bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency in the Ubiquitin Conjugating Enzyme UBE2A in Alzheimer’s Disease (AD) is Linked to Deficits in a Natural Circular miRNA-7 Sponge (circRNA; ciRS-7)
Authors: Zhao Yuhai , Alexandrov Peter , Jaber Vivian , Lukiw Walter
Published: December 2016

Our understanding of the highly specialized functions for small non-coding single-stranded RNA (ssRNA) in the transcriptome of the human central nervous system (CNS) continues to evolve. Circular RNAs (circRNAs), a recently discovered class of ssRNA enriched in the brain and retina, are extremely stable and intrinsically resilient to degradation by exonuclease. Conventional methods of ssRNA, microRNA (miRNA), or messenger RNA (mRNA) detection and quantitation requiring free ribonucleotide ends may have considerably underestimated the quantity and significance of CNS circRNA in the CNS. Highly-specific small ssRNAs, such as the ~23 nucleotide (nt) Homo sapien microRNA-7 (hsa-miRNA-7; chr 9q21.32), are not only abundant in the human limbic system but are, in addition, associated with a ~1400 nt circRNA for miRNA-7 (ciRS-7) in the same anatomical region. Structurally, ciRS-7 contains about ~70 tandem anti-miRNA-7 sequences and acts as an endogenous, anti-complementary miRNA-7 “sponge” that attracts, binds, and, hence, quenches, natural miRNA-7 functions. Using a combination of DNA and miRNA array technologies, enhanced LED-Northern and Western blot hybridization, and the magnesium-dependent exoribonuclease and circRNA-sensitive probe RNaseR, here we provide evidence of a significantly misregulated ciRS-7-miRNA-7-UBE2A circuit in sporadic Alzheimer’s disease (AD) neocortex (Brodmann A22) and hippocampal CA1. Deficits in ciRS-7-mediated “sponging events”, resulting in excess ambient miRNA-7 appear to drive the selective down-regulation in the expression of miRNA-7-sensitive mRNA targets, such as that encoding the ubiquitin conjugating enzyme E2A (UBE2A; chr Xq24). UBE2A, which normally serves as a central effector in the ubiquitin-26S proteasome system, coordinates the clearance of amyloid peptides via proteolysis, is known to be depleted in sporadic AD brain and, hence, contributes to amyloid accumulation and the formation of senile plaque deposits. Dysfunction of circRNA-miRNA-mRNA regulatory systems appears to represent another important layer of epigenetic control over pathogenic gene expression programs in the human CNS that are targeted by the sporadic AD process.
Cord Blood DNA Methylation Biomarkers for Predicting Neurodevelopmental Outcomes
Authors: Hodyl Nicolette , Roberts Claire , Bianco-Miotto Tina
Published: December 2016

Adverse environmental exposures in pregnancy can significantly alter the development of the fetus resulting in impaired child neurodevelopment. Such exposures can lead to epigenetic alterations like DNA methylation, which may be a marker of poor cognitive, motor and behavioral outcomes in the infant. Here we review studies that have assessed DNA methylation in cord blood following maternal exposures that may impact neurodevelopment of the child. We also highlight some key studies to illustrate the potential for DNA methylation to successfully identify infants at risk for poor outcomes. While the current evidence is limited, in that observations to date are largely correlational, in time and with larger cohorts analyzed and longer term follow-up completed, we may be able to develop epigenetic biomarkers that not only indicate adverse early life exposures but can also be used to identify individuals likely to be at an increased risk of impaired neurodevelopment even in the absence of detailed information regarding prenatal environment.
New Oligonucleotide Probes for ND-FISH Analysis to Identify Barley Chromosomes and to Investigate Polymorphisms of Wheat Chromosomes
Authors: Tang Shuyao , Qiu Ling , Xiao Zhiqiang , Fu Shulan , Tang Zongxiang
Published: December 2016

Oligonucleotide probes that can be used for non-denaturing fluorescence in situ hybridization (ND-FISH) analysis are convenient tools for identifying chromosomes of wheat (Triticum aestivum L.) and its relatives. New oligonucleotide probes, Oligo-HvT01, Oligo-pTa71-1, Oligo-s120.1, Oligo-s120.2, Oligo-s120.3, Oligo-275.1, Oligo-275.2, Oligo-k566 and Oligo-713, were designed based on the repetitive sequences HVT01, pTa71, pTa-s120, pTa-275, pTa-k566 and pTa-713. All these probes can be used for ND-FISH analysis and some of them can be used to detect polymorphisms of wheat chromosomes. Probes Oligo-HvT01, Oligo-pTa71-1, Oligo-s120.3, Oligo-275.1, Oligo-k566 and Oligo-713 can, respectively, replace the roles of their original sequences to identify chromosomes of some barley (Hordeum vulgare ssp. vulgare) and the common wheat variety Chinese Spring. Oligo-s120.1, Oligo-s120.2 and Oligo-275.2 produced different hybridization patterns from the ones generated by their original sequences. In addition, Oligo-s120.1, Oligo-s120.2 and Oligo-s120.3, which were derived from pTa-s120, revealed different signal patterns. Likewise, Oligo-275.1 and Oligo-275.2, which were derived from pTa-275, also displayed different hybridization patterns. These results imply that differently arranged or altered structural statuses of tandem repeats might exist on different chromosome regions. These new oligonucleotide probes provide extra convenience for identifying some wheat and barley chromosomes, and they can display polymorphisms of wheat chromosomes.
Association between the Osteoporosis Self-Assessment Tool for Asians Score and Mortality in Patients with Isolated Moderate and Severe Traumatic Brain Injury: A Propensity Score-Matched Analysis
Authors: Rau Cheng-Shyuan , Kuo Pao-Jen , Wu Shao-Chun , Chen Yi-Chun , Hsieh Hsiao-Yun , Hsieh Ching-Hua
Published: December 2016

