bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Climate Change on Burn Probability of Forests in Daxing’anling
Authors: Tian Xiaorui , Cui Wenbin , Shu Lifu , Zong Xuezheng
Published: July 2019

Projecting the burn probability (BP) under future climate scenarios would provide a scientific basis for the implementation of forest fire adaptation technology. This study compared the changes in the climate, fire weather, and burn probability during the fire season in Daxing’anling, China. A burn probability model was established and used to simulate the daily fire occurrence and spread at baseline (1971–2000) and into the 2030s (2021–2050) based on the outputs from five global climate models (GCMs) (GFDL-ESM2M, Had GEM2-ES, IPSL-CM5A-LR, MIROC-ESM-CHEM, and Nor ESM1-M) under four climate scenarios (RCP2.6, RCP4.5, RCP6.0, and RCP8.5). The results showed that the average daily maximum temperature in the fire season will be increased by 2.1 °C (+16.6%) in the 2030s compared with the baseline and precipitation in the fire season will be increased by 7.1%. The average fire weather index (FWI) of the fire season in the 2030s will be increased by 4.2%, but this change is not significant. There will be 39 fires per year in the 2030s, representing an increase of 11.4%. The accuracy of simulated burned areas was 71.2% for the 1991–2010 period. The simulated and observed burned areas showed similar interannual fluctuations during period 1971–2010. The potential burned areas in the 2030s will increase by 18.8% over those in the baseline period and the BP will increase by 19.4%. The implementation of proactive fire management in areas with high predicted BP values will be key for an effective mitigation of future wildfire impacts.
Enhancing the Punching Load Capacity of Reinforced Concrete Slabs Using an External Epoxy-Steel Wire Mesh Composite
Authors: Jaafer Abdulkhaliq A. , AL-Shadidi Raid , Kareem Saba L.
Published: July 2019

The present experimental work investigates the applicability and performance of a new strengthening method for concrete slabs, intended to increase their punching resistance using combination layers of steel wire mesh with epoxy attached to the concrete slabs’ tension face. Six simply supported square reinforced concrete slab specimens were tested up to failure under a central concentrated load. The main parameters in the study are the concrete compressive strength (30 MPa and 65 MPa) and the configuration of a bundle externally fixed to the tension side of the tested slabs. The experimental results appeared to greatly enhance the performance of the specimens, as they were externally strengthenined under this new method. When compared to the control slabs, the punching load and stiffness of the strengthened slabs increased up to 28% and 21%, respectively.
Lactic Acid Bacteria and Yeast Inocula Modulate the Volatile Profile of Spanish-Style Green Table Olive Fermentations
Authors: Benítez-Cabello Antonio , Rodríguez-Gómez Francisco , Morales M. Lourdes , Garrido-Fernández Antonio , Jiménez-Díaz Rufino , Arroyo-López Francisco Noé
Published: July 2019

In this work, Manzanilla Spanish-style green table olive fermentations were inoculated with Lactobacillus pentosus LPG1, Lactobacillus pentosus Lp13, Lactobacillus plantarum Lpl15, the yeast Wickerhanomyces anomalus Y12 and a mixed culture of all them. After fermentation (65 days), their volatile profiles in brines were determined by gas chromatography-mass spectrometry analysis. A total of 131 volatile compounds were found, but only 71 showed statistical differences between at least, two fermentation processes. The major chemical groups were alcohols (32), ketones (14), aldehydes (nine), and volatile phenols (nine). Results showed that inoculation with Lactobacillus strains, especially L. pentosus Lp13, reduced the formation of volatile compounds. On the contrary, inoculation with W. anomalus Y12 increased their concentrations with respect to the spontaneous process, mainly of 1-butanol, 2-phenylethyl acetate, ethanol, and 2-methyl-1-butanol. Furthermore, biplot and biclustering analyses segregated fermentations inoculated with Lp13 and Y12 from the rest of the processes. The use of sequential lactic acid bacteria and yeasts inocula, or their mixture, in Spanish-style green table olive fermentation could be advisable practice for producing differentiated and high-quality products with improved aromatic profile.
Antioxidant Rich Extracts of Terminalia ferdinandiana Inhibit the Growth of Foodborne Bacteria
Authors: Akter Saleha , Netzel Michael E. , Tinggi Ujang , Osborne Simone A. , Fletcher Mary T. , Sultanbawa Yasmina
Published: July 2019

