bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Vehicle Suspension with Anti-Roll System Based on Advanced Sliding Mode Controller
Authors: Konieczny Jarosław , Sibielak Marek , Rączka Waldemar
Published: October 2020

In the paper authors consider the active suspension of the wheeled vehicle. The proposed controller consists of a sliding mode controller used to roll reduction and linear regulators with quadratic performance index (LQRs) for struts control was shown. The energy consumption optimization was taken into account at the stage of strut controllers synthesis. The studied system is half of the active vehicle suspension using hydraulic actuators to increase the ride comfort and keeping safety. Instead of installing additional actuators in the form of active anti-roll bars, it has been decided to expand the active suspension control algorithm by adding extra functionality that accounts for the roll. The suggested algorithm synthesis method is based on the object decomposition into two subsystems whose controllers can be synthesized separately. Individual suspension struts are controlled by actuators that use the controllers whose parameters have been calculated with the LQR method. The mathematical model of the actuator applied in the work takes into account its nonlinear nature and the dynamics of the servovalve. The simulation tests of the built active suspension control system have been performed. In the proposed solution, the vertical displacements caused by uneven road surface are reduced by controllers related directly to suspension strut actuators.
Reliability Predictors for Solar Irradiance Satellite-Based Forecast
Authors: Cros Sylvain , Badosa Jordi , Szantaï André , Haeffelin Martial
Published: October 2020

The worldwide growing development of PV capacity requires an accurate forecast for a safer and cheaper PV grid penetration. Solar energy variability mainly depends on cloud cover evolution. Thus, relationships between weather variables and forecast uncertainties may be quantified to optimize forecast use. An intraday solar energy forecast algorithm using satellite images is fully described and validated over three years in the Paris (France) area. For all tested horizons (up to 6 h), the method shows a positive forecast skill score compared to persistence (up to 15%) and numerical weather predictions (between 20% and 40%). Different variables, such as the clear-sky index (Kc), solar zenith angle (SZA), surrounding cloud pattern observed by satellites and northern Atlantic weather regimes have been tested as predictors for this forecast method. Results highlighted an increasing absolute error with a decreasing SZA and Kc. Root mean square error (RMSE) is significantly affected by the mean and the standard deviation of the observed Kc in a 10 km surrounding area. The highest (respectively, lowest) errors occur at the Atlantic Ridge (respectively, Scandinavian Blocking) regime. The differences of relative RMSE between these two regimes are from 8% to 10% in summer and from 18% to 30% depending on the time horizon. These results can help solar energy users to anticipate—at the forecast start time and up to several days in advance—the uncertainties of the intraday forecast. The results can be used as inputs for other solar energy forecast methods.
Analysis of Stress-Strain States in the Vicinity of Mining Excavations in a Rock Mass with Variable Mechanical Properties
Authors: Jendryś Marek , Duży Stanisław , Dyduch Grzegorz
Published: October 2020

Rock mass is a medium created through processes that have lasted over four billion years, and its intrinsic feature is the variability of the parameters that describe it. A particularly high variability of mechanical parameters is observed in Carboniferous sedimentary and metamorphic rocks. The mechanical properties, especially the rock mass strength, are essential for the design and maintenance of the stability of excavations conducted in it and for the safe conduct of mining operations. This article presents the test results confirming the random variability of the mechanical parameters of the rock mass. The second part of the article presents the results of numerical simulations mapping the Carboniferous rock mass along with a 1000 m deep tunnel excavation protected by steel arch supports. Numerical simulations were carried out for models with different variability coefficients of strength and deformation parameters, and the obtained results were analyzed in terms of damage zones and rock mass stress state as well as axial forces in the modelled supports. The results of the simulation demonstrate the impact of the variability of rock mass properties on its state in the vicinity of the excavation and, consequently, on the internal forces in the steel supports and their uneven loading along the length of the excavation. This fact should be taken into account in their design.
Space Charge Accumulation Characteristics in HVDC Cable under Temperature Gradient
Authors: Zhou Yifan , Wang Wei , Guo Tailong
Published: October 2020