Background: The purpose of this study was to use a propensity score-matched analysis to investigate the association between the Osteoporosis Self-Assessment Tool for Asians (OSTA) scores and clinical outcomes of patients with isolated moderate and severe traumatic brain injury (TBI). Methods: The study population comprised 7855 patients aged ≥40 years who were hospitalized for treatment of isolated moderate and severe TBI (an Abbreviated Injury Scale (AIS) ≥3 points only in the head and not in other regions of the body) between 1 January 2009 and 31 December 2014. Patients were categorized as high-risk (OSTA score < −4; n = 849), medium-risk (−4 ≤ OSTA score ≤ −1; n = 1647), or low-risk (OSTA score > −1; n = 5359). Two-sided Pearson’s chi-squared, or Fisher’s exact tests were used to compare categorical data. Unpaired Student’s t-test and Mann-Whitney U test were performed to analyze normally and non-normally distributed continuous data, respectively. Propensity score-matching in a 1:1 ratio was performed using NCSS software, with adjustment for covariates. Results: Compared to low-risk patients, high- and medium-risk patients were significantly older and injured more severely. The high- and medium-risk patients had significantly higher mortality rates, longer hospital length of stay, and a higher proportion of admission to the intensive care unit than low-risk patients. Analysis of propensity score-matched patients with adjusted covariates, including gender, co-morbidity, blood alcohol concentration level, Glasgow Coma Scale score, and Injury Severity Score revealed that high- and medium-risk patients still had a 2.4-fold (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.39–4.15; p = 0.001) and 1.8-fold (OR, 1.8; 95% CI, 1.19–2.86; p = 0.005) higher mortality, respectively, than low-risk patients. However, further addition of age as a covariate for the propensity score-matching demonstrated that there was no significant difference between high-risk and low-risk patients or between medium-risk and low-risk patients, implying that older age may contribute to the significantly higher mortality associated with a lower OSTA score. Conclusions: Older age may be able to explain the association of lower OSTA score and higher mortality rates in patients with isolated moderate and severe TBI.
Comments on Quaak, et al. The Dynamics of Autism Spectrum Disorders: How Neurotoxic Compounds and Neurotransmitters Interact. Int. J. Environ. Res. Public Health 2013, 10, 3384–3408
Authors: Mohammadi Moslem
Published: December 2016

I have read the article entitled “The dynamics of autism spectrum disorders: how neurotoxic compounds and neurotransmitters interact”. There are some errors in the interpretation of results obtained from our previous studies that should be explained.
A Quantitative Model to Estimate Drug Resistance in Pathogens
Authors: Baker Frazier , Cushion Melanie , Porollo Aleksey
Published: December 2016

Pneumocystis pneumonia (PCP) is an opportunistic infection that occurs in humans and other mammals with debilitated immune systems. These infections are caused by fungi in the genus Pneumocystis, which are not susceptible to standard antifungal agents. Despite decades of research and drug development, the primary treatment and prophylaxis for PCP remains a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) that targets two enzymes in folic acid biosynthesis, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), respectively. There is growing evidence of emerging resistance by Pneumocystis jirovecii (the species that infects humans) to TMP-SMX associated with mutations in the targeted enzymes. In the present study, we report the development of an accurate quantitative model to predict changes in the binding affinity of inhibitors (Ki, IC50) to the mutated proteins. The model is based on evolutionary information and amino acid covariance analysis. Predicted changes in binding affinity upon mutations highly correlate with the experimentally measured data. While trained on Pneumocystis jirovecii DHFR/TMP data, the model shows similar or better performance when evaluated on the resistance data for a different inhibitor of PjDFHR, another drug/target pair (PjDHPS/SMX) and another organism (Staphylococcus aureus DHFR/TMP). Therefore, we anticipate that the developed prediction model will be useful in the evaluation of possible resistance of the newly sequenced variants of the pathogen and can be extended to other drug targets and organisms.
The Effect of Monitoring Committees on the Relationship between Board Structure and Firm Performance
Authors: Ammari Aymen , Amdouni Sarra , Zemzem Ahmed , Ellouze Abderrazak
Published: December 2016

