the organism’s aminopeptidase activity. However, the enzyme’s absence does not affect bacterial growth in synthetic broth, although it interfered with biofilm synthesis and osmoregulation. To the best of our knowledge, this report describes the first detailed characterization of aminopeptidase from Mesorhizobium and suggests its importance in biofilm formation and osmotic stress tolerance. In summary, this work lays the foundation for potential biotechnological applications and/or the development of environmentally friendly technologies and describes the first solvent- and halo-tolerant aminopeptidases identified from the Mesorhizobium genus and its importance in bacterial metabolism.
Maximum extent and decay of the Laurentide Ice Sheet in Western Baffin Bay during the Last glacial episode
Authors: Brouard Etienne , Lajeunesse Patrick
Published: August 2017

Reconstructing the extent, flow and decay of the Laurentide Ice Sheet (LIS) on the continental shelves of North America during the last glaciation provides paleoglaciological analogues that are essential for understanding and predicting how modern marine-based ice-sheets will respond to future climate change and sea level fluctuations. The geometry of the LIS during Marine isotope stage 2 (MIS-2; 29–14 ka BP) is one key element for ice-sheet modelling. The maximum extent of the LIS during this stage is well constrained for most sectors of the ice sheet, but major uncertainties remain, especially along the continental shelves of Arctic Canada. Despite a series of recent papers, the extent of the LIS in Western Baffin Bay, an area draining large volumes of glacial ice through multiple ice streams and likely characterized by ice shelves, remains highly speculative. Here we present unequivocal marine geophysical evidence that during the MIS-2 the LIS extended to the edge of the continental shelf, seaward of the previously proposed limits and subsequently retreated episodically westward during deglaciation. These data support interpretations of deep glacial ice grounding in Western Baffin Bay.
Impact of nutritional supplements on cognitive development of children in developing countries: A meta-analysis
Authors: Ip Patrick , Ho Frederick Ka Wing , Rao Nirmala , Sun Jin , Young Mary Eming , Chow Chun Bong , Tso Winnie , Hon Kam Lun
Published: August 2017

Nutritional supplements may be important on cognition but the evidence is heterogeneous. This meta-analysis aimed (1) to determine whether nutritional supplements provided to pregnant women or young children could improve cognitive development of children in developing countries, and (2) to explore how supplementation characteristics could improve children’s cognitive outcomes. This meta-analysis examined nutritional supplementation studies in 9 electronic databases and 13 specialist websites. Experimental studies were included if they were published from 1992 to 2016, were conducted in developing countries, had nutritional supplementation for pregnant women or children aged ≤8, and reported effect sizes on cognitive outcomes. Interventions with confounded components, such as stimulation and parenting, were excluded. 67 interventions (48 studies) for 29814 children from 20 developing countries were evaluated. Childhood nutritional supplementation could improve children’s cognitive development (d 0.08, 95% CI 0.03–0.13) and those with ≥5 nutrients was particularly beneficial (0.15, 0.08–0.22). Antenatal supplementation did not improve cognitive development (0.02, -0.01 to 0.06) except for those implemented in the first trimester (0.15, 0.03–0.28). In conclusion, childhood nutritional supplementation was beneficial to cognitive development but could be optimised by providing multiple nutrients; antenatal supplementation should target pregnancy women in the first trimester for better cognitive benefits.
Structural basis for CRMP2-induced axonal microtubule formation
Authors: Niwa Shinsuke , Nakamura Fumio , Tomabechi Yuri , Aoki Mari , Shigematsu Hideki , Matsumoto Takashi , Yamagata Atsushi , Fukai Shuya , Hirokawa Nobutaka , Goshima Yoshio , Shirouzu Mikako , Nitta Ryo
Published: August 2017

Microtubule associated protein Collapsin response mediator protein 2 (CRMP2) regulates neuronal polarity in developing neurons through interactions with tubulins or microtubules. However, how CRMP2 promotes axonal formation by affecting microtubule behavior remains unknown. This study aimed to obtain the structural basis for CRMP2–tubulin/microtubule interaction in the course of axonogenesis. The X-ray structural studies indicated that the main interface to the soluble tubulin-dimer is the last helix H19 of CRMP2 that is distinct from the known C-terminal tail-mediated interaction with assembled microtubules. In vitro structural and functional studies also suggested that the H19-mediated interaction promoted the rapid formation of GTP-state microtubules directly, which is an important feature of the axon. Consistently, the H19 mutants disturbed axon elongation in chick neurons, and failed to authorize the structural features for axonal microtubules in Caenorhabditis elegans. Thus, CRMP2 induces effective axonal microtubule formation through H19-mediated interactions with a soluble tubulin-dimer allowing axonogenesis to proceed.
High temperature in-situ synchrotron-based XRD study on the crystal structure evolution of C/C composite impregnated by FLiNaK molten salt
Authors: Feng Shanglei , Yang Yingguo , Li Li , Zhang Dongsheng , Yang Xinmei , Xia Huihao , Yan Long , Tsang Derek K. L. , Huai Ping , Zhou Xingtai
Published: August 2017

