bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple Equations for Cost of Premature Failure of Flexible Pavements in Low-Volume Roads
Authors: Praticò Filippo Giammaria
Published: July 2015

The performance of low-volume roads depends mainly on layer-bearing capacity and surface properties (friction, drainability, and acoustic absorption). Furthermore, in many projects different layers are constructed by different contractors. Thus, research is needed to develop reliable contracts and acceptance criteria for pavements, taking into account a variety of characteristics and layers. The goal of the study described in this paper was twofold: (a) to set up a method (algorithm) well-grounded in logic and based on life-cycle cost analysis to derive pay adjustments (PAs), that is, penalties or bonuses, when multiple layers, qualities, or both can be defective and (b) to derive a new set of equations for the straightforward derivation of PAs from position indicators (i.e., averages) to synergistically meet practitioners' needs and allow for advanced approaches. A method based on life-cycle cost analysis and the superposition principle was formulated and applied. It can also be applied to low-volume roads (for which environmental issues can suggest the use of innovative solutions and premium surfaces, for example, porous asphalt concretes) and high-volume roads. The model presented provides a straightforward process that comes complete with a full array of equations tailored specifically for practitioners. Analyses and applications have demonstrated that the model is able to provide a solution that is well-grounded in logic, even in cases in which more layers and premium characteristics are involved.
Development of Condition Indicator for Managing Sealed Rural Road Networks
Authors: Rivera Felipe , Chamorro Alondra , Lucero Robinson , Aravena Claudio
Published: July 2015

Rural roads may be defined as low-volume roads that provide access and mobility to rural populations. In developing countries they commonly represent 80% of the total road network length and play a key role in economic and social development. Rural roads are divided into unsealed (gravel and earth) and sealed roads (roads with thin bituminous surfaces and stabilized roads). Network management methods recommend the use of objective condition evaluations, such as the pavement condition index and the unpaved roads condition indicator, to assist in decision making. However, none of these indicators properly apply to sealed rural roads; the performance of these roads is different because of climate and traffic demands. The lack of an objective indicator specially calibrated for sealed rural roads was addressed in this study. The main goal was to calibrate a condition indicator for managing sealed rural road networks. As a result of the study, a condition indicator that was preliminarily developed for double treatment surfaces was successfully validated for thin bituminous surfaces. In addition, a stabilized roads condition index (SRCI) was developed on the basis of field evaluations of various surface distresses observed in stabilized roads, which were contrasted with the evaluations of an expert panel. Two forms of the SRCI were calibrated: with and without roughness. Finally, a qualitative scale ranging from very good condition to very poor condition was defined for thin bituminous surfaces and stabilized roads, on the basis of the effect of three types of climates and roads hierarchy.
Visual Assessment System for Rating Unsealed Roads
Authors: Huntington George , Ksaibati Khaled
Published: July 2015

During the past decade the Wyoming Technology Transfer Center has developed two complementary guides for visually assessing unsealed roads. The Ride Quality Rating Guide (RQRG) assesses the quality of an unsealed road's ride as perceived by the traveling public. The Gravel Roads Rating System (GRRS) provides standard evaluations of seven distresses, including potholes, rutting, washboards, loose aggregate, dust, crown, and roadside drainage. These guides have been used by many individuals on several projects. The guides described in this paper have been revised, updated, and improved several times. Manual methods are better than automated systems for assessing the condition of unsealed roads because the conditions can change quickly and sensors provide a measurement only for the path or location on which they are placed. Some methods are too simplified, and others are so complex that they require excessive resources to perform. The RQRG and the GRRS rating systems were developed by combining the use of photographs that illustrate the various rating levels resulting from different types and combinations of distresses, rating of seven distresses, use of a rating scale of 1 to 10 (a rating of ≤ 2 equals failed; a rating of ≥ 9 equals excellent), and simplified data collection procedures. The guides described are based most directly on the pavement surface evaluation and rating (PASER) manuals produced by Wisconsin's Transportation Information Center. The primary source is the Gravel PASER Manual, which rates roads as failed, poor, fair, good, or excellent; assigns numerical values of 1 to 5, respectively; and incorporates many of the same distresses as the guides presented in this paper.
Implementation of a Strain-Based Policy for Managing Weight Restrictions during the Spring
Authors: Kavanagh Leonnie , Shalaby Ahmed
Published: July 2015

A strain-based concept for managing spring weight restrictions (SWRs) on load levels and duration for low-volume roads was developed and applied to a low-volume road in Manitoba, Canada. Local fatigue and rutting damage models were used to predict limiting failure strains during the spring. The limiting failure strains were compared with predicted strains at SWR loads during the spring. On the basis of the results, the strain-based concept can be used to manage SWR load levels and the duration of SWR during the spring. Analysis of limiting failure strain should be applied to other pavements to verify the findings. For the strain-based concept to be practical, use of the Minnesota thawing index procedure based on climatic data is recommended for estimating the start of the SWR period.
Effect of Tire Configuration on the Performance of a Low-Volume Road Exposed to Heavy Axle Loads
Authors: Kalliainen Antti , Kolisoja Pauli , Haakana Ville
Published: July 2015

