bluuebunny/crossref_metadata_2025 huggingface dataset:
A Current Frequency Component-Based Fault-Location Method for Voltage-Source Converter-Based High-Voltage Direct Current (VSC-HVDC) Cables Using the S Transform
Authors: Zhao Pu , Chen Qing , Sun Kongming , Xi Chuanxin
Published: August 2017

This paper proposes a fault-location method for voltage-source converter (VSC)-based high-voltage direct current (VSC-HVDC) systems. This method relies on the current frequency components generated by faults in the cable, and requires the arrival time of the frequency components at two terminals. The S transform is a time–frequency analysis tool that is superior to the wavelet transform in some respects. Therefore, the S transform was employed to determine the arrival time in this paper. To obtain a reliable criterion, a novel phase-mode transform method for bipolar cables was developed, and the propagation characteristics of the current frequency components through out the cable were analyzed. A two-terminal VSC-HVDC system was modeled in power system computer aided design/electromagnetic transients including DC (PSCAD/EMTDC). Various faults under different conditions were simulated on the basis of this model, and the simulation results verified a high accuracy, robustness against fault-resistance, and noise immunity of the proposed method.
Energy Refurbishment of an Office Building with Hybrid Photovoltaic System and Demand-Side Management
Authors: Almeida Dávi Giovani , López de Asiain José , Solano Juan , Caamaño-Martín Estefanía , Bedoya César
Published: August 2017

On-site photovoltaic (PV) and battery systems intend to improve buildings energy performance, however battery costs and monetary incentives are a major drawback for the introduction of these technologies into the electricity grids. This paper proposes an energy refurbishment of an office building based on multi-objective simulations. An innovative demand-side management approach is analyzed through the PV and battery control with the purpose of reducing grid power peaks and grid imported energy, as well as improving the project economy. Optimization results of load matching and grid interaction parameters, complemented with an economic analysis, are investigated in different scenarios. By means of battery use, the equivalent use of the grid connection is reduced by 12%, enhancing the grid interaction potential, and 10% of load matching rates can be increased. Project improvements indicate the grid connection capacity can be reduced by 13% and significant savings of up to 48% are achieved on yearly bills. The economy demonstrates the grid parity is only achieved for battery costs below 100 €/kWh and the payback period is large: 28 years. In the case with only PV system, the grid parity achieves better outcomes and the payback time is reduced by a half, making this a more attractive option.
A New Combined Boost Converter with Improved Voltage Gain as a Battery-Powered Front-End Interface for Automotive Audio Amplifiers
Authors: Lai Ching-Ming , Cheng Yu-Huei , Teh Jiashen , Lin Yuan-Chih
Published: August 2017

High boost DC/DC voltage conversion is always indispensable in a power electronic interface of certain battery-powered electrical equipment. However, a conventional boost converter works for a wide duty cycle for such high voltage gain, which increases power consumption and has low reliability problems. In order to solve this issue, a new battery-powered combined boost converter with an interleaved structure consisting of two phases used in automotive audio amplifier is presented. The first phase uses a conventional boost converter; the second phase employs the inverted type. With this architecture, a higher boost voltage gain is able to be achieved. A derivation of the operating principles of the converter, analyses of its topology, as well as a closed-loop control designs are performed in this study. Furthermore, simulations and experiments are also performed using input voltage of 12 V for a 120 W circuit. A reasonable duty cycle is selected to reach output voltage of 60 V, which corresponds to static voltage gain of five. The converter achieves a maximum measured conversion efficiency of 98.7% and the full load efficiency of 89.1%.
Investigation of the Dynamic Melting Process in a Thermal Energy Storage Unit Using a Helical Coil Heat Exchanger
Authors: Yang Xun , Xiong Teng , Dong Jing Liang , Li Wen Xin , Wang Yong
Published: August 2017

In this study, the dynamic melting process of the phase change material (PCM) in a vertical cylindrical tube-in-tank thermal energy storage (TES) unit was investigated through numerical simulations and experimental measurements. To ensure good heat exchange performance, a concentric helical coil was inserted into the TES unit to pipe the heat transfer fluid (HTF). A numerical model using the computational fluid dynamics (CFD) approach was developed based on the enthalpy-porosity method to simulate the unsteady melting process including temperature and liquid fraction variations. Temperature measurements using evenly spaced thermocouples were conducted, and the temperature variation at three locations inside the TES unit was recorded. The effects of the HTF inlet parameters were investigated by parametric studies with different temperatures and flow rate values. Reasonably good agreement was achieved between the numerical prediction and the temperature measurement, which confirmed the numerical simulation accuracy. The numerical results showed the significance of buoyancy effect for the dynamic melting process. The system TES performance was very sensitive to the HTF inlet temperature. By contrast, no apparent influences can be found when changing the HTF flow rates. This study provides a comprehensive solution to investigate the heat exchange process of the TES system using PCM.
Near-Real-Time Monitoring of Insect Defoliation Using Landsat Time Series
Authors: Pasquarella Valerie , Bradley Bethany , Woodcock Curtis
Published: August 2017