An in-situ real-time synchrotron-based grazing incidence X-ray diffraction was systematically used to investigate the crystal structural evolution of carbon fiber reinforced carbon matrix (C/C) composite impregnated with FLiNaK molten salt during the heat-treatment process. It was found that the crystallographic thermal expansion and contraction rate of interlayer spacing d002 in C/C composite with FLiNaK salt impregnation is smaller than that in the virgin sample, indicating the suppression on interlayer spacing from FLiNaK salt impregnated. Meanwhile the crystallite size LC002 of C/C composite with FLiNaK salt impregnation is larger than the virgin one after whole heat treatment process, indicating that FLiNaK salt impregnation could facilitate the crystallization of C/C composite after heat treatment process. This improved crystallization in C/C composite with FLiNaK salt impregnation suggests the synthetic action of the salt squeeze effect on crooked carbon layer and the release of internal residual stress after heating-cooling process. Thus, the present study not only contribute to reveal the interaction mechanism between C/C composite and FLiNaK salt in high temperature environment, but also promote the design of safer and more reliable C/C composite materials for the next generation molten salt reactor.
Oxidative damage and impairment of protein quality control systems in keratinocytes exposed to a volatile organic compounds cocktail
Authors: Dezest Marlène , Le Bechec Mickael , Chavatte Laurent , Desauziers Valérie , Chaput Benoît , Grolleau Jean-Louis , Descargues Pascal , Nizard Carine , Schnebert Sylvianne , Lacombe Sylvie , Bulteau Anne-Laure
Published: August 2017

Compelling evidence suggests that volatile organic compounds (VOCs) have potentially harmful effects to the skin. However, knowledge about cellular signaling events and toxicity subsequent to VOC exposure to human skin cells is still poorly documented. The aim of this study was to focus on the interaction between 5 different VOCs (hexane, toluene, acetaldehyde, formaldehyde and acetone) at doses mimicking chronic low level environmental exposure and the effect on human keratinocytes to get better insight into VOC-cell interactions. We provide evidence that the proteasome, a major intracellular proteolytic system which is involved in a broad array of processes such as cell cycle, apoptosis, transcription, DNA repair, protein quality control and antigen presentation, is a VOC target. Proteasome inactivation after VOC exposure is accompanied by apoptosis, DNA damage and protein oxidation. Lon protease, which degrades oxidized, dysfunctional, and misfolded proteins in the mitochondria is also a VOC target. Using human skin explants we found that VOCs prevent cell proliferation and also inhibit proteasome activity in vivo. Taken together, our findings provide insight into potential mechanisms of VOC-induced proteasome inactivation and the cellular consequences of these events.
A complete investigation of monocular and binocular functions in clinically treated amblyopia
Authors: Zhao Wuxiao , Jia Wu-Li , Chen Ge , Luo Yan , Lin Borong , He Qing , Lu Zhong-Lin , Li Min , Huang Chang-Bing
Published: August 2017

The gold standard of a successful amblyopia treatment is full recovery of visual acuity (VA) in the amblyopic eye, but there has been no systematic study on both monocular and binocular visual functions. In this research, we aimed to quantify visual qualities with a variety of perceptual tasks in subjects with treated amblyopia. We found near stereoacuity and pAE dominance in binocular rivalry in “treated” amblyopia were largely comparable to those of normal subjects. CSF of the pAE remained deficient in high spatial frequencies. The binocular contrast summation ratio is significantly lower than normal standard. The interocular balance point is 34%, indicating that contrast in pAE is much less effective as the same contrast in pFE in binocular phase combination. Although VA, stereoacuity and binocular rivalry at low spatial frequency in treated amblyopes were normal or nearly normal, the pAE remained “lazy” in high frequency domain, binocular contrast summation, and interocular phase combination. Our results suggest that structured monocular and binocular training are necessary to fully recover deficient functions in amblyopia.
A TCR-based Chimeric Antigen Receptor
Authors: Walseng Even , Köksal Hakan , Sektioglu Ibrahim M. , Fåne Anne , Skorstad Gjertrud , Kvalheim Gunnar , Gaudernack Gustav , Inderberg Else Marit , Wälchli Sébastien
Published: August 2017

Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods have emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although very potent, CAR recognition is limited to membrane antigens which represent around 1% of the total proteins expressed, whereas TCRs have the advantage of targeting any peptide resulting from cellular protein degradation. However, TCRs depend on heavy signalling machinery only present in T cells which restricts the type of eligible therapeutic cells. Hence, an introduced therapeutic TCR will compete with the endogenous TCR for the signalling proteins and carries the potential risk of mixed dimer formation giving rise to a new TCR with unpredictable specificity. We have fused a soluble TCR construct to a CAR-signalling tail and named the final product TCR-CAR. We here show that, if expressed, the TCR-CAR conserved the specificity and the functionality of the original TCR. In addition, we demonstrate that TCR-CAR redirection was not restricted to T cells. Indeed, after transduction, the NK cell line NK-92 became TCR positive and reacted against pMHC target. This opens therapeutic avenues combing the killing efficiency of NK cells with the diversified target recognition of TCRs.
RNA Sequencing and Co-expressed Long Non-coding RNA in Modern and Wild Wheats
Authors: Cagirici Halise Busra , Alptekin Burcu , Budak Hikmet
Published: August 2017

There is an urgent need for the improvement of drought-tolerant bread and durum wheat. The huge and complex genome of bread wheat (BBAADD genome) stands as a vital obstruction for understanding the molecular mechanism underlying drought tolerance. However, tetraploid wheat (Triticum turgidum ssp., BBAA genome) is an ancestor of modern bread wheat and offers an important model for studying the drought response due to its less complex genome. Additionally, several wild relatives of tetraploid wheat have already shown a significant drought tolerance. We sequenced root transcriptome of three tetraploid wheat varieties with varying stress tolerance profiles, and built differential expression library of their transcripts under control and drought conditions. More than 5,000 differentially expressed transcripts were identified from each genotype. Functional characterization of transcripts specific to drought-tolerant genotype, revealed their association with osmolytes production and secondary metabolite pathways. Comparative analysis of differentially expressed genes and their non-coding RNA partners, long noncoding RNAs and microRNAs, provided valuable insight to gene expression regulation in response to drought stress. LncRNAs as well as coding transcripts share similar structural features in different tetraploid species; yet, lncRNAs slightly differ from coding transcripts. Several miRNA-lncRNA target pairs were detected as differentially expressed in drought stress. Overall, this study suggested an important pool of transcripts where their manipulations confer a better performance of wheat varieties under drought stress.
Peroxisome Proliferator-Activated Receptor Gamma in Obesity and Colorectal Cancer: the Role of Epigenetics
Authors: Motawi T. K. , Shaker O. G. , Ismail M. F. , Sayed N. H.
Published: August 2017

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that is deregulated in obesity. PPARγ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARγ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARγ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARγ promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPARγ level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARγ. A significant negative correlation was found between PPARγ levels and the studied microRNAs. There was a significant PPARγ promoter hypermethylation in CRC patients that correlated to low PPARγ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARγ downregulation. Hypermethylation of PPARγ gene promoter is associated with CRC through suppression of PPARγ regardless of BMI.
Genetic Mechanisms Contribute to the Development of Heart Failure in Patients with Atrioventricular Block and Right Ventricular Apical Pacing
Authors: Liu Nana , Zheng Min , Li Shijie , Bai Hui , Liu Zhouying , Hou Cui hong , Zhang Shu , Pu Jielin
Published: August 2017

Right ventricular apical (RVA) pacing can lead to progressive left ventricular dysfunction and heart failure (HF), even in patients with normal cardiac structure and function. Our study conducted candidate gene screening and lentivirus transfected neonatal rat cardiomyocytes (NRCMs) to explore the genetic and pathogenic mechanisms of RVA pacing induced cardiomyopathy in third degree atrioventricular block (III AVB) patients. We followed 887 III AVB patients with baseline normal cardiac function and RVA pacing. After a median follow-up of 2.5 years, 10 patients (four males, mean age 47.6 ± 10.0 years) were diagnosed with RVA pacing induced HF with left ventricular ejection fraction (LVEF) reducing dramatically to 37.8 ± 7.1% (P  < 0.05). Candidate genes sequencing found cardiomyopathy associated genetic variations in all ten HF patients and six SCN5A variations in 6 of 20 control patients. Transfected NRCMs of Lamin A/C mutations (R216C and L379F) disrupted Lamin A/C location on nucleus membrane and finally resulted in increased apoptotic rate after serum starvation. In conclusion, cardiomyopathy associated genetic variations play an essential role in occurrence of newly onset HF in the III AVB patients with RVA pacing. RVA pacing, serving as extra stimulator, might accelerate the deterioration of cardiac structure and function.
Immunoregulation by IL-7R-targeting antibody-drug conjugates: overcoming steroid-resistance in cancer and autoimmune disease
Authors: Yasunaga Masahiro , Manabe Shino , Matsumura Yasuhiro
Published: August 2017