A series of response measurements was conducted at an instrumented low-volume road test site to determine the effects of different tire con-figurations of a heavy vehicle on the performance of the road structure. After the measurements were made, a true three-dimensional finite element model was developed with PLAXIS 3D 2012 software. The aim of the modeling was to find explanatory factors between the measured stress–strain relationships and confirmed permanent deformations, rutting in particular, at test site conditions. A model was created with reasonable material parameters. The model produced stress levels and road surface deflections that are comparable with the measured values. The mobilizing levels of shear strains seem to explain the notable permanent deformation at the test site despite the relatively low amount of heavy traffic. The shear strain levels can also be used as an efficient tool in evaluating the effects of other variables, such as road structural layers, construction materials, and environmental conditions, on the risk that structural deterioration of roads may occur when the intensity of loading increases.
Rethinking Rural Road Infrastructure Delivery
Authors: Muzira Stephen , de Díaz Damaris Hernández , Mota Bexi Francina Jimέnez
Published: July 2015

This paper presents a development case study on alternative thinking in rural road infrastructure delivery. The delivery advances the agendas of green growth, social inclusion, and cost-effectiveness. The empirical evidence presented in this case study focuses on 6 years of engagement in a specific road program—the Fourth Roads Rehabilitation and Maintenance Project—financed by the government of Nicaragua and the World Bank. “Green,” in this case, refers to the use of road construction materials that are clean, durable, and friendly to the environment. The use of adoquines, also known as concrete cobblestones or pavers, has proved to be an economic and environmentally friendly paving alternative at the secondary and tertiary classification levels. “Inclusion” refers to the empowerment of all citizens to participate in and benefit from the development process and the removal of barriers against those who are often excluded. The community development approach presented in this paper is implemented by specially formed community development modules or módulos comunitarios de adoquinados (MCAs). The benefits of the MCAs include the provision of short-term employment opportunities, the building of technical and entrepreneurial skills, and the engendering of a sense of ownership in and responsibility for the roads. This paper presents the MCA model, as applied on a large scale and in a cost-effective way without compromising quality or the speed of completion. The model is presented as a best practice that could be emulated in similar development work. More importantly, the authors aim to encourage a debate and challenge the “business as usual” approach to the choice of surfacing and the modality of delivery of rural road infrastructure.
Developing a Methodology to Assess and Prioritize Culvert Conditions on County Roads
Authors: Werbelow Wesley , Ksaibati Khaled
Published: July 2015

As hydraulic analysis technology increases and funds become more and more limited, the investment in culvert pipes becomes more substantial. However, even with this considerable investment, transportation agencies at every level in Wyoming, as well as other states, lack a formal methodology for assessing the condition of culvert pipes. Over time, as these pipes are ignored, they deteriorate without the government agency responsible for them taking necessary maintenance steps. In most cases, deteriorated states are not noticed until a larger problem arises. Counties in Wyoming are currently suffering a lack in funding. With an ample methodology in place, funds could be more adequately appropriated to pipes that are in need of maintenance. A systematic procedure for rating culverts would also aid in obtaining additional funding. Through an examination of the inspection procedures of other agencies across the nation and the Wyoming Department of Transportation's bridge inspection procedure, a comprehensive methodology for obtaining an overall pipe rating was developed. This methodology was implemented in Goshen County in Wyoming as a case study. The information and results from this study will be presented to various entities to facilitate statewide implementation. Local agencies in other states can implement the developed methodology with minor adjustments to reflect local conditions.
Percent within Limits for Hot-Mix Asphalt on Low-Volume Agricultural Roads in Egypt
Authors: Mahgoub Hesham , Basha Ismail
Published: July 2015

Replacement of traditional, method-based specifications, which use average deviations to determine payment for materials, with percent-within-limits (PWL) specifications is essential for highway agencies. The PWL approach recognizes that construction material properties follow a normal distribution. When the appropriate standard deviations for each material property are known, then upper and lower test limits can be set around the target value of the material property. The contractor's payment is then based on the percentage of the test results that fall within these upper and lower limits. The main goal of this research study was to investigate the potential of developing a PWL specification system for low-volume agricultural roads in Egypt that included the selection of the material properties used for payment, the frequency of testing for these properties, development of the standard deviations and specification limits, and development of a payment system. The proposed system is capable of providing guidelines for determining acceptable quality level, rejectable quality level, and appropriate sampling frequency with operating characteristic curves based on known standard deviation to achieve the recommended risk levels. Field data were used to evaluate the implications of implementing PWL and the risk between PWL and the current specifications.
Sensors of Infection: Viral Nucleic Acid PRRs in Fish
Authors: Poynter Sarah , Lisser Graeme , Monjo Andrea , DeWitte-Orr Stephanie
Published: July 2015

