bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxicity of Urban PM10 and Relation with Tracers of Biomass Burning
Authors: Van Den Heuvel Rosette , Staelens Jeroen , Koppen Gudrun , Schoeters Greet
Published: February 2018

The chemical composition of particles varies with space and time and depends on emission sources, atmospheric chemistry and weather conditions. Evidence suggesting that particles differ in toxicity depending on their chemical composition is growing. This in vitro study investigated the biological effects of PM10 in relation to PM-associated chemicals. PM10 was sampled in ambient air at an urban traffic site (Borgerhout) and a rural background location (Houtem) in Flanders (Belgium). To characterize the toxic potential of PM10, airway epithelial cells (Beas-2B cells) were exposed to particles in vitro. Different endpoints were studied including cell damage and death (cell viability) and the induction of interleukin-8 (IL-8). The mutagenic capacity was assessed using the Ames II Mutagenicity Test. The endotoxin levels in the collected samples were analyzed and the oxidative potential (OP) of PM10 particles was evaluated by electron paramagnetic resonance (EPR) spectroscopy. Chemical characteristics of PM10 included tracers for biomass burning (levoglucosan, mannosan and galactosan), elemental and organic carbon (EC/OC) and polycyclic aromatic hydrocarbons (PAHs). Most samples displayed dose-dependent cytotoxicity and IL-8 induction. Spatial and temporal differences in PM10 toxicity were seen. PM10 collected at the urban site was characterized by increased pro-inflammatory and mutagenic activity as well as higher OP and elevated endotoxin levels compared to the background area. Reduced cell viability (−0.46 < rs < −0.35, p < 0.01) and IL-8 induction (−0.62 < rs < −0.67, p < 0.01) were associated with all markers for biomass burning, levoglucosan, mannosan and galactosan. Furthermore, direct and indirect mutagenicity were associated with tracers for biomass burning, OC, EC and PAHs. Multiple regression analyses showed levoglucosan to explain 16% and 28% of the variance in direct and indirect mutagenicity, respectively. Markers for biomass burning were associated with altered cellular responses and increased mutagenic activity. These findings may indicate a role of biomass burning in the observed adverse health effect of particulate matter.
High-Fat-Diet-Induced Obesity Produces Spontaneous Ventricular Arrhythmias and Increases the Activity of Ryanodine Receptors in Mice
Authors: Sánchez Gina , Araneda Felipe , Peña Juan , Finkelstein José , Riquelme Jaime , Montecinos Luis , Barrientos Genaro , Llanos Paola , Pedrozo Zully , Said Matilde , Bull Ricardo , Donoso Paulina
Published: February 2018

Ventricular arrhythmias are a common cause of sudden cardiac death, and their occurrence is higher in obese subjects. Abnormal gating of ryanodine receptors (RyR2), the calcium release channels of the sarcoplasmic reticulum, can produce ventricular arrhythmias. Since obesity promotes oxidative stress and RyR2 are redox-sensitive channels, we investigated whether the RyR2 activity was altered in obese mice. Mice fed a high fat diet (HFD) became obese after eight weeks and exhibited a significant increase in the occurrence of ventricular arrhythmias. Single RyR2 channels isolated from the hearts of obese mice were more active in planar bilayers than those isolated from the hearts of the control mice. At the molecular level, RyR2 channels from HFD-fed mice had substantially fewer free thiol residues, suggesting that redox modifications were responsible for the higher activity. Apocynin, provided in the drinking water, completely prevented the appearance of ventricular arrhythmias in HFD-fed mice, and normalized the activity and content of the free thiol residues of the protein. HFD increased the expression of NOX4, an isoform of NADPH oxidase, in the heart. Our results suggest that HFD increases the activity of RyR2 channels via a redox-dependent mechanism, favoring the appearance of ventricular arrhythmias.
Site-Specific Cleavage by Topoisomerase 2: A Mark of the Core Centromere
Authors: Mills Walter , Spence Jennifer , Fukagawa Tatsuo , Farr Christine
Published: February 2018

In addition to its roles in transcription and replication, topoisomerase 2 (topo 2) is crucial in shaping mitotic chromosomes and in ensuring the orderly separation of sister chromatids. As well as its recruitment throughout the length of the mitotic chromosome, topo 2 accumulates at the primary constriction. Here, following cohesin release, the enzymatic activity of topo 2 acts to remove residual sister catenations. Intriguingly, topo 2 does not bind and cleave all sites in the genome equally; one preferred site of cleavage is within the core centromere. Discrete topo 2-centromeric cleavage sites have been identified in α-satellite DNA arrays of active human centromeres and in the centromere regions of some protozoans. In this study, we show that topo 2 cleavage sites are also a feature of the centromere in Schizosaccharomyces pombe, the metazoan Drosophila melanogaster and in another vertebrate species, Gallus gallus (chicken). In vertebrates, we show that this site-specific cleavage is diminished by depletion of CENP-I, an essential constitutive centromere protein. The presence, within the core centromere of a wide range of eukaryotes, of precise sites hypersensitive to topo 2 cleavage suggests that these mark a fundamental and conserved aspect of this functional domain, such as a non-canonical secondary structure.
Comparative Membrane-Associated Proteomics of Three Different Immune Reactions in Potato
Authors: Burra Dharani Dhar , Lenman Marit , Levander Fredrik , Resjö Svante , Andreasson Erik
Published: February 2018