Steroid-resistance is a common complication in the treatment of malignancies and autoimmune diseases. IL-7/IL-7R signaling, which regulates lymphocyte growth and survival, has been implicated in the development of malignancies and autoimmune diseases. However, the biological significance of IL-7/IL-7R signaling in steroid treatment is poorly understood. Here, we identified a novel relationship between IL-7R signaling and steroid-resistance, and showed that an anti-IL-7R antibody conjugated with SN-38 (A7R-ADC-SN-38) has strong anti-tumor effects against both parental and steroid-resistant malignant cells. Furthermore, inflammation in the mouse autoimmune arthritis model was suppressed to greater extent by A7R-ADC conjugated to MMAE than by A7R-ADC-SN-38. Given that an increased proportion of IL-7R-positive cells is a common mechanism underlying the pathogenesis of autoimmunity, we found that specific depletion of this cell population abrogated the progression of disease. This suggests that the cytotoxicity and immunosuppressive capacity of A7R-ADC could be modulated to treat specific malignancies or autoimmune diseases through the introduction of different payloads, and represents a novel alternative to steroid therapy.
The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant
Authors: Tomás-Cortázar Julen , Martín-Ruiz Itziar , Barriales Diego , Pascual-Itoiz Miguel Ángel , de Juan Virginia Gutiérrez , Caro-Maldonado Alfredo , Merino Nekane , Marina Alberto , Blanco Francisco J. , Flores Juana María , Sutherland James D. , Barrio Rosa , Rojas Adriana , Martínez-Chantar María Luz , Carracedo Arkaitz , Simó Carolina , García-Cañas Virginia , Abecia Leticia , Lavín José Luis , Aransay Ana M. , Rodríguez Héctor , Anguita Juan
Published: August 2017

Salp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in the inhibition of early signaling events and the production of the autocrine growth factor, interleukin-2. The fate of the CD4 T cells activated in the presence of Salp15 or its long-term effects are, however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished cross-antigenic antibody production even after interruption of the treatment with the protein. Transcriptionally, the salivary protein provokes an acute effect that includes known activation markers, such as Il2 or Cd44, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with Salp15 does not result in B cell anergy or the generation of myeloid suppressor cells. However, Salp15 induces the increased expression of the ectoenzyme, CD73, in regulatory T cells and increased production of adenosine. Our study provides a profound characterization of the immunomodulatory activity of Salp15 and suggests that its long-term effects are due to the specific regulation of CD73.
Molecular mechanisms governing microRNA-125a expression in human hepatocellular carcinoma cells
Authors: Potenza Nicoletta , Panella Marta , Castiello Filomena , Mosca Nicola , Amendola Elena , Russo Aniello
Published: August 2017

MicroRNA-125a-5p (miR-125a) is a vertebrate homolog of lin-4, the first discovered microRNA, and plays a fundamental role in embryo development by downregulating Lin-28 protein. MiR-125a is also expressed in differentiated cells where it generally acts as an antiproliferative factor by targeting membrane receptors or intracellular transductors of mitogenic signals. MiR-125a expression is downregulated in several tumors, including hepatocellular carcinoma (HCC) where it targets sirtuin-7, matrix metalloproteinase-11, VEGF-A, Zbtb7a, and c-Raf. In this study, we have isolated the transcription promoter of human miR-125a and characterized its activity in HCC cells. It is a TATA-less Pol II promoter provided with an initiator element and a downstream promoter element, located 3939 bp upstream the genomic sequence of the miRNA. The activity of the promoter is increased by the transcription factor NF-kB, a master regulator of inflammatory response, and miR-125a itself was found to strengthen this activation through inhibition of TNFAIP3, a negative regulator of NF-kB. This finding contributes to explain the increased levels of miR-125a observed in the liver of patients with chronic hepatitis B.
Cholesterol-modified Hydroxychloroquine-loaded Nanocarriers in Bleomycin-induced Pulmonary Fibrosis
Authors: Liu Li , Ren Jun , He Zhiyao , Men Ke , Mao Ye , Ye Tinghong , Chen Hua , Li Ling , Xu Bocheng , Wei Yuquan , Wei Xiawei
Published: August 2017