The purpose of this study is to investigate the impact of board structure on the performance of French firms in the presence of several monitoring committees. We studied 80 publicly listed French firms spanning from 2001 to 2013. We concluded that large board size has a negative effect on market performance. While large board size in combination with the existence of at least three committees enhances accounting performance and does not have any impact on market performance, the existence of a board dominated by independent directors with the presence of at least three committees seems to have only a negative impact on accounting performance. Our findings indicate that monitoring committees are beneficial for shareholders only for corporations with a large board size.
Multi-Objective Optimization of a Spring Diaphragm Clutch on an Automobile Based on the Non-Dominated Sorting Genetic Algorithm (NSGA-II)
Authors: Zhou Junchao , Wang Chun , Zhu Junjun
Published: December 2016

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09% by the new algorithm and the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.
Identification of Phlogacantholide C as a Novel ADAM10 Enhancer from Traditional Chinese Medicinal Plants
Authors: Meineck Myriam , Schuck Florian , Abdelfatah Sara , Efferth Thomas , Endres Kristina
Published: December 2016

Background: Alzheimer’s disease is one of the most prevalent dementias in the elderly population with increasing numbers of patients. One pivotal hallmark of this disorder is the deposition of protein aggregates stemming from neurotoxic amyloid-beta peptides. Synthesis of those peptides has been efficiently prevented in AD model mice by activation of an enzyme called alpha-secretase. Therefore, drugs with the capability to increase the expression of this enzyme, named ADAM10, have been suggested as a valuable therapeutic medication. Methods: We investigated 69 substances from a drug library derived from traditional Chinese medicine by luciferase reporter assay in human neuronal cells for their potential to selectively induce alpha-secretase expression. Western blot analysis was used to confirm results on the protein level. Results: Ten of the 69 investigated compounds led to induction of ADAM10 transcriptional activity while BACE-1 (beta-site APP cleaving enzyme 1) and APP (amyloid precursor protein) expression were not induced. Two of them—Norkurarinol and Phlogacantholide C—showed substantial elevation of ADAM10 protein levels and Phlogacantholide C also increased secretion of the ADAM10-derived cleavage product APPs-alpha. Conclusion: Phlogacantholide C represents a novel ADAM10 gene expression enhancer from traditional Chinese medicinal herbs that may lay the groundwork for evolving potential novel therapeutics in Alzheimer’s disease.
Significant Corrosion Resistance in an Ultrafine-Grained Al6063 Alloy with a Bimodal Grain-Size Distribution through a Self-Anodic Protection Mechanism
Authors: Shakoori Oskooie Mahdieh , Asgharzadeh Hamed , Sadighikia Sina , Salehi Mozhgan
Published: December 2016

The bimodal microstructures of Al6063 consisting of 15, 30, and 45 vol. % coarse-grained (CG) bands within the ultrafine-grained (UFG) matrix were synthesized via blending of high-energy mechanically milled powders with unmilled powders followed by hot powder extrusion. The corrosion behavior of the bimodal specimens was assessed by means of polarization, steady-state cyclic polarization and impedance tests, whereas their microstructural features and corrosion products were examined using optical microscopy (OM), scanning transmission electron microscopy (STEM), field emission scanning electron microscopy (FE-SEM), electron backscattered diffraction (EBSD), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD) techniques. The bimodal Al6063 containing 15 vol. % CG phase exhibits the highest corrosion resistance among the bimodal microstructures and even superior electrochemical behavior compared with the plain UFG and CG materials in the 3.5% NaCl solution. The enhanced corrosion resistance is attributed to the optimum cathode to anode surface area ratio that gives rise to the formation of an effective galvanic couple between CG areas and the UFG matrix. The operational galvanic coupling leads to the domination of a “self-anodic protection system” on bimodal microstructure and consequently forms a uniform thick protective passive layer over it. In contrast, the 45 vol. % CG bimodal specimen shows the least corrosion resistance due to the catastrophic galvanic corrosion in UFG regions. The observed results for UFG Al6063 suggest that metallurgical tailoring of the grain structure in terms of bimodal microstructures leads to simultaneous enhancement in the electrochemical behavior and mechanical properties of passivable alloys that are usually inversely correlated. The mechanism of self-anodic protection for passivable metals with bimodal microstructures is discussed here for the first time.
A Study on the Influence of the Nozzle Lead Angle on the Performance of Liquid Metal Electromagnetic Micro-Jetting
Authors: Luo Zhiwei , Zheng Gaofeng , Wang Lingyun
Published: December 2016

To improve the jetting performance of liquid metals, an electromagnetic micro-jetting (EMJ) valve that realizes drop-on-demand (DOD) jetting while not involving any valve core or moving parts was designed. The influence of the lead angle of the nozzle on the jetting of liquid metal gallium (Ga) was investigated. It was found that the Lorentz force component parallel to the nozzle that jets the electrified liquid Ga is always larger than its internal friction; thus, jet can be generated with any lead angle but with different kinetic energies. Experimental results show that the mass of the jetting liquid, the jetting distance, the initial velocity of the jet, and the resulting kinetic energy of the jet increase first and then decrease. When the lead angle is 90°, the mass of the jetting liquid and the kinetic energy are at their maximum. When the angle is 80°, the initial velocity achieves its maximum, with a calculated value of 0.042 m/s. Moreover, very close and comparatively high kinetic energies are obtained at 80° and 90°, indicating that angles in between this range can produce a preferable performance. This work provides an important theoretical basis for the design of the EMJ valve, and may promote the development and application of micro electromagnetic jetting technology.
Temporal Transition of Mechanical Characteristics of HUVEC/MSC Spheroids Using a Microfluidic Chip with Force Sensor Probes
Authors: Ito Keitaro , Sakuma Shinya , Kimura Masaki , Takebe Takanori , Kaneko Makoto , Arai Fumihito
Published: December 2016