Introduced insects and pathogens impact millions of acres of forested land in the United States each year, and large-scale monitoring efforts are essential for tracking the spread of outbreaks and quantifying the extent of damage. However, monitoring the impacts of defoliating insects presents a significant challenge due to the ephemeral nature of defoliation events. Using the 2016 gypsy moth (Lymantria dispar) outbreak in Southern New England as a case study, we present a new approach for near-real-time defoliation monitoring using synthetic images produced from Landsat time series. By comparing predicted and observed images, we assessed changes in vegetation condition multiple times over the course of an outbreak. Initial measures can be made as imagery becomes available, and season-integrated products provide a wall-to-wall assessment of potential defoliation at 30 m resolution. Qualitative and quantitative comparisons suggest our Landsat Time Series (LTS) products improve identification of defoliation events relative to existing products and provide a repeatable metric of change in condition. Our synthetic-image approach is an important step toward using the full temporal potential of the Landsat archive for operational monitoring of forest health over large extents, and provides an important new tool for understanding spatial and temporal dynamics of insect defoliators.
Tropical-Forest Structure and Biomass Dynamics from TanDEM-X Radar Interferometry
Authors: Treuhaft Robert , Lei Yang , Gonçalves Fabio , Keller Michael , Santos João , Neumann Maxim , Almeida André
Published: August 2017

Changes in tropical-forest structure and aboveground biomass (AGB) contribute directly to atmospheric changes in CO 2 , which, in turn, bear on global climate. This paper demonstrates the capability of radar-interferometric phase-height time series at X-band (wavelength = 3 cm) to monitor changes in vertical structure and AGB, with sub-hectare and monthly spatial and temporal resolution, respectively. The phase-height observation is described, with a focus on how it is related to vegetation-density, radar-power vertical profiles, and mean canopy heights, which are, in turn, related to AGB. The study site covers 18 × 60 km in the Tapajós National Forest in the Brazilian Amazon. Phase-heights over Tapajós were measured by DLR’s TanDEM-X radar interferometer 32 times in a 3.2 year period from 2011–2014. Fieldwork was done on 78 secondary and primary forest plots. In the absence of disturbance, rates of change of phase-height for the 78 plots were estimated by fitting the phase-heights to time with a linear model. Phase-height time series for the disturbed plots were fit to the logistic function to track jumps in phase-height. The epochs of clearing for the disturbed plots were identified with ≈1-month accuracy. The size of the phase-height change due to disturbance was estimated with ≈2-m accuracy. The monthly time resolution will facilitate REDD+ monitoring. Phase-height rates of change were shown to correlate with LiDAR RH90 height rates taken over a subset of the TanDEM-X data’s time span (2012–2013). The average rate of change of phase-height across all 78 plots was 0.5 m-yr - 1 with a standard deviation of 0.6 m-yr - 1 . For 42 secondary forest plots, the average rate of change of phase-height was 0.8 m-yr - 1 with a standard deviation of 0.6 m-yr - 1 . For 36 primary forest plots, the average phase-height rate was 0.1 m-yr - 1 with a standard deviation of 0.5 m-yr - 1 . A method for converting phase-height rates to AGB-rates of change was developed using previously measured phase-heights and field-estimated AGB. For all 78 plots, the average AGB-rate was 1.7 Mg-ha - 1 -yr - 1 with a standard deviation of 4.0 Mg-ha - 1 -yr - 1 . The secondary-plot average AGB-rate was 2.1 Mg-ha - 1 -yr - 1 , with a standard deviation of 2.4 Mg-ha - 1 -yr - 1 . For primary plots, the AGB average rate was 1.1 Mg-ha - 1 -yr - 1 with a standard deviation of 5.2 Mg-ha - 1 -yr - 1 . Given the standard deviations and the number of plots in each category, rates in secondary forests and all forests were significantly different from zero; rates in primary forests were consistent with zero. AGB-rates were compared to change models for Tapajós and to LiDAR-based change measurements in other tropical forests. Strategies for improving AGB dynamical monitoring with X-band interferometry are discussed.
A Multimodal Perception Framework for Users Emotional State Assessment in Social Robotics
Authors: Cominelli Lorenzo , Carbonaro Nicola , Mazzei Daniele , Garofalo Roberto , Tognetti Alessandro , De Rossi Danilo
Published: August 2017

In this work, we present an unobtrusive and non-invasive perception framework based on the synergy between two main acquisition systems: the Touch-Me Pad, consisting of two electronic patches for physiological signal extraction and processing; and the Scene Analyzer, a visual-auditory perception system specifically designed for the detection of social and emotional cues. It will be explained how the information extracted by this specific kind of framework is particularly suitable for social robotics applications and how the system has been conceived in order to be used in human-robot interaction scenarios.
Fabrication and Characterization of Polymer Optical Fibers Doped with Perylene-Derivatives for Fluorescent Lighting Applications
Authors: Parola Itxaso , Arrospide Eneko , Recart Federico , Illarramendi María , Durana Gaizka , Guarrotxena Nekane , García Olga , Zubia Joseba
Published: August 2017