An increasing number of reports have suggested the use of hydroxychloroquine (HCQ) as an adjunct anti-cancer treatment to enhance the chemotherapeutic response, as well as for the treatment of several fibrotic skin diseases and cystic fibrosis. In this study, we synthesized a cholesterol-modified HCQ (Chol-HCQ) and hypothesized that a systemic delivery system with Chol-HCQ nanocarriers could be effective for the treatment of bleomycin-induced pulmonary fibrosis. Chol-HCQ significantly inhibits the proliferation of rat lung fibroblasts, regulates inflammation and ameliorates bleomycin-induced pulmonary fibrosis in rats. It regulates the expression of pro-inflammatory cytokines, such as TNF-α; reduces the infiltration of inflammatory neutrophils; and inhibits the phosphorylation of NF-κB. Chol-HCQ also reduces the expression of connective tissue growth factor (CTGF) and phosphorylation of extracellular regulated protein kinase (p-ERK) in rats with bleomycin-induced pulmonary fibrosis. Chol-HCQ nanocarriers reduce early pulmonary inflammation and inhibit the CTGF/ERK signalling pathway in bleomycin-induced pulmonary fibrosis. These results demonstrate that Chol-HCQ liposomes suppress pulmonary inflammation and reduce pulmonary fibrosis induced by bleomycin. The systemic administration safety of Chol-HCQ liposomes was confirmed after intravenous administration for 28 days in rats. The present study provides evidence that Chol-HCQ liposomes may be a potential therapeutic agent for inflammation associated with pulmonary fibrosis.
Precision cardio-oncology: understanding the cardiotoxicity of cancer therapy
Authors: Han Xinqiang , Zhou Yun , Liu Wendi
Published: August 2017

Current oncologic treatments have brought a strong reduction in mortality in cancer patients. However, the cancer therapy-related cardiovascular complications, in particular chemo-therapy and radiation therapy-induced cardiotoxicities are a major cause of morbidity and mortality in people living with or surviving cancer. The simple fact is that all antineoplastic agents and radiation therapy target tumor cells but also result in collateral damage to other tissues including the cardiovascular system. The commonly used anthracycline chemotherapy agents can induce cardiomyopathy and congestive heart failure. Targeted therapies with human epidermal growth factor antibodies, tyrosine kinase inhibitors or vascular endothelial growth factor antibodies, and the antimetabolites also have shown to induce cardiomyopathy and myocardial ischemia. Cardiac arrhythmias and hypertension have been well described with the use of tyrosine kinase inhibitors and antimicrotubule agents. Pericarditis can happen with the use of cyclophosphamide or cytarabine. Mediastinal radiation can cause constrictive pericarditis, myocardial fibrosis, valvular lesions, and coronary artery disease. Despite significant progresses in the understanding of the molecular and pathophysiologic mechanisms behind the cardiovascular toxicity of cancer therapy, there is still lack of evidence-based approach for the monitoring and management of patients. This review will focus mainly on the recent advances in the molecular mechanisms of cardiotoxicity related to common cancer therapies while introducing the concept of cardio-oncology service. Applying the general principles of multi-disciplinary approaches toward the diagnosis, prevention, monitoring, and treatment of cancer therapy-induced cardiomyopathy and heart failure will also be discussed.
Electrochemical ion transfer mediated by a lipophilic Os(ii)/Os(iii) dinonyl bipyridyl probe incorporated in thin film membranes
Authors: Jansod Sutida , Wang Lu , Cuartero Maria , Bakker Eric
Published: August 2017

A new lipophilic dinonyl bipyridyl Os(ii)/Os(iii) complex successfully mediates ion transfer processes across voltammetric thin membranes.
Electrochemical estimation of the active site density on metal-free nitrogen-doped carbon using catechol as an adsorbate
Authors: Chakraborty Arup , Devivaraprasad Ruttala , Bera Bapi , Neergat Manoj
Published: August 2017

An electrochemical method to estimate the active site density of metal-free electrocatalysts using catechol adsorption.
Cisplatin and transplatin interaction with methionine: bonding motifs assayed by vibrational spectroscopy in the isolated ionic complexes
Authors: Paciotti Roberto , Corinti Davide , De Petris Alberto , Ciavardini Alessandra , Piccirillo Susanna , Coletti Cecilia , Re Nazzareno , Maitre Philippe , Bellina Bruno , Barran Perdita , Chiavarino Barbara , Elisa Crestoni Maria , Fornarini Simonetta
Published: August 2017

IRMPD spectroscopy discloses N- versus S-platination.
Charge transmission channel construction between a MOF and rGO by means of Co–Mo–S modification
Authors: Liu Duanduan , Jin Zhiliang , Bi Yingpu
Published: August 2017

Efficient hydrogen evolution was obtained by means of charge transmission channel construction between a MOF and rGO with Co–Mo–S modification.
Synthesis, characterization and catalytic epoxidation properties of lanthanide-stabilized peroxoisopolytungstates
Authors: Guo Jipeng , Niu Yanjun , Song Lanying , Xu Qiaofei , Lu Jingkun , Ma Pengtao , Zhang Dongdi , Zhang Chao , Niu Jingyang , Wang Jingping
Published: August 2017