Terminalia ferdinandiana (Kakadu plum) is a native Australian plant containing phytochemicals with antioxidant capacity. In the search for alternatives to synthetic preservatives, antioxidants from plants and herbs are increasingly being investigated for the preservation of food. In this study, extracts were prepared from Terminalia ferdinandiana fruit, leaves, seedcoats, and bark using different solvents. Hydrolysable and condensed tannin contents in the extracts were determined, as well as antioxidant capacity, by measuring the total phenolic content (TPC) and free radical scavenging activity using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. Total phenolic content was higher in the fruits and barks with methanol extracts, containing the highest TPC, hydrolysable tannins, and DPPH-free radical scavenging capacity (12.2 ± 2.8 g/100 g dry weight (DW), 55 ± 2 mg/100 g DW, and 93% respectively). Saponins and condensed tannins were highest in bark extracts (7.0 ± 0.2 and 6.5 ± 0.7 g/100 g DW). The antimicrobial activity of extracts from fruit and leaves showed larger zones of inhibition, compared to seedcoats and barks, against the foodborne bacteria Listeria monocytogenes, Bacillus cereus, Methicillin resistant Staphylococcus aureus, and clinical isolates of Pseudomonas aeruginosa. The minimum inhibitory concentration and minimum bactericidal concentration in response to the different extracts ranged from 1.0 to 3.0 mg/mL. Scanning electron microscopy images of the treated bacteria showed morphological changes, leading to cell death. These results suggest that antioxidant rich extracts of Terminalia ferdinandiana fruits and leaves have potential applications as natural antimicrobials in food preservation.
GWEHS: A Genome-Wide Effect Sizes and Heritability Screener
Authors: López-Cortegano Eugenio , Caballero Armando
Published: July 2019

During the last decade, there has been a huge development of Genome-Wide Association Studies (GWAS), and thousands of loci associated to complex traits have been detected. These efforts have led to the creation of public databases of GWAS results, making a huge source of information available on the genetic background of many diverse traits. Here we present GWEHS (Genome-Wide Effect size and Heritability Screener), an open-source online application to screen loci associated to human complex traits and diseases from the NHGRI-EBI GWAS Catalog. This application provides a way to explore the distribution of effect sizes of loci affecting these traits, as well as their contribution to heritability. Furthermore, it allows for making predictions on the change in the expected mean effect size, as well as in the heritability as new loci are found. The application enables inferences on whether the additive contribution of loci expected to be discovered in the future will be able to explain the estimates of familial heritability for the different traits. We illustrate the use of this tool, compare some of the results obtained with those from a previous meta-analysis, and discuss its uses and limitations.
Perspectives on Modifying Attentional Biases Amongst Individuals with Tobacco Use Disorder Using Technology: A Review
Authors: Tan Yi Zhuang , Zhang Melvyn W.B. , Choo Carol C.
Published: July 2019

Smoking remains a significant health problem. Attentional biases influence smoking behaviours, but have not been the target of psychosocial interventions. The first part of this perspective article will provide an overview of the theoretical constructs underlying attentional biases, methods of measuring attentional biases, and evidence for attentional bias modification amongst individuals with tobacco use disorders. The second part of this article will outline how the advent of technological advances could be harnessed in attentional bias modification for smokers. As there is potential for attentional bias training to be delivered via mobile app, literature was reviewed over the recent decade, 2009 to 2019, to examine available research evidence. The search terms were “web-based” or “mobile based”, and “attention bias modification” or “attentional bias” and “smoking” or “tobacco use”. The PsycINFO, Scopus, and PubMed databases were initially used to identify papers with the above-mentioned inclusion criteria. Five papers were included in the review. Lastly, an integrated perspective will be provided, from both clinical and research standpoints. In conclusion, more research is needed to address the gaps in knowledge and to provide an evidence base for the implementation of mobile phone technologies for attention retraining in smokers.
Multi-Criteria High Voltage Power Line Routing—An Open Source GIS-Based Approach
Authors: Zipf Michael , Kumar Samarth , Scharf Hendrik , Zöphel Christoph , Dierstein Constantin , Möst Dominik
Published: July 2019

The integration of different stakeholders’ perspectives when planning large-scale infrastructure projects such as power transmission lines is becoming increasingly important in the public debate. Partly conflicting interests of stakeholders should be taken into account in order to allow for best possible routing of new lines. Particularly when transmission lines which are bridging large distances are considered, externalities within this complex setting include social, ecological, economical and technical dimensions. An optimal routing of lines may help address different issues, such as public resistance. Models for the investigation of these large-area impacts for optimal route formation often only cover small regions or lack the georeferenced data necessary to quantify different criteria. We develop an open-source approach which allows for transparent and replicable route determination, tracing, and assessment covering the whole of Europe. Therefore, we provide several friction layers with high spatial resolution. Each layer represents a criterion affecting the routing of a power line. Together with the start and end point of a construction project, this allows for creating accumulated cost rasters for various relationships between the weightings of the perspectives which are relevant during line infrastructure routing processes. The present work explains the underlying methods of data collection, processing, and algorithms of data preparation, route generation, and assessment. Subsequently, this approach is verified with two case studies of HVDC transmission lines which are currently in the planning stages. All processed datasets and applied scripts described in this paper are open-access and made publicly available. Hence, this should support the current project routing debate by providing more transparency and by improving stakeholder involvement.
Geo-Referencing and Mapping 1901 Census Addresses for England and Wales
Authors: Lan Tian , Longley Paul
Published: July 2019

Geocoding historical addresses is a primary yet nontrivial application of spatial analysis in historical geographic information systems (GIS) and spatial humanities. We demonstrate our endeavours of geo-referencing and visualising historical census addresses in England and Wales, by matching the residential addresses to a historical gazetteer and a contemporary address database of Britain. The results indicate that it is feasible to standardise and geocode a large share of unique addresses from the historical database. The historical gazetteer and the modern address registers are two complementary data assets that can be used to geo-reference both well-formatted addresses in urban areas and non-standard addresses such as place names or building names in rural areas. The geo-referenced historical census data open up new opportunities for a broad spectrum of geo-demographic research on historical population characteristics at the micro level in England and Wales.
Clinical Therapeutic Strategy and Neuronal Mechanism Underlying Post-Traumatic Stress Disorder (PTSD)
Authors: Yabuki Yasushi , Fukunaga Kohji
Published: July 2019