In this paper, we focus on the mechanical characterization of co-cultured spheroids of human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSC) (HUVEC/MSC spheroids). HUVEC/MSC spheroids aggregate during culture, thereby decreasing in size. Since this size decrease can be caused by the contractility generated by the actomyosin of MSCs, which are intracellular frames, we can expect that there is a temporal transition for the mechanical characteristics, such as stiffness, during culture. To measure the mechanical characteristics, we use a microfluidic chip that is integrated with force sensor probes. We show the details of the measurement configuration and the results of mechanical characterization of the HUVEC/MSC spheroids. To evaluate the stiffness of the spheroids, we introduce the stiffness index, which essentially shows a spring constant per unit size of the spheroid at a certain time during measurement. From the measurement results, we confirmed that the stiffness index firstly increased during the days of culture, although after four days of culture, the stiffness index decreased. We confirmed that the proposed system can measure the stiffness of HUVEC/MSC spheroids.
Activity of Eribulin in a Primary Culture of Well-Differentiated/Dedifferentiated Adipocytic Sarcoma
Authors: De Vita Alessandro , Miserocchi Giacomo , Recine Federica , Mercatali Laura , Pieri Federica , Medri Laura , Bongiovanni Alberto , Cavaliere Davide , Liverani Chiara , Spadazzi Chiara , Amadori Dino , Ibrahim Toni
Published: December 2016

Eribulin mesylate is a novel, non-taxane, synthetic microtubule inhibitor showing antitumor activity in a wide range of tumors including soft tissue sarcomas (STS). Eribulin has been recently approved for the treatment of metastatic liposarcoma (LPS) patients previously treated with anthracyclines. This work investigated the mechanism of action of this innovative antitubulin agent in well-differentiated/dedifferentiated LPS (ALT/DDLPS) which represents one of the most common adipocytic sarcoma histotypes. A primary culture of ALT/DDLPS from a 54-year-old patient was established. The anticancer activity of eribulin on the patient-derived primary culture was assessed by MTT and tunel assays. Eribulin efficacy was compared to other drugs approved for the treatment of STS. Cell migration and morphology were examined after exposure to eribulin to better understand the drug mechanism of action. Finally, Western blot analysis of apoptosis and migration proteins was performed. The results showed that eribulin exerts its antiproliferative effect by the arrest of cell motility and induction of apoptosis. Our results highlighted the activity of eribulin in the treatment of ALT/DDLPS patients.
Motion of Adsorbed Nano-Particles on Azobenzene Containing Polymer Films
Authors: Loebner Sarah , Jelken Joachim , Yadavalli Nataraja , Sava Elena , Hurduc Nicolae , Santer Svetlana
Published: December 2016

We demonstrate in situ recorded motion of nano-objects adsorbed on a photosensitive polymer film. The motion is induced by a mass transport of the underlying photoresponsive polymer material occurring during irradiation with interference pattern. The polymer film contains azobenzene molecules that undergo reversible photoisomerization reaction from trans- to cis-conformation. Through a multi-scale chain of physico-chemical processes, this finally results in the macro-deformations of the film due to the changing elastic properties of polymer. The topographical deformation of the polymer surface is sensitive to a local distribution of the electrical field vector that allows for the generation of dynamic changes in the surface topography during irradiation with different light interference patterns. Polymer film deformation together with the motion of the adsorbed nano-particles are recorded using a homemade set-up combining an optical part for the generation of interference patterns and an atomic force microscope for acquiring the surface deformation. The particles undergo either translational or rotational motion. The direction of particle motion is towards the topography minima and opposite to the mass transport within the polymer film. The ability to relocate particles by photo-induced dynamic topography fluctuation offers a way for a non-contact simultaneous manipulation of a large number of adsorbed particles just in air at ambient conditions.
Assessment of the Potential Energy Hypersurfaces in Thymine within Multiconfigurational Theory: CASSCF vs. CASPT2
Authors: Segarra-Martí Javier , Francés-Monerris Antonio , Roca-Sanjuán Daniel , Merchán Manuela
Published: December 2016