Plants have evolved different types of immune reactions but large-scale proteomics about these processes are lacking, especially in the case of agriculturally important crop pathosystems. We have established a system for investigating PAMP-triggered immunity (PTI) and two different effector-triggered immunity (ETI; triggered by Avr2 or IpiO) responses in potato. The ETI responses are triggered by molecules from the agriculturally important Phytophthora infestans interaction. To perform large-scale membrane protein-based comparison of these responses, we established a method to extract proteins from subcellular compartments in leaves. In the membrane fractions that were subjected to quantitative proteomics analysis, we found that most proteins regulated during PTI were also regulated in the same way in ETI. Proteins related to photosynthesis had lower abundance, while proteins related to oxidative and biotic stress, as well as those related to general antimicrobial defense and cell wall degradation, were found to be higher in abundance. On the other hand, we identified a few proteins—for instance, an ABC transporter-like protein—that were only found in the PTI reaction. Furthermore, we also identified proteins that were regulated only in ETI interactions. These included proteins related to GTP binding and heterotrimeric G-protein signaling, as well as those related to phospholipase signaling.
Impact of Arginine to Cysteine Mutations in Collagen II on Protein Secretion and Cell Survival
Authors: Chakkalakal Salin , Heilig Juliane , Baumann Ulrich , Paulsson Mats , Zaucke Frank
Published: February 2018

Inherited point mutations in collagen II in humans affecting mainly cartilage are broadly classified as chondrodysplasias. Most mutations occur in the glycine (Gly) of the Gly-X-Y repeats leading to destabilization of the triple helix. Arginine to cysteine substitutions that occur at either the X or Y position within the Gly-X-Y cause different phenotypes like Stickler syndrome and congenital spondyloepiphyseal dysplasia (SEDC). We investigated the consequences of arginine to cysteine substitutions (X or Y position within the Gly-X-Y) towards the N and C terminus of the triple helix. Protein expression and its secretion trafficking were analyzed. Substitutions R75C, R134C and R704C did not alter the thermal stability with respect to wild type; R740C and R789C proteins displayed significantly reduced melting temperatures (Tm) affecting thermal stability. Additionally, R740C and R789C were susceptible to proteases; in cell culture, R789C protein was further cleaved by matrix metalloproteinases (MMPs) resulting in expression of only a truncated fragment affecting its secretion and intracellular retention. Retention of misfolded R740C and R789C proteins triggered an ER stress response leading to apoptosis of the expressing cells. Arginine to cysteine mutations towards the C-terminus of the triple helix had a deleterious effect, whereas mutations towards the N-terminus of the triple helix (R75C and R134C) and R704C had less impact.
Alternative Splicing as a Target for Cancer Treatment
Authors: Martinez-Montiel Nancy , Rosas-Murrieta Nora , Anaya Ruiz Maricruz , Monjaraz-Guzman Eduardo , Martinez-Contreras Rebeca
Published: February 2018

Alternative splicing is a key mechanism determinant for gene expression in metazoan. During alternative splicing, non-coding sequences are removed to generate different mature messenger RNAs due to a combination of sequence elements and cellular factors that contribute to splicing regulation. A different combination of splicing sites, exonic or intronic sequences, mutually exclusive exons or retained introns could be selected during alternative splicing to generate different mature mRNAs that could in turn produce distinct protein products. Alternative splicing is the main source of protein diversity responsible for 90% of human gene expression, and it has recently become a hallmark for cancer with a full potential as a prognostic and therapeutic tool. Currently, more than 15,000 alternative splicing events have been associated to different aspects of cancer biology, including cell proliferation and invasion, apoptosis resistance and susceptibility to different chemotherapeutic drugs. Here, we present well established and newly discovered splicing events that occur in different cancer-related genes, their modification by several approaches and the current status of key tools developed to target alternative splicing with diagnostic and therapeutic purposes.
Biochemical Mechanism of Rhododendrol-Induced Leukoderma
Authors: Ito Shosuke , Wakamatsu Kazumasa
Published: February 2018

RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol (RD))—a skin-whitening ingredient—was reported to induce leukoderma in some consumers. We have examined the biochemical basis of the RD-induced leukoderma by elucidating the metabolic fate of RD in the course of tyrosinase-catalyzed oxidation. We found that the oxidation of racemic RD by mushroom tyrosinase rapidly produces RD-quinone, which gives rise to secondary quinone products. Subsequently, we confirmed that human tyrosinase is able to oxidize both enantiomers of RD. We then showed that B16 cells exposed to RD produce high levels of RD-pheomelanin and protein-SH adducts of RD-quinone. Our recent studies showed that RD-eumelanin—an oxidation product of RD—exhibits a potent pro-oxidant activity that is enhanced by ultraviolet-A radiation. In this review, we summarize our biochemical findings on the tyrosinase-dependent metabolism of RD and related studies by other research groups. The results suggest two major mechanisms of cytotoxicity to melanocytes. One is the cytotoxicity of RD-quinone through binding with sulfhydryl proteins that leads to the inactivation of sulfhydryl enzymes and protein denaturation that leads to endoplasmic reticulum stress. The other mechanism is the pro-oxidant activity of RD-derived melanins that leads to oxidative stress resulting from the depletion of antioxidants and the generation of reactive oxygen radicals.
Prostaglandin D2-Mediated DP2 and AKT Signal Regulate the Activation of Androgen Receptors in Human Dermal Papilla Cells
Authors: Jeong Kwan , Jung Ji , Kim Jung , Kang Hoon
Published: February 2018

Prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (DP2) is known to be an important factor in androgenetic alopecia (AGA). However, the effect of PGD2 in human dermal papilla cells (hDPCs) is not fully understood. The function of PGD2-induced expression of the androgen receptor (AR), DP2, and AKT (protein kinase B) signal were examined by using real time-PCR (qRT-PCR), western blot analysis, immunocytochemistry (ICC), and siRNA transfection system. PGD2 stimulated AR expression and AKT signaling through DP2. PGD2 stimulated AR related factors (transforming growth factor beta 1 (TGFβ1), Creb, lymphoid enhancer binding factor 1 (LEF1), and insulin-like growth factor 1, (IGF-1)) and AKT signaling (GSK3β and Creb) on the AR expression in hDPCs. However, these factors were down-regulated by DP2 antagonist (TM30089) and AKT inhibitor (LY294002) as well as DP2 knockdown in hDPCs decreased AR expression and AKT signaling. Finally, we confirmed that PGD2 stimulates the expression of AR related target genes, and that AKT and its downstream substrates are involved in AR expression on hDPCs. Taken together, our data suggest that PGD2 promotes AR and AKT signal via DP2 in hDPCs, thus, PGD2 and DP2 signal plays a critical role in AR expression. These findings support the additional explanation for the development of AGA involving PGD2-DP2 in hDPCs.
A Practical Review of the Emerging Direct Anticoagulants, Laboratory Monitoring, and Reversal Agents
Authors: Joppa Stephanie , Salciccioli Justin , Adamski Jill , Patel Salma , Wysokinski Waldemar , McBane Robert , Al-Saffar Farah , Esser Heidi , Shamoun Fadi
Published: February 2018

Millions of patients in the United States use anticoagulation for a variety of indications, such as the prevention of stroke in those with atrial fibrillation (AF) and the treatment and prevention of venous thrombosis. For over six decades warfarin was the only available oral anticoagulant, but now several DOACs are available and their use has become more prevalent in recent years. In spite of this increased use, many physicians remain reluctant to prescribe DOACs due to concerns about bleeding and reversibility.
Update on the Non-Pharmacological Management of Stroke Prevention in Patients with Atrial Fibrillation
Authors: Tolat Aneesh , Lippman Neal
Published: February 2018

Non-surgical left atrial appendage occlusion has emerged as an alternative to anticoagulant therapy in the management of stroke risk in patients with atrial fibrillation. This review reports on some of the more common devices that are currently being used to manage patients in this challenging group.
The Level of Automation in Emergency Quick Disconnect Decision Making
Authors: Marius Imset , Kristin Falk , Marianne Kjørstad , Salman Nazir
Published: February 2018

As a key measure for safety and environmental protection during offshore well operations, drill rigs are equipped with Emergency Quick Disconnect (EQD) systems. However, an EQD operation is in itself considered a risky operation with a major economic impact. For this reason, it is of great importance to aid the operators in their assessment of the situation at all times, and help them make the best decisions. However, despite the availability of such systems, accidents do happen. This demonstrates the vulnerability of our human decision-making capabilities in extremely stressful situations. One way of improving the overall human-system performance with respect to EQD is to increase the level and quality of the automation and decision support systems. Although there is plenty of evidence that automated systems have weaknesses, there is also evidence that advanced software systems outperform humans in complex decision-making. The major challenge is to make sure that EQD is performed when necessary, but there is also a need to decrease the number of false EQDs. This paper applies an existing framework for levels of automation in order to explore the critical decision process leading to an EQD. We provide an overview of the benefits and drawbacks of existing automation and decision support systems vs. manual human decision-making. Data are collected from interviews of offshore users, suppliers, and oil companies, as well as from formal operational procedures. Findings are discussed using an established framework for the level of automation. Our conclusion is that there is an appropriate level of automation in critical situations related to the loss of the position of the drill rig, and that there is the promising potential to increase the autonomy level in a mid- and long-term situation assessment.
Bioactivity Assessment of Indian Origin—Mangrove Actinobacteria against Candida albicans
Authors: Pavan Kumar J. , Gomathi Ajitha , Vasconcelos Vitor , Gothandam K.
Published: February 2018