Post-traumatic stress disorder (PTSD) is characterized by an exaggerated response to contextual memory and impaired fear extinction, with or without mild cognitive impairment, learning deficits, and nightmares. PTSD is often developed by traumatic events, such as war, terrorist attack, natural calamities, etc. Clinical and animal studies suggest that aberrant susceptibility of emotion- and fear-related neurocircuits, including the amygdala, prefrontal cortex (PFC), and hippocampus may contribute to the development and retention of PTSD symptoms. Psychological and pharmacological therapy, such as cognitive behavioral therapy (CBT), and treatment with anti-depressive agents and/or antipsychotics significantly attenuate PTSD symptoms. However, more effective therapeutics are required for improvement of quality of life in PTSD patients. Previous studies have reported that ω3 long-chain polyunsaturated fatty acid (LCPUFA) supplements can suppress the development of PTSD symptoms. Fatty acid binding proteins (FABPs) are essential for LCPUFA intracellular trafficking. In this review, we have introduced Fabp3 null mice as an animal model of PTSD with impaired fear extinction. Moreover, we have addressed the neuronal circuits and novel therapeutic strategies for PTSD symptoms.
Yeast-Derived β-Glucan in Cancer: Novel Uses of a Traditional Therapeutic
Authors: Geller Anne , Shrestha Rejeena , Yan Jun
Published: July 2019

An increased understanding of the complex mechanisms at play within the tumor microenvironment (TME) has emphasized the need for the development of strategies that target immune cells within the TME. Therapeutics that render the TME immune-reactive have a vast potential for establishing effective cancer interventions. One such intervention is β-glucan, a natural compound with immune-stimulatory and immunomodulatory potential that has long been considered an important anti-cancer therapeutic. β-glucan has the ability to modulate the TME both by bridging the innate and adaptive arms of the immune system and by modulating the phenotype of immune-suppressive cells to be immune-stimulatory. New roles for β-glucan in cancer therapy are also emerging through an evolving understanding that β-glucan is involved in a concept called trained immunity, where innate cells take on memory phenotypes. Additionally, the hollow structure of particulate β-glucan has recently been harnessed to utilize particulate β-glucan as a delivery vesicle. These new concepts, along with the emerging success of combinatorial approaches to cancer treatment involving β-glucan, suggest that β-glucan may play an essential role in future strategies to prevent and inhibit tumor growth. This review emphasizes the various characteristics of β-glucan, with an emphasis on fungal β-glucan, and highlights novel approaches of β-glucan in cancer therapy.
Evaluating the Efficiency of gRNAs in CRISPR/Cas9 Mediated Genome Editing in Poplars
Authors: Bruegmann Tobias , Deecke Khira , Fladung Matthias
Published: July 2019

CRISPR/Cas9 has become one of the most promising techniques for genome editing in plants and works very well in poplars with an Agrobacterium-mediated transformation system. We selected twelve genes, including SOC1, FUL, and their paralogous genes, four NFP-like genes and TOZ19 for three different research topics. The gRNAs were designed for editing, and, together with a constitutively expressed Cas9 nuclease, transferred either into the poplar hybrid Populus × canescens or into P. tremula. The regenerated lines showed different types of editing and revealed several homozygous editing events which are of special interest in perennial species because of limited back-cross ability. Through a time series, we could show that despite the constitutive expression of the Cas9 nuclease, no secondary editing of the target region occurred. Thus, constitutive Cas9 expression does not seem to pose any risk to additional editing events. Based on various criteria, we obtained evidence for a relationship between the structure of gRNA and the efficiency of gene editing. In particular, the GC content, purine residues in the gRNA end, and the free accessibility of the seed region seemed to be highly important for genome editing in poplars. Based on our findings on nine different poplar genes, efficient gRNAs can be designed for future efficient editing applications in poplars.
Human Activity Recognition for Production and Logistics—A Systematic Literature Review
Authors: Reining Christopher , Niemann Friedrich , Moya Rueda Fernando , Fink Gernot A. , ten Hompel Michael
Published: July 2019

This contribution provides a systematic literature review of Human Activity Recognition for Production and Logistics. An initial list of 1243 publications that complies with predefined Inclusion Criteria was surveyed by three reviewers. Fifty-two publications that comply with the Content Criteria were analysed regarding the observed activities, sensor attachment, utilised datasets, sensor technology and the applied methods of HAR. This review is focused on applications that use marker-based Motion Capturing or Inertial Measurement Units. The analysed methods can be deployed in industrial application of Production and Logistics or transferred from related domains into this field. The findings provide an overview of the specifications of state-of-the-art HAR approaches, statistical pattern recognition and deep architectures and they outline a future road map for further research from a practitioner’s perspective.
Probabilistic Identification of Seismic Response Mechanism in a Class of Similar Arch Dams
Authors: Hariri-Ardebili M. A. , Heshmati M. , Boodagh P. , Salamon J. W.
Published: July 2019