The present study provides new insights into the topography of the potential energy hypersurfaces (PEHs) of the thymine nucleobase in order to rationalize its main ultrafast photochemical decay paths by employing two methodologies based on the complete active space self-consistent field (CASSCF) and the complete active space second-order perturbation theory (CASPT2) methods: (i) CASSCF optimized structures and energies corrected with the CASPT2 method at the CASSCF geometries and (ii) CASPT2 optimized geometries and energies. A direct comparison between these strategies is drawn, yielding qualitatively similar results within a static framework. A number of analyses are performed to assess the accuracy of these different computational strategies under study based on a variety of numerical thresholds and optimization methods. Several basis sets and active spaces have also been calibrated to understand to what extent they can influence the resulting geometries and subsequent interpretation of the photochemical decay channels. The study shows small discrepancies between CASSCF and CASPT2 PEHs, displaying a shallow planar or twisted 1(ππ*) minimum, respectively, and thus featuring a qualitatively similar scenario for supporting the ultrafast bi-exponential deactivation registered in thymine upon UV-light exposure. A deeper knowledge of the PEHs at different levels of theory provides useful insight into its correct characterization and subsequent interpretation of the experimental observations. The discrepancies displayed by the different methods studied here are then discussed and framed within their potential consequences in on-the-fly non-adiabatic molecular dynamics simulations, where qualitatively diverse outcomes are expected.
Xanthines Studied via Femtosecond Fluorescence Spectroscopy
Authors: Changenet-Barret Pascale , Kovács Lajos , Markovitsi Dimitra , Gustavsson Thomas
Published: December 2016

Xanthines represent a wide class of compounds closely related to the DNA bases adenine and guanine. Ubiquitous in the human body, they are capable of replacing natural bases in double helices and give rise to four-stranded structures. Although the use of their fluorescence for analytical purposes was proposed, their fluorescence properties have not been properly characterized so far. The present paper reports the first fluorescence study of xanthine solutions relying on femtosecond spectroscopy. Initially, we focus on 3-methylxanthine, showing that this compound exhibits non-exponential fluorescence decays with no significant dependence on the emission wavelength. The fluorescence quantum yield (3 × 10−4) and average decay time (0.9 ps) are slightly larger than those found for the DNA bases. Subsequently, we compare the dynamical fluorescence properties of seven mono-, di- and tri-methylated derivatives. Both the fluorescence decays and fluorescence anisotropies vary only weakly with the site and the degree of methylation. These findings are in line with theoretical predictions suggesting the involvement of several conical intersections in the relaxation of the lowest singlet excited state.
Clarification of the Antagonistic Effect of the Lipopeptides Produced by Bacillus amyloliquefaciens BPD1 against Pyricularia oryzae via In Situ MALDI-TOF IMS Analysis
Authors: Liao Jen-Hung , Chen Pi-Yu , Yang Yu-Liang , Kan Shu-Chen , Hsieh Feng-Chia , Liu Yung-Chang
Published: December 2016

This study tried to clarify the antagonistic effect of the lipopeptides secreted by Bacillus amyloliquefaciens strain BPD1 (Ba-BPD1) against Pyricularia oryzae Cavara (PO). To determine the major antifungal lipopeptides effective against PO, single and dual cultures were carried out in solid-state media. The matrix-assisted laser desorption/ionization–time of flight imaging mass spectrometry (MALDI-TOF IMS) was used to identify the most effective lipopeptide in situ. Meanwhile, the morphology of pathogen fungi treated with lipopeptides was observed via the SEM. Of the three lipopeptide families, surfactin, iturin, and fengycin, the last was identified as the most effective for inhibiting mycelium growth and conidial germination of PO. The conidia and hyphae of fengycin-treated PO were shown to become deformed and tumorous under exposure. This study provides insights into the antagonistic effect of Ba-BPD1 against fungal phytopathogens. Such insights are helpful in the development of reagents for biological control applications.
Extraction and Quantification of Bioactive Tyrian Purple Precursors: A Comparative and Validation Study from the Hypobranchial Gland of a Muricid Dicathais orbita
Authors: Valles-Regino Roselyn , Mouatt Peter , Rudd David , Yee Lachlan , Benkendorff Kirsten
Published: December 2016

Muricidae are marine molluscs known for the production of Tyrian purple and bioactive precursor compounds. A validation study for the extraction and analysis of secondary metabolites found in the hypobranchial gland of the muricid Dicathais orbita is reported, using high performance liquid chromatography–mass spectrometry (HPLC-MS) with diode array detector (DAD). Quantification of the dominant secondary metabolites from D. orbita is described, followed by a comparison of solvent extraction procedures and stability studies. The intra- and inter-day relative standard deviation (RSD) for tyrindoxyl sulphate was 0.46% and 0.17%, respectively. The quantification was linear for standards murexine, 6-bromoisatin, and tyrindoxyl sulphate. The limits of detection were 0.03, 0.004, and 0.07 mg/mL, respectively, and the limits of quantification were 0.09, 0.01, and 0.22 mg/mL, respectively. The results showed that alcoholic solvents were better for extracting choline ester and indoxyl sulphate ultimate precursors, while chloroform was more suitable for the extraction of the intermediate precursors. Multivariate analysis revealed significant differences in extract composition according to the solvent used. Stability testing showed an increase of the oxidative compounds 6-bromoisatin and putative tyrindoxyl S-oxide sulphate in the ethanol extracts while more degradation products were seen in the chloroform extracts after months of cold storage. The validated method was found to be simple, reproducible, precise, and suitable for quantification of the secondary metabolites of muricid molluscs for dye precursor and nutraceutical quality control, as well as applications in marine chemical ecology.
The Change of Electronic Transport Behaviors by P and B Doping in Nano-Crystalline Silicon Films with Very High Conductivities
Authors: Shan Dan , Qian Mingqing , Ji Yang , Jiang Xiaofan , Xu Jun , Chen Kunji
Published: December 2016