Actinobacteria is found to have a potent metabolic activity against pathogens. The present study reveals the assessment of potent antifungal secondary metabolites from actinobacteria isolated from Indian marine mangrove sediments. The samples were collected from the coastal regions of Muthupet, Andaman and the Nicobar Islands. Identification was carried out using 16S rRNA analysis and biosynthetic genes (Polyketide synthase type I/II and Non-ribosomal peptide synthase) were screened. Actinobacteria were assayed for their antifungal activity against 16 clinical Candida albicans and the compound analysis was performed using gas chromatography-mass spectrometry GC-MS. The 31 actinobacterial strains were isolated and 16S rRNA gene sequencing revealed that this ecosystem is rich on actinobacteria, with Streptomyces as the predominant genus. The PCR based screening of biosynthetic genes revealed the presence of PKS-I in six strains, PKS-II in four strains and NRPS in 11 strains. The isolated actinobacteria VITGAP240 and VITGAP241 (two isolates) were found to have a potential antifungal activity against all the tested C. albicans. GC-MS results revealed that the actinobacterial compounds were belonging to heterocyclic, polyketides and peptides. Overall, the strains possess a wide spectrum of antifungal properties which affords the production of significant bioactive metabolites as potential antibiotics.
Slurry Erosion Behavior of AlxCoCrFeNiTi0.5 High-Entropy Alloy Coatings Fabricated by Laser Cladding
Authors: Zhao Jianhua , Ma Aibin , Ji Xiulin , Jiang Jinghua , Bao Yayun
Published: February 2018

High-entropy alloys (HEAs) have gained extensive attention due to their excellent properties and the related scientific value in the last decade. In this work, AlxCoCrFeNiTi0.5 HEA coatings (x: molar ratio, x = 1.0, 1.5, 2.0, and 2.5) were fabricated on Q345 steel substrate by laser-cladding process to develop a practical protection technology for fluid machines. The effect of Al content on their phase evolution, microstructure, and slurry erosion performance of the HEA coatings was studied. The AlxCoCrFeNiTi0.5 HEA coatings are composed of simple face-centered cubic (FCC), body-centered cubic (BCC) and their mixture phase. Slurry erosion tests were conducted on the HEA coatings with a constant velocity of 10.08 m/s and 16–40 meshs and particles at impingement angles of 15, 30, 45, 60 and 90 degrees. The effect of three parameters, namely impingement angle, sand concentration and erosion time, on the slurry erosion behavior of AlxCoCrFeNiTi0.5 HEA coatings was investigated. Experimental results show AlCoCrFeNiTi0.5 HEA coating follows a ductile erosion mode and a mixed mode (neither ductile nor brittle) for Al1.5CoCrFeNiTi0.5 HEA coating, while Al2.0CoCrFeNiTi0.5 and Al2.5CoCrFeNiTi0.5 HEA coatings mainly exhibit brittle erosion mode. AlCoCrFeNiTi0.5 HEA coating has good erosion resistance at all investigated impingement angles due to its high hardness, good plasticity, and low stacking fault energy (SFE).
Corrosion: Critical Challenge in Wider Use of Magnesium Alloys
Authors: Singh Raman , Venkatesh Vijayaraghavan , Kumar Vinod
Published: February 2018

Magnesium alloys, given their high strength-to-weight ratio, are very attractive materials for applications such as aerospace and automotive components.[...]
Functional Magnetic Mesoporous Silica Microparticles Capped with an Azo-Derivative: A Promising Colon Drug Delivery Device
Authors: Teruel Adrián , Coll Carmen , Costero Ana , Ferri Daniel , Parra Margarita , Gaviña Pablo , González-Álvarez Marta , Merino Virginia , Marcos M. , Martínez-Máñez Ramón , Sancenón Félix
Published: February 2018

