bluuebunny/crossref_metadata_2025 huggingface dataset:
A Group Decision Framework for Renewable Energy Source Selection under Interval-Valued Probabilistic linguistic Term Set
Authors: Krishankumar Raghunathan , Mishra Arunodaya Raj , Ravichandran Kattur Soundarapandian , Peng Xindong , Zavadskas Edmundas Kazimieras , Cavallaro Fausto , Mardani Abbas
Published: February 2020

In recent years, the assessment of desirable renewable energy alternative has been an extremely important concern that could change the environment and economic growth. To tackle the circumstances, some authors have paid attention to selecting the desirable renewable energy option by employing the decision-making assessment and linguistic term sets. With a fast-growing interest in multi-criteria group decision-making (MCGDM) problems, researchers are tirelessly working towards new techniques for better decision-making. Decision makers (DMs) generally rate alternatives linguistically with different probabilities occurring for each term. Previous studies on linguistic decision-making have either ignored this idea or have used an only a single value for representing the weight of the linguistic term. Since expression of the complete probability distribution is hard and implicit hesitation exists, representation of weights of the linguistic terms using a single value becomes imprecise and unreasonable. To avoid this challenge, an interval-valued probabilistic linguistic term set (IVPLTS) is used, which is a generalization of (probabilistic linguistic term set) PLTS. Inspired by the usefulness of IVPLTS concept, we develop a decision framework for rational decision making. Initially, some operational laws and axioms are presented. Further, a novel aggregation operator known as interval-valued probabilistic linguistic simple weighted geometry (IVPLSWG) is developed for aggregating DMs’ preferences. Also, criteria weights are determined using the newly developed interval-valued probabilistic linguistic standard variance (IVPLSV) approach and alternatives are ranked using the extended VIKOR (VlseKriterijumskaOptimizacijaKompromisnoResenje) method under IVPLTS environment. Finally, a numerical example of renewable energy assessment is demonstrated to show the practicality of the developed decision framework. Also, the strengths and weaknesses of the developed decision framework are illustrated by comparison with existing ones.
A Criterion of Heat Transfer Deterioration for Supercritical Organic Fluids Flowing Upward and Its Heat Transfer Correlation
Authors: Li Yung-Ming , Liaw Jane-Sunn , Wang Chi-Chuan
Published: February 2020

The main objective of this study was to develop the supercritical heat transfer correlation applicable for organic fluids when flowing upward in smooth tubes based on the available experimental data. The organic fluids contain R-22, R-134a, R-245fa and Ethanol and the associated heat transfer characteristics were compared with non-organic fluids like water and carbon-dioxide (CO2). It was found that the limit heat flux may result in heat transfer deterioration (HTD) of organic fluid and the corresponding values are much smaller than water or CO2. A new criterion to predict the HTD was developed and this criterion yields the best predictive ability against database. It was found that HTD occurs can be well described by the acceleration parameter evaluated at the wall condition rather than at bulk condition. For estimation of the supercritical heat transfer coefficient (HTC) for organic fluid, the present study proposes a new correlation with a physically based correction factor, which gives satisfactory predictions against the HTC of supercritical organic fluid. The new correlation can offer the smallest average deviation of 0.007 and standard deviation of 0.181 among the existing correlations.
Effect of Injection Strategies in Diesel/NG Direct-Injection Engines on the Combustion Process and Emissions under Low-Load Operating Conditions
Authors: Li Jinze , Deng Longfei , Guo Jianjun , Zhang Min , Zi Zhenyuan , Zhang Jie , Wu Binyang
Published: February 2020

The direct injection of natural gas (NG), which is an important research direction in the development of NG engines, has the potential to improve thermal efficiency and emissions. When NG engines operate in low-load conditions, combustion efficiency decreases and hydrocarbon (HC) emissions increase due to lean fuel mixtures and slow flame propagation speeds. The effect of two combustion modes (partially premixed compression ignition (PPCI) and high pressure direct injection (HPDI)) on combustion processes was investigated by CFD (Computational Fluid Dynamics), with a focus on different injection strategies. In the PPCI combustion mode, NG was injected early in the compression stroke and premixed with air, and then the pilot diesel was injected to cause ignition near the top dead center. This combustion mode produced a faster heat release rate, but the HC emissions were higher, and the combustion efficiency was lower. In the HPDI combustion mode, the diesel was injected first and ignited, and then the NG was injected into the flame. This combustion mode resulted in higher emissions of NOx and soot, with a diffusion combustion in the cylinder. HC emissions significantly decreased. Compared with PPCI combustion, HPDI had a higher thermal efficiency.
Simulation-Based Methodology for Determining the Dynamic Strength of Tire Inflation Restraining Devices
Authors: Karliński Jacek , Ptak Mariusz , Chybowski Leszek
Published: February 2020