Four different dye-doped polymer optical fibers (POFs) have been fabricated following a two-step fabrication process of preform extrusion and fiber drawing, using poly-(methyl methacrylate) (PMMA) as host material and dye derivatives from perylene and naphtalimide as active dopants. The side illumination technique (SIT) has been employed in order to determine some optical properties of the fabricated fibers, such as the side illumination coupling efficiency, optical loss coefficients, and their performance under solar simulator excitation. The aim of this work is to investigate the performance of the manufactured fibers for fluorescent lighting applications, specially targeting on fluorescent fiber based solar concentrators.
Genome-Wide Analysis Reveals Extensive Changes in LncRNAs during Skeletal Muscle Development in Hu Sheep
Authors: Ren Caifang , Deng Mingtian , Fan Yixuan , Yang Hua , Zhang Guomin , Feng Xu , Li Fengzhe , Wang Dan , Wang Feng , Zhang Yanli
Published: August 2017

As an important type of noncoding RNA molecules, long non-coding RNAs (lncRNAs) act as versatile players in various biological processes. However, little is known about lncRNA regulators during sheep muscle growth. To explore functional lncRNAs during sheep muscle growth, we systematically investigated lncRNAs using strand-specific Ribo-Zero RNA sequencing at three key developmental stages in Hu sheep. A total of 6924 lncRNAs were obtained, and the differentially expressed lncRNAs and genes were screened from (control vs. experiment) fetus vs. lamb, lamb vs. adult, and fetus vs. adult comparisons, respectively. The quantitative real-time polymerase chain reaction (qRT-PCR) analysis results correlated well with the sequencing data. Moreover, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases showed that the target genes of the differentially expressed lncRNAs were significantly enriched in organ morphogenesis, skeletal system development as well as response to stimulus and some other terms related to muscle. Furthermore, a co-expression network of the differentially expressed target genes and lncRNAs was constructed and well-known muscle growth regulators such as retrotransposon-like 1 and Junctophilin-2 were included. Finally, we investigated the expression profiles of seven lncRNAs and their target genes, and found that they played vital roles in muscle growth. This study extends the sheep muscle lncRNA database and provides novel candidate regulators for future genetic and molecular studies on sheep muscle growth, which is helpful for optimizing the production of mutton.
Proteins Recognizing DNA: Structural Uniqueness and Versatility of DNA-Binding Domains in Stem Cell Transcription Factors
Authors: Yesudhas Dhanusha , Batool Maria , Anwar Muhammad , Panneerselvam Suresh , Choi Sangdun
Published: August 2017

Proteins in the form of transcription factors (TFs) bind to specific DNA sites that regulate cell growth, differentiation, and cell development. The interactions between proteins and DNA are important toward maintaining and expressing genetic information. Without knowing TFs structures and DNA-binding properties, it is difficult to completely understand the mechanisms by which genetic information is transferred between DNA and proteins. The increasing availability of structural data on protein-DNA complexes and recognition mechanisms provides deeper insights into the nature of protein-DNA interactions and therefore, allows their manipulation. TFs utilize different mechanisms to recognize their cognate DNA (direct and indirect readouts). In this review, we focus on these recognition mechanisms as well as on the analysis of the DNA-binding domains of stem cell TFs, discussing the relative role of various amino acids toward facilitating such interactions. Unveiling such mechanisms will improve our understanding of the molecular pathways through which TFs are involved in repressing and activating gene expression.
Treatment of Human Placental Choriocarcinoma Cells with Formaldehyde and Benzene Induced Growth and Epithelial Mesenchymal Transition via Induction of an Antioxidant Effect
Authors: Lee Hae-Miru , Kim Soo-Min , Choi Kyung-Chul
Published: August 2017

Cigarette smoke (CS) causes about 480,000 deaths each year worldwide, and it is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In this study, the effects of formaldehyde (FA) and benzene (Bz), the main components of CS, on cell proliferation and epithelial mesenchymal transition (EMT) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS components and placenta carcinoma. Upon MTT assay, FA (10−8 M to 10−5 M) and Bz (10−11 M to 10−8 M) increased JEG-3 cell proliferation. Western blot assay revealed that the protein expression of cyclin D1 and E1 increased, while the levels of p21 and p27 were reduced following treatment. In Scratch assay, FA (10−8 M and 10−5 M) and Bz (10−11 M and 10−8 M) increased migration of JEG-3 cells at 24 h and 48 h compared with that at 0 h. In addition, the expression of the epithelial marker, E-cadherin, was significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by FA (10−8 M and 10−5 M) and Bz (10−11 M and 10−8 M). snail and slug transcriptional factors were associated with EMT, which were also up-regulated by FA and Bz, indicating that FA and Bz lead to an increase in the EMT process in JEG-3 choriocarcinoma cells. We further evaluated reactive oxygen species (ROS) and activation of antioxidant effect using dichlorofluorescin diacetate (DCFH-DA) and Western blot assay. FA and Bz increased the ROS production and an antioxidant related marker, Nrf2, in JEG-3 cells. However, eIF2α levels were reduced by FA and Bz via activation of the antioxidant reaction. Taken together, these results indicated that FA and Bz induce the growth and migration of human choriocarcinoma cells via regulation of the cell cycle and EMT and activation of ROS and antioxidant related markers.
Residence in Proximity of a Coal-Oil-Fired Thermal Power Plant and Risk of Lung and Bladder Cancer in North-Eastern Italy. A Population-Based Study: 1995–2009
Authors: Collarile Paolo , Bidoli Ettore , Barbone Fabio , Zanier Loris , Del Zotto Stefania , Fuser Simonetta , Stel Fulvio , Panato Chiara , Gallai Irene , Serraino Diego
Published: August 2017