A series of new lanthanide-containing peroxoisopolyoxotungstates, K6Na4[H32{Ln4(WO4)(H2O)16[W7O22(O2)2]4}3]·105H2O [Ln = CeIII(1), NdIII(2), SmIII(3), TbIII(4), ErIII(5)], have been successfully synthesized and structurally characterized.
Inter-cluster distance dependence of electrical properties in single crystals of a mixed-valence polyoxometalate
Authors: Tsunashima Ryo , Nakamura Ippei , Oue Rika , Koga Seiya , Oki Hirofumi , Noro Shin-ichiro , Nakamura Takayoshi , Akutagawa Tomoyuki
Published: August 2017

Electrical conductivity of [MoV2MoVI16O54(SO3)2]6− was investigated through dependence on the inter-cluster distance controlled by tetraethylammonium, tetrapropylammonium, and tetrabutylammonium cations.
A pentadentate nitrogen-rich copper electrocatalyst for water reduction with pH-dependent molecular mechanisms
Authors: Ekanayake Danushka M. , Kulesa Krista M. , Singh Jaffarguriqbal , Kpogo Kenneth K. , Mazumder Shivnath , Bernhard Schlegel H. , Verani Cláudio N.
Published: August 2017

A copper catalyst is active towards water reduction with distinctive pH-dependent mechanisms. The CuIII–H− intermediate is bypassed by PCET processes.
A series of Mg–Zn heterometallic coordination polymers: synthesis, characterization, and fluorescence sensing for Fe3+, CS2, and nitroaromatic compounds
Authors: Wu Zhao-Feng , Huang Xiao-Ying
Published: August 2017

Herein, three luminescent Mg–Zn coordination polymers were constructed, which demonstrated high fluorescence sensing of Fe3+, CS2, and nitro explosive compounds.
Urea-glass preparation of titanium niobium nitrides and subsequent oxidation to photoactive titanium niobium oxynitrides
Authors: Brancho James J. , Proctor Aaron D. , Panuganti Shobhana , Bartlett Bart M.
Published: August 2017

Titanium niobium oxynitrides (TiNbON) are an attractive category of potential photocatalysts, but strategies for preparing them remain limited.
Rare earth elements in freshwater, marine, and terrestrial ecosystems in the eastern Canadian Arctic
Authors: MacMillan Gwyneth Anne , Chételat John , Heath Joel P. , Mickpegak Raymond , Amyot Marc
Published: August 2017

Rare earth elements show consistent bioaccumulation patterns yet limited biomagnification in remote northern ecosystems.
Nut consumption in relation to all-cause and cause-specific mortality: a meta-analysis 18 prospective studies
Authors: Chen Guo-Chong , Zhang Ru , Martínez-González Miguel A. , Zhang Zeng-Li , Bonaccio Marialaura , van Dam Rob M. , Qin Li-Qiang
Published: August 2017

Nut consumption is associated with lower all-cause and cause-specific mortality risk and most of the survival benefits may be achieved at a relative low level of nut consumption (about 12 g d−1).
Recent progress in interface engineering of organic thin film transistors with self-assembled monolayers
Authors: Liu Danqing , Miao Qian
Published: August 2017

This review introduces basic concepts and recent progress in self-assembled monolayers as a powerful tool for interface engineering of organic thin film transistors.
Chemoselective C(α)–C(β) bond cleavage of saturated aryl ketones with amines leading to α-ketoamides: a copper-catalyzed aerobic oxidation process with air
Authors: Liu Chengkou , Yang Zhao , Zeng Yu , Fang Zheng , Guo Kai
Published: August 2017

An unprecedented chemoselective C(α)–C(β) bond cleavage of simple saturated aryl ketones with amines leading to α-ketoamidesvia a copper-catalyzed aerobic oxidation process with air has been disclosed.
Simple synthesis and molecular engineering of low-cost and star-shaped carbazole-based hole transporting materials for highly efficient perovskite solar cells
Authors: Lu Chunyuan , Choi In Taek , Kim Jeongho , Kim Hwan Kyu
Published: August 2017

SGT-405(3,6), developed by tuning the substitution position from (2,7) to (3,6) position of carbazole moiety, is an promising alternative non-spiro type small molecular HTM with low-cost, highTgand excellent performance for existing cost ineffective and synthetically-challenging spiro-OMeTADin perovskite solar cells.
Gold atom-decorated CoSe2nanobelts with engineered active sites for enhanced oxygen evolution
Authors: Zhao Xu , Gao Pengfei , Yan Yu , Li Xingqi , Xing Yulin , Li Hongliang , Peng Zhenmeng , Yang Jinlong , Zeng Jie
Published: August 2017