Different numerical models have been proposed for seismic analysis of concrete dams by taking into account the nonlinear behavior of concrete and joints; interaction between the dam, foundation, and reservoir; and other seismic hazard considerations. Less focus, however, has been placed on the real seismic performance of the dams and their relative correlation. This paper investigates the linear and nonlinear seismic performance of two similar high arch dams with relatively different response mechanisms. The response correlation is performed from statistical and probabilistic points of view. Similarities and differences are highlighted, and the best practice to compare the responses in a class of dams is presented. It is found that some demand parameters and seismic intensity measures can reduce the dispersion of the results and increase the correlation. In general, the dam geometry has a direct relation with the deformation and spatial distribution of potential damaged area. However, it is not related to the localized damage at the most critical location. Moreover, the real crack pattern (from nonlinear analysis) is more discrete compared to the continuous overstressed/overstrained regions (from linear analysis).
Blood Pressure Abnormalities Associated with Gut Microbiota-Derived Short Chain Fatty Acids in Children with Congenital Anomalies of the Kidney and Urinary Tract
Authors: Hsu Chien-Ning , Lu Pei-Chen , Hou Chih-Yao , Tain You-Lin
Published: July 2019

Both kidney disease and hypertension can originate from early life. Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of chronic kidney disease (CKD) in children. Since gut microbiota and their metabolite short chain fatty acids (SCFAs) have been linked to CKD and hypertension, we examined whether gut microbial composition and SCFAs are correlated with blood pressure (BP) load and renal outcome in CKD children with CAKUT. We enrolled 78 children with CKD stage G1–G4. Up to 65% of children with CAKUT had BP abnormalities on 24 h ambulatory blood pressure monitoring (ABPM). CKD children with CAKUT had lower risk of developing BP abnormalities and CKD progression than those with non-CAKUT. Reduced plasma level of propionate was found in children with CAKUT, which was related to increased abundance of phylum Verrucomicrobia, genus Akkermansia, and species Bifidobacterium bifidum. CKD children with abnormal ABPM profile had higher plasma levels of propionate and butyrate. Our findings highlight that gut microbiota-derived SCFAs like propionate and butyrate are related to BP abnormalities in children with an early stage of CKD. Early assessments of these microbial markers may aid in developing potential targets for early life intervention for lifelong hypertension prevention in childhood CKD.
Experimental Investigations on Hydrodynamic Responses of a Semi-Submersible Offshore Fish Farm in Waves
Authors: Zhao Yunpeng , Guan Changtao , Bi Chunwei , Liu Hangfei , Cui Yong
Published: July 2019

A series of physical model experiments was performed to investigate the hydrodynamic responses of a semi-submersible offshore fish farm in waves. The structural configuration of the fish farm primarily refers to that of the world’s first offshore fish farm, Ocean Farm 1, developed by SalMar in Norway. The mooring line tension and motion response of the fish farm were measured at three draughts. The study indicated that the tension on the windward mooring line is greater than that on the leeward mooring line. As the wave height increases, the mooring line tension and motion responses including the heave, surge, and pitch exhibit an upward trend. The windward mooring line tension decreased slightly with increasing draught. The existence of net resulted in approximately 42% reduction in mooring line tension and approximately 51% reduction in surge motion. However, the heave and pitch of the fish farm increased slightly with the existence of net. It was found that the wave parameters, draught, and net have noticeable effect on the hydrodynamic response. Thus, these factors are suggested to be considered in structural designs and optimization to guarantee the ability of the fish farm to resist destruction and ensure safety of workers during intense waves.
Regulation of the Crypto-Economy: Managing Risks, Challenges, and Regulatory Uncertainty
Authors: Cumming Douglas J. , Johan Sofia , Pant Anshum
Published: July 2019

Distributed ledger technology, also known as the blockchain, is gaining traction globally. Blockchain offers a secure validation mechanism and decentralized mass collaboration. Cryptocurrencies make use of this technology as a new asset class for investors worldwide. Cryptocurrencies are being used by companies to raise capital via initial coin offerings (ICOs). The substantial inflow of unregulated capital into a transactional and transnational industry has aroused interest from not just investors, but also national securities and monetary regulatory agencies. In this paper, we review the Security and Exchange Commission’s initial statements and subsequent pronouncements on ICO’s to illustrate the potential problems with applying an older legal framework to an ever-evolving ecosystem. Recognizing the inability of enforcement within existing regulatory frameworks, we discuss the importance of regulation of the crypto asset class and internal collaboration between government agencies and developers in the establishment of an ecosystem that integrates investor protection and investments.
Investigating the Mechanics of Hybrid Metal Extrusion and Bonding Additive Manufacturing by FEA
Authors: Blindheim Jørgen , Welo Torgeir , Steinert Martin
Published: July 2019