The article suggests and supports a simulation-based methodology for determining whether the dynamic strength of tire inflation restraining devices for tire inflation meet quality requirements and ensure operator safety during a potential tire explosion. Dynamic strength tests using an NM-600 safety shield and NK-0728 safety cage during a 29.5 R25X tire explosion at a pressure of 10 bar were presented as an example application of this methodology. The shield was subjected to destructive tests involving the use of a 2200 kg impactor, dropping it so that the minimum kinetic energy reached 20 kJ at the time of impact. Analyzed devices were constructed of S355 steel in accordance with EN 10025. The Cowper–Symonds model of material for strain rate phenomena was used in the calculations. Simulations of a 20 kJ ring impact against the cage were performed. The equivalent stress distribution was determined, and displacement contour lines for the maximum dynamic deformation value and plastic deformation were calculated. The plastic displacement obtained in numerical tests was equal to the permanent deformation recorded in the experimental test. Further, the simulations showed that the examined cage met the assumed strength criteria. The conducted tests confirmed the usefulness of the proposed methodology for assessing the dynamic strength of safety cages and shields for tire inflation. The full-scale, physical cage testing is difficult to implement because it requires placing a ring impacting the cage wall. This is a major boundary for closed cages, as considered in this publication. Thus, simulation-based methods are becoming a principal tool for safety assessment of tire inflation restraining devices.
Mitigation Life Cycle Assessment: Best Practices from LCA of Energy and Water Infrastructure That Incurs Impacts to Mitigate Harm
Authors: Grubert Emily , Stokes-Draut Jennifer
Published: February 2020

Climate change will require societal-scale infrastructural changes. Balancing priorities for water, energy, and climate will demand that approaches to water and energy management deviate from historical practice. Infrastructure designed to mitigate environmental harm, particularly related to climate change, is likely to become increasingly prevalent. Understanding the implications of such infrastructure for environmental quality is thus of interest. Environmental life cycle assessment (LCA) is a common sustainability assessment tool that aims to quantify the total, multicriteria environmental impact caused by a functional unit. Notably, however, LCA quantifies impacts in the form of environmental “costs” of delivering the functional unit. In the case of mitigation infrastructures, LCA results can be confusing because they are generally reported as the harmful impacts of performing mitigation rather than as net impacts that incorporate benefits of successful mitigation. This paper argues for defining mitigation LCA as a subtype of LCA to facilitate better understanding of results and consistency across studies. Our recommendations are informed by existing LCA literature on mitigation infrastructure, focused particularly on stormwater and carbon management. We specifically recommend that analysts: (1) use a performance-based functional unit; (2) be attentive to burden shifting; and (3) assess and define uncertainty, especially related to mitigation performance.
A New Framework to Quantify the Wetting Behaviour of Carbonate Rock Surfaces Based on the Relationship between Zeta Potential and Contact Angle
Authors: Rezaei Gomari Sina , Amrouche Farida , Santos Ronaldo G. , Greenwell Hugh Christopher , Cubillas Pablo
Published: February 2020

This study introduces a new framework to quantify the wettability of powdered carbonate rock from existing correlations between zeta potential and contact angle. The new framework has the potential to be faster and cheaper than conventional approaches and could increase confidence in surface wetting quantification, since the results are insensitive to the inherent heterogeneity of rock surfaces. The obtained results from experiments were used to develop a set of equations for determining the carbonate rock contact angle from streaming potential data. The equations were validated for the evaluation of changes in the wettability of carbonate rock using different stearic acid oily solutions. The contact angles calculated from the proposed equations were then compared with measured values on the calcite surface. The results show that the proposed framework was able to quantify the wettability of carbonate rock with an acceptable range of error of about 4%–14%.
Study on the Effectiveness of Sulfate-Reducing Bacteria Combined with Coal Gangue in Repairing Acid Mine Drainage Containing Fe and Mn
Authors: Dong Yanrong , Di Junzhen , Yang Zhenhua , Zhang Yuanling , Wang Xianjun , Guo Xuying , Li Zhennan , Jiang Guoliang
Published: February 2020

In view of the characteristics of the high content of SO42−, Fe2+ and Mn2+ in acid mine drainage (AMD) and low pH value, based on adsorption and biological methods, coal gangue was combined with sulfate-reducing bacteria (SRB). On this basis, four dynamic columns, including Column 1 (SRB combined with spontaneous combustion gangue from the Gaode coal mine), Column 2 (SRB combined with spontaneous combustion gangue from Haizhou), Column 3 (SRB combined with gangue from Haizhou), and Column 4 (SRB combined with gangue from Shanxi), were constructed. The efficacy of four columns was compared by the inflow of AMD with different pollution load. Results showed that the repair effect of four columns was: Column 3 > Column 2 > Column 1 > Column 4. In the second stage of the experiment, the repair effect of Column 3 was the best. The average effluent pH value and oxidation reduction potential (ORP) value were 9.09 and –262.83 mV, the highest removal percentages of chemical oxygen demand (COD) and SO42− were 84.41% and 72.73%, and the average removal percentages of Fe2+, Mn2+ were 98.70% and 79.97%, respectively. At the end of the experiment, when deionized water was injected, the fixed effect of AMD in the four columns was stable and no secondary release appeared.
Sensitivity Analysis of an Implanted Antenna within Surrounding Biological Environment
Authors: Ding Shuoliang , Pichon Lionel
Published: February 2020