This study investigated the risk of lung and bladder cancers in people residing in proximity of a coal-oil-fired thermal power plant in an area of north-eastern Italy, covered by a population-based cancer registry. Incidence rate ratios (IRR) by sex, age, and histology were computed according to tertiles of residential exposure to benzene, nitrogen dioxide (NO2), particular matter, and sulfur dioxide (SO2) among 1076 incident cases of lung and 650 cases of bladder cancers. In men of all ages and in women under 75 years of age, no significant associations were observed. Conversely, in women aged ≥75 years significantly increased risks of lung and bladder cancers were related to high exposure to benzene (IRR for highest vs. lowest tertile: 2.00 for lung cancer and 1.94 for bladder cancer) and NO2 (IRR: 1.72 for lung cancer; and 1.94 for bladder cancer). In these women, a 1.71-fold higher risk of lung cancer was also related to a high exposure to SO2. Acknowledging the limitations of our study, in particular that we did not have information regarding cigarette smoking habits, the findings of this study indicate that air pollution exposure may have had a role with regard to the risk of lung and bladder cancers limited to women aged ≥75 years. Such increased risk warrants further analytical investigations.
Removal Efficiency and Risk Assessment of Polycyclic Aromatic Hydrocarbons in a Typical Municipal Wastewater Treatment Facility in Guangzhou, China
Authors: Liu Zhineng , Li Qing , Wu Qihang , Kuo Dave , Chen Shejun , Hu Xiaodong , Deng Mingjun , Zhang Haozhi , Luo Min
Published: August 2017

The loading and removal efficiency of 16 US EPA polycyclic aromatic hydrocarbons (PAHs) were examined in an inverted A2/O wastewater treatment plant (WWTP) located in an urban area in China. The total PAH concentrations were 554.3 to 723.2 ng/L in the influent and 189.6 to 262.7 ng/L in the effluent. The removal efficiencies of ∑PAHs in the dissolved phase ranged from 63 to 69%, with the highest observed in naphthalene (80% removal). Concentration and distribution of PAHs revealed that the higher molecular weight PAHs became more concentrated with treatment in both the dissolved phase and the dewatered sludge. The sharpest reduction was observed during the pretreatment and the biological phase. Noncarcinogenic risk, carcinogenic risk, and total health risk of PAHs found in the effluent and sewage sludge were also assessed. The effluent BaP toxic equivalent quantities (TEQBaP) were above, or far above, standards in countries. The potential toxicities of PAHs in sewage effluent were approximately 10 to 15 times higher than the acceptable risk level in China. The health risk associated with the sewage sludge also exceeded international recommended levels and was mainly contributed from seven carcinogenic PAHs. Given that WWTP effluent is a major PAH contributor to surface water bodies in China and better reduction efficiencies are achievable, the present study highlights the possibility of utilizing WWTPs for restoring water quality in riverine and coastal regions heavily impacted by PAHs contamination.
Stonin 2 Overexpression is Correlated with Unfavorable Prognosis and Tumor Invasion in Epithelial Ovarian Cancer
Authors: Sun Xiaoying , Zhang Weijing , Li Han , Niu Chunhao , Ou Yulan , Song Libing , Zhang Yanna
Published: August 2017

Stonin 2 (STON2), which functions in adjusting endocytotic complexes, is probably involved in the monitoring of the internalization of dopamine D2 receptors which have an inhibitory action of dopamine on tumor progression. However, its clinical significance in tumor progression and prognosis remains unclear. We explored the association between STON2 and the clinicopathological characteristics of epithelial ovarian cancer (EOC). The STON2 levels in ovarian cancer and normal cell lines and tissues were detected by real-time PCR and Western blot analyses. STON2 protein expression was also detected by an immunohistochemical analysis. The clinical significance of STON2 expression in ovarian cancer was statistically analyzed. STON2 significantly increased in the ovarian cancer cell lines and tissues compared to the normal ones. In the 89 EOC samples tested, STON2 expression was significantly correlated with intraperitoneal metastasis, intestinal metastasis, intraperitoneal recurrence, ascites containing tumor cells, and CA153 level. Moreover, patients with STON2 protein overexpression were more likely to exhibit platinum resistance and to have undergone neoadjuvant chemotherapy. Patients with high STON2 protein expression had a tendency to have a shorter overall survival and a poor prognosis. A multivariate analysis showed that STON2 was an independent prognostic predictor for EOC patients. In conclusion, STON2 plays an important role in the progression and prognosis of ovarian carcinoma, especially in platinum resistance, intraperitoneal metastasis, and recurrence. STON2 can be a novel antitumor drug target and biomarker which predicts an unfavorable prognosis for EOC patients.
Nrf2-Knockout Protects from Intestinal Injuries in C57BL/6J Mice Following Abdominal Irradiation with γ Rays
Authors: Yang Wenyan , Sun Zhijuan , Yang Bing , Wang Qin
Published: August 2017