Hybrid Metal Extrusion & Bonding Additive Manufacturing (HYB-AM) is a hybrid manufacturing technology for the deposition of layered metal structures. This new deposition process is a complex metal forming operation, yet there is significant lack of knowledge regarding the governing mechanisms. In this work, we have used finite element analysis (FEA) to study material flow in the extruder, as well as the conditions at the interfaces of the deposited extrudate and the substrate, aiming to identify and characterize the process parameters involved. Analysis of the material flow shows that the extrusion pressure is virtually independent of the deposition rate. Furthermore, from the simulations of the material deposition sequence, it is clearly visible how the contact pressure at the interface will drop below the bonding threshold if the feed speed is too high relative to the material flow through the die. The reduced pressure also leads to the formation of a ‘gas-pocket’ inside the die, thus further degrading the conditions for bonding. The analyses of the process have provided valuable insights for the further development and industrialization of the process.
The Research of Low-Oxygen Control and Oxygen Behavior during RH Process in Silicon-Deoxidization Bearing Steel
Authors: Xiao Wei , Wang Min , Bao Yanping
Published: July 2019

The variation of total oxygen (T.O) content, characterization of inclusions, slag composition, and off-gas behavior during the smelting process of silicon-deoxidization bearing steel were investigated with industrial experiments. The change of content of combined oxygen during RH (Ruhrstahl–Hereaeus vacuum degassing furnace) process was calculated and compared with T.O content change. It is found that the decrease of oxygen content is mainly caused by the removal of dissolved oxygen rather than the removal of oxides during RH process. Carbon was found to be a strong deoxidizer (stronger than aluminum) in high vacuum degree. Top slag is an oxygen source of the deoxidization process, leading to the re-oxidization of liquid steel, even though the FeO content is low in top slag. During the RH process, the change of oxygen mainly exists in three processes: 1) Deoxidization reaction in vacuum chamber, 2) oxygen mass transfer process between liquid steel out from a vacuum chamber and in ladle, and 3) oxygen mass transfer between ladle slag and liquid steel. It depends mainly on the mass transfer of the oxygen in the liquid steel.
Trends in Diatom Research Since 1991 Based on Topic Modeling
Authors: Zhang Yun , Tao Juan , Wang Jun , Ding Liuyong , Ding Chengzhi , Li Yanling , Zhou Qichao , Li Dunhai , Zhang Hucai
Published: July 2019

Diatoms are fundamental carbon sources in a wide range of aquatic food webs and have the potential for wide application in addressing environmental change. Understanding the evolution of topics in diatom research will provide a clear and needed guide to strengthen research on diatoms. However, such an overview remains unavailable. In this study, we used Latent Dirichlet Allocation (LDA), a generative model, to identify topics and determine their trends (i.e., cold and hot topics) by analyzing the abstracts of 19,000 publications from the Web of Science that were related to diatoms during 1991–2018. A total of 116 topics were identified from a Bayesian model selection. The hot topics (diversity, environmental indicator, climate change, land use, and water quality) that were identified by LDA indicated that diatoms are increasingly used as indicators to assess water quality and identify modern climate change impacts due to intensive anthropogenic activities. In terms of cold topics (growth rate, culture growth, cell life history, copepod feeding, grazing by microzooplankton, zooplankton predation, and primary productivity) and hot topics (spatial-temporal distribution, morphology, molecular identification, gene expression, and review), we determined that basic studies on diatoms have decreased and that studies tend to be more comprehensive. This study notes that future directions in diatom research will be closely associated with the application of diatoms in environmental management and climate change to cope with environmental challenges, and more comprehensive issues related to diatoms should be considered.
An Updated Review on Pharmaceutical Properties of Gamma-Aminobutyric Acid
Authors: Ngo Dai-Hung , Vo Thanh Sang
Published: July 2019

Gamma-aminobutyric acid (Gaba) is a non-proteinogenic amino acid that is widely present in microorganisms, plants, and vertebrates. So far, Gaba is well known as a main inhibitory neurotransmitter in the central nervous system. Its physiological roles are related to the modulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of sleeplessness and depression. Besides, various pharmaceutical properties of Gaba on non-neuronal peripheral tissues and organs were also reported due to anti-hypertension, anti-diabetes, anti-cancer, antioxidant, anti-inflammation, anti-microbial, anti-allergy, hepato-protection, reno-protection, and intestinal protection. Therefore, Gaba may be considered as potential alternative therapeutics for prevention and treatment of various diseases. Accordingly, this updated review was mainly focused to describe the pharmaceutical properties of Gaba as well as emphasize its important role regarding human health.
The Flow Dependent Adhesion of von Willebrand Factor (VWF)-A1 Functionalized Nanoparticles in an in Vitro Coronary Stenosis Model
Authors: Asaad Yathreb , Epshtein Mark , Yee Andrew , Korin Netanel
Published: July 2019