The paper describes the sensitivity analysis of a wireless power transfer link involving an implanted antenna within the surrounding biological environment. The approach combines a 3D electromagnetic modeling and a surrogate model (based polynomial chaos expansion). The analysis takes into account geometrical parameters of the implanted antenna and physical properties of the biological tissue. It allows researchers to identify at low cost the main parameters affecting the efficiency of the transmission link.
Growth-Ring Analysis of Diploknema butyracea Is a Potential Tool for Revealing Indigenous Land Use History in the Lower Himalayan Foothills of Nepal
Authors: Chowdhury Md. Qumruzzaman , Bhattarai Teeka Ram , De Ridder Maaike , Beeckman Hans
Published: February 2020

Slash-and-burn is a farming practice of the indigenous communities in the Himalayan foothills of Nepal. The traditional land-tenure system is based on a customary oral tradition. However, the government’s persistent denial of land rights has fueled the indigenous conflicts in the last few decades. Deliverance of scientific evidence-based arguments may underpin the ongoing conflict-resolution dialogues between the authorities and the indigenous communities. Dating growth rings of trees in a slash-and-burn system might help the indigenous people to find evidence of their historic land uses in the mountainous landscape. In this pilot study, we examined the potential of Diploknema butyracea (Roxb.) H. J. Lam growth rings for documenting land use history of Nepalese indigenous farming practices, as this species is being preserved during the slash-and-burn practices. The species is an economically important and ecologically interesting (as it flushes leaves when everything is dry, and sheds leaves while everything is green) deciduous tree species belonging to Sapotaceae family and widely distributed in Sub-Himalayan tracts. Five stem discs were studied which were originated from the Kandrang valley of the Chitwan district, Nepal. For the first time, we revealed distinct growth rings in this species which are marked by fibers with thicker cell walls. Growth-ring anomalies, i.e., wedging and partially missing rings, were also found. Four out of five samples could be crossdated at a marginal level (GLK ≥ 60 and t ≥ 2.0) which is a confirmation of the annual nature of growth rings. One of the samples showed black spots of oxidized wood which are traces of fire, suggesting evidence of slash-and-burn practices in the study area since 1933. This study suggests a strong potential of D. butyracea for growth-ring analysis to reconstruct indigenous land use history in Nepal.
Detrital Zircon Provenance and Lithofacies Associations of Montmorillonitic Sands in the Maastrichtian Ripley Formation: Implications for Mississippi Embayment Paleodrainage Patterns and Paleogeography
Authors: Gifford Jennifer N. , Vitale Elizabeth J. , Platt Brian F. , Malone David H. , Widanagamage Inoka H.
Published: February 2020

We provide new detrital zircon evidence to support a Maastrichtian age for the establishment of the present-day Mississippi River drainage system. Fieldwork conducted in Pontotoc County, Mississippi, targeted two sites containing montmorillonitic sand in the Maastrichtian Ripley Formation. U-Pb detrital zircon (DZ) ages from these sands (n = 649) ranged from Mesoarchean (~2870 Ma) to Pennsylvanian (~305 Ma) and contained ~91% Appalachian-derived grains, including Appalachian–Ouachita, Gondwanan Terranes, and Grenville source terranes. Other minor source regions include the Mid-Continent Granite–Rhyolite Province, Yavapai–Mazatzal, Trans-Hudson/Penokean, and Superior. This indicates that sediment sourced from the Appalachian Foreland Basin (with very minor input from a northern or northwestern source) was being routed through the Mississippi Embayment (MSE) in the Maastrichtian. We recognize six lithofacies in the field areas interpreted as barrier island to shelf environments. Statistically significant differences between DZ populations and clay mineralogy from both sites indicate that two distinct fluvial systems emptied into a shared back-barrier setting, which experienced volcanic ash input. The stratigraphic positions of the montmorillonitic sands suggest that these deposits represent some of the youngest Late Cretaceous volcanism in the MSE.
An Exploration of Differences Between Deliberate Self-Harm with and without Suicidal Intent Amongst a Clinical Sample of Young People in Singapore: A Cross-Sectional Study
Authors: Samari Ellaisha , Shahwan Shazana , Abdin Edimansyah , Zhang YunJue , Sambasivam Rajeswari , Teh Wen Lin , Ong Say How , Chong Siow Ann , Subramaniam Mythily
Published: February 2020