Radiation-induced intestinal injuries (RIII) commonly occur in patients who suffer from pelvic or abdominal cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of antioxidant, and the radioprotective role of Nrf2 is found in bone marrow, lung, and intestine, etc. Here, we investigated the effect of Nrf2 knockout on radiation-induced intestinal injuries using Nrf2 knockout (Nrf2−/−) mice and wild-type (Nrf2+/+) C57BL/6J mice following 13 Gy abdominal irradiation (ABI). It was found that Nrf2 knockout promoted the survival of irradiated mice, protected the crypt-villus structure of the small intestine, and elevated peripheral blood lymphocyte count and thymus coefficients. The DNA damage of peripheral blood lymphocytes and the apoptosis of intestinal epithelial cells (IECs) of irradiated Nrf2−/− mice were decreased. Furthermore, compared with that of Nrf2+/+ mice, Nrf2 knockout increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells including Ki67+ transient amplifying cells, Villin+ enterocytes, and lysozyme+ Paneth cells. Nuclear factor-κB (NF-κB) was accumulated in the crypt base nuclei of the small intestine, and the mRNA expression of NF-κB target genes Bcl-2, uPA, and Xiap of the small intestine from irradiated Nrf2−/− mice were increased. Collectively, Nrf2 knockout has the protective effect on small intestine damage following abdominal irradiation by prompting the proliferation and differentiation of Lgr5+ intestinal stem cells and activation of NF-κB.
Polycomb Repressor Complex 2 in Genomic Instability and Cancer
Authors: Veneti Zoe , Gkouskou Kalliopi , Eliopoulos Aristides
Published: August 2017

Polycomb repressor complexes PRC1 and PRC2 regulate chromatin compaction and gene expression, and are widely recognized for their fundamental contributions to developmental processes. Herein, we summarize the existing evidence and molecular mechanisms linking PRC-mediated epigenetic aberrations to genomic instability and malignancy, with a particular focus on the role of deregulated PRC2 in tumor suppressor gene expression, the DNA damage response, and the fidelity of DNA replication. We also discuss some of the recent advances in the development of pharmacological and dietary interventions affecting PRC2, which point to promising applications for the prevention and management of human malignancies.
Elevated Soluble Urokinase Plasminogen Activator Receptor and Proenkephalin Serum Levels Predict the Development of Acute Kidney Injury after Cardiac Surgery
Authors: Mossanen Jana , Pracht Jessica , Jansen Tobias , Buendgens Lukas , Stoppe Christian , Goetzenich Andreas , Struck Joachim , Autschbach Rüdiger , Marx Gernot , Tacke Frank
Published: August 2017

Acute kidney injury (AKI) develops in up to 40% of patients after cardiac surgery. The soluble urokinase plasminogen activator receptor (suPAR) has been identified as a biomarker for incident chronic kidney disease (CKD). Proenkephalin (proENK) also has been shown to be a biomarker for renal dysfunction. We hypothesized that pre-surgery suPAR and proENK levels might predict AKI in patients undergoing cardiac surgery. Consecutive patients (n = 107) undergoing elective cardiac surgery were studied prospectively. Clinical data, laboratory parameters, suPAR and proENK serum levels were assessed before operation, after operation and days one and four post-operatively. A total of 21 (19.6%) patients developed AKI within the first four days after elective surgery. Serum levels of suPAR and proENK, but not of creatinine, were significantly higher before surgery in these patients compared to those patients without AKI. This difference remained significant for suPAR, if patients with or without AKI were matched for risk factors (hypertension, diabetes, CKD). If cardiac surgery patients with pre-existing CKD (n = 10) were excluded, only pre-operative suPAR but not proENK serum levels remained significantly elevated in patients with subsequent AKI. Thus, our findings indicate that suPAR may be a predictive biomarker for AKI in the context of cardiac surgery, even in patients without underlying CKD.
Appearance of New Cutaneous Superficial Basal Cell Carcinomas during Successful Nivolumab Treatment of Refractory Metastatic Disease: Implications for Immunotherapy in Early Versus Late Disease
Authors: Cohen Philip , Kato Shumei , Goodman Aaron , Ikeda Sadakatsu , Kurzrock Razelle
Published: August 2017