Nano-crystalline Si films with high conductivities are highly desired in order to develop the new generation of nano-devices. Here, we first demonstrate that the grain boundaries played an important role in the carrier transport process in un-doped nano-crystalline Si films as revealed by the temperature-dependent Hall measurements. The potential barrier height can be well estimated from the experimental results, which is in good agreement with the proposed model. Then, by introducing P and B doping, it is found that the scattering of grain boundaries can be significantly suppressed and the Hall mobility is monotonously decreased with the temperature both in P- and B-doped nano-crystalline Si films, which can be attributed to the trapping of P and B dopants in the grain boundary regions to reduce the barriers. Consequently, a room temperature conductivity as high as 1.58 × 103 S/cm and 4 × 102 S/cm is achieved for the P-doped and B-doped samples, respectively.
Current perspectives in Set7 mediated stem cell differentiation
Authors: Karimnia Nazanin , Rafehi Haloom , Tuano Natasha , Ziemann Mark , K.N Harikrishnan , Okabe Jun , El-Osta Assam
Published: December 2016

Set7 is a key regulatory enzyme involved in the methylation of lysine residues of histone and non-histone proteins. This lysine methyltransferase is induced during stem cell differentiation and regulates lineage specific gene transcription and cell fate. In this article we discuss recent experimental evidence identifying regulatory targets under the control of Set7 as well as emerging evidence of regulation in stem cell differentiation. Furthermore, we discuss the function of non-coding RNAs regulated by Set7 implicated in cell plasticity.
Polyphenols and DNA Damage: A Mixed Blessing
Authors: Azqueta Amaya , Collins Andrew
Published: December 2016

Polyphenols are a very broad group of chemicals, widely distributed in plant foods, and endowed with antioxidant activity by virtue of their numerous phenol groups. They are widely studied as putative cancer-protective agents, potentially contributing to the cancer preventive properties of fruits and vegetables. We review recent publications relating to human trials, animal experiments and cell culture, grouping them according to whether polyphenols are investigated in whole foods and drinks, in plant extracts, or as individual compounds. A variety of assays are in use to study genetic damage endpoints. Human trials, of which there are rather few, tend to show decreases in endogenous DNA damage and protection against DNA damage induced ex vivo in blood cells. Most animal experiments have investigated the effects of polyphenols (often at high doses) in combination with known DNA-damaging agents, and generally they show protection. High concentrations can themselves induce DNA damage, as demonstrated in numerous cell culture experiments; low concentrations, on the other hand, tend to decrease DNA damage.
Mapping Deforestation in North Korea Using Phenology-Based Multi-Index and Random Forest
Authors: Jin Yihua , Sung Sunyong , Lee Dong , Biging Gregory , Jeong Seunggyu
Published: December 2016

Phenology-based multi-index with the random forest (RF) algorithm can be used to overcome the shortcomings of traditional deforestation mapping that involves pixel-based classification, such as ISODATA or decision trees, and single images. The purpose of this study was to investigate methods to identify specific types of deforestation in North Korea, and to increase the accuracy of classification, using phenological characteristics extracted with multi-index and random forest algorithms. The mapping of deforestation area based on RF was carried out by merging phenology-based multi-indices (i.e., normalized difference vegetation index (NDVI), normalized difference water index (NDWI), and normalized difference soil index (NDSI)) derived from MODIS (Moderate Resolution Imaging Spectroradiometer) products and topographical variables. Our results showed overall classification accuracy of 89.38%, with corresponding kappa coefficients of 0.87. In particular, for forest and farm land categories with similar phenological characteristic (e.g., paddy, plateau vegetation, unstocked forest, hillside field), this approach improved the classification accuracy in comparison with pixel-based methods and other classes. The deforestation types were identified by incorporating point data from high-resolution imagery, outcomes of image classification, and slope data. Our study demonstrated that the proposed methodology could be used for deciding on the restoration priority and monitoring the expansion of deforestation areas.
A Geometry-Based Cycle Slip Detection and Repair Method with Time-Differenced Carrier Phase (TDCP) for a Single Frequency Global Position System (GPS) + BeiDou Navigation Satellite System (BDS) Receiver
Authors: Qian Chuang , Liu Hui , Zhang Ming , Shu Bao , Xu Longwei , Zhang Rufei
Published: December 2016