This study examined differences between young people with mental illness who engage in deliberate self-harm with and without suicidal intent, as well as socio-demographic and clinical factors that are related to the increased likelihood of suicide attempt amongst self-harming young people. A total of 235 outpatients with mental illness who had engaged in deliberate self-harm were recruited from a tertiary psychiatric hospital in Singapore. Participants completed a self-report questionnaire which collected information on their socio-demographic background, self-harm history, diagnosis, depressive symptoms and childhood trauma. A total of 31.1% had reported a history of attempted suicide. Multiple logistic regression conducted found that engaging in self-harm ideation between 1 and 7 days (OR = 4.3, p = 0.30), and more than 1 week (OR = 10.5, p < 0.001) (versus no engagement in any self-harm ideation at all), were significantly associated with greater likelihood of attempted suicide. This study reports a relatively high prevalence rate of reported suicide attempts amongst young people with mental illness who engaged in self-harm. Identifying self-harm behaviors and treating it early could be the first step in managing potential suicidal behaviors among those who engage in self-harm.
The Influence of the Teacher’s Prosocial Skills on the Mindwandering, Creative Intelligence, Emotions, and Academic Performance of Secondary Students in the Area of Physical Education Classes
Authors: Trigueros Ruben , García-Tascón Marta , Gallardo Ana M. , Alías Antonio , Aguilar-Parra José M.
Published: February 2020

Physical Education classes are a key context for the development of creativity due to interactions with peers and the resolution of complex motor skills. Therefore, the aim of this study is to analyze the influence of the teacher’s social behaviors on the mindwandering, emotional state, and academic performance of Physical Education students. The study involved 606 high school students and 36 physical education teachers. A structural equation model was used to analyze the relationship between the variables of the study. The results showed how the teacher’s prosocial and antisocial behaviors had a negative influence on mindwandering. In turn, mindwandering negatively predicted creative intelligence. Likewise, creative intelligence positively predicted a positive emotional state and academic performance and negatively predicted a negative emotional state. Finally, a positive emotional state positively predicted academic performance, while a negative emotional state predicted it negatively. Therefore, the results achieved in the study showed how mindwandering should be promoted in the educational field as a means of encouraging creativity and therefore increasing the well-being of students, which is conducive to academic performance.
Behavioural Determinants of Hand Washing and Glove Recontamination before Aseptic Procedures at Birth: A Time-and-Motion Study and Survey in Zanzibar Labour Wards
Authors: Gon Giorgia , Virgo Sandra , de Barra Mícheál , Ali Said M. , Campbell Oona M. , Graham Wendy J. , Nash Stephen , Woodd Susannah L. , de Bruin Marijn
Published: February 2020

Recent research calls for distinguishing whether the failure to comply with World Health Organisation hand hygiene guidelines is driven by omitting to rub/wash hands, or subsequently recontamination of clean hands or gloves prior to a procedure. This study examined the determinants of these two behaviours. Across the 10 highest-volume labour wards in Zanzibar, we observed 103 birth attendants across 779 hand hygiene opportunities before aseptic procedures (time-and-motion methods). They were then interviewed using a structured cross-sectional survey. We used mixed-effect multivariable logistic regressions to investigate the independent association of candidate determinants with hand rubbing/washing and avoiding glove recontamination. After controlling for confounders, we found that availability of single-use material to dry hands (OR:2.9; CI:1.58–5.14), a higher workload (OR:29.4; CI:12.9–67.0), more knowledge about hand hygiene (OR:1.89; CI:1.02–3.49), and an environment with more reminders from colleagues (OR:1.20; CI:0.98–1.46) were associated with more hand rubbing/washing. Only the length of time elapsed since donning gloves (OR:4.5; CI:2.5–8.0) was associated with avoiding glove recontamination. We identified multiple determinants of hand washing/rubbing. Only time elapsed since washing/rubbing was reliably associated with avoiding glove recontamination. In this setting, these two behaviours require different interventions. Future studies should measure them separately.
Behavioural Effects of Spatially Structured Scoring Systems in Location-Based Serious Games—A Case Study in the Context of OpenStreetMap
Authors: Westerholt Rene , Lorei Heinrich , Höfle Bernhard
Published: February 2020

Location-based games have become popular in recent years, with Pokémon Go and Ingress being two very prominent examples. Some location-based games, known as Serious Games, go beyond entertainment and serve additional purposes such as data collection. Such games are also found in the OpenStreetMap context and playfully enrich the project’s geodatabase. Examples include Kort and StreetComplete. This article examines the role of spatially structured scoring systems as a motivational element. It is analysed how spatial structure in scoring systems is correlated with changes observed in the game behaviour. For this purpose, our study included two groups of subjects who played a modified game based on StreetComplete in a real urban environment. One group played the game with a spatially structured scoring system and the other with a spatially random scoring system. We evaluated different indicators and analysed the players’ GPS trajectories. In addition, the players filled out questionnaires to investigate whether they had become aware of the scoring system they were playing. The results obtained show that players who are confronted with a spatially structured scoring system are more likely to be in areas with high scores, have a longer playing time, walk longer distances and are more willing to take detours. Furthermore, discrepancies between the perception of a possible system in the scoring system and corresponding actions were revealed. The results are informative for game design, but also for a better understanding of how players interact with their geographical context during location-based games.
Spatiotemporal Characteristics and Driving Force Analysis of Flash Floods in Fujian Province
Authors: Xiong Junnan , Pang Quan , Fan Chunkun , Cheng Weiming , Ye Chongchong , Zhao Yunliang , He Yuanrong , Cao Yifan
Published: February 2020