In arterial thrombosis, von Willebrand factor (VWF) bridges platelets to sites of vascular injury. The adhesive properties of VWF are controlled by its different domains, which may be engineered into ligands for targeting nanoparticles to vascular injuries. Here, we functionalized 200 nm polystyrene nanoparticles with the VWF-A1 domain and studied their spatial adhesion to collagen or collagen-VWF coated, real-sized coronary stenosis models under physiological flow. When VWF-A1 nano-particles (A1-NPs) were perfused through a 75% stenosis model coated with collagen-VWF, the particles preferentially adhered at the post stenotic region relative to the pre-stenosis region while much less adhesion was detected at the stenosis neck (~ 65-fold less). When infused through collagen-coated models or when the A1 coating density of nanoparticles was reduced by 100-fold, the enhanced adhesion at the post-stenotic site was abolished. In a 60% stenosis model, the adhesion of A1-NPs to collagen-VWF-coated models depended on the location examined within the stenosis. Altogether, our results indicate that VWF-A1 NPs exhibit a flow-structure dependent adhesion to VWF and illustrate the important role of studying cardiovascular nano-medicines in settings that closely model the size, geometry, and hemodynamics of pathological environments.
Development and Optimization of Alpha-Pinene-Loaded Solid Lipid Nanoparticles (SLN) Using Experimental Factorial Design and Dispersion Analysis
Authors: Zielińska Aleksandra , Ferreira Nuno R. , Durazzo Alessandra , Lucarini Massimo , Cicero Nicola , Mamouni Soukaina El , Silva Amélia M. , Nowak Izabela , Santini Antonello , Souto Eliana B.
Published: July 2019

The encapsulation of bicyclic monoterpene α-pinene into solid lipid nanoparticles (SLN) is reported using experimental factorial design, followed by high-end dispersion analyzer LUMiSizer®. This equipment allows the characterization of the α-pinene-loaded SLN instability phenomena (e.g., sedimentation, flotation or coagulation), as well as the determination of the velocity distribution in the centrifugal field and the particle size distribution. In this work, SLN were produced by hot high-pressure homogenization technique. The influence of the independent variables, surfactant and lipid ratio on the physicochemical properties of SLN, such as mean particle size (Z-Ave), polydispersity index (PDI) and zeta potential (ZP), was estimated using a 22-factorial design. The Z-Ave and PDI were analyzed by dynamic light scattering, while ZP measurements were recorded by electrophoretic light scattering. Based on the obtained results, the optimal SLN dispersion was composed of 1 wt.% of α-pinene, 4 wt.% of solid lipid (Imwitor® 900 K) and 2.5 wt.% of surfactant (Poloxamer 188), depicting 136.7 nm of Z-Ave, 0.170 of PDI and 0 mV of ZP. Furthermore, LUMISizer® has been successfully used in the stability analysis of α-pinene-loaded SLN.
Long-Acting Injectable Statins—Is It Time for a Paradigm Shift?
Authors: Tatham Lee M. , Liptrott Neill J. , Rannard Steve P. , Owen Andrew
Published: July 2019

In recent years, advances in pharmaceutical processing technologies have resulted in development of medicines that provide therapeutic pharmacokinetic exposure for a period ranging from weeks to months following a single parenteral administration. Benefits for adherence, dose and patient satisfaction have been witnessed across a range of indications from contraception to schizophrenia, with a range of long-acting medicines also in development for infectious diseases such as HIV. Existing drugs that have successfully been formulated as long-acting injectable formulations have long pharmacokinetic half-lives, low target plasma exposures, and low aqueous solubility. Of the statins that are clinically used currently, atorvastatin, rosuvastatin, and pitavastatin may have compatibility with this approach. The case for development of long-acting injectable statins is set out within this manuscript for this important class of life-saving drugs. An overview of some of the potential development and implementation challenges is also presented.
The Antiglycoxidative Ability of Selected Phenolic Compounds—An In Vitro Study
Authors: Piwowar Agnieszka , Rorbach-Dolata Anna , Fecka Izabela
Published: July 2019

Hyperglycemia and oxidative stress may be observed in different diseases as important factors connected with their development. They often occur simultaneously and are considered together as one process: Glycoxidation. This can influence the function or structure of many macromolecules, for example albumin, by changing their physiological properties. This disturbs the homeostasis of the organism, so the search for natural compounds able to inhibit the glycoxidation process is a current and important issue. The aim of this study was the examination of the antiglycoxidative capacity of 16 selected phenolic compounds, belonging to three phenolic groups, as potential therapeutic agents. Their antiglycoxidative ability, in two concentrations (2 and 20 µM), were examined by in vitro study. The inhibition of the formation of both glycoxidative products (advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)) were assayed. Stronger antiglycoxidative action toward the formation of both AOPPs and AGEs was observed for homoprotocatechuic and ferulic acids in lower concentrations, as well as catechin, quercetin, and 8-O-methylurolithin A in higher concentrations. Homoprotocatechuic acid demonstrated the highest antiglycoxidative capacity in both examined concentrations and amongst all of them. A strong, significant correlation between the percentage of AOPPs and AGEs inhibition by compounds from all phenolic groups, in both examined concentrations, was observed. The obtained results give an insight into the antiglycoxidative potential of phenolic compounds and indicate homoprotocatechuic acid to be the most promising antiglycoxidative agent, but further biological and pharmacological studies are needed.
Discovery of a Nitric Oxide-Responsive Protein in Arabidopsis thaliana
Authors: Zarban Randa , Vogler Malvina , Wong Aloysius , Eppinger Joerg , Al-Babili Salim , Gehring Chris
Published: July 2019