As the field of high-precision applications based on carriers continues to expand, the development of low-cost, small, modular receivers and their application in diverse scenarios and situations with complex data quality has increased the requirements of carrier-phase data preprocessing. A new geometry-based cycle slip detection and repair method based on Global Position System (GPS) + BeiDou Navigation Satellite System (BDS) is proposed. The method uses a Time-differenced Carrier Phase (TDCP) model, which eliminates the Inner-System Bias (ISB) between GPS and BDS, and it is conducive to the effective combination of GPS and BDS. It avoids the interference of the noise of the pseudo-range with cycle slip detection, while the cycle slips are preserved as integers. This method does not limit the receiver frequency number, and it is applicable to single-frequency data. The process is divided into two steps to detect and repair cycle slip. The first step is cycle slip detection, using the Improved Local Analysis Method (ILAM) to find satellites that have cycle slips; The second step is to repair the cycle slips, including estimating the float solution of changes in ambiguities at the satellites that have cycle slips with the least squares method and the integer solution of the cycle slips by rounding. In the process of rounding, in addition to the success probability, a decimal test is carried out to validate the result. Finally, experiments with filed test data are carried out to prove the effectiveness of this method. The results show that the detectable cycle slips number with GPS + BDS is much greater than that with GPS. The method can also detect the non-integer outliers while fixing the cycle slip. The maximum decimal bias in repair is less than that with GPS. It implies that this method takes full advantages of multi-system.
Exploring Community-Oriented Approaches in Demand Side Management Projects in Europe
Authors: Mengolini Anna , Gangale Flavia , Vasiljevska Julija
Published: December 2016

This paper seeks to investigate if the theoretical and political trends towards a more collective dimension of energy use are reflected in the design and development of demand side management (DSM) pilot projects in Europe. Specifically, the paper analyses DSM projects in the database of the Joint Research Centre (JRC) of the European Commission to capture signs of a new attention towards the wider context in which consumers live and towards the social dimension associated with energy consumption. To this end, the paper investigates the projects’ scope (in terms of project’s partners, end-use sectors and targeted services) as well as the consumer engagement strategies that projects use. These elements reflect the projects’ consideration for the socio-economic dimension of the community where the pilots take place and their inclination to build on community dynamics. The analysis shows that DSM projects in the EU are increasingly being designed and developed with a collegial approach to energy consumption in mind, although an integrated approach is still missing. In addition, research is still needed to link the use of this innovative approach to project results. A closer look at the developments and results of these projects can help to identify what works and what doesn’t in real life experiences, thus supporting effective policy making at the EU and national level.
Designing Computer-Supported Complex Systems Curricula for the Next Generation Science Standards in High School Science Classrooms
Authors: Yoon Susan , Anderson Emma , Klopfer Eric , Koehler-Yom Jessica , Sheldon Josh , Schoenfeld Ilana , Wendel Daniel , Scheintaub Hal , Oztok Murat , Evans Chad , Goh Sao-Ee
Published: December 2016

We present a curriculum and instruction framework for computer-supported teaching and learning about complex systems in high school science classrooms. This work responds to a need in K-12 science education research and practice for the articulation of design features for classroom instruction that can address the Next Generation Science Standards (NGSS) recently launched in the USA. We outline the features of the framework, including curricular relevance, cognitively rich pedagogies, computational tools for teaching and learning, and the development of content expertise, and provide examples of how the framework is translated into practice. We follow this up with evidence from a preliminary study conducted with 10 teachers and 361 students, aimed at understanding the extent to which students learned from the activities. Results demonstrated gains in students’ complex systems understanding and biology content knowledge. In interviews, students identified influences of various aspects of the curriculum and instruction framework on their learning.
A P-Glycoprotein Is Linked to Resistance to the Bacillus thuringiensis Cry3Aa Toxin in a Leaf Beetle
Authors: Pauchet Yannick , Bretschneider Anne , Augustin Sylvie , Heckel David
Published: December 2016

Chrysomela tremula is a polyvoltine oligophagous leaf beetle responsible for massive attacks on poplar trees. This beetle is an important model for understanding mechanisms of resistance to Bacillus thuringiensis (Bt) insecticidal toxins, because a resistant C. tremula strain has been found that can survive and reproduce on transgenic poplar trees expressing high levels of the Cry3Aa Bt toxin. Resistance to Cry3Aa in this strain is recessive and is controlled by a single autosomal locus. We used a larval midgut transcriptome for C. tremula to search for candidate resistance genes. We discovered a mutation in an ABC protein, member of the B subfamily homologous to P-glycoprotein, which is genetically linked to Cry3Aa resistance in C. tremula. Cultured insect cells heterologously expressing this ABC protein swell and lyse when incubated with Cry3Aa toxin. In light of previous findings in Lepidoptera implicating A subfamily ABC proteins as receptors for Cry2A toxins and C subfamily proteins as receptors for Cry1A and Cry1C toxins, this result suggests that ABC proteins may be targets of insecticidal three-domain Bt toxins in Coleoptera as well.
Metabolism of HT-2 Toxin and T-2 Toxin in Oats
Authors: Meng-Reiterer Jacqueline , Bueschl Christoph , Rechthaler Justyna , Berthiller Franz , Lemmens Marc , Schuhmacher Rainer
Published: December 2016