Flash floods are one of the most destructive natural disasters. The comprehensive identification of the spatiotemporal characteristics and driving factors of a flash flood is the basis for the scientific understanding of the formation mechanism and the distribution characteristics of flash floods. In this study, we explored the spatiotemporal patterns of flash floods in Fujian Province from 1951 to 2015. Then, we analyzed the driving forces of flash floods in geomorphic regions with three different grades based on three methods, namely, geographical detector, principal component analysis, and multiple linear regression. Finally, the sensitivity of flash floods to the gross domestic product, village point density, annual maximum one-day precipitation (Rx1day), and annual total precipitation from days > 95th percentile (R95p) was analyzed. The analytical results indicated that (1) The counts of flash floods rose sharply from 1988, and the spatial distribution of flash floods mainly extended from the coastal low mountains, hills, and plain regions of Fujian (IIA2) to the low-middle mountains, hills, and valley regions in the Wuyi mountains (IIA4) from 1951 to 2015. (2) From IIA2 to IIA4, the impact of human activities on flash floods was gradually weakened, while the contribution of precipitation indicators gradually strengthened. (3) The sensitivity analysis results revealed that the hazard factors of flash floods in different periods and regions had significant differences in Fujian Province. Based on the above results, it is necessary to accurately forecast extreme precipitation and improve the economic development model of the IIA2 region.
Galectin 3 Deficiency Alters Chondrocyte Primary Cilium Formation and Exacerbates Cartilage Destruction via Mitochondrial Apoptosis
Authors: Hafsia Narjès , Forien Marine , Renaudin Félix , Delacour Delphine , Reboul Pascal , Van Lent Peter , Cohen-Solal Martine , Lioté Frédéric , Poirier Françoise , Ea Hang Korng
Published: February 2020

Mechanical overload and aging are the main risk factors of osteoarthritis (OA). Galectin 3 (GAL3) is important in the formation of primary cilia, organelles that are able to sense mechanical stress. The objectives were to evaluate the role of GAL3 in chondrocyte primary cilium formation and in OA in mice. Chondrocyte primary cilium was detected in vitro by confocal microscopy. OA was induced by aging and partial meniscectomy of wild-type (WT) and Gal3-null 129SvEV mice (Gal3−/−). Primary chondrocytes were isolated from joints of new-born mice. Chondrocyte apoptosis was assessed by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), caspase 3 activity and cytochrome c release. Gene expression was assessed by qRT-PCR. GAL3 was localized at the basal body of the chondrocyte primary cilium. Primary cilia of Gal3−/− chondrocytes were frequently abnormal and misshapen. Deletion of Gal3 triggered premature OA during aging and exacerbated joint instability-induced OA. In both aging and surgery-induced OA cartilage, levels of chondrocyte catabolism and hypertrophy markers and apoptosis were more severe in Gal3−/− than WT samples. In vitro, Gal3 knockout favored chondrocyte apoptosis via the mitochondrial pathway. GAL3 is a key regulator of cartilage homeostasis and chondrocyte primary cilium formation in mice. Gal3 deletion promotes OA development.
Glioblastoma Cells Do Not Affect Axitinib-Dependent Senescence of HUVECs in a Transwell Coculture Model
Authors: Merolle Matilde , Mongiardi Maria Patrizia , Piras Maurizia , Levi Andrea , Falchetti Maria Laura
Published: February 2020

Axitinib is an orally available inhibitor of tyrosine kinases, with high specificity for vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. It is approved for the treatment of advanced renal cell carcinoma and is in phase II clinical trials for recurrent glioblastoma (GBM). GBM is a brain tumor peculiar in its ability to induce neoangiogenesis. Since both GBM tumor cells and endothelial cells of tumor vasculature express VEGFRs, Axitinib exerts its inhibitory action on both tumor and endothelial cells. We and others previously demonstrated that Axitinib triggers cellular senescence. In particular, Axitinib-dependent senescence of HUVECs (human umbilical vein endothelial cells) is accompanied by intracellular reactive oxygen species(ROS) increase and early ataxia telangiectasia mutated(ATM) activation. Here we wondered if the presence of glioblastoma tumor cells could affect the HUVEC senescence upon Axitinib exposure. To address this issue, we cocultured HUVECs together with GBM tumor cells in transwell plates. HUVEC senescence did not result in being affected by GBM cells, neither in terms of β galactosidase activity nor of proliferation index or ATM phosphorylation. Conversely, Axitinib modulation of HUVEC gene expression was altered by cocultured GBM cells. These data demonstrate that the GBM secretome modifies HUVECs’ transcriptomic profile upon Axitinib exposure, but does not prevent drug-induced senescence.
Alpha 1-Antitrypsin Deficiency: A Disorder of Proteostasis-Mediated Protein Folding and Trafficking Pathways
Authors: Karatas Esra , Bouchecareilh Marion
Published: February 2020