Metastatic basal cell carcinoma may be treated with hedgehog pathway inhibitors, including vismodegib and sonidegib. However, patients can demonstrate resistance to these agents. We describe a man with metastatic basal cell carcinoma who did not respond well to vismodegib and sonidegib. Next generation sequencing of his metastatic liver tumor demonstrated a high tumor mutational burden (103 mutations per megabase) and the genomic amplification of PD-L1, both of which are features that predict response to anti-PD1/PD-L1 immunotherapy. Treatment with nivolumab, an anti-PD1 checkpoint inhibitor, resulted in near complete remission. Yet, he developed new primary cutaneous basal cell carcinomas while receiving immunotherapy and while his metastatic disease showed an ongoing response. His new superficial skin cancer had a lower tumor mutational burden (45 mutations per megabase) than the metastatic disease. Since immunotherapy response rates are higher in patients with more genomically complex tumors, our observations suggest that, in contrast with the premise of earlier treatment is better, which holds true for targeted and cytotoxic therapies, immunotherapy may be better suited to more advanced disease.
Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder
Authors: Cameron Jessie M. , Levandovskiy Valeriy , Roberts Wendy , Anagnostou Evdokia , Scherer Stephen , Loh Alvin , Schulze Andreas
Published: August 2017

Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase (GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase (GAMT gene), and creatine transporter deficiency (SLC6A8 gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM, GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions). A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM, and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium (ExAC) databases). A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF) in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher’s exact test). Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism spectrum disorder (ASD) in children.
Tricetin Induces Apoptosis of Human Leukemic HL-60 Cells through a Reactive Oxygen Species-Mediated c-Jun N-Terminal Kinase Activation Pathway
Authors: Chien Ming-Hsien , Chow Jyh-Ming , Lee Wei-Jiunn , Chen Hui-Yu , Tan Peng , Wen Yu-Ching , Lin Yung-Wei , Hsiao Pei-Ching , Yang Shun-Fa
Published: August 2017

Tricetin is a dietary flavonoid with cytostatic properties and antimetastatic activities in various solid tumors. The anticancer effect of tricetin in nonsolid tumors remains unclear. Herein, the molecular mechanisms by which tricetin exerts its anticancer effects on acute myeloid leukemia (AML) cells were investigated. Results showed that tricetin inhibited cell viability in various types of AML cell lines. Tricetin induced morphological features of apoptosis such as chromatin condensation and phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Of note, tricetin-induced cell growth inhibition was dramatically reversed by a pan caspase and caspase-8- and -9-specific inhibitors, suggesting that this compound mainly acts through a caspase-dependent pathway. Moreover, treatment of HL-60 cells with tricetin induced sustained activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), and inhibition of ERK and JNK by their specific inhibitors respectively promoted and abolished tricetin-induced cell apoptosis. Dichlorofluorescein (DCF) staining showed that intracellular reactive oxygen species (ROS) levels were higher in tricetin-treated HL-60 cells compared to the control group. Moreover, an ROS scavenger, N-acetylcysteine (NAC), reversed tricetin-induced JNK activation and subsequent cell apoptosis. In conclusion, our results indicated that tricetin induced cell death of leukemic HL-60 cells through induction of intracellular oxidative stress following activation of a JNK-mediated apoptosis pathway. A combination of tricetin and an ERK inhibitor may be a better strategy to enhance the anticancer activities of tricetin in AML.
Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics?
Authors: Grodecká Lucie , Buratti Emanuele , Freiberger Tomáš
Published: August 2017

For more than three decades, researchers have known that consensus splice sites alone are not sufficient regulatory elements to provide complex splicing regulation. Other regulators, so-called splicing regulatory elements (SREs) are needed. Most importantly, their sequence variants often underlie the development of various human disorders. However, due to their variable location and high degeneracy, these regulatory sequences are also very difficult to recognize and predict. Many different approaches aiming to identify SREs have been tried, often leading to the development of in silico prediction tools. While these tools were initially expected to be helpful to identify splicing-affecting mutations in genetic diagnostics, we are still quite far from meeting this goal. In fact, most of these tools are not able to accurately discern the SRE-affecting pathological variants from those not affecting splicing. Nonetheless, several recent evaluations have given appealing results (namely for EX-SKIP, ESRseq and Hexplorer predictors). In this review, we aim to summarize the history of the different approaches to SRE prediction, and provide additional validation of these tools based on patients’ clinical data. Finally, we evaluate their usefulness for diagnostic settings and discuss the challenges that have yet to be met.
Variation within Variation: Comparison of 24-h Rhythm in Rodent Infarct Size between Ischemia Reperfusion and Permanent Ligation
Authors: Du Pré Bastiaan , Van Veen Toon , Crnko Sandra , Vos Marc , Deddens Janine , Doevendans Pieter , Van Laake Linda
Published: August 2017

The detrimental effects of myocardial infarction in humans and rodents have a 24-h rhythm. In some human cohorts however, rhythmicity was absent, while the time of maximum damage differs between cohorts. We hypothesized that the type of damage influences the 24-h rhythm in infarct size. Myocardial infarction was induced in 12-week-old C57BL/six mice at four different time-points during the day using either permanent ligation (PL) or 30-min of ischemia followed by reperfusion (IR), with a control group wherein no ligation was applied. Infarct size was measured by echocardiography and histology at a 1-month follow-up. Rhythmicity in infarct size was present in the PL group at the functional and histological level, with maximal damage occurring when the infarct was induced at noon. In the IR group, no circadian rhythm was found. The time of the coronary artery ligation determines the outcome of myocardial infarction. Our data showed that in rodents, the presence of circadian rhythmicity and time of peak infarct size varies between experimental setups.
Gastro-Esophageal Reflux in Children
Authors: Rybak Anna , Pesce Marcella , Thapar Nikhil , Borrelli Osvaldo
Published: August 2017