Isolated Au atom-decorated CoSe2nanobelts with strengthened H2O adsorption and sufficient exposure of active sites for enhanced oxygen evolution.
Mg-doped Ta3N5nanorods coated with a conformal CoOOH layer for water oxidation: bulk and surface dual modification of photoanodes
Authors: Pei Lang , Xu Zhe , Shi Zhan , Zhu Heng , Yan Shicheng , Zou Zhigang
Published: August 2017

Benefiting from Mg doping to enhance electrical conductivity and carrier density together with a high conformal CoOOH layer as an OEC to make maximum use of surface reaching holes, the Ta3N5nanorod photoanode exhibits an over 4-fold increase in photocurrent.
Vanadium nitride encapsulated carbon fibre networks with furrowed porous surfaces for ultrafast asymmetric supercapacitors with robust cycle life
Authors: An Geon-Hyoung , Lee Do-Young , Ahn Hyo-Jin
Published: August 2017

Transition metal nitrides have received significant attention in view of their application as pseudocapacitive electrodes in high performance supercapacitors owing to their high capacitance, excellent electrical conductivity, high electrochemical selectivity, and low environmental impact.
Rapid delivery of paclitaxel with an organic solvent-free system based on a novel cell penetrating peptide for suppression of tumor growth
Authors: Wei Yuping , Zhang Liang , Fu Yankai , Xu Xia
Published: August 2017

PTX is rapidly translocated into HeLa cells with the help of R7. The intracellular PTX concentration of R7/PTX complex group is 3 fold that of the free PTX group. This delivery system does not contain any organic solvent. The tumor growth is significantly suppressed by a tail vein injection of the R7/PTX complex.
Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids
Authors: Grijalvo Santiago , Alagia Adele , Puras Gustavo , Zárate Jon , Mayr Judith , Pedraz José Luis , Eritja Ramon , Díaz David Díaz
Published: August 2017

Two polysaccharide-based hydrogels made of only κ-carrageenan (4%; w/v) or of a mixture of methylcellulose:κ-carrageenan (2%; w/v) were used to encapsulate cationic nioplexes.
Lanthanide/nucleotide coordination polymers: an excellent host platform for encapsulating enzymes and fluorescent nanoparticles to enhance ratiometric sensing
Authors: Gao Jie , Wang Caihong , Tan Hongliang
Published: August 2017

The co-encapsulation of GOx and CDs endows the resulting composite with excellent catalytic and fluorescence activities and enhanced sensing performances.
Applying Item Response Theory to the Development of a Screening Adaptation of the Goldman-Fristoe Test of Articulation–Second Edition
Authors: Brackenbury Tim , Zickar Michael J. , Munson Benjamin , Storkel Holly L.
Published: August 2017

Purpose

Item response theory (IRT) is a psychometric approach to measurement that uses latent trait abilities (e.g., speech sound production skills) to model performance on individual items that vary by difficulty and discrimination. An IRT analysis was applied to preschoolers' productions of the words on the Goldman-Fristoe Test of Articulation–Second Edition (GFTA-2) to identify candidates for a screening measure of speech sound production skills.

Method

The phoneme accuracies from 154 preschoolers, with speech skills on the GFTA-2 ranging from the 1st to above the 90th percentile, were analyzed with a 2-parameter logistic model.

Results

A total of 108 of the 232 phonemes from stimuli in the sounds-in-words subtest fit the IRT model. These phonemes, and subgroups of the most difficult of these phonemes, correlated significantly with the children's overall percentile scores on the GFTA-2. Regression equations calculated for the 5 and 10 most difficult phonemes predicted overall percentile score at levels commensurate with other screening measures.

Conclusions

These results suggest that speech production accuracy can be screened effectively with a small number of sounds. They motivate further research toward the development of a screening measure of children's speech sound production skills whose stimuli consist of a limited number of difficult phonemes.
Detecting age groups using touch interaction based on neuromotor characteristics
Authors: Hernandez‐Ortega J. , Morales A. , Fierrez J. , Acien A.
Published: August 2017

A new parental control method to prevent unauthorised usage of touch devices by kids is proposed. The impact of rapidly advancing technology on the developing child has seen an increase exposition to new forms of danger. Studies reveal that 97% of US children under the age of four use mobile devices. A reliable and efficient method to prevent the use of touch devices by preschool children is proposed. The proposed method is based on the analysis of the neuromotor characteristics of the users according to the decomposition of simple drag and drop tasks using the kinematic theory of rapid human movements. The experimentation is conducted on a publicly available database with samples obtained from 89 children between 3 and 6 years old and 30 adults. The results are compared with an existent system based only on task time and accuracy. Finally, both systems are combined at score level to achieve better performances. The results, with correct classification rates over 96% in the combined system, show the discriminative ability of the proposed neuromotor‐inspired features and the possibility of combining this system with others to improve their final performance.
Single channel 224 Gbit/s (56‐GBaud) PAM‐16 transmission using linear digital pre‐distortion
Authors: Yang Chao , Li Wei , Yu Shaohua
Published: August 2017