Human cells express large amounts of different proteins continuously that must fold into well-defined structures that need to remain correctly folded and assemble in order to ensure their cellular and biological functions. The integrity of this protein balance/homeostasis, also named proteostasis, is maintained by the proteostasis network (PN). This integrated biological system, which comprises about 2000 proteins (chaperones, folding enzymes, degradation components), control and coordinate protein synthesis folding and localization, conformational maintenance, and degradation. This network is particularly challenged by mutations such as those found in genetic diseases, because of the inability of an altered peptide sequence to properly engage PN components that trigger misfolding and loss of function. Thus, deletions found in the ΔF508 variant of the Cystic Fibrosis (CF) transmembrane regulator (CFTR) triggering CF or missense mutations found in the Z variant of Alpha 1-Antitrypsin deficiency (AATD), leading to lung and liver diseases, can accelerate misfolding and/or generate aggregates. Conversely to CF variants, for which three correctors are already approved (ivacaftor, lumacaftor/ivacaftor, and most recently tezacaftor/ivacaftor), there are limited therapeutic options for AATD. Therefore, a more detailed understanding of the PN components governing AAT variant biogenesis and their manipulation by pharmacological intervention could delay, or even better, avoid the onset of AATD-related pathologies.
Peptidylarginine Deiminase Isozyme-Specific PAD2, PAD3 and PAD4 Inhibitors Differentially Modulate Extracellular Vesicle Signatures and Cell Invasion in Two Glioblastoma Multiforme Cell Lines
Authors: Uysal-Onganer Pinar , MacLatchy Amy , Mahmoud Rayan , Kraev Igor , Thompson Paul R. , Inal Jameel M. , Lange Sigrun
Published: February 2020

Glioblastoma multiforme (GBM) is an aggressive adult brain tumour with poor prognosis. Roles for peptidylarginine deiminases (PADs) in GBM have recently been highlighted. Here, two GBM cell lines were treated with PAD2, PAD3 and PAD4 isozyme-specific inhibitors. Effects were assessed on extracellular vesicle (EV) signatures, including EV-microRNA cargo (miR21, miR126 and miR210), and on changes in cellular protein expression relevant for mitochondrial housekeeping (prohibitin (PHB)) and cancer progression (stromal interaction molecule 1 (STIM-1) and moesin), as well as assessing cell invasion. Overall, GBM cell-line specific differences for the three PAD isozyme-specific inhibitors were observed on modulation of EV-signatures, PHB, STIM-1 and moesin protein levels, as well as on cell invasion. The PAD3 inhibitor was most effective in modulating EVs to anti-oncogenic signatures (reduced miR21 and miR210, and elevated miR126), to reduce cell invasion and to modulate protein expression of pro-GBM proteins in LN229 cells, while the PAD2 and PAD4 inhibitors were more effective in LN18 cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins relating to cancer, metabolism and inflammation differed between the two GBM cell lines. Our findings highlight roles for the different PAD isozymes in the heterogeneity of GBM tumours and the potential for tailored PAD-isozyme specific treatment.
Genetic Dissection of Phomopsis Stem Canker Resistance in Cultivated Sunflower Using High Density SNP Linkage Map
Authors: Talukder Zahirul I. , Underwood William , Ma Guojia , Seiler Gerald J. , Misar Christopher G. , Cai Xiwen , Qi Lili
Published: February 2020

Phomopsis stem canker (PSC) caused by Diaporthe helianthi is increasingly becoming a global threat for sunflower production. In this study, the genetic basis of PSC resistance was investigated in a recombinant inbred line (RIL) population developed from a cross between HA 89 (susceptible) and HA-R3 (resistant). The RIL population was evaluated for PSC disease incidence (DI) in seven screening trials at multiple locations during 2016–2018. The distribution of PSC DI in the RIL population was continuous, confirming a polygenic inheritance of the trait. A moderately high broad-sense heritability (H2, 0.76) was estimated for the trait across environments. In the combined analysis, both the genotype and the genotype × environment interactions were highly significant. A linkage map spanning 1505.33 cM was constructed using genotyping-by-sequencing derived markers. Marker–trait association analysis identified a total of 15 quantitative trait loci (QTL) associated with PSC resistance on 11 sunflower chromosomes, each explaining between 5.24 and 17.39% of the phenotypic variation. PSC resistance QTL were detected in two genomic regions each on chromosomes 3, 5, 13, and 17, while one QTL each was detected in the remaining seven chromosomes. Tightly linked single nucleotide polymorphism (SNP) markers flanking the PSC resistance QTL will facilitate marker-assisted selection in PSC resistance sunflower breeding.
Beyond IgE: Alternative Mast Cell Activation Across Different Disease States
Authors: Lyons David O. , Pullen Nicholas A.
Published: February 2020