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines.
A Practical Point Cloud Based Road Curb Detection Method for Autonomous Vehicle
Authors: Huang Rulin , Chen Jiajia , Liu Jian , Liu Lu , Yu Biao , Wu Yihua
Published: August 2017

Robust and quick road curb detection under various situations is critical in developing intelligent vehicles. However, the road curb detection is easily affected by the obstacles in the road area when Lidar based method is applied. A practical road curb detection method using point cloud from a three-dimensional Lidar for autonomous vehicle is reported in this paper. First, a multi-feature, loose-threshold, varied-scope ground segmentation method is presented to increase the robustness of ground segmentation with which obstacles above the ground can be detected. Second, the road curb is detected by applying the global road trend and an extraction-update mechanism. Experiments show the robustness and efficiency of the road curb detection under various environments. The road curb detection method is 10 times the speed of traditional method and the accuracy is much higher than existing methods.
Ultrasound for Early Detection of Joint Disease in Patients with Hemophilic Arthropathy
Authors: Di Minno Matteo , Pasta Gianluigi , Airaldi Sonia , Zaottini Federico , Storino Antonio , Cimino Ernesto , Martinoli Carlo
Published: August 2017

Joint bleeding represents the most commonly reported type of hemorrhage in patients affected by hemophilia. Although the widespread use of prophylaxis has been able to significantly reduce the onset of arthropathy, it has been shown that a non-negligible percentage of patients develop degenerative changes in their joints despite this type of treatment. Thus, periodic monitoring of the joint status in hemophilia patients has been recommended to identify early arthropathic changes and prevent the development or progression of hemophilic arthropathy. Ultrasound (US) has proven able to detect and quantify the most relevant biomarkers of disease activity (i.e., joint effusion and synovial hypertrophy) and degenerative damages (i.e., osteo-chondral changes) by means of scoring scales of increasing disease severity. In the present review, we have detailed major literature evidence about the use of US to assess joint status in hemophilia patients, focusing on signs of disease activity and degenerative damages. In particular, we have discussed recent evidence about “point-of-care” use patients with hemophilia.
Ultra-Low Power Consuming Direct Radiation Sensors Based on Floating Gate Structures
Authors: Pikhay Evgeny , Roizin Yakov , Nemirovsky Yael
Published: August 2017

In this paper, we report on ultra-low power consuming single poly floating gate direct radiation sensors. The developed devices are intended for total ionizing dose (TID) measurements and fabricated in a standard CMOS process flow. Sensor design and operation is discussed in detail. Original array sensors were suggested and fabricated that allowed high statistical significance of the radiation measurements and radiation imaging functions. Single sensors and array sensors were analyzed in combination with the specially developed test structures. This allowed insight into the physics of sensor operations and exclusion of the phenomena related to material degradation under irradiation in the interpretation of the measurement results. Response of the developed sensors to various sources of ionizing radiation (Gamma, X-ray, UV, energetic ions) was investigated. The optimal design of sensor for implementation in dosimetry systems was suggested. The roadmap for future improvement of sensor performance is suggested.
UK Macro-Algae Biofuels: A Strategic Management Review and Future Research Agenda
Authors: Gegg Per , Wells Victoria
Published: August 2017

Macro-algae is increasingly gaining attention as a potential feedstock for biofuels and as a potential alternative fuel for aviation. Technological aspects are showing promise, and being examined more widely. This paper uses a strategic management perspective to complete an initial macro-environmental scan of the potential opportunities and threats to a seaweed biofuels industry. This is in response to calls to look beyond technological aspects, and highlights the importance of social acceptance. It is clear that very little is known about the potential economic, social, environmental and political/legal issues that might arise in the development of this industry. While we can look at the development of other, more established renewable technologies and seaweed industries away from the UK to highlight potential issues this does not give us a clear picture. Further research is needed to ensure that a proactive approach is used to research and inform stakeholders who will affect the further technological development and commercialization of the industry.
Nitrogenous Derivatives of Phosphorus and the Origins of Life: Plausible Prebiotic Phosphorylating Agents in Water
Authors: Karki Megha , Gibard Clémentine , Bhowmik Subhendu , Krishnamurthy Ramanarayanan
Published: August 2017