Magnetic micro-sized mesoporous silica particles were used for the preparation of a gated material able to release an entrapped cargo in the presence of an azo-reducing agent and, to some extent, at acidic pH. The magnetic mesoporous microparticles were loaded with safranin O and the external surface was functionalized with an azo derivative 1 (bearing a carbamate linkage) yielding solid S1. Aqueous suspensions of S1 at pH 7.4 showed negligible safranin O release due to the presence of the bulky azo derivative attached onto the external surface of the inorganic scaffold. However, in the presence of sodium dithionite (azoreductive agent), a remarkable safranin O delivery was observed. At acidic pH, a certain safranin O release from S1 was also found. The pH-triggered safranin O delivery was ascribed to the acid-induced hydrolysis of the carbamate moiety that linked the bulky azo derivatives onto the mesoporous inorganic magnetic support. The controlled release behavior of S1 was also tested using a model that simulated the gastro intestinal tract.
Synthesis and Fluorescent Property Study of Novel 1,8-Naphthalimide-Based Chemosensors
Authors: Fu Ying , Pang Xiao-Xiao , Wang Zhi-Qiang , Qu Hai-Tao , Ye Fei
Published: February 2018

A series of novel mono- and di-substituted N-n-butyl-1,8-naphthalimide derivatives were synthesized simultaneously via a three-step reaction. The single crystal structure of N-n-butyl-4-[N′,N′-bis(2′,4′-dichlorobenzoyl)ethylamino]-1,8-naphthalimide (3f) was determined. The UV-vis and fluorescence properties of compound 3f were investigated. The 3f showed highly selective and sensitive fluorescence changes response towards Pb2+. A titration of monomer with Pb2+ ion was performed. When Pb2+ ion concentration increased from 0 to 10 eq., the fluorescent intensity of 3f decreased from 199.97 to 48.21. The pH effect on 3f showed that it is stable in a wide range of pH. The results indicated that 3f might be a probe molecule for Pb2+.
Melatonin Alleviates High Temperature-Induced Pollen Abortion in Solanum lycopersicum
Authors: Qi Zhen-Yu , Wang Kai-Xin , Yan Meng-Yu , Kanwar Mukesh , Li Dao-Yi , Wijaya Leonard , Alyemeni Mohammed , Ahmad Parvaiz , Zhou Jie
Published: February 2018

Melatonin is a pleiotropic signal molecule that plays critical roles in regulating plant growth and development, as well as providing physiological protections against various environmental stresses. Nonetheless, the mechanisms for melatonin-mediated pollen thermotolerance remain largely unknown. In this study, we report that irrigation treatment with melatonin (20 µM) effectively ameliorated high temperature-induced inactivation of pollen and inhibition of pollen germination in tomato (Solanum lycopersicum) plants. Melatonin alleviated reactive oxygen species production in tomato anthers under high temperature by the up-regulation of the transcription and activities of several antioxidant enzymes. Transmission electron micrograph results showed that high temperature-induced pollen abortion is associated with a premature degeneration of the tapetum cells and the formation of defective pollen grains with degenerated nuclei at the early uninuclear microspore stage, whilst melatonin protected degradation of organelles by enhancing the expression of heat shock protein genes to refold unfolded proteins and the expression of autophagy-related genes and formation of autophagosomes to degrade denatured proteins. These findings suggest a novel function of melatonin to protect pollen activity under high temperature and support the potential effects of melatonin on reproductive development of plants.
Anti-Cancer Activities of Diterpenoids Derived from Euphorbia fischeriana Steud
Authors: Jian Baiyu , Zhang Hao , Han Cuicui , Liu Jicheng
Published: February 2018

Euphorbia fischeriana Steud is an essential oriental folk medicine used for healing cancer, edema and tuberculosis. Recently, its anticancer activitity has attracted more attention. A volume of research has indicated that diterpenoids are the major anticancer active constituents from this medicinal herb. In this review, we aimed to provide a summary of the promising anticancer diterpenoids from this plant; many diterpenoids mentioned in this article are newly discovered diterpenoids. According to the carbon skeleton and substituents, they can be classified into eight subtypes: ent-abietane, daphnane, tigliane, ingenane, ent-atisane, ent-rosane, ent-kaurane, and lathyrane. Futhermore, their key anticancer mechanisms and protein targets of these compounds will be discussed. These natural diterpenoids could provide a reservoir for drug discovery.
Cytotoxic and Antimicrobial Compounds from the Marine-Derived Fungus, Penicillium Species
Authors: Youssef Diaa , Alahdal Abdulrahman
Published: February 2018

The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the previously reported cyclo(R-Pro–S-Phe) (3) and cyclo(R-Pro–R-Phe) (4). The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS). The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities.
Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection
Authors: Matta Murali , Beekman Christopher , Gandhi Adarsh , Narayanasamy Suresh , Thomas Christopher , Mohammad Adil , Stewart Sharron , Xu Lin , Chockalingam Ashok , Shea Katherine , Patel Vikram , Rouse Rodney
Published: February 2018