With linear digital pre‐distortion (DPD) and 8‐bit digital to analogue converter (DAC), a single channel 224 Gbit/s (56‐GBaud) 16‐level pulse amplitude modulation (PAM‐16) signal is experimentally transmitted over a 100 m standard single‐mode fibre (SSMF) for the first time using intensity modulation and direct detection (IM/DD). The 3 dB bandwidth of the whole system is around 22 GHz, which is far below the bandwidth of the 56‐GBuad PAM‐16 signal. The strong inter‐symbol interference caused by the limited system bandwidth is pre‐compensated by the proposed linear DPD technique. The experimental results indicate that the linear DPD process can effectively avoid the noise enhancement by the aggressive feed‐forward equalisation at the receiver, and also improves the system performance at the cost of additional finite impulse response filter at the transmitter.
Review of different fault detection methods and their impact on pre‐emptive VSC‐HVDC dc protection performance
Authors: Chang Bin , Cwikowski Oliver , Barnes Mike , Shuttleworth Roger , Beddard Antony , Coventry Paul
Published: August 2017

Multi‐terminal voltage‐sourced converters (VSC) high‐voltage direct current (HVDC) transmission system is expected to play a vital role in future power systems. Compared with ac power transmission, dc transmission is more vulnerable to faults due to low dc‐side impedances and sensitive power electronics in the converters. Dc protection issues must be tackled before any multi‐terminal VSC‐HVDC grid can be built. The multi‐terminal VSC‐HVDC system is studied in detail using switching models for two‐level converters, detailed equivalent models for the modular multi‐level converters, detailed hybrid circuit breaker switching models and frequency‐dependent phase models for dc cables. Using such high‐fidelity system models, a systematic study of HVDC fault protection methodologies in more detail than previous studies is conducted. This is the first comprehensive study that includes pre‐emptive circuit breaker operation. The results presented in this study underline the benefits of such a detailed treatment of the breaker, and of considering it as part of a fast power electronics system rather than isolated dc equipment. The study identifies the best existing fault detection method and tests it extensively. In order to further improve post‐fault system recovery response, which is a key but often neglected part of previous studies, a novel bump‐less transfer control has been implemented in the converters.
SVM‐based PQ disturbance recognition system
Authors: Huang Jiansheng , Jiang Zhuhan , Rylands Leanne , Negnevitsky Michael
Published: August 2017

The quality of power delivered by modern electricity grids is of interest as disturbances to power quality (PQ) have the potential to cause malfunction of control systems, interfere with communication networks, increase power losses and reduce the life of electrical components. It is, therefore, necessary to determine if there are PQ disturbances in a grid, and if so what forms these disturbances take. On the basis of site measurements at power distribution systems, a waveform generator is designed to emulate 11 types of PQ disturbances as well as harmonics, and a prototype for recognising these undesirable disturbances is presented. The first step is to use the discrete wavelet transform (DWT) to extract the most representative transients at different time spans from the original waveform. The second step is to use the output of the DWT to construct two sets of classifiers, which can recognise the types of disturbances present. Non‐linear support vector machine (SVM)‐based techniques are exploited for this step. Case studies are carried out to verify the prototype system. Simulations show that the SVM classifiers developed can achieve superior performance in recognising PQ disturbances compared with conventional counterparts.
Automatic choroid layer segmentation using normalized graph cut
Authors: Masood Saleha , Sheng Bin , Li Ping , Shen Ruimin , Fang Ruogu , Wu Qiang
Published: August 2017

Optical coherence tomography is an immersive technique for depth analysis of retinal layers. Automatic choroid layer segmentation is a challenging task because of the low contrast inputs. Existing methodologies carried choroid layer segmentation manually or semi‐automatically. The authors proposed automated choroid layer segmentation based on normalised cut algorithm, which aims at extracting the global impression of images and treats the segmentation as a graph partitioning problem. Due to the structure complexity of retinal and choroid layers, the authors employed a series of pre‐processing to make the cut more deterministic and accurate. The proposed method divided the image into several patches and ran the normalised cut algorithm on every patch separately. The aim was to avoid insignificant vertical cuts and focus on horizontal cutting. After processing every patch, the authors acquired a global cut on the original image by combining all the patches. Later the authors measured the choroidal thickness which is highly helpful in the diagnosis of several retinal diseases. The results were computed on a total of 525 images of 21 real patients. Experimental results showed that the mean relative error rate of the proposed method was around 0.4 when compared with the manual segmentation performed by the experts.