Phosphorylation under plausible prebiotic conditions continues to be one of the defining issues for the role of phosphorus in the origins of life processes. In this review, we cover the reactions of alternative forms of phosphate, specifically the nitrogenous versions of phosphate (and other forms of reduced phosphorus species) from a prebiotic, synthetic organic and biochemistry perspective. The ease with which such amidophosphates or phosphoramidate derivatives phosphorylate a wide variety of substrates suggests that alternative forms of phosphate could have played a role in overcoming the “phosphorylation in water problem”. We submit that serious consideration should be given to the search for primordial sources of nitrogenous versions of phosphate and other versions of phosphorus.
Rac-2′,3a,6,6,6′,6′-Hexamethyl-3a,3b,6,7-tetra-hydrospiro-[benzo[2,3]cyclopropa[1,2-c]pyrazole-1,1′-cyclo-hepta[2,4]diene]
Authors: Baumann Marcus , Lapraille Sophie , Baxendale Ian
Published: August 2017

This note describes a novel reaction cascade in which a tosylhydrazone derivative of eucarvone undergoes a non-classical dimerization process under basic conditions. The key step in this sequence is a dipolar cycloaddition between a diazo species and a transient cyclopropene. A proposed mechanism for this sequence is presented that is supported by single crystal X-ray analysis of the resulting dimer. We believe this unique transformation is of note as it highlights a neat and efficient entry to complex polycyclic architectures containing an embedded pyrazoline moiety.
Low-Concentration Indium Doping in Solution-Processed Zinc Oxide Films for Thin-Film Transistors
Authors: Zhang Xue , Lee Hyeonju , Kwon Jung-Hyok , Kim Eui-Jik , Park Jaehoon
Published: August 2017

We investigated the influence of low-concentration indium (In) doping on the chemical and structural properties of solution-processed zinc oxide (ZnO) films and the electrical characteristics of bottom-gate/top-contact In-doped ZnO thin-film transistors (TFTs). The thermogravimetry and differential scanning calorimetry analysis results showed that thermal annealing at 400 °C for 40 min produces In-doped ZnO films. As the In content of ZnO films was increased from 1% to 9%, the metal-oxygen bonding increased from 5.56% to 71.33%, while the metal-hydroxyl bonding decreased from 72.03% to 9.63%. The X-ray diffraction peaks and field-emission scanning microscope images of the ZnO films with different In concentrations revealed a better crystalline quality and reduced grain size of the solution-processed ZnO thin films. The thickness of the In-doped ZnO films also increased when the In content was increased up to 5%; however, the thickness decreased on further increasing the In content. The field-effect mobility and on/off current ratio of In-doped ZnO TFTs were notably affected by any change in the In concentration. Considering the overall TFT performance, the optimal In doping concentration in the solution-processed ZnO semiconductor was determined to be 5% in this study. These results suggest that low-concentration In incorporation is crucial for modulating the morphological characteristics of solution-processed ZnO thin films and the TFT performance.
Impact Load Behavior between Different Charge and Lifter in a Laboratory-Scale Mill
Authors: Yin Zixin , Peng Yuxing , Zhu Zhencai , Yu Zhangfa , Li Tongqing
Published: August 2017

The impact behavior between the charge and lifter has significant effect to address the mill processing, and is affected by various factors including mill speed, mill filling, lifter height and media shape. To investigate the multi-body impact load behavior, a series of experiments and Discrete Element Method (DEM) simulations were performed on a laboratory-scale mill, in order to improve the grinding efficiency and prolong the life of the lifter. DEM simulation hitherto has been extensively applied as a leading tool to describe diverse issues in granular processes. The research results shown as follows: The semi-empirical power draw of Bond model in this paper does not apply very satisfactorily for the ball mills, while the power draw determined by DEM simulation show a good approximation for the measured power draw. Besides, the impact force on the lifter was affected by mill speed, grinding media filling, lifter height and iron ore particle. The maximum percent of the impact force between 600 and 1400 N is at 70–80% of critical speed. The impact force can be only above 1400 N at the grinding media filling of 20%, and the maximum percent of impact force between 200 and 1400 N is obtained at the grinding media filling of 20%. The percent of impact force ranging from 0 to 200 N decreases with the increase of lifter height. However, this perfect will increase above 200 N. The impact force will decrease when the iron ore particles are added. Additionally, for the 80% of critical speed, the measured power draw has a maximum value. Increasing the grinding media filling increases the power draw and increasing the lifter height does not lead to any variation in power draw.
Metallic Biomaterials: Current Challenges and Opportunities
Authors: Prasad Karthika , Bazaka Olha , Chua Ming , Rochford Madison , Fedrick Liam , Spoor Jordan , Symes Richard , Tieppo Marcus , Collins Cameron , Cao Alex , Markwell David , Ostrikov Kostya (Ken) , Bazaka Kateryna
Published: August 2017

Metallic biomaterials are engineered systems designed to provide internal support to biological tissues and they are being used largely in joint replacements, dental implants, orthopaedic fixations and stents. Higher biomaterial usage is associated with an increased incidence of implant-related complications due to poor implant integration, inflammation, mechanical instability, necrosis and infections, and associated prolonged patient care, pain and loss of function. In this review, we will briefly explore major representatives of metallic biomaterials along with the key existing and emerging strategies for surface and bulk modification used to improve biointegration, mechanical strength and flexibility of biometals, and discuss their compatibility with the concept of 3D printing.