A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry method was developed and validated for the quantification of non-transferrin bound iron (NTBI), transferrin bound iron (TBI), drug bound iron (DI) and total iron (TI) in the same rat serum sample after intravenous (IV) administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit®). Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum. Isolated fractions were subjected to inductively-coupled mass spectrometric analysis after microwave digestion in 4% nitric acid. The reproducibility of the method was evaluated by precision and accuracy. The calibration curve demonstrated linearity from 5–500 ng/mL with a regression (r2) of more than 0.998. This method was effectively implemented to quantify rat pharmacokinetic study samples after intravenous administration of Ferrlecit®. The method was successfully applied to a pharmacokinetic (PK) study of Ferrlecit in rats. The colloidal iron followed first order kinetics with half-life of 2.2 h and reached background or pre-dose levels after 12 h post-dosing. The drug shown a clearance of 0.31 mL/min/kg and volume of distribution of 0.05 L/kg. 19.4 ± 2.4 mL/h/kg.
Advances in Targeted Pesticides with Environmentally Responsive Controlled Release by Nanotechnology
Authors: Huang Bingna , Chen Feifei , Shen Yue , Qian Kun , Wang Yan , Sun Changjiao , Zhao Xiang , Cui Bo , Gao Fei , Zeng Zhanghua , Cui Haixin
Published: February 2018

Pesticides are the basis for defending against major biological disasters and important for ensuring national food security. Biocompatible, biodegradable, intelligent, and responsive materials are currently an emerging area of interest in the field of efficient, safe, and green pesticide formulation. Using nanotechnology to design and prepare targeted pesticides with environmentally responsive controlled release via compound and chemical modifications has also shown great potential in creating novel formulations. In this review, special attention has been paid to intelligent pesticides with precise controlled release modes that can respond to micro-ecological environment changes such as light-sensitivity, thermo-sensitivity, humidity sensitivity, soil pH, and enzyme activity. Moreover, establishing intelligent and controlled pesticide release technologies using nanomaterials are reported. These technologies could increase pesticide-loading, improve the dispersibility and stability of active ingredients, and promote target ability.
Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis
Authors: Baldassarre Maria , Di Mauro Antonio , Tafuri Silvio , Rizzo Valentina , Gallone Maria , Mastromarino Paola , Capobianco Daniela , Laghi Luca , Zhu Chenglin , Capozza Manuela , Laforgia Nicola
Published: February 2018

Introduction: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx®, Visbiome®, DeSimone Formulation®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo. Methods: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426). Results: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21, 26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported. Conclusions: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants.
Dietary Inflammatory Index and Cardiovascular Risk and Mortality—A Meta-Analysis
Authors: Shivappa Nitin , Godos Justyna , Hébert James , Wirth Michael , Piuri Gabriele , Speciani Attilio , Grosso Giuseppe
Published: February 2018

Diet and chronic inflammation have been suggested to be risk factors in the development of cardiovascular disease (CVD) and related mortality. The possible link between the inflammatory potential of diet measured through the Dietary Inflammatory Index (DII®) and CVD has been investigated in several populations across the world. The aim of this study was to conduct a meta-analysis on studies exploring this association. Data from 14 studies were eligible, of which two were case-control, eleven were cohort, and one was cross-sectional. Results from the random-effects meta-analysis showed a positive association between increasing DII, indicating a pro-inflammatory diet, and CVD. Individuals in the highest versus the lowest (reference) DII category showed a 36% increased risk of CVD incidence and mortality, with moderate evidence of heterogeneity (relative risk (RR) = 1.36, 95% confidence interval (CI): 1.19, 1.57; heterogeneity index I2 = 69%, p < 0.001). When analyzed as a continuous variable, results showed an increased risk of CVD risk and mortality of 8% for each one-point increase in the DII score. Results remained unchanged when analyses were restricted to the prospective studies. Results of our meta-analysis support the importance of adopting a healthier anti-inflammatory diet for preventing CVD incidence and related mortality. In conclusion, a pro-inflammatory diet is associated with increased risk of CVD and CVD mortality. These results further substantiate the utility of DII as tool to characterize the inflammatory potential of diet and to predict CVD incidence and mortality.
Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice
Authors: Chung Kyung-Sook , Cheon Se-Yun , Roh Seong-Soo , Lee Minho , An Hyo-Jin
Published: February 2018

Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG) on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF)-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα), leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2) family and inhibitors of apoptosis proteins (IAPs), in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.
Pilot Study on Mass Spectrometry–Based Analysis of the Proteome of CD34+CD123+ Progenitor Cells for the Identification of Potential Targets for Immunotherapy in Acute Myeloid Leukemia
Authors: Schmidt Johannes , Rücker-Braun Elke , Heidrich Katharina , Von Bonin Malte , Stölzel Friedrich , Thiede Christian , Middeke Jan , Ehninger Gerhard , Bornhäuser Martin , Schetelig Johannes , Schubert Kristin , Von Bergen Martin , Heidenreich Falk
Published: February 2018