Mast cells are often regarded through the lens of IgE-dependent reactions as a cell specialized only for anti-parasitic and type I hypersensitive responses. However, recently many researchers have begun to appreciate the expansive repertoire of stimuli that mast cells can respond to. After the characterization of the interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) axis of mast cell activation—a pathway that is independent of the adaptive immune system—researchers are revisiting other stimuli to induce mast cell activation and/or subsequent degranulation independent of IgE. This discovery also underscores that mast cells act as important mediators in maintaining body wide homeostasis, especially through barrier defense, and can thus be the source of disease as well. Particularly in the gut, inflammatory bowel diseases (Crohn’s disease, ulcerative colitis, etc.) are characterized with enhanced mast cell activity in the context of autoimmune disease. Mast cells show phenotypic differences based on tissue residency, which could manifest as different receptor expression profiles, allowing for unique mast cell responses (both IgE and non-IgE mediated) across varying tissues as well. This variety in receptor expression suggests mast cells respond differently, such as in the gut where immunosuppressive IL-10 stimulates the development of food allergy or in the lungs where transforming growth factor-β1 (TGF-β1) can enhance mast cell IL-6 production. Such differences in receptor expression illustrate the truly diverse effector capabilities of mast cells, and careful consideration must be given toward the phenotype of mast cells observed in vitro. Given mast cells’ ubiquitous tissue presence and their capability to respond to a broad spectrum of non-IgE stimuli, it is expected that mast cells may also contribute to the progression of autoimmune disorders and other disease states such as metastatic cancer through promoting chronic inflammation in the local tissue microenvironment and ultimately polarizing toward a unique Th17 immune response. Furthermore, these interconnected, atypical activation pathways may crosstalk with IgE-mediated signaling differently across disorders such as parasitism, food allergies, and autoimmune disorders of the gut. In this review, we summarize recent research into familiar and novel pathways of mast cells activation and draw connections to clinical human disease.
Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases
Authors: Raffaeli William , Malafoglia Valentina , Bonci Antonello , Tenti Michael , Ilari Sara , Gremigni Paola , Iannuccelli Cristina , Gioia Chiara , Di Franco Manuela , Mollace Vincenzo , Vitiello Laura , Tomino Carlo , Muscoli Carolina
Published: February 2020

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease.
From R-Loops to G-Quadruplexes: Emerging New Threats for the Replication Fork
Authors: Maffia Antonio , Ranise Cecilia , Sabbioneda Simone
Published: February 2020

Replicating the entire genome is one of the most complex tasks for all organisms. Research carried out in the last few years has provided us with a clearer picture on how cells preserve genomic information from the numerous insults that may endanger its stability. Different DNA repair pathways, coping with exogenous or endogenous threat, have been dissected at the molecular level. More recently, there has been an increasing interest towards intrinsic obstacles to genome replication, paving the way to a novel view on genomic stability. Indeed, in some cases, the movement of the replication fork can be hindered by the presence of stable DNA: RNA hybrids (R-loops), the folding of G-rich sequences into G-quadruplex structures (G4s) or repetitive elements present at Common Fragile Sites (CFS). Although differing in their nature and in the way they affect the replication fork, all of these obstacles are a source of replication stress. Replication stress is one of the main hallmarks of cancer and its prevention is becoming increasingly important as a target for future chemotherapeutics. Here we will try to summarize how these three obstacles are generated and how the cells handle replication stress upon their encounter. Finally, we will consider their role in cancer and their exploitation in current chemotherapeutic approaches.
Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme
Authors: Mazurek Marek , Litak Jakub , Kamieniak Piotr , Osuchowska Ida , Maciejewski Ryszard , Roliński Jacek , Grajkowska Wiesława , Grochowski Cezary
Published: February 2020

Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%–3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients’ bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.
LDAI-ISPS: LncRNA–Disease Associations Inference Based on Integrated Space Projection Scores
Authors: Zhang Yi , Chen Min , Li Ang , Cheng Xiaohui , Jin Hong , Liu Yarong
Published: February 2020

Long non-coding RNAs (long ncRNAs, lncRNAs) of all kinds have been implicated in a range of cell developmental processes and diseases, while they are not translated into proteins. Inferring diseases associated lncRNAs by computational methods can be helpful to understand the pathogenesis of diseases, but those current computational methods still have not achieved remarkable predictive performance: such as the inaccurate construction of similarity networks and inadequate numbers of known lncRNA–disease associations. In this research, we proposed a lncRNA–disease associations inference based on integrated space projection scores (LDAI-ISPS) composed of the following key steps: changing the Boolean network of known lncRNA–disease associations into the weighted networks via combining all the global information (e.g., disease semantic similarities, lncRNA functional similarities, and known lncRNA–disease associations); obtaining the space projection scores via vector projections of the weighted networks to form the final prediction scores without biases. The leave-one-out cross validation (LOOCV) results showed that, compared with other methods, LDAI-ISPS had a higher accuracy with area-under-the-curve (AUC) value of 0.9154 for inferring diseases, with AUC value of 0.8865 for inferring new lncRNAs (whose associations related to diseases are unknown), with AUC value of 0.7518 for inferring isolated diseases (whose associations related to lncRNAs are unknown). A case study also confirmed the predictive performance of LDAI-ISPS as a helper for traditional biological experiments in inferring the potential LncRNA–disease associations and isolated diseases.
GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease–A Systematic Review
Authors: Mori Yusaku , Matsui Takanori , Hirano Tsutomu , Yamagishi Sho-ichi
Published: February 2020