Viruses produce nucleic acids during their replication, either during genomic replication or transcription. These nucleic acids are present in the cytoplasm or endosome of an infected cell, or in the extracellular space to be sensed by neighboring cells during lytic infections. Cells have mechanisms of sensing virus-generated nucleic acids; these nucleic acids act as flags to the cell, indicating an infection requiring defense mechanisms. The viral nucleic acids are called pathogen-associated molecular patterns (PAMPs) and the sensors that bind them are called pattern recognition receptors (PRRs). This review article focuses on the most recent findings regarding nucleic acids PRRs in fish, including: Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), cytoplasmic DNA sensors (CDSs) and class A scavenger receptors (SR-As). It also discusses what is currently known of the downstream signaling molecules for each PRR family and the resulting antiviral response, either type I interferons (IFNs) or pro-inflammatory cytokine production. The review highlights what is known but also defines what still requires elucidation in this economically important animal. Understanding innate immune systems to virus infections will aid in the development of better antiviral therapies and vaccines for the future.
The Mitigative Potential of Urban Environments and Their Microclimates
Authors: Schiano-Phan Rosa , Weber Filippo , Santamouris Mat
Published: July 2015

Cities play a crucial role in climate change: More than 50% of the growing population lives in cities producing most of the global GDP but also 78% of greenhouse gases (GHG) responsible for climate change. Moreover, due to their highly modified land-use and intensive activities, cities are at the forefront of the most rapid environmental and climatic change ever experienced by mankind. Yet, cities’ potential to mitigate both climate change and their own environment is underexploited. This paper explores ideas related to the potential of urban environments to modify their microclimates, reflecting on the overlapping potential between mitigative and adaptive actions. These actions in cities can not only tackle some of the largest contributing factors to global climate change but offer short- to medium-term benefits that could drive more immediate socioeconomic and behavioral changes. This review proposes and discusses a new preliminary definition of urban environments as microclimate modifiers—Mitigative urban Environments and Microclimates (MitEM)—and calls for further research into: (a) inter-connecting the full range of mitigative and adaptive initiatives already being undertaken in many cities and maximizing their input systemically; (b) developing a common and holistic definition of MitEM; (c) promoting its uptake at policy level and amongst the key stakeholders, based on its social and public value beyond the environmental.
Claudin11 Promoter Hypermethylation Is Frequent in Malignant Melanoma of the Skin, but Uncommon in Nevus Cell Nevi
Authors: Walesch Sara , Richter Antje , Helmbold Peter , Dammann Reinhard
Published: July 2015

Epigenetic inactivation of tumor-related genes is an important characteristic in the pathology of human cancers, including melanomagenesis. We analyzed the epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the skin, including six melanoma cell lines, 39 primary melanoma, 41 metastases of MM and 52 nevus cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19 out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases, but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003, respectively). Moreover, a significant increase in the methylation level of CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003). Methylation of CLDN11 was significantly more frequent in skin metastases (79%) compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found in five out of six MM cell lines (83%) and its promoter hypermethylation correlated with a reduced expression. Treatment of MM cell lines with a DNA methylation inhibitor reactivated CLDN11 transcription by its promoter demethylation. In summary, CLDN11 proved to be an epigenetically inactivated tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level represents a potential tool for assisting in the discrimination between malignant melanoma and nevus cell nevi.
Surfactant-Template Preparation of Polyaniline Semi-Tubes for Oxygen Reduction
Authors: Zhang Shiming , Chen Shengli
Published: July 2015

Nitrogen and metal doped nanocarbons derived from polyaniline (PANI) have been widely explored as electrocatalysts for the oxygen reduction reaction (ORR) in fuel cells. In this work, we report surfactant-template synthesis of PANI nanostructures and the ORR electrocatalysts derived from them. By using cationic surfactant such as the cetyl trimethyl ammonium bromide (CTAB) as the template and the negatively charged persulfate ions as the oxidative agent to stimulate the aniline polymerization in the micelles of CTAB, PANI with a unique 1-D semi-tubular structure can be obtained. The semi-tubular structure can be maintained even after high-temperature treatment at 900 °C, which yields materials exhibiting promising ORR activity.
The Role of Human Milk Immunomodulators in Protecting Against Viral Bronchiolitis and Development of Chronic Wheezing Illness
Authors: Dixon Dani-Louise
Published: July 2015