Targeting of leukemic stem cells with specific immunotherapy would be an ideal approach for the treatment of myeloid malignancies, but suitable epitopes are unknown. The comparative proteome-level characterization of hematopoietic stem and progenitor cells from healthy stem cell donors and patients with acute myeloid leukemia has the potential to reveal differentially expressed proteins which can be used as surface-markers or as proxies for affected molecular pathways. We employed mass spectrometry methods to analyze the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia. As a reference, CD34+CD123+ normal hematopoietic progenitor cells from five healthy, granulocyte-colony stimulating factor (G-CSF) mobilized stem cell donors were analyzed. In this Tandem Mass Tag (TMT) 10-plex labelling–based approach, 2070 proteins were identified with 171 proteins differentially abundant in one or both cellular compartments. This proof-of-principle-study demonstrates the potential of mass spectrometry to detect differentially expressed proteins in two compartment fractions of the entire proteome of leukemic stem cells, compared to their non-malignant counterparts. This may contribute to future immunotherapeutic target discoveries and individualized AML patient characterization.
Against Vaiṣṇava Deviance: Brāhmaṇical and Bhadralok Alliance in Bengal
Authors: Wong Lucian
Published: February 2018

This article sets out to problematise the notion that late nineteenth and early twentieth century Vaiṣṇava anti-sahajiyā polemics can be taken as a definitive index of colonial wrought rupture within Gauḍīya Vaiṣṇavism. It proceeds by (1) drawing attention to oblique, yet unmistakably polemical, forms of response to sahajiyā currents in pre-colonial Gauḍīya literature that are indicative of a movement towards a brāhmaṇically-aligned Vaiṣṇava normativity; and (2) highlighting how this movement towards normativity was further fostered in colonial times by Gauḍīya gosvāmī types, who were often extensively involved in bhadralok Vaiṣṇava domains.
Interrogating the Comparative Method: Whither, Why, and How?1
Authors: Holdrege Barbara
Published: February 2018

This essay seeks to illuminate the problematics, methods, and dynamics of comparison by interrogating how certain analytical categories in the study of religion, such as scripture and the body, can be fruitfully reimagined through a comparative analysis of their Hindu and Jewish instantiations. I consider a range of issues that are critical to any productive comparative study, and I reflect more specifically on the principal components of my own comparative method in light of Oliver Freiberger’s analytical framework: the goals of comparative analysis; the modes of comparison; the parameters that define the scope and the scale of the comparative inquiry; and the operations involved in the comparative process, beginning with selection of the specific traditions and analytical categories to be addressed and formulation of the organizational design of the study and culminating in the re-visioned categories and models in the study of religion that constitute the fruits of the comparative inquiry.
Longevity Risk Management and the Development of a Value-Based Longevity Index
Authors: Chang Yang , Sherris Michael
Published: February 2018

The design and development of post-retirement income products require the assessment of longevity risk, as well as a basis for hedging these risks. Most indices for longevity risk are age-period based. We develop and assess a cohort-based value index for life insurers and pension funds to manage longevity risk. There are two innovations in the development of this index. Firstly, the underlying variables of most existing longevity indices are based on mortality experience only. The value index is based on the present value of future cash flow obligations, capturing all the risks in retirement income products. We use the index to manage both longevity risk and interest rate risk. Secondly, we capture historical dependencies between ages and cohorts with a cohort-based stochastic mortality model. We achieve this by introducing age-dependent model parameters. With our mortality model, we obtain realistic cohort correlation structures and improve the fitting performance, particularly for very old ages.
Evaluation of Coastal Sea Level Offshore Hong Kong from Jason-2 Altimetry
Authors: Xu Xi-Yu , Birol Florence , Cazenave Anny
Published: February 2018

As altimeter satellites approach coastal areas, the number of valid sea surface height measurements decrease dramatically because of land contamination. In recent years, different methodologies have been developed to recover data within 10–20 km from the coast. These include computation of geophysical corrections adapted to the coastal zone and retracking of raw radar echoes. In this paper, we combine for the first time coastal geophysical corrections and retracking along a Jason-2 satellite pass that crosses the coast near the Hong-Kong tide gauge. Six years and a half of data are analyzed, from July 2008 to December 2014 (orbital cycles 1–238). Different retrackers are considered, including the ALES retracker and the different retrackers of the PISTACH products. For each retracker, we evaluate the quality of the recovered sea surface height by comparing with data from the Hong Kong tide gauge (located 10 km away). We analyze the impact of the different geophysical corrections available on the result. We also compute sea surface height bias and noise over both open ocean (>10 km away from coast) and coastal zone (within 10 km or 5 km coast-ward). The study shows that, in the Hong Kong area, after outlier removal, the ALES retracker performs better in the coastal zone than the other retrackers, both in terms of noise level and trend uncertainty. It also shows that the choice of the ocean tide solution has a great impact on the results, while the wet troposphere correction has little influence. By comparing short-term trends computed over the 2008.5–2014 time span, both in the coastal zone and in the open ocean (using the Climate Change Initiative sea level data as a reference), we find that the coastal sea level trend is about twice the one observed further offshore. It suggests that in the Hong Kong region, the short-term sea level trend significantly increases when approaching the coast.
Achieving Crossed Strong Barrier Coverage in Wireless Sensor Network
Authors: Han Ruisong , Yang Wei , Zhang Li
Published: February 2018