The Fusarium mycotoxins HT-2 toxin (HT2) and T-2 toxin (T2) are frequent contaminants in oats. These toxins, but also their plant metabolites, may contribute to toxicological effects. This work describes the use of 13C-assisted liquid chromatography–high-resolution mass spectrometry for the first comprehensive study on the biotransformation of HT2 and T2 in oats. Using this approach, 16 HT2 and 17 T2 metabolites were annotated including novel glycosylated and hydroxylated forms of the toxins, hydrolysis products, and conjugates with acetic acid, putative malic acid, malonic acid, and ferulic acid. Further targeted quantitative analysis was performed to study toxin metabolism over time, as well as toxin and conjugate mobility within non-treated plant tissues. As a result, HT2-3-O-β-d-glucoside was identified as the major detoxification product of both parent toxins, which was rapidly formed (to an extent of 74% in HT2-treated and 48% in T2-treated oats within one day after treatment) and further metabolised. Mobility of the parent toxins appeared to be negligible, while HT2-3-O-β-d-glucoside was partly transported (up to approximately 4%) through panicle side branches and stem. Our findings demonstrate that the presented combination of untargeted and targeted analysis is well suited for the comprehensive elucidation of mycotoxin metabolism in plants.
Using Bronson Equation to Accurately Predict the Dog Brain Weight Based on Body Weight Parameter
Authors: Carreira L.
Published: December 2016

The study used 69 brains (n = 69) from adult dog cadavers, divided by their skull type into three groups, brachi (B), dolicho (D) and mesaticephalic (M) (n = 23 each), and aimed: (1) to determine whether the Bronson equation may be applied, without reservation, to estimate brain weight (BW) in brachy (B), dolicho (D), and mesaticephalic (M) dog breeds; and (2) to evaluate which breeds are more closely related to each other in an evolutionary scenario. All subjects were identified by sex, age, breed, and body weight (bw). An oscillating saw was used for a circumferential craniotomy to open the skulls; the brains were removed and weighed using a digital scale. For statistical analysis, p-values < 0.05 were considered significant. The work demonstrated a strong relationship between the observed and predicted BW by using the Bronson equation. It was possible to hypothesize that groups B and D present a greater encephalization level than M breeds, that B and D dog breeds are more closely related to each other than to M, and from the three groups, the D individuals presented the highest brain mass mean.
Conversion of Blue Water into Green Water for Improving Utilization Ratio of Water Resources in Degraded Karst Areas
Authors: Chen Ke , Yang Shengtian , Zhao Changsen , Li Zongli , Luo Ya , Wang Zhiwei , Liu Xiaolin , Guan Yabing , Bai Juan , Zhou Qiuwen , Yu Xinyi
Published: December 2016

Vegetation deterioration and soil loss are the main causes of more precipitation leakages and surface water shortages in degraded karst areas. In order to improve the utilization of water resources in such regions, water storage engineering has been considered; however, site selection and cost associated with the special karstic geological structure have made this difficult. According to the principle of the Soil Plant Atmosphere Continuum, increasing both vegetation cover and soil thickness would change water cycle process, resulting in a transformation from leaked blue water (liquid form) into green water (gas or saturated water form) for terrestrial plant ecosystems, thereby improving the utilization of water resources. Using the Soil Vegetation Atmosphere Transfer model and the geographical distributed approach, this study simulated the conversion from leaked blue water (leakage) into green water in the environs of Guiyang, a typical degraded karst area. The primary results were as follows: (1) Green water in the area accounted for <50% of precipitation, well below the world average of 65%; (2) Vegetation growth played an important role in converting leakage into green water; however, once it increased to 56%, its contribution to reducing leakage decreased sharply; (3) Increasing soil thickness by 20 cm converted the leakage considerably. The order of leakage reduction under different precipitation scenarios was dry year > normal year > rainy year. Thus, increased soil thickness was shown effective in improving the utilization ratio of water resources and in raising the amount of plant ecological water use; (4) The transformation of blue water into green water, which avoids constructions of hydraulic engineering, could provide an alternative solution for the improvement of the utilization of water resources in degraded karst area. Although there are inevitable uncertainties in simulation process, it has important significance for overcoming similar problems.
Integrated Water Resources Management in a Lake System: A Case Study in Central Italy
Authors: Casadei Stefano , Pierleoni Arnaldo , Bellezza Michele
Published: December 2016

Lake Trasimeno is a closed lake in Central Italy and in historically its water level has been affected by wide fluctuations mostly depending on the climate. The lake has suffered many water crises due to water scarcity and in recent decades, droughts have also severely affected the economic and environmental situation. The aim of this study was to analyze the possibility of limiting these severe level fluctuations by evaluating of feasible water resource management policies that could also reduce the environmental stress of this area. Therefore, a specific decision support system (DSS) has been developed in order to simulate different scenarios for the entire water system of the Trasimeno area. In particular, the hydrological model implemented in the DSS allowed for the simulation and validation of different management policy hypotheses for the water resource in order to mitigate environmental and water crises for the Lake Trasimeno. Results indicated that it is possible to transfer a certain amount of water from nearby reservoirs without affecting the availability of the resource for specific users. In this way, Lake Trasimeno can benefit both from an increase in water levels in the lake, so a possible better situation in quantitatively and qualitatively.