In plants, much like in animals, nitric oxide (NO) has been established as an important gaseous signaling molecule. However, contrary to animal systems, NO-sensitive or NO-responsive proteins that bind NO in the form of a sensor or participating in redox reactions have remained elusive. Here, we applied a search term constructed based on conserved and functionally annotated amino acids at the centers of Heme Nitric Oxide/Oxygen (H-NOX) domains in annotated and experimentally-tested gas-binding proteins from lower and higher eukaryotes, in order to identify candidate NO-binding proteins in Arabidopsis thaliana. The selection of candidate NO-binding proteins identified from the motif search was supported by structural modeling. This approach identified AtLRB3 (At4g01160), a member of the Light Response Bric-a-Brac/Tramtrack/Broad Complex (BTB) family, as a candidate NO-binding protein. AtLRB3 was heterologously expressed and purified, and then tested for NO-response. Spectroscopic data confirmed that AtLRB3 contains a histidine-ligated heme cofactor and importantly, the addition of NO to AtLRB3 yielded absorption characteristics reminiscent of canonical H-NOX proteins. Furthermore, substitution of the heme iron-coordinating histidine at the H-NOX center with a leucine strongly impaired the NO-response. Our finding therefore established AtLRB3 as a NO-interacting protein and future characterizations will focus on resolving the nature of this response.
An Inexpensive Staining Alternative for Gelatin Zymography Gels
Authors: Wechselberger Christian , Doppler Christian , Bernhard David
Published: July 2019

Zymography is a widely used electrophoretic method to determine proteolytic activities in samples from various sources. The method is based on copolymerizing a suitable protein substrate within a sodium dodecyl sulfate-polyacrylamide gel. Following electrophoretic separation of the protease containing samples and a suitable incubation period, degradation of the substrate can be visualized through staining with Coomassie blue. Sites of proteolysis become visible as white bands on a dark blue background. However, this staining protocol requires considerable amounts of ethanol and acetic acid to remove unbound dye molecules. In this report, we describe a new staining protocol using Ponceau S which offers substantial advantages in terms of assay usability and cost reduction, especially when performing large quantities of zymograms or in resource-limited settings. Fast and reproducible staining of zymograms with our protocol is demonstrated, and reliable quantitation of proteolytic activity in comparison to the standard Coomassie staining procedure is shown.
Fabrication of Stable Nanofiber Matrices for Tissue Engineering via Electrospinning of Bare Laser-Synthesized Au Nanoparticles in Solutions of High Molecular Weight Chitosan
Authors: Nirwan Viraj P. , Al-Kattan Ahmed , Fahmi Amir , Kabashin Andrei V.
Published: July 2019

We report a methodology for the fabrication of neutralized chitosan-based nanofiber matrices decorated with bare Au nanoparticles, which demonstrate stable characteristics even after prolonged contact with a biological environment. The methodology consists of electrospinning of a mixture of bare (ligand-free) laser-synthesized Au nanoparticles (AuNPs) and solutions of chitosan/polyethylene oxide (ratio 1/3) containing chitosan of a relatively high molecular weight (200 kDa) and concentration of 3% (w/v). Our studies reveal a continuous morphology of hybrid nanofibers with the mean fiber diameter of 189 nm ± 86 nm, which demonstrate a high thermal stability. Finally, we describe a protocol for the neutralization of nanofibers, which enabled us to achieve their structural stability in phosphate-buffered saline (PBS) for more than six months, as confirmed by microscopy and FTIR measurements. The formed hybrid nanofibers exhibit unique physicochemical properties essential for the development of future tissue engineering platforms.
Validation of Surrogate Anthropometric Indices in Older Adults: What Is the Best Indicator of High Cardiometabolic Risk Factor Clustering?
Authors: Ramírez-Vélez Robinson , Pérez-Sousa Miguel Ángel , Izquierdo Mikel , Cano-Gutierrez Carlos A. , González-Jiménez Emilio , Schmidt-RioValle Jacqueline , González-Ruíz Katherine , Correa-Rodríguez María
Published: July 2019

The present study evaluated the ability of five obesity-related parameters, including a body shape index (ABSI), conicity index (CI), body roundness index (BRI), body mass index (BMI), and waist-to-height ratio (WtHR) for predicting increased cardiometabolic risk in a population of elderly Colombians. A cross-sectional study was conducted on 1502 participants (60.3% women, mean age 70 ± 7.6 years) and subjects’ weight, height, waist circumference, serum lipid indices, blood pressure, and fasting plasma glucose were measured. A cardiometabolic risk index (CMRI) was calculated using the participants’ systolic and diastolic blood pressure, triglycerides, high-density lipoprotein and fasting glucose levels, and waist circumference. Following the International Diabetes Federation definition, metabolic syndrome was defined as having three or more metabolic abnormalities. All surrogate anthropometric indices correlated significantly with CMRI (p < 0.01). Receiver operating characteristic curve analysis of how well the anthropometric indices identified high cardiometabolic risk showed that WtHR and BRI were the most accurate indices. The best WtHR and BRI cut-off points in men were 0.56 (area under curve, AUC 0.77) and 4.71 (AUC 0.77), respectively. For women, the WtHR and BRI cut-off points were 0.63 (AUC 0.77) and 6.20 (AUC 0.77), respectively. In conclusion, BRI and WtHR have a moderate discriminating power for detecting high cardiometabolic risk in older Colombian adults, supporting the idea that both anthropometric indices are useful screening tools for use in the elderly.
Role of Personalized Nutrition in Chronic-Degenerative Diseases
Authors: Di Renzo Laura , Gualtieri Paola , Romano Lorenzo , Marrone Giulia , Noce Annalisa , Pujia Alberto , Perrone Marco Alfonso , Aiello Vincenzo , Colica Carmela , De Lorenzo Antonino
Published: July 2019

Human nutrition is a branch of medicine based on foods biochemical interactions with the human body. The phenotypic transition from health to disease status can be attributed to changes in genes and/or protein expression. For this reason, a new discipline has been developed called “-omic science”. In this review, we analyzed the role of “-omics sciences” (nutrigenetics, nutrigenomics, proteomics and metabolomics) in the health status and as possible therapeutic tool in chronic degenerative diseases. In particular, we focused on the role of nutrigenetics and the relationship between eating habits, changes in the DNA sequence and the onset of nutrition-related diseases. Moreover, we examined nutrigenomics and the effect of nutrients on gene expression. We perused the role of proteomics and metabolomics in personalized nutrition. In this scenario, we analyzed also how dysbiosis of gut microbiota can influence the onset and progression of chronic degenerative diseases. Moreover, nutrients influencing and regulating gene activity, both directly and indirectly, paves the way for personalized nutrition that plays a key role in the prevention and treatment of chronic degenerative diseases.
In Vitro Cytotoxicity of Oleanolic/Ursolic Acids-Loaded in PLGA Nanoparticles in Different Cell Lines
Authors: Silva Amélia M. , Alvarado Helen L. , Abrego Guadalupe , Martins-Gomes Carlos , Garduño-Ramirez Maria L. , García María L. , Calpena Ana C. , Souto Eliana B.
Published: July 2019

Oleanolic (OA) and ursolic (UA) acids are recognized triterpenoids with anti-cancer properties, showing cell-specific activity that can be enhanced when loaded into polymeric nanoparticles. The cytotoxic activity of OA and UA was assessed by Alamar Blue assay in three different cell lines, i.e., HepG2 (Human hepatoma cell line), Caco-2 (Human epithelial colorectal adenocarcinoma cell line) and Y-79 (Human retinoblastoma cell line). The natural and synthetic mixtures of these compounds were tested as free and loaded in polymeric nanoparticles in a concentration range from 2 to 32 µmol/L. The highest tested concentrations of the free triterpene mixtures produced statistically significant cell viability reduction in HepG2 and Caco-2 cells, compared to the control (untreated cells). When loaded in the developed PLGA nanoparticles, no differences were recorded for the tested concentrations in the same cell lines. However, in the Y-79 cell line, a decrease on cell viability was observed when testing the lowest concentration of both free triterpene mixtures, and after their loading into PLGA nanoparticles.
An Ethnobotanical Survey of Medicinal Plants Used in Papantla, Veracruz, Mexico
Authors: Lara Reimers Eduardo Alberto , C. Eloy Fernández , Lara Reimers David J. , Chaloupkova Petra , Zepeda del Valle Juan Manuel , Milella Luigi , Russo Daniela
Published: July 2019

An ethnobotanical study was performed to collect information on the use of medicinal plants in Papantla, Veracruz, Mexico. The area has a high number of endemic species, and the social importance of the medicinal plants in the community is essential for public health and the conservation of traditional knowledge. This study identified the medicinal plants currently used, registered traditional knowledge, and documented the patterns of ailments treated in the indigenous communities of Totonacas. A total of 101 medicinal plants belonging to 51 families were described by 85 local informants. Asteraceae was the family with the highest number of plant species identified by these informants. Plant parts are used to treat several ailments, including venomous bites, gastro-intestinal disorders, infectious diseases and other disorders. Informants reported that the most common plant part used was the leaf tissue (55%), and they also took the herbal remedies orally (72%), and decoctions (38%) as well as infusions (29%) were the forms used to prepare these natural remedies. This study provides documentation of medicinal plants used in the Veracruz area of Mexico. Mexican people are still dependent upon medicinal plants, and in order to avoid their loss, certain measures of conservation for medicinal plants are needed.
Enhancing the Interfacial Adhesion with Rubber Matrix by Grafting Polydopamine-Carbon Nanotubes onto Poly(p-phenylene terephthalamide) Fibers
Authors: Yang Xuan , Tu Qunzhang , Shen Xinmin , Yin Qin , Pan Ming , Jiang Chengming , Hu Caibing
Published: July 2019

To enhance the interfacial adhesion between poly(p-phenylene terephthalamide) (PPTA) fibers and a rubber matrix without damaging the fiber structures, aminated carbon nanotubes (NH2-CNTs) were mildly deposited onto the fiber surface by combining the biomimetic modification of dopamine via the Michael addition reaction. Furthermore, differences between the “one-step” method and the “two-step” method were researched through adjusting the addition sequence of NH2-CNTs. The surface morphologies and chemical structures of PPTA fibers before and after modification were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). The mechanical properties of fibers and the adhesive properties with rubber were tested using an electronic tensile tester of single-filament and universal testing machine, respectively. After modification by the “one-step” method for 24 h, the single-filament tensile strength of the modified fibers increased by 16.5%, meanwhile, the pull-out force of the modified fibers to rubber increased by approximately 59.7%. Compared with the “two-step” method, the “one-step” method had superiority due to the short reaction time and the large deposition rate of CNTs.