bluuebunny/crossref_metadata_2025 huggingface dataset:
Pressure Transient Model of Water-Hydraulic Pipelines with Cavitation
Authors: Jiang Dan , Ren Cong , Zhao Tianyang , Cao Wenzhi
Published: March 2018

Transient pressure investigation of water-hydraulic pipelines is a challenge in the fluid transmission field, since the flow continuity equation and momentum equation are partial differential, and the vaporous cavitation has high dynamics; the frictional force caused by fluid viscosity is especially uncertain. In this study, due to the different transient pressure dynamics in upstream and downstream pipelines, the finite difference method (FDM) is adopted to handle pressure transients with and without cavitation, as well as steady friction and frequency-dependent unsteady friction. Different from the traditional method of characteristics (MOC), the FDM is advantageous in terms of the simple and convenient computation. Furthermore, the mechanism of cavitation growth and collapse are captured both upstream and downstream of the water-hydraulic pipeline, i.e., the cavitation start time, the end time, the duration, the maximum volume, and the corresponding time points. By referring to the experimental results of two previous works, the comparative simulation results of two computation methods are verified in experimental water-hydraulic pipelines, which indicates that the finite difference method shows better data consistency than the MOC.
Numerical Simulation of Early Age Cracking of Reinforced Concrete Bridge Decks with a Full-3D Multiscale and Multi-Chemo-Physical Integrated Analysis
Authors: Ishida Tetsuya , Pen Kolneath , Tanaka Yasushi , Kashimura Kosuke , Iwaki Ichiro
Published: March 2018

In November 2011, the Japanese government resolved to build “Revival Roads” in the Tohoku region to accelerate the recovery from the Great East Japan Earthquake of March 2011. Because the Tohoku region experiences such cold and snowy weather in winter, complex degradation from a combination of frost damage, chloride attack from de-icing agents, alkali–silica reaction, cracking and fatigue is anticipated. Thus, to enhance the durability performance of road structures, particularly reinforced concrete (RC) bridge decks, multiple countermeasures are proposed: a low water-to-cement ratio in the mix, mineral admixtures such as ground granulated blast furnace slag and/or fly ash to mitigate the risks of chloride attack and alkali–silica reaction, anticorrosion rebar and 6% entrained air for frost damage. It should be noted here that such high durability specifications may conversely increase the risk of early age cracking caused by temperature and shrinkage due to the large amounts of cement and the use of mineral admixtures. Against this background, this paper presents a numerical simulation of early age deformation and cracking of RC bridge decks with full 3D multiscale and multi-chemo-physical integrated analysis. First, a multiscale constitutive model of solidifying cementitious materials is briefly introduced based on systematic knowledge coupling microscopic thermodynamic phenomena and microscopic structural mechanics. With the aim to assess the early age thermal and shrinkage-induced cracks on real bridge deck, the study began with extensive model validations by applying the multiscale and multi-physical integrated analysis system to small specimens and mock-up RC bridge deck specimens. Then, through the application of the current computational system, factors that affect the generation and propagation of early age thermal and shrinkage-induced cracks are identified via experimental validation and full-scale numerical simulation on real RC slab decks.
Analysis of Network Attack and Defense Strategies Based on Pareto Optimum
Authors: Sun Yang , Xiong Wei , Yao Zhonghua , Moniz Krishna , Zahir Ahmed
Published: March 2018

Improving network security is a difficult problem that requires balancing several goals, such as defense cost and need for network efficiency, to achieve proper results. Modeling the network as a game and using optimization problems to select the best move in such a game can assist network administrators in determining an ideal defense strategy. However, most approaches for determining optimal game solutions tend to focus on either single objective games or merely scalarize the multiple objectives to a single of objective. In this paper, we devise a method for modeling network attacks in a zero-sum multi-objective game without scalarizing the objectives. We use Pareto Fronts to determine the most harmful attacks and Pareto Optimization to find the best defense against those attacks. By determining the optimal solutions through those means, we allow network administrators to make the final defense decision from a much smaller set of defense options. The included experiment uses minimum distance as selection method and compares the results with a minimax algorithm for the determination of the Nash Equilibrium. The proposed algorithm should help network administrators in search of a hands-on method of improving network security.
The Efficacy of Nile Tilapia (Oreochromis niloticus) Broodstock and Larval Immunization against Streptococcus agalactiae and Aeromonas hydrophila
Authors: Pasaribu Wesly , Sukenda Sukenda , Nuryati Sri
Published: March 2018