Barrier coverage has been widely used to detect intrusions in wireless sensor networks (WSNs). It can fulfill the monitoring task while extending the lifetime of the network. Though barrier coverage in WSNs has been intensively studied in recent years, previous research failed to consider the problem of intrusion in transversal directions. If an intruder knows the deployment configuration of sensor nodes, then there is a high probability that it may traverse the whole target region from particular directions, without being detected. In this paper, we introduce the concept of crossed barrier coverage that can overcome this defect. We prove that the problem of finding the maximum number of crossed barriers is NP-hard and integer linear programming (ILP) is used to formulate the optimization problem. The branch-and-bound algorithm is adopted to determine the maximum number of crossed barriers. In addition, we also propose a multi-round shortest path algorithm (MSPA) to solve the optimization problem, which works heuristically to guarantee efficiency while maintaining near-optimal solutions. Several conventional algorithms for finding the maximum number of disjoint strong barriers are also modified to solve the crossed barrier problem and for the purpose of comparison. Extensive simulation studies demonstrate the effectiveness of MSPA.
Potential and Limitations of an Improved Method to Produce Dynamometric Wheels
Authors: Bueno-López José , Cardenal Jesús , Deibe Álvaro , García de Jalón Javier
Published: February 2018

A new methodology for the estimation of tyre-contact forces is presented. The new procedure is an evolution of a previous method based on harmonic elimination techniques developed with the aim of producing low cost dynamometric wheels. While the original method required stress measurement in many rim radial lines and the fulfillment of some rigid conditions of symmetry, the new methodology described in this article significantly reduces the number of required measurement points and greatly relaxes symmetry constraints. This can be done without compromising the estimation error level. The reduction of the number of measuring radial lines increases the ripple of demodulated signals due to non-eliminated higher order harmonics. Therefore, it is necessary to adapt the calibration procedure to this new scenario. A new calibration procedure that takes into account angular position of the wheel is completely described. This new methodology is tested on a standard commercial five-spoke car wheel. Obtained results are qualitatively compared to those derived from the application of former methodology leading to the conclusion that the new method is both simpler and more robust due to the reduction in the number of measuring points, while contact forces’ estimation error remains at an acceptable level.
Sub-THz Imaging Using Non-Resonant HEMT Detectors
Authors: Delgado-Notario Juan , Velazquez-Perez Jesus , Meziani Yahya , Fobelets Kristel
Published: February 2018

Plasma waves in gated 2-D systems can be used to efficiently detect THz electromagnetic radiation. Solid-state plasma wave-based sensors can be used as detectors in THz imaging systems. An experimental study of the sub-THz response of II-gate strained-Si Schottky-gated MODFETs (Modulation-doped Field-Effect Transistor) was performed. The response of the strained-Si MODFET has been characterized at two frequencies: 150 and 300 GHz: The DC drain-to-source voltage transducing the THz radiation (photovoltaic mode) of 250-nm gate length transistors exhibited a non-resonant response that agrees with theoretical models and physics-based simulations of the electrical response of the transistor. When imposing a weak source-to-drain current of 5 μA, a substantial increase of the photoresponse was found. This increase is translated into an enhancement of the responsivity by one order of magnitude as compared to the photovoltaic mode, while the NEP (Noise Equivalent Power) is reduced in the subthreshold region. Strained-Si MODFETs demonstrated an excellent performance as detectors in THz imaging.
EDDA: An Efficient Distributed Data Replication Algorithm in VANETs
Authors: Zhu Junyu , Huang Chuanhe , Fan Xiying , Guo Sipei , Fu Bin
Published: February 2018

Efficient data dissemination in vehicular ad hoc networks (VANETs) is a challenging issue due to the dynamic nature of the network. To improve the performance of data dissemination, we study distributed data replication algorithms in VANETs for exchanging information and computing in an arbitrarily-connected network of vehicle nodes. To achieve low dissemination delay and improve the network performance, we control the number of message copies that can be disseminated in the network and then propose an efficient distributed data replication algorithm (EDDA). The key idea is to let the data carrier distribute the data dissemination tasks to multiple nodes to speed up the dissemination process. We calculate the number of communication stages for the network to enter into a balanced status and show that the proposed distributed algorithm can converge to a consensus in a small number of communication stages. Most of the theoretical results described in this paper are to study the complexity of network convergence. The lower bound and upper bound are also provided in the analysis of the algorithm. Simulation results show that the proposed EDDA can efficiently disseminate messages to vehicles in a specific area with low dissemination delay and system overhead.