One of the main issues that affect the development of high-voltage direct-current (HVDC) cable insulation is the accumulation of space charge. The load operation of an HVDC cable leads to the formation of a radially distributed temperature gradient (TG) across the insulation. In this study, the space charge accumulation in a cross-linked polyethylene (XLPE) cable is measured under a DC electric field and TG using the pulsed electro-acoustic (PEA) method, and the effect of the TG on the space charge behavior is investigated. In addition, the bipolar charge transport (BCT) model and the conductivity model based on an improved cylindrical geometry are used to simulate the charge behavior in the HVDC XLPE cable under TG, and the experimental and simulated results are compared. The results show that the higher temperature of the cable conductor promotes the accumulation of homocharge near the side of high temperature. Additionally, with the increase of the TG, not only does more heterocharge accumulates adjacent to the side of low temperature, but more space charge also extends into the bulk of the cable insulation. More attention should be paid to the conductor shield layer and the insulation shield layer in HVDC cables. Moreover, the BCT model can more accurately describe the experimental results than the conductivity model.
Parameterization, Analysis, and Risk Management in a Comprehensive Management System with Emphasis on Energy and Performance (ISO 50001: 2018)
Authors: Poveda-Orjuela P. Pablo , García-Díaz J. Carlos , Pulido-Rojano Alexander , Cañón-Zabala Germán
Published: October 2020

The future of business development relies on the effective management of risks, opportunities, and energy and water resources. Here, we evaluate the application of best practices to identify, analyze, address, monitor, and control risks and opportunities (R/O) according to ISO 31000 and 50000. Furthermore, we shed light on tools, templates, ISO guides, and international documents that contribute to classifying, identifying, formulating control, and managing R/O parameterization in a comprehensive management system model, namely CMS QHSE3+, which consists of quality (Q), health and safety (HS), environmental management (E), energy efficiency (E2), and other risk components (+) that include comprehensive biosecurity and biosafety. By focusing on the deployment of R/O-based thinking (ROBT) at strategic and operational levels, we show vulnerability reduction in CMS QHSE3+ by managing energy, efficiency, and sustainability.
Oil Price, Energy Consumption, and CO2 Emissions in Turkey. New Evidence from a Bootstrap ARDL Test
Authors: Abumunshar Mohammed , Aga Mehmet , Samour Ahmed
Published: October 2020

The main objective of this research was to test the effect of oil prices, renewable and non-renewable energy consumption, and economic growth on Turkey’s carbon emissions by using three co-integration tests, namely, the newly-developed bootstrap autoregressive distributed lag (ARDL) testing technique as proposed by (McNown et al., 2018); the new approach involving the Bayer–Hanck (2013) combined co-integration test; and the H-J (2008) co-integration technique, which induces two dates of structural breaks. The autoregressive distributed lag model (ARDL), dynamic ordinary least squares (DOLS), canonical cointegrating regression (CCR), and fully modified ordinary least square (FMOLS) approaches were utilized to test the long-run interaction between the examined variables. The Granger causality (GC) analysis was utilized to investigate the direction of causality among the variables. The long-run coefficients of ARDL, DOLS, CCR, and FMOLS showed that the oil prices had a negative influence on CO2 emissions in Turkey in the long run. Furthermore, the findings demonstrate that non-renewable energy, which includes oil, natural gas, and coal, increased CO2 emissions. In contrast, renewable energy can decrease the environmental pollution. These empirical findings can be attributed to the fact that Turkey is heavily dependent on imported oil; more than 50% of the energy requirement has been supplied by imports. Hence, oil price fluctuations have severe effects on the economic performance in Turkey, which in turn affects energy consumption and the level of carbon emissions. The study suggests that the rate of imported oil in Turkey must be decreased by finding more renewable energy sources for the energy supply formula to avoid any undesirable effects of oil price fluctuations on the CO2 emissions, and also to achieve sustainable development.
Genetic Improvement of Cereals and Grain Legumes
Authors: Nawaz Muhammad Amjad , Chung Gyuhwa
Published: October 2020