Streptococcus agalactiae and Aeromonas hydrophila have been recognized as the causative agents of mortality in tilapia larvae with single infection and coinfection. The objective of this study was to evaluate the efficacy of maternal transfer and offspring protection from the immunization of monovalent and bivalent vaccines on Nile tilapia (Oreochromis niloticus) broodstock and larval immunization. Four groups of broodstock were intraperitoneally injected with formalin killed whole-cells of S. agalactiae (Sa group), A. hydrophila (Ah group), the bivalent mixed vaccine of them (Biv group), and phosphate-buffered saline as a control (Pbs group). Immunization of the larvae produced from immunized broodstock with a bivalent vaccine (Biv1 group) and Pbs (Pbs1 group) was performed by immersion at 20 days after hatch. Larvae produced from the Pbs group were unvaccinated as the control (Pbs2 group). Changes in the specific antibody and relative percent survival were measured. The Sa and Ah groups that could increase specific antibodies and protection against pathogenic bacteria were challenged with the homologous bacteria. The Biv group stimulated and protected against both S. agalactiae and A. hydrophila. The specific antibody of the Biv1 group was higher than the Pbs1 and Pbs2 groups. The last observation in this study showed that the relative percent survival of the Biv group after challenged S. agalactiae, A. hydrophila, and coinfection were 74.74 ± 3.18%, 73.81 ± 8.58%, and 71.48 ± 5.70%, respectively. The use of bivalent vaccines on the broodstock and larvae may be a strategy to reduce mortality in Nile tilapia larvae caused by single pathogen infection of S. agalactiae and A. hydrophila, or coinfection with both S. agalactiae and A. hydrophila.
Correction: Littink, K. W.; et al. Autosomal Recessive NRL Mutations in Patients with Enhanced S-Cone Syndrome. Genes 2018, 9, 68
Authors: Littink Karin , Stappers Patricia , Riemslag Frans , Talsma Herman , Van Genderen Maria , Cremers Frans , Collin Rob , Van den Born L.
Published: March 2018

The authors wish to make the following correction to this paper [1]. [...]
Repetitive Rockfall Trajectory Testing
Authors: Volkwein Axel , Brügger Lucas , Gees Fabio , Gerber Werner , Krummenacher Barbara , Kummer Peter , Lardon Jessica , Sutter Tobias
Published: March 2018

Numerical simulations of rockfall trajectories are a standard procedure for evaluating rockfall hazards. For these simulations, corresponding software codes must be calibrated and evaluated based on field data. This study addresses methods of repeatable rockfall tests, and investigates whether it is possible to produce traceable and statistically analysable data. A testing series is described extensively covering how to conduct rockfall experiments and how certain elements of rockfall trajectories can be measured. The tests use acceleration and rotation sensors inside test blocks, a system to determine block positions over time, surveying measurements, and video recordings. All systems are evaluated regarding their usability in the field and for analyses. The highly detailed description of testing methods is the basis for sound understanding and reproducibility of the tests. This article serves as a reference for future publications and other rockfall field tests, both as a guide and as a basis for comparisons. First analyses deliver information on runout with a shadow angle ranging between 21 and 45 degrees for a slope consisting of homogeneous soft soil. A digital elevation model of the test site as well as point clouds of the used test blocks are part of this publication.
Generalized Unsafety Theory of Stress: Unsafe Environments and Conditions, and the Default Stress Response
Authors: Brosschot Jos , Verkuil Bart , Thayer Julian
Published: March 2018

Prolonged physiological stress responses form an important risk factor for disease. According to neurobiological and evolution-theoretical insights the stress response is a default response that is always “on” but inhibited by the prefrontal cortex when safety is perceived. Based on these insights the Generalized Unsafety Theory of Stress (GUTS) states that prolonged stress responses are due to generalized and largely unconsciously perceived unsafety rather than stressors. This novel perspective necessitates a reconstruction of current stress theory, which we address in this paper. We discuss a variety of very common situations without stressors but with prolonged stress responses, that are not, or not likely to be caused by stressors, including loneliness, low social status, adult life after prenatal or early life adversity, lack of a natural environment, and less fit bodily states such as obesity or fatigue. We argue that in these situations the default stress response may be chronically disinhibited due to unconsciously perceived generalized unsafety. Also, in chronic stress situations such as work stress, the prolonged stress response may be mainly caused by perceived unsafety in stressor-free contexts. Thus, GUTS identifies and explains far more stress-related physiological activity that is responsible for disease and mortality than current stress theories.
Neighborhood Variation of Sustainable Urban Morphological Characteristics
Authors: Lai Poh-Chin , Chen Si , Low Chien-Tat , Cerin Ester , Stimson Robert , Wong Pui
Published: March 2018

Compact cities and their urban forms have implications on sustainable city development because of high density urban settlement, increased accessibility, and a balanced land use mix. This paper uses quantitative means of understanding urban morphological characteristics with reference to the differing qualities of the urban form (i.e., street patterns, building volumes, land uses and greenery). The results, based on 89 neighborhood communities of Hong Kong, show varying degrees of regional differences in the urban built form supported by numerical statistics and graphical illustrations. This paper offers empirical evidence on some morphological characteristics that can be estimated objectively using modern geospatial technologies and applied universally to inform urban planning. However, more studies linking these quantifiable measures of the physical form with sustainable urban living are needed to account for human comfort in the totality of environmental, social, and economic responsibilities.
Wetlands and Malaria in the Amazon: Guidelines for the Use of Synthetic Aperture Radar Remote-Sensing
Authors: Catry Thibault , Li Zhichao , Roux Emmanuel , Herbreteau Vincent , Gurgel Helen , Mangeas Morgan , Seyler Frédérique , Dessay Nadine
Published: March 2018

The prevention and control of mosquito-borne diseases, such as malaria, are important health issues in tropical areas. Malaria transmission is a multi-scale process strongly controlled by environmental factors, and the use of remote-sensing data is suitable for the characterization of its spatial and temporal dynamics. Synthetic aperture radar (SAR) is well-adapted to tropical areas, since it is capable of imaging independent of light and weather conditions. In this study, we highlight the contribution of SAR sensors in the assessment of the relationship between vectors, malaria and the environment in the Amazon region. More specifically, we focus on the SAR-based characterization of potential breeding sites of mosquito larvae, such as man-made water collections and natural wetlands, providing guidelines for the use of SAR capabilities and techniques in order to optimize vector control and malaria surveillance. In light of these guidelines, we propose a framework for the production of spatialized indicators and malaria risk maps based on the combination of SAR, entomological and epidemiological data to support malaria risk prevention and control actions in the field.
Use of Metabolomics as a Complementary Omic Approach to Implement Risk Criteria for First-Degree Relatives of Gastric Cancer Patients
Authors: Corona Giuseppe , Cannizzaro Renato , Miolo Gianmaria , Caggiari Laura , De Zorzi Mariangela , Repetto Ombretta , Steffan Agostino , De Re Valli
Published: March 2018

A positive family history is a strong and consistently reported risk factor for gastric cancer (GC). So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC. The main purpose of this study was to investigate serum metabolomic profiles to find additional biomarkers that could be integrated with serum PGs and G17 to improve the diagnosis of GC and the selection of first-degree relatives (FDR) at higher risk of GC development. Serum metabolomic profiles included 188 serum metabolites, covering amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, sphingomyelins and hexoses. Serum metabolomic profiles were performed with tandem mass spectrometry using the Biocrates AbsoluteIDQ p180 kit. The initial cohort (training set) consisted of n = 49 GC patients and n = 37 FDR. Differential metabolomic signatures among the two groups were investigated by univariate and multivariate partial least square differential analysis. The most significant metabolites were further selected and validated in an independent group of n = 22 GC patients and n = 17 FDR (validation set). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic power and the optimal cut-off for each of the discriminant markers. Multivariate analysis was applied to associate the selected serum metabolites, PGs, G17 and risk factors such as age, gender and Helicobacter pylori (H. pylori) infection with the GC and FDR has been performed and an integrative risk prediction algorithm was developed. In the training set, 40 metabolites mainly belonging to phospholipids and acylcarnitines classes were differentially expressed between GC and FDR. Out of these 40 metabolites, 9 were further confirmed in the validation set. Compared with FDR, GC patients were characterized by lower levels of hydroxylated sphingomyelins (SM(OH)22:1, SM(OH)22:2, SM(OH)24:1) and phosphatidylcholines (PC ae 40:1, PC ae 42:2, PC ae 42:3) and by higher levels of acylcarnitines derivatives (C2, C16, C18:1). The specificity and sensitivity of the integrative risk prediction analysis of metabolites for GC was 73.47% and 83.78% respectively with an area under the curve of the ROC curve of 0.811 that improves to 0.90 when metabolites were integrated with the serum PGs. The predictive risk algorithm composed of the C16, SM(OH)22:1 and PG-II serum levels according to the age of individuals, could be used to stratify FDR at high risk of GC development, and then this can be addressed with diagnostic gastroscopy.
Antisense Oligonucleotide-Based Splicing Correction in Individuals with Leber Congenital Amaurosis due to Compound Heterozygosity for the c.2991+1655A>G Mutation in CEP290
Authors: Duijkers Lonneke , Van den Born L. , Neidhardt John , Bax Nathalie , Pierrache Laurence , Klevering B. , Collin Rob , Garanto Alejandro
Published: March 2018

Leber congenital amaurosis (LCA) is a rare inherited retinal disorder affecting approximately 1:50,000 people worldwide. So far, mutations in 25 genes have been associated with LCA, with CEP290 (encoding the Centrosomal protein of 290 kDa) being the most frequently mutated gene. The most recurrent LCA-causing CEP290 mutation, c.2991+1655A>G, causes the insertion of a pseudoexon into a variable proportion of CEP290 transcripts. We previously demonstrated that antisense oligonucleotides (AONs) have a high therapeutic potential for patients homozygously harbouring this mutation, although to date, it is unclear whether rescuing one single allele is enough to restore CEP290 function. Here, we assessed the AON efficacy at RNA, protein and cellular levels in samples that are compound heterozygous for this mutation, together with a protein-truncating mutation in CEP290. We demonstrate that AONs can efficiently restore splicing and increase protein levels. However, due to a high variability in ciliation among the patient-derived cell lines, the efficacy of the AONs was more difficult to assess at the cellular level. This observation points towards the importance of the severity of the second allele and possibly other genetic variants present in each individual. Overall, AONs seem to be a promising tool to treat CEP290-associated LCA, not only in homozygous but also in compound heterozygous carriers of the c.2991+1655A>G variant.
Selection and Characterization of a DNA Aptamer Specifically Targeting Human HECT Ubiquitin Ligase WWP1
Authors: Tucker Wesley , Kinghorn Andrew , Fraser Lewis , Cheung Yee-Wai , Tanner Julian
Published: March 2018

Nucleic acid aptamers hold promise as therapeutic tools for specific, tailored inhibition of protein targets with several advantages when compared to small molecules or antibodies. Nuclear WW domain containing E3 ubiquitin ligase 1 (WWP1) ubiquitin ligase poly-ubiquitinates Runt-related transcription factor 2 (Runx2), a key transcription factor associated with osteoblast differentiation. Since WWP1 and an adapter known as Schnurri-3 are negative regulators of osteoblast function, the disruption of this complex has the potential to increase bone deposition for osteoporosis therapy. Here, we develop new DNA aptamers that bind and inhibit WWP1 then investigate efficacy in an osteoblastic cell culture. DNA aptamers were selected against three different truncations of the HECT domain of WWP1. Aptamers which bind specifically to a C-lobe HECT domain truncation were observed to enrich during the selection procedure. One particular DNA aptamer termed C3A was further evaluated for its ability to bind WWP1 and inhibit its ubiquitination activity. C3A showed a low µM binding affinity to WWP1 and was observed to be a non-competitive inhibitor of WWP1 HECT ubiquitin ligase activity. When SaOS-2 osteoblastic cells were treated with C3A, partial localization to the nucleus was observed. The C3A aptamer was also demonstrated to specifically promote extracellular mineralization in cell culture experiments. The C3A aptamer has potential for further development as a novel osteoporosis therapeutic strategy. Our results demonstrate that aptamer-mediated inhibition of protein ubiquitination can be a novel therapeutic strategy.
The ADAMTS5 Metzincin Regulates Zebrafish Somite Differentiation
Authors: Dancevic Carolyn , Gibert Yann , Berger Joachim , Smith Adam , Liongue Clifford , Stupka Nicole , Ward Alister , McCulloch Daniel
Published: March 2018

The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated.
Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach
Authors: Sarin Navin , Engel Florian , Rothweiler Florian , Cinatl Jindrich , Michaelis Martin , Frötschl Roland , Fröhlich Holger , Kalayda Ganna
Published: March 2018

The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell’s reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array for relevant gene candidates. By combining statistical methods with available gene annotations and without a previously defined hypothesis HRas, MAPK14 (p38), CCL2, DOK1 and PTK2B were identified as genes possibly relevant for cisplatin resistance. These and related genes were further validated on transcriptome (qRT-PCR) and proteome (Western blot) level to select candidates contributing to resistance. HRas, p38, CCL2, DOK1, PTK2B and JNK3 were integrated into a model of resistance-associated signalling alterations describing differential gene and protein expression between cisplatin-sensitive and -resistant cells in reaction to cisplatin exposure.
Structural Biology of the TNFα Antagonists Used in the Treatment of Rheumatoid Arthritis
Authors: Lim Heejin , Lee Sang , Lee Hyun , Lee Jee , Son Ji , Shin Woori , Heo Yong-Seok
Published: March 2018

The binding of the tumor necrosis factor α (TNFα) to its cognate receptor initiates many immune and inflammatory processes. The drugs, etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), certolizumab-pegol (Cimzia®), and golimumab (Simponi®), are anti-TNFα agents. These drugs block TNFα from interacting with its receptors and have enabled the development of breakthrough therapies for the treatment of several autoimmune inflammatory diseases, including rheumatoid arthritis, Crohn’s disease, and psoriatic arthritis. In this review, we describe the latest works on the structural characterization of TNFα–TNFα antagonist interactions related to their therapeutic efficacy at the atomic level. A comprehensive comparison of the interactions of the TNFα blockers would provide a better understanding of the molecular mechanisms by which they neutralize TNFα. In addition, an enhanced understanding of the higher order complex structures and quinary structures of the TNFα antagonists can support the development of better biologics with the improved pharmacokinetic properties. Accumulation of these structural studies can provide a basis for the improvement of therapeutic agents against TNFα for the treatment of rheumatoid arthritis and other autoimmune inflammatory diseases in which TNFα plays an important role in pathogenesis.
Oxidative DNA Damage and Carotid Intima Media Thickness as Predictors of Cardiovascular Disease in Prediabetic Subjects
Authors: Mahat Roshan , Singh Neelima , Gupta Akshara , Rathore Vedika
Published: March 2018

Prediabetes is considered as a risk factor for the development of diabetes mellitus and cardiovascular disease. The present study was conducted with the aim of finding out the relationship between oxidative DNA damage and carotid intima media thickness for the prediction of cardiovascular disease in prediabetic subjects. The study included 100 prediabetic subjects and 100 normal individuals as controls. In both cases and controls, 8-OHdG was measured by ELISA, and CIMT was measured by B mode ultrasonography. Both 8-OHdG and CIMT were significantly higher in subjects with prediabetes as compared to controls (185.80 ± 10.72 pg/mL vs. 126.13 ± 16.01 pg/mL, p < 0.001 and 0.70 ± 0.04 mm vs. 0.57 ± 0.03 mm, p < 0.001, respectively). There was significant and positive correlation of IGT with 8-OHdG (r = 0.783; p < 0.001) and CIMT (r = 0.787; p < 0.001) in prediabetic subjects. Moreover, 8-OHdG showed significant positive correlation with CIMT (r = 0.704; p < 0.001) in prediabetic subjects. In conclusion, increased 8-OHdG and CIMT in prediabetic subjects indicate that biochemical changes of atherosclerosis start even before the onset of diabetes mellitus. Hence, 8-OHdG and CIMT could be used as indicators of cardiovascular disease risk in these subjects.
Improving Object-Based Land Use/Cover Classification from Medium Resolution Imagery by Markov Chain Geostatistical Post-Classification
Authors: Wang Wenjie , Li Weidong , Zhang Chuanrong , Zhang Weixing
Published: March 2018

Land use/land cover maps derived from remotely sensed imagery are often insufficient in quality for some quantitative application purposes due to a variety of reasons such as spectral confusion. Although object-based classification has some advantages over pixel-based classification in identifying relatively homogeneous land use/cover areas from medium resolution remotely sensed images, the classification accuracy is usually still relatively low. In this study, we aimed to test whether the recently proposed Markov chain random field (MCRF) post-classification method, that is, the spectral similarity-enhanced MCRF co-simulation (SS-coMCRF) model, can effectively improve object-based land use/cover classifications on different landscapes. Four study areas (Cixi, Yinchuan and Maanshan in China and Hartford in USA) with different landscapes and classification schemes were chosen for case studies. Expert-interpreted sample data (0.087% to 0.258% of total pixels) were obtained for each study area from the original Landsat images used in object-based pre-classification and other sources (e.g., Google satellite imagery). Post-classification results showed that the overall classification accuracies of the four cases were obviously improved over the corresponding pre-classification results by 14.1% for Cixi, 5% for Yinchuan, 11.8% for Maanshan and 5.6% for Hartford, respectively. At the meantime, SS-coMCRF also reduced the noise and minor patches contained in pre-classifications. This means that the Markov chain geostatistical post-classification method is capable of improving the accuracy and quality of object-based land use/cover classification from medium resolution remotely sensed imagery in various landscape situations.
Erratum: Andreotti, S.; Franzoni, E.; Fabbri, P. Poly(hydroxyalkanoate)s-Based Hydrophobic Coatings for the Protection of Stone in Cultural Heritage. Materials 2018, 11, 165
Authors: Andreotti Serena , Franzoni Elisa , Degli Esposti Micaela , Fabbri Paola
Published: March 2018

The authors wish to add a new author, Micaela Degli Esposti, who also contributed to performing the experiments and analyzing the data of this published paper [1]. [...]
Surface Treatment of PEOT/PBT (55/45) with a Dielectric Barrier Discharge in Air, Helium, Argon and Nitrogen at Medium Pressure
Authors: Cools Pieter , Asadian Mahtab , Nicolaus Wannes , Declercq Heidi , Morent Rino , De Geyter Nathalie
Published: March 2018

This work describes the surface modification of 300PEO-PEOT/PBT 55/45 thin films using a medium pressure dielectric barrier discharge system operated in argon, helium, nitrogen or dry air to improve cell-surface interactions of this established biomaterial. The first part of the paper describes the optimization of the plasma processing parameters using water contact angle goniometry. The optimized samples are then characterized for changes in surface topography and surface chemical composition using atomic force microscopy (AFM) and X-ray fluorescence spectroscopy (XPS) respectively. For all plasma treatments, a pronounced increase in surface wettability was observed, of which the extent is dependent on the used plasma discharge gas. Except for dry air, only minor changes in surface topography were noted, while XPS confirmed that the changes in wettability were mainly chemical in nature with the incorporation of 5–10% of extra oxygen as a variety of polar groups. Similarly, for the nitrogen plasma, 3.8% of nitrogen polar groups were additionally incorporated. Human foreskin fibroblast (HFF) in vitro analysis showed that within the first 24 h after cell seeding, the effects on cell-surface interactivity were highly dependent on the used discharge gas, nitrogen plasma treatment being the most efficient. Differences between untreated and plasma-treated samples were less pronounced compared to other biodegradable materials, but a positive influence on cell adhesion and proliferation was still observed.
Protein-Based Nanoparticle Preparation via Nanoprecipitation Method
Authors: Tarhini Mohamad , Benlyamani Ihsane , Hamdani Selim , Agusti Géraldine , Fessi Hatem , Greige-Gerges Hélène , Bentaher Abderrazzak , Elaissari Abdelhamid
Published: March 2018

Nanoparticles are nowadays largely investigated in the field of drug delivery. Among nanoparticles, protein-based particles are of paramount importance since they are natural, biodegradable, biocompatible, and nontoxic. There are several methods to prepare proteins containing nanoparticles, but only a few studies have been dedicated to the preparation of protein- based nanoparticles. Then, the aim of this work was to report on the preparation of bovine serum albumin (BSA)-based nanoparticles using a well-defined nanoprecipitation process. Special attention has been dedicated to a systematic study in order to understand separately the effect of each operating parameter of the method (such as protein concentration, solvent/non-solvent volume ratio, non-solvent injection rate, ionic strength of the buffer solution, pH, and cross-linking) on the colloidal properties of the obtained nanoparticles. In addition, the mixing processes (batch or drop-wise) were also investigated. Using a well-defined formulation, submicron protein-based nanoparticles have been obtained. All prepared particles have been characterized in terms of size, size distribution, morphology, and electrokinetic properties. In addition, the stability of nanoparticles was investigated using Ultraviolet (UV) scan and electrophoresis, and the optimal conditions for preparing BSA nanoparticles by the nanoprecipitation method were concluded.
Mg-MOF-74/MgF2 Composite Coating for Improving the Properties of Magnesium Alloy Implants: Hydrophilicity and Corrosion Resistance
Authors: Liu Wei , Yan Zhijie , Ma Xiaolu , Geng Tie , Wu Haihong , Li Zhongyue
Published: March 2018

Surface modification on Mg alloys is highly promising for their application in the field of bone repair. In this study, a new metal–organic framework/MgF2 (Mg-MOF-74/MgF2) composite coating was prepared on the surface of AZ31B Mg alloy via pre-treatment of hydrofluoric acid and in situ hydrothermal synthesis methods. The surface topography of the composite coating is compact and homogeneous, and Mg-MOF-74 has good crystallinity. The corrosion resistance of this composite coating was investigated through Tafel polarization test and immersion test in simulated body fluid at 37 °C. It was found that Mg-MOF-74/MgF2 composite coating significantly slowed down the corrosion rate of Mg alloy. Additionally, Mg-MOF-74/MgF2 composite coating expresses super-hydrophilicity with the water contact angle of nearly 0°. In conclusion, on the basis of MgF2 anticorrosive coating, the introduction of Mg-MOF-74 further improves the biological property of Mg alloys. At last, we propose that the hydrophilicity of the composite coating is mainly owing to the large number of hydroxyl groups, the high specific surface area of Mg-MOF-74, and the rough coating produced by Mg-MOF-74 particles. Hence, Mg-MOF-74 has a great advantage in enhancing the hydrophilicity of Mg alloy surface.
Structural, Electronic, and Thermodynamic Properties of Tetragonal t-SixGe3−xN4
Authors: Han Chenxi , Chai Changchun , Fan Qingyang , Yang Jionghao , Yang Yintang
Published: March 2018

The structural, mechanical, anisotropic, electronic, and thermal properties of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 in the tetragonal phase are systematically investigated in the present work. The mechanical stability is proved by the elastic constants of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4. Moreover, they all demonstrate brittleness, because B/G < 1.75, and v < 0.26. The elastic anisotropy of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 is characterized by Poisson’s ratio, Young’s modulus, the percentage of elastic anisotropy for bulk modulus AB, the percentage of elastic anisotropy for shear modulus AG, and the universal anisotropic index AU. The electronic structures of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 are all wide band gap semiconductor materials, with band gaps of 4.26 eV, 3.94 eV, 3.83 eV, and 3.25 eV, respectively, when using the Heyd-Scuseria-Ernzerhof (HSE06) hybrid functional. Moreover, t-Ge3N4 is a quasi-direct gap semiconductor material. The thermodynamic properties of t-Si3N4, t-Si2GeN4, t-SiGe2N4, and t-Ge3N4 are investigated utilizing the quasi-harmonic Debye model. The effects of temperature and pressure on the thermal expansion coefficient, heat capacity, Debye temperature, and Grüneisen parameters are discussed in detail.
Interface Bond Improvement of Sisal Fibre Reinforced Polylactide Composites with Added Epoxy Oligomer
Authors: Hao Mingyang , Wu Hongwu , Qiu Feng , Wang Xiwen
Published: March 2018

To improve the interfacial bonding of sisal fiber-reinforced polylactide biocomposites, polylactide (PLA) and sisal fibers (SF) were melt-blended to fabricate bio-based composites via in situ reactive interfacial compatibilization with addition of a commercial grade epoxy-functionalized oligomer Joncryl ADR@-4368 (ADR). The FTIR (Fourier Transform infrared spectroscopy) analysis and SEM (scanning electron microscope) characterization demonstrated that the PLA molecular chain was bonded to the fiber surface and the epoxy-functionalized oligomer played a hinge-like role between the sisal fibers and the PLA matrix, which resulted in improved interfacial adhesion between the fibers and the PLA matrix. The interfacial reaction and microstructures of composites were further investigated by thermal and rheological analyses, which indicated that the mobility of the PLA molecular chain in composites was restricted because of the introduction of the ADR oligomer, which in turn reflected the improved interfacial interaction between SF and the PLA matrix. These results were further justified with the calculation of activation energies of glass transition relaxation (∆Ea) by dynamic mechanical analysis. The mechanical properties of PLA/SF composites were simultaneously reinforced and toughened with the addition of ADR oligomer. The interfacial interaction and structure–properties relationship of the composites are the key points of this study.
Gas Separation Properties of Polyimide Thin Films on Ceramic Supports for High Temperature Applications
Authors: Escorihuela Sara , Tena Alberto , Shishatskiy Sergey , Escolástico Sonia , Brinkmann Torsten , Serra Jose , Abetz Volker
Published: March 2018

Novel selective ceramic-supported thin polyimide films produced in a single dip coating step are proposed for membrane applications at elevated temperatures. Layers of the polyimides P84®, Matrimid 5218®, and 6FDA-6FpDA were successfully deposited onto porous alumina supports. In order to tackle the poor compatibility between ceramic support and polymer, and to get defect-free thin films, the effect of the viscosity of the polymer solution was studied, giving the entanglement concentration (C*) for each polymer. The C* values were 3.09 wt. % for the 6FDA-6FpDA, 3.52 wt. % for Matrimid®, and 4.30 wt. % for P84®. A minimum polymer solution concentration necessary for defect-free film formation was found for each polymer, with the inverse order to the intrinsic viscosities (P84® ≥ Matrimid® >> 6FDA-6FpDA). The effect of the temperature on the permeance of prepared membranes was studied for H2, CH4, N2, O2, and CO2. As expected, activation energy of permeance for hydrogen was higher than for CO2, resulting in H2/CO2 selectivity increase with temperature. More densely packed polymers lead to materials that are more selective at elevated temperatures.
Metal Injection Moulding of High Nb-Containing TiAl Alloy and Its Oxidation Behaviour at 900 °C
Authors: Liu Chengcheng , Lu Xin , Yang Fei , Xu Wei , Wang Zhe , Qu Xuanhui
Published: March 2018

High Nb-containing TiAl alloy with a nominal composition of Ti-45Al-8.5Nb-0.2W-0.2B-0.02Y (at %) was fabricated by metal injection moulding (MIM) technology with an improved wax-based binder. The critical powder loading and feedstock rheological behaviour were determined. The influence of sintering temperature on microstructures and mechanical properties of the sintered samples and their oxidation behaviour were also investigated. Results showed that a feedstock, with a powder loading of 68 vol % and good flowability, could be obtained by using the improved binder, and oxygen pick-up was lower than that of the sample prepared by using a traditional binder. The ultimate tensile strength (UTS) and plastic elongation of the sample sintered at 1480 °C for 2 h were 412 MPa and 0.33%, at room temperature, respectively. The 1480 °C-sintered sample consisted of γ/α2 lamellar microstructure with the average colony size of about 70 µm, and its porosity was about 4%. The sintered alloy showed better oxidation resistance than that of the cast alloy counterpart.
Dietary Patterns Are Associated with Cardiovascular and Cancer Mortality among Swiss Adults in a Census-Linked Cohort
Authors: Krieger Jean-Philippe , Cabaset Sophie , Pestoni Giulia , Rohrmann Sabine , Faeh David ,   Swiss National Cohort Study Group
Published: March 2018

Defining dietary guidelines requires a quantitative assessment of the influence of diet on the development of diseases. The aim of the study was to investigate how dietary patterns were associated with mortality in a general population sample of Switzerland. We included 15,936 participants from two population-based studies (National Research Program 1A (NRP1A) and Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)—1977 to 1993) who fully answered a simplified 24-h dietary recall. Mortality data were available through anonymous record linkage with the Swiss National Cohort (follow-up of up to 37.9 years). Multiple correspondence analysis and hierarchical clustering were used to define data-driven qualitative dietary patterns. Mortality hazard ratios were calculated for all-cause, cancer and cardiovascular mortality using Cox regression. Two patterns were characterized by a low dietary variety (“Sausage and Vegetables”, “Meat and Salad”), two by a higher variety (“Traditional”, “High-fiber foods”) and one by a high fish intake (“Fish”). Males with unhealthy lifestyle (smokers, low physical activity and high alcohol intake) were overrepresented in the low-variety patterns and underrepresented in the high-variety and “Fish” patterns. In multivariable-adjusted models, the “Fish” (hazard ratio = 0.82, 95% CI (0.68–0.99)) and “High-fiber foods” (0.85 (0.72–1.00)) patterns were associated with lower cancer mortality. In men, the “Fish” (0.73 (0.55–0.97)) and “Traditional” (0.76 (0.59–0.98)) patterns were associated with lower cardiovascular mortality. In summary, our results support the notion that dietary patterns affect mortality and that these patterns strongly cluster with other health determinants.
Effects of Chinese Cooking Methods on the Content and Speciation of Selenium in Selenium Bio-Fortified Cereals and Soybeans
Authors: Lu Xiaoqi , He Zisen , Lin Zhiqing , Zhu Yuanyuan , Yuan Linxi , Liu Ying , Yin Xuebin
Published: March 2018

Cereals and soybeans are the main food sources for the majority of Chinese. This study evaluated the effects of four common cooking methods including steaming, boiling, frying, and milking on selenium (Se) content and speciation in seven selenium bio-fortified cereals and soybeans samples. The Se concentrations in the selected samples ranged from 0.91 to 110.8 mg/kg and selenomethionine (SeMet) was detected to be the main Se species. Total Se loss was less than 8.1% during the processes of cooking except milking, while 49.1% of the total Se was lost in milking soybean for soy milk due to high level of Se in residuals. It was estimated that about 13.5, 24.0, 3.1, and 46.9% of SeMet were lost during the processes of steaming, boiling, frying, and milking, respectively. Meanwhile, selenocystine (SeCys2) and methylselenocysteine (SeMeCys) were lost completely from the boiled cereals. Hence, steaming and frying were recommended to cook Se-biofortified cereals in order to minimize the loss of Se.
ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion
Authors: Niwa Hiroyuki , Iizuka Katsumi , Kato Takehiro , Wu Wudelehu , Tsuchida Hiromi , Takao Ken , Horikawa Yukio , Takeda Jun
Published: March 2018

The regulation of hepatic very-low-density lipoprotein (VLDL) secretion plays an important role in the pathogenesis of dyslipidemia and fatty liver diseases. VLDL is controlled by hepatic microsomal triglyceride transfer protein (MTTP). Mttp is regulated by carbohydrate response element binding protein (ChREBP) and small heterodimer partner (SHP). However, it is unclear whether both coordinately regulate Mttp expression and VLDL secretion. Here, adenoviral overexpression of ChREBP and SHP in rat primary hepatocytes induced and suppressed Mttp mRNA, respectively. However, Mttp induction by ChREBP was much more potent than suppression by SHP. Promoter assays of Mttp and the liver type pyruvate kinase gene revealed that SHP and ChREBP did not affect the transcriptional activity of each other. Mttp mRNA and protein levels of Shp−/− mice were similar to those of wild-types; however, those of Chrebp−/−Shp−/− and Chrebp−/− mice were significantly much lower. Consistent with this, the VLDL particle number and VLDL secretion rates in Shp−/− mice were similar to wild-types but were much lower in Chrebp−/− and Chrebp−/−Shp−/− mice. These findings suggest that ChREBP, rather than SHP, regulates VLDL secretion under normal conditions and that ChREBP and SHP do not affect the transcriptional activities of each other.
Pharmacological Agents Targeting the Cellular Prion Protein
Authors: Barreca Maria , Iraci Nunzio , Biggi Silvia , Cecchetti Violetta , Biasini Emiliano
Published: March 2018

Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates in brain tissues of affected individuals. PrPSc is a self-catalytic protein assembly capable of recruiting native conformers of PrPC, and causing their rearrangement into new PrPSc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrPSc, and a number of compounds have shown potent anti-prion effects in experimental models. Unfortunately, so far, none of these molecules has successfully been translated into effective therapies for prion diseases. Moreover, mounting evidence suggests that PrPSc might be a difficult pharmacological target because of its poorly defined structure, heterogeneous composition, and ability to generate different structural conformers (known as prion strains) that can elude pharmacological intervention. In the last decade, a less intuitive strategy to overcome all these problems has emerged: targeting PrPC, the common substrate of any prion strain replication. This alternative approach possesses several technical and theoretical advantages, including the possibility of providing therapeutic effects also for other neurodegenerative disorders, based on recent observations indicating a role for PrPC in delivering neurotoxic signals of different misfolded proteins. Here, we provide an overview of compounds claimed to exert anti-prion effects by directly binding to PrPC, discussing pharmacological properties and therapeutic potentials of each chemical class.
EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts
Authors: Dojcinov Stefan , Fend Falko , Quintanilla-Martinez Leticia
Published: March 2018

The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored.
Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy
Authors: Ousset Aymeric , Chavez Pierre-François , Meeus Joke , Robin Florent , Schubert Martin , Somville Pascal , Dodou Kalliopi
Published: March 2018

The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD) manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling), and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width), and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs). Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w). Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC) and X-ray powder diffraction (XRPD). Principal component analysis (PCA) was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development.