Infants who are breastfed are at an immunological advantage when compared with formula fed infants, evidenced by decreased incidence of infections and diminished propensity for long term conditions, including chronic wheeze and/or asthma. Exclusive breastfeeding reduces the duration of hospital admission, risk of respiratory failure and requirement for supplemental oxygen in infants hospitalised with bronchiolitis suggesting a potentially protective mechanism. This review examines the evidence and potential pathways for protection by immunomodulatory factors in human milk against the most common viral cause of bronchiolitis, respiratory syncytial virus (RSV), and subsequent recurrent wheeze in infants. Further investigations into the interplay between respiratory virus infections such as RSV and how they affect, and are affected by, human milk immunomodulators is necessary if we are to gain a true understanding of how breastfeeding protects many infants but not all against infections, and how this relates to long-term protection against conditions such as chronic wheezing illness or asthma.
Adverse-Mode FFF: Multi-Force Ideal Retention Theory
Authors: Shendruk Tyler , Slater Gary
Published: July 2015

A novel field-flow fractionation (FFF) technique, in which two opposing external forces act on the solute particles, is proposed. When the two external forces are sufficiently strong and scale differently as a function of the solutes’ property of interest (such as the solute particle size), a sharp peak in the retention ratio (dramatic drop in elution time) is predicted to exist. Because the external forces oppose one another, we refer to this novel technique as adverse-mode FFF. The location of this peak is theoretically predicted and its ideal width estimated. The peak can become quite sharp by simultaneously increasing the strength of both fields, suggesting that adverse-mode FFF could be a useful technique for accurately measuring single species solute size.
A High Performance PSO-Based Global MPP Tracker for a PV Power Generation System
Authors: Chao Kuei-Hsiang
Published: July 2015

This paper aims to present an improved version of a typical particle swarm optimization (PSO) algorithm, such that the global maximum power point (MPP) on a P-V characteristic curve with multiple peaks can be located in an efficient and precise manner for a photovoltaic module array. A series of instrumental measurements are conducted on variously configured arrays built with SANYO HIP2717 PV modules, either unshaded, partially shaded, or malfunctioning, as the building blocks. There appear two, triple and quadruple peaks on the corresponding P-V characteristic curves. Subsequently, the tracking performance comparisons, made by some practical experiments, indicate the superiority of this improved MPP tracking algorithm over the typical one.
Ecological Conservation, Ecotourism, and Sustainable Management: The Case of Penang National Park
Authors: Kaffashi Sara , Radam Alias , Shamsudin Mad , Yacob Mohd , Nordin Nor
Published: July 2015

Penang National Park (PNP), as Malaysia’s smallest national park, is one of the few naturally forested areas left on Penang Island, in Peninsular Malaysia. The main objective was to analyse users’ preferences and willingness to pay to enhance improved management of PNP for the dual aim of conservation and recreation. Structural equation modelling (SEM) was used to analyse the formation of attitudes towards different aspects of PNP. Results showed that implementing enforcements with rules and regulations and imposing permits and charges on certain activities were the most influential variables of PNPs’ perceptions. The results of a random parameter logit model (RPL) demonstrated that visitors placed the highest value on having adequate information about PNP, and the second-highest value on improvements in the park’s ecological management. The welfare measure for improvement in management of PNP against status quo is estimated at about MYR 9. Results also showed that demand for better conservation and management of PNP is relatively price-inelastic. Simulations of the results showed, under a MYR10 admission fee, that improvement in management would have 96% of market share compared with status quo. This study concluded that visitor entrance fees can and ought to be introduced as a means of financing conservation initiatives and possibly preventing congestion.
EDAS: An Evaluation Prototype for Autonomic Event-Driven Adaptive Security in the Internet of Things
Authors: Aman Waqas , Snekkenes Einar
Published: July 2015

In Internet of Things (IoT), the main driving technologies are considered to be tiny sensory objects. These objects cannot host traditional preventive and detective technologies to provide protection against the increasing threat sophistication. Furthermore, these solutions are limited to analyzing particular contextual information, for instance network information or files, and do not provide holistic context for risk analysis and response. Analyzing a part of a situation may lead to false alarms and later to unnecessary and incorrect configurations. To overcome these concerns, we proposed an event-driven adaptive security (EDAS) model for IoT. EDAS aims to observe security events (changes) generated by various things in the monitored IoT environment, investigates any intentional or unintentional risks associated with the events and adapts to it autonomously. It correlates different events in time and space to reduce any false alarms and provides a mechanism to predict attacks before they are realized. Risks are responded to autonomically by utilizing a runtime adaptation ontology. The mitigation action is chosen after assessing essential information, such as the risk faced, user preferences, device capabilities and service requirements. Thus, it selects an optimal mitigation action in a particular adverse situation. The objective of this paper is to investigate EDAS feasibility and its aptitude as a real-world prototype in a remote patient monitoring context. It details how EDAS can be a practical choice for IoT-eHealth in terms of the security, design and implementation features it offers as compared to traditional security controls. We have explained the prototype’s major components and have highlighted the key technical challenges.
Hedgehog Signaling in Malignant Pleural Mesothelioma
Authors: Felley-Bosco Emanuela , Opitz Isabelle , Meerang Mayura
Published: July 2015

Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition.
The Prevalence of Dry Eye Syndrome’s and the Likelihood to Develop Sjögren’s Syndrome in Taiwan: A Population-Based Study
Authors: Yen Ju-Chuan , Hsu Chia-An , Li Yu-Chuan , Hsu Min-Huei
Published: July 2015

Background: Dry eye syndrome (DES) is one of the key clinical features and possibly an early clinical presentation of Sjögren’s syndrome (SS). We explore DES prevalence and assess the likelihood of DES patients to develop SS in Taiwan through the National Health Insurance Research Database (NHIRD). Methods: Through a cohort comparison study, longitudinal data from the NHIRD (2000 to 2008) in Taiwan was used to probe the prevalence of DES and the odds that DES patients would later develop SS. Results: The prevalence of DES in the present study is 4.87%. The incidence rates of developing SS were 4.8% for the DES group and 1.5% for comparison group. The median age and interquartile range of DES and comparison patients was 49.8 (10) and 48.7 (15) years old, respectively. The crude hazard ratio (with 95% confidence interval) for DES patients to develop SS was 3.13 (3.10–3.50) for the DES group, and the adjusted hazard ratio (with 95% confidence interval) was 3.64 (3.43–3.87). The observation period and interquartile range for DES and comparison patients to develop SS later were 1418 (781–2316) versus 1641 (971–2512) days respectively. Conclusions: DES patients carried a higher risk for developing SS (hazard ratio 3.13) and presented for SS 3.88 years earlier than comparison group patients in this study.
Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria
Authors: Inaoka Daniel , Shiba Tomoo , Sato Dan , Balogun Emmanuel , Sasaki Tsuyoshi , Nagahama Madoka , Oda Masatsugu , Matsuoka Shigeru , Ohmori Junko , Honma Teruki , Inoue Masayuki , Kita Kiyoshi , Harada Shigeharu
Published: July 2015

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.
β-Radiation Stress Responses on Growth and Antioxidative Defense System in Plants: A Study with Strontium-90 in Lemna minor
Authors: Van Hoeck Arne , Horemans Nele , Van Hees May , Nauts Robin , Knapen Dries , Vandenhove Hildegarde , Blust Ronny
Published: July 2015

In the following study, dose dependent effects on growth and oxidative stress induced by β-radiation were examined to gain better insights in the mode of action of β-radiation induced stress in plant species. Radiostrontium (90Sr) was used to test for β-radiation induced responses in the freshwater macrophyte Lemna minor. The accumulation pattern of 90Sr was examined for L. minor root and fronds separately over a seven-day time period and was subsequently used in a dynamic dosimetric model to calculate β-radiation dose rates. Exposing L. minor plants for seven days to a 90Sr activity concentration of 25 up to 25,000 kBq·L−1 resulted in a dose rate between 0.084 ± 0.004 and 97 ± 8 mGy·h−1. After seven days of exposure, root fresh weight showed a dose dependent decrease starting from a dose rate of 9.4 ± 0.5 mGy·h−1. Based on these data, an EDR10 value of 1.5 ± 0.4 mGy·h−1 was estimated for root fresh weight and 52 ± 17 mGy·h−1 for frond fresh weight. Different antioxidative enzymes and metabolites were further examined to analyze if β-radiation induces oxidative stress in L. minor.
Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists
Authors: Fratev Filip , Tsakovska Ivanka , Al Sharif Merilin , Mihaylova Elina , Pajeva Ilza
Published: July 2015

The structural and dynamical properties of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor have been broadly studied in its agonist state but little is known about the key features required for the receptor antagonistic activity. Here we report a series of molecular dynamics (MD) simulations in combination with free energy estimation of the recently discovered class of non-covalent PPARγ antagonists. Their binding modes and dynamical behavior are described in details. Two key interactions have been detected within the cavity between helices H3, H11 and the activation helix H12, as well as with H12. The strength of the ligand-amino acid residues interactions has been analyzed in relation to the specificity of the ligand dynamical and antagonistic features. According to our results, the PPARγ activation helix does not undergo dramatic conformational changes, as seen in other nuclear receptors, but rather perturbations that occur through a significant ligand-induced reshaping of the ligand-receptor and the receptor-coactivator binding pockets. The H12 residue Tyr473 and the charge clamp residue Glu471 play a central role for the receptor transformations. Our results also demonstrate that MD can be a helpful tool for the compound phenotype characterization (full agonists, partial agonists or antagonists) when insufficient experimental data are available.
A Review: Proteomics in Nasopharyngeal Carcinoma
Authors: Chen Ze-Tan , Liang Zhong-Guo , Zhu Xiao-Dong
Published: July 2015

Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.
Long-Term Visual Outcomes for a Treat and Extend Anti-Vascular Endothelial Growth Factor Regimen in Eyes with Neovascular Age-Related Macular Degeneration
Authors: Mrejen Sarah , Jung Jesse , Chen Christine , Patel Samir , Gallego-Pinazo Roberto , Yannuzzi Nicolas , Xu Luna , Marsiglia Marcela , Boddu Sucharita , Freund K.
Published: July 2015

With the advent of anti-vascular endothelial growth factor (VEGF) therapy, clinicians are now focused on various treatment strategies to better control neovascular age-related macular degeneration (NVAMD), a leading cause of irreversible blindness. Herein, we retrospectively reviewed consecutive patients with treatment-naïve NVAMD initially classified based on fluorescein angiography (FA) alone or with an anatomic classification utilizing both FA and optical coherence tomography (OCT) and correlated long-term visual outcomes of these patients treated with an anti-VEGF Treat-and-Extend Regimen (TER) with baseline characteristics including neovascular phenotype. Overall, 185 patients (210 eyes) were followed over an average of 3.5 years (range 1–6.6) with a retention rate of 62.9%, and visual acuity significantly improved with a TER that required a mean number of 8.3 (±1.6) (± standard deviation) intravitreal anti-VEGF injections/year (range 4–13). The number of injections and the anatomic classification were independent predictors of visual acuity at 6 months, 1, 2, 3 and 4 years. Patients with Type 1 neovascularization had better visual outcomes and received more injections than the other neovascular subtypes. There were no serious adverse events. A TER provided sustained long-term visual gains. Eyes with Type 1 neovascularization had better visual outcomes than those with other neovascular subtypes.
Correlation between Mechanical Properties with Specific Wear Rate and the Coefficient of Friction of Graphite/Epoxy Composites
Authors: Alajmi Mahdi , Shalwan Abdullah
Published: July 2015

The correlation between the mechanical properties of Fillers/Epoxy composites and their tribological behavior was investigated. Tensile, hardness, wear, and friction tests were conducted for Neat Epoxy (NE), Graphite/Epoxy composites (GE), and Data Palm Fiber/Epoxy with or without Graphite composites (GFE and FE). The correlation was made between the tensile strength, the modulus of elasticity, elongation at the break, and the hardness, as an individual or a combined factor, with the specific wear rate (SWR) and coefficient of friction (COF) of composites. In general, graphite as an additive to polymeric composite has had an eclectic effect on mechanical properties, whereas it has led to a positive effect on tribological properties, whilst date palm fibers (DPFs), as reinforcement for polymeric composite, promoted a mechanical performance with a slight improvement to the tribological performance. Statistically, this study reveals that there is no strong confirmation of any marked correlation between the mechanical and the specific wear rate of filler/Epoxy composites. There is, however, a remarkable correlation between the mechanical properties and the friction coefficient of filler/Epoxy composites.
Microscopic Characterization of Individual Submicron Bubbles during the Layer-by-Layer Deposition: Towards Creating Smart Agents
Authors: Kato Riku , Frusawa Hiroshi
Published: July 2015

We investigated the individual properties of various polyion-coated bubbles with a mean diameter ranging from 300 to 500 nm. Dark field microscopy allows one to track the individual particles of the submicron bubbles (SBs) encapsulated by the layer-by-layer (LbL) deposition of cationic and anionic polyelectrolytes (PEs). Our focus is on the two-step charge reversals of PE-SB complexes: the first is a reversal from negatively charged bare SBs with no PEs added to positive SBs encapsulated by polycations (monolayer deposition), and the second is overcharging into negatively charged PE-SB complexes due to the subsequent addition of polyanions (double-layer deposition). The details of these phenomena have been clarified through the analysis of a number of trajectories of various PE-SB complexes that experience either Brownian motion or electrophoresis. The contrasted results obtained from the analysis were as follows: an amount in excess of the stoichiometric ratio of the cationic polymers was required for the first charge-reversal, whereas the stoichiometric addition of the polyanions lead to the electrical neutralization of the PE-SB complex particles. The recovery of the stoichiometry in the double-layer deposition paves the way for fabricating multi-layered SBs encapsulated solely with anionic and cationic PEs, which provides a simple protocol to create smart agents for either drug delivery or ultrasound contrast imaging.
Structure and Effects of Cyanobacterial Lipopolysaccharides
Authors: Durai Prasannavenkatesh , Batool Maria , Choi Sangdun
Published: July 2015

Lipopolysaccharide (LPS) is a component of the outer membrane of mainly Gram-negative bacteria and cyanobacteria. The LPS molecules from marine and terrestrial bacteria show structural variations, even among strains within the same species living in the same environment. Cyanobacterial LPS has a unique structure, since it lacks heptose and 3-deoxy-d-manno-octulosonic acid (also known as keto-deoxyoctulosonate (KDO)), which are present in the core region of common Gram-negative LPS. In addition, the cyanobacterial lipid A region lacks phosphates and contains odd-chain hydroxylated fatty acids. While the role of Gram-negative lipid A in the regulation of the innate immune response through Toll-like Receptor (TLR) 4 signaling is well characterized, the role of the structurally different cyanobacterial lipid A in TLR4 signaling is not well understood. The uncontrolled inflammatory response of TLR4 leads to autoimmune diseases such as sepsis, and thus the less virulent marine cyanobacterial LPS molecules can be effective to inhibit TLR4 signaling. This review highlights the structural comparison of LPS molecules from marine cyanobacteria and Gram-negative bacteria. We discuss the potential use of marine cyanobacterial LPS as a TLR4 antagonist, and the effects of cyanobacterial LPS on humans and marine organisms.
Copahue Geothermal System: A Volcanic Environment with Rich Extreme Prokaryotic Biodiversity
Authors: Urbieta María , Porati Graciana , Segretín Ana , González-Toril Elena , Giaveno María , Donati Edgardo
Published: July 2015

The Copahue geothermal system is a natural extreme environment located at the northern end of the Cordillera de los Andes in Neuquén province in Argentina. The geochemistry and consequently the biodiversity of the area are dominated by the activity of the Copahue volcano. The main characteristic of Copahue is the extreme acidity of its aquatic environments; ponds and hot springs of moderate and high temperature as well as Río Agrio. In spite of being an apparently hostile location, the prokaryotic biodiversity detected by molecular ecology techniques as well as cultivation shows a rich and diverse environment dominated by acidophilic, sulphur oxidising bacteria or archaea, depending on the conditions of the particular niche studied. In microbial biofilms, found in the borders of the ponds where thermal activity is less intense, the species found are completely different, with a high presence of cyanobacteria and other photosynthetic species. Our results, collected during more than 10 years of work in Copahue, have enabled us to outline geomicrobiological models for the different environments found in the ponds and Río Agrio. Besides, Copahue seems to be the habitat of novel, not yet characterised autochthonous species, especially in the domain Archaea.
Calophyllolide Content in Calophyllum inophyllum at Different Stages of Maturity and Its Osteogenic Activity
Authors: Liu Wei-Hsien , Liu Yen-Wenn , Chen Zih-Fong , Chiou Wen-Fei , Tsai Ying-Chieh , Chen Chien-Chih
Published: July 2015

Calophyllum inophyllum is a coastal plant rich in natural substances. Its ingredients have been used for the development of an anti-human immunodeficiency virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the ethanol extract of the fruit was chromatographically separated using silica gel and Sephadex LH-20 columns to obtain the major compound, calophyllolide. The fruits were harvested from September to December in 2011; a quantitative analysis of the calophyllolide content was conducted using HPLC to explore the differences between the different parts of the fruit during the growing season. The results showed that in fruits of C. inophyllum, calophyllolide exists only in the nuts, and dried nuts contain approximately 2 mg·g−1 of calophyllolide. The calophyllolide levels in the nuts decreased during maturity. In addition, calophyllolide dose-dependently enhanced alkaline phosphatase (ALP) activity in murine osteoblastic MC3T3-E1 cells, without significant cytotoxicity. The expression of osteoblastic genes, ALP and osteocalcin (OCN), were increased by calophyllolide. Calophyllolide induced osteoblasts differentiation also evidenced by increasing mineralization and ALP staining.
Synthetic Development of New 3-(4-Arylmethylamino)butyl-5-arylidene-rhodanines under Microwave Irradiation and Their Effects on Tumor Cell Lines and against Protein Kinases
Authors: Dago Camille , Ambeu Christelle , Coulibaly Wacothon-Karime , Békro Yves-Alain , Mamyrbékova Janat , Defontaine Audrey , Baratte Blandine , Bach Stéphane , Ruchaud Sandrine , Guével Rémy , Ravache Myriam , Corlu Anne , Bazureau Jean-Pierre
Published: July 2015

A new route to 3-(4-arylmethylamino)butyl-5-arylidene-2-thioxo-1,3-thiazolidine-4-one 9 was developed in six steps from commercial 1,4-diaminobutane 1 as starting material. The key step of this multi-step synthesis involved a solution phase “one-pot two-steps” approach assisted by microwave dielectric from N-(arylmethyl)butane-1,4-diamine hydrochloride 6a–f (as source of the first point diversity) and commercial bis-(carboxymethyl)-trithiocarbonate reagent 7 for construction of the rhodanine platform. This platform was immediately functionalized by Knoevenagel condensation under microwave irradiation with a series of aromatic aldehydes 3 as second point of diversity. These new compounds were prepared in moderate to good yields and the fourteen synthetic products 9a–n have been obtained with a Z-geometry about their exocyclic double bond. These new 5-arylidene rhodanines derivatives 9a–n were tested for their kinase inhibitory potencies against four protein kinases: Human cyclin-dependent kinase 5-p25, HsCDK5-p25; porcine Glycogen Synthase Kinase-3, GSK-3α/β; porcine Casein Kinase 1, SsCK1 and human HsHaspin. They have also been evaluated for their in vitro inhibition of cell proliferation (HuH7 D12, Caco 2, MDA-MB 231, HCT 116, PC3, NCI-H727, HaCat and fibroblasts). Among of all these compounds, 9j presented selective micromolar inhibition activity on SsCK1 and 9i exhibited antitumor activities in the HuH7 D12, MDA-MBD231 cell lines.
Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome
Authors: Legeay Samuel , Rodier Marion , Fillon Laetitia , Faure Sébastien , Clere Nicolas
Published: July 2015

Obesity and being overweight are linked with a cluster of metabolic and vascular disorders that have been termed the metabolic syndrome. This syndrome promotes the incidence of cardiovascular diseases that are an important public health problem because they represent a major cause of death worldwide. Whereas there is not a universally-accepted set of diagnostic criteria, most expert groups agree that this syndrome is defined by an endothelial dysfunction, an impaired insulin sensitivity and hyperglycemia, dyslipidemia, abdominal obesity and hypertension. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in green tea are, in part, mediated by their flavonoid content, with particular benefits provided by members of this family such as epigallocatechin gallate (EGCG). Although their bioavailability is discussed, various studies suggest that EGCG modulates cellular and molecular mechanisms of various symptoms leading to metabolic syndrome. Therefore, according to in vitro and in vivo model data, this review attempts to increase our understanding about the beneficial properties of EGCG to prevent metabolic syndrome.
Analysis of Body Composition and Food Habits of Spanish Celiac Women
Authors: Churruca Itziar , Miranda Jonatan , Lasa Arrate , Bustamante María , Larretxi Idoia , Simon Edurne
Published: July 2015

The purpose of the present work was both to analyze composition of Spanish celiac women and to study the food habits and gluten-free diet of these celiac patients, in order to determine whether they achieve a balanced and healthy diet as well as to highlight nutritional qualitative and/or quantitative differences. 54 adult celiac women (34 ± 13 years) took part in the six-month study. Height, weight and body composition were measured. An analysis of energy consumption and of the macronutrient distribution of their diet was carried out. Their fulfillment of micronutrient intake recommendations was verified. Participants showed a Body Mass Index of 21.6 ± 2.4 kg/m2. Energy Intake was slightly lower than the Dietary Reference Intakes. Excessive protein apart from over-consumption of fat was observed. More than three quarters of participants consumed meat in excess. Carbohydrate consumption along with that of fiber was below recommended levels. Vitamin D, iron, and iodine had a low percentage of recommendation compliance. In general, participants followed the recommendations of dairy products and fruit intake whereas vegetable consumption was not enough for the vast majority. We conclude that although the diet of celiac women does not differ much from the diet of general population, some considerations, such as reducing fat and protein consumption and increasing fiber intake, must be taken into account.
Thermal Conductivity and Specific Heat Capacity of Dodecylbenzenesulfonic Acid-Doped Polyaniline Particles—Water Based Nanofluid
Authors: Chew Tze , Daik Rusli , Hamid Muhammad
Published: July 2015

Nanofluid has attracted great attention due to its superior thermal properties. In this study, chemical oxidative polymerization of aniline was carried out in the presence of dodecylbenzenesulfonic acid (DBSA) as a dopant. Particles of DBSA-doped polyaniline (DBSA-doped PANI) with the size range of 15 to 50 nm were obtained, as indicated by transmission electron microscope (TEM). Results of ultra violet-visible (UV-Vis) absorption and Fourier transform infrared (FTIR) spectroscopies as well as thermogravimetric analysis showed that PANI nanoparticles were doped with DBSA molecules. The doping level found was 36.8%, as calculated from elemental analysis data. Thermal conductivity of water was enhanced by 5.4% when dispersed with 1.0 wt% of DBSA-PANI nanoparticles. Specific heat capacity of water-based nanofluids decreased with increasing amount of DBSA-PANI nanoparticles.