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that are secreted from enteroendocrine L cells and K cells in response to digested nutrients, respectively. They are also referred to incretin for their ability to stimulate insulin secretion from pancreatic beta cells in a glucose-dependent manner. Furthermore, GLP-1 exerts anorexic effects via its actions in the central nervous system. Since native incretin is rapidly inactivated by dipeptidyl peptidase-4 (DPP-4), DPP-resistant GLP-1 receptor agonists (GLP-1RAs), and DPP-4 inhibitors are currently used for the treatment of type 2 diabetes as incretin-based therapy. These new-class agents have superiority to classical oral hypoglycemic agents such as sulfonylureas because of their low risks for hypoglycemia and body weight gain. In addition, a number of preclinical studies have shown the cardioprotective properties of incretin-based therapy, whose findings are further supported by several randomized clinical trials. Indeed, GLP-1RA has been significantly shown to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes. However, the role of GIP in cardiovascular disease remains to be elucidated. Recently, pharmacological doses of GIP receptor agonists (GIPRAs) have been found to exert anti-obesity effects in animal models. These observations suggest that combination therapy of GLP-1R and GIPR may induce superior metabolic and anti-diabetic effects compared with each agonist individually. Clinical trials with GLP-1R/GIPR dual agonists are ongoing in diabetic patients. Therefore, in this review, we summarize the cardiovascular effects of GIP and GIPRAs in cell culture systems, animal models, and humans.
Green Synthesis of Silver Nanoparticles Using Pseudoduganella eburnea MAHUQ-39 and Their Antimicrobial Mechanisms Investigation against Drug Resistant Human Pathogens
Authors: Huq Md. Amdadul
Published: February 2020

Silver nanoparticles (AgNPs) have shown great promise in biomedical applications. The exact mechanism and mode of action of AgNPs regarding antimicrobial activity are still not well known. Moreover, synthesis of nanoparticles by physical and chemical methods is expensive and not ecofriendly. This study highlights the green, rapid, facile, cost-effective and ecofriendly synthesis of AgNPs using Pseudoduganella eburnea MAHUQ-39 and also investigates their antibacterial mechanisms. The transmission electron microscopy (TEM) image revealed a spherical shape of the AgNPs. The size of the synthesized AgNPs was 8 to 24 nm. The elemental mapping and selected area electron diffraction (SAED) and X-ray diffraction (XRD) patterns revealed the crystalline structure of AgNPs. Fourier-transform infrared spectroscopy (FTIR) analysis identified the functional groups that are involved in the reduction of silver ion to AgNPs. The green synthesized AgNPs exhibited strong antimicrobial activity against multidrug-resistant pathogenic microbes. Minimal inhibitory concentrations (MICs) of Staphylococcus aureus and Pseudomonas aeruginosa were 100 μg/mL and 6.25 μg/mL, respectively, and the minimum bactericidal concentrations (MBCs) of S. aureus and P. aeruginosa were 200 μg/mL and 50 μg/mL, respectively. Our data demonstrated that synthesized AgNPs created structural changes of cells and destroyed the membrane integrity of strains S. aureus and P. aeruginosa. Therefore, AgNPs synthesized by strain MAHUQ-39 can be used as a powerful antimicrobial agent for various therapeutic applications.
Dynamics of the Transcriptome Response to Heat in the Moss, Physcomitrella patens
Authors: Elzanati Osama , Mouzeyar Said , Roche Jane
Published: February 2020

Thermal stress negatively impacts crop yields, and as the overall temperature of the earth’s atmosphere is gradually increasing, the identification of the temperature transduction pathway of the heat signal is essential in developing new strategies in order to adapt plant breeding to warmer climates. Heat stress damages the molecular structures and physiological processes in plants in proportion to the level and duration of the stress, which leads to different types of responses. In general, plants respond more efficiently when they are first subjected to a moderate temperature increase before being subjected to a higher temperature stress. This adaptive response is called the acclimation period and has been investigated in several plant species. However, there is a lack of information on the dynamic of the Heat Shock Response (HSR) over a continuous period of temperature rise without an acclimation period. In this paper, we investigated the effects of mild (30 °C) and high (37 °C) continuous heat stress over a 24-h period. Through RNA-Seq analysis, we assessed the remodeling of the transcriptome in the moss Physcomitrella patens. Our results showed that the 30 °C treatment particularly affected the expression of a few genes at 1 and 24 h, suggesting a biphasic response. Up-regulated genes at 1 h encode mainly HSR proteins (protein folding and endoplasmic reticulum stress), indicating an early heat response; while the up-regulated genes at 24 h belong to the thiamine biosynthesis pathway. In contrast, the genes involved in photosynthesis and carbon partitioning were repressed by this treatment. Under a higher temperature stress (37 °C), the induction of the HSR occurred rapidly (1 h) and was then attenuated throughout the time points investigated. A network approach (Weighted Gene Correlation Network Analysis, WGCNA) was used to identify the groups of genes expressing similar profiles, highlighting a HsfA1E binding motif within the promoters of some unrelated genes which displayed rapid and transient heat-activation. Therefore, it could be suggested that these genes could be direct targets of activation by a HsfA1E transcription factors.