The anticipated population growth by 2050 will be coupled with increased food demand. To achieve higher and sustainable food supplies in order to feed the global population by 2050, a 2.4% rise in the yield of major crops is required. The key to yield improvement is a better understanding of the genetic variation and identification of molecular markers, quantitative trait loci, genes, and pathways related to higher yields and increased tolerance to biotic and abiotic stresses. Advances in genetic technologies are enabling plant breeders and geneticists to breed crop plants with improved agronomic traits. This Special Issue is an effort to report the genetic improvements by adapting genomic techniques and genomic selection.
Generic Health Literacy Measurements for Adults: A Scoping Review
Authors: Tian Cindy Yue , Xu Richard Huan , Mo Phoenix Kit-Han , Dong Dong , Wong Eliza Lai-Yi
Published: October 2020

Background: Generic health literacy measurement (GHLM) is an important tool to identify individuals with limited health literacy and can assist the design of tailored interventions for improving public health literacy. However, there is no consensus on measuring generic health literacy. The present study aims to review current GHLM used for adults in the literature. Methods: A scoping review was undertaken to map the available measurements designed to assess generic health literacy. Results: The review identified 19 GHLM for adults. Most of them applied a multidimensional definition of health literacy with a focus on individuals’ abilities to access, appraise, understand, and apply health information and services. Nutbeam’s conceptual model and Sørensen’s integrated model were widely used among the identified measures as the theoretical foundation. While the social determinants of health (SDH) were acknowledged in the two models, it remains unmentioned in many of the identified measures based on the Nutbeam’s model and needs further development in the measure based on the Sørensen’s model. A total of 39 different domains were assessed in the 19 measurements: prose was identified in 8 measurements and was the most prominent domain; followed by numeracy (n = 7) and interactive (n = 7). SDH related domains such as social support (n = 3), social capital (n = 1) were seldom included in the identified measurements. Conclusions: Although current GHLM adopted a multidimensional construct, they mainly focused on individuals’ abilities and SDH has not been well-developed in the assessment. Further research is required to advance the measuring of the interaction between SDH and health literacy.
Source Identification Analysis of Lead in the Blood of Japanese Children by Stable Isotope Analysis
Authors: Takagi Mai , Tanaka Atsushi , Seyama Haruhiko , Uematsu Ayumi , Kaji Masayuki , Yoshinaga Jun
Published: October 2020

Considering the negative effect of lead (Pb) on children’s neurodevelopment, Pb exposure should be minimized to the lowest extent possible, though the blood Pb (BPb) concentrations in Japanese children are among the lowest in the world. To identify the sources of Pb in blood, isotope ratios (IRs: 207Pb/206Pb and 208Pb/206Pb) of Pb (PbIR) in whole blood from eight Japanese children were measured by multi-collector ICP mass spectrometry. Further, samples of house dust, soil, duplicate diet, and tobacco, collected from home environments, were also measured and were compared with PbIR of blood case by case. The relative contribution of Pb in the home environment to BPb were estimated by linear programming (finding an optimal solution which satisfy the combination of IRs and intakes from various sources) when appropriate. Source apportionment for three children could be estimated, and contributions of diet, soil, and house dust were 19–34%, 0–55%, and 20–76%, respectively. PbIR for the remaining five children also suggested that non-dietary sources also contributed to Pb exposure, though quantitative contributions could not be estimated. Non-dietary sources such as soil, house dust, and passive tobacco smoke are also important contributors to Pb exposure for Japanese children based on PbIR results.
Frontal and Axial Evaluation of Craniofacial Morphology in Repaired Unilateral Cleft Lip and Palate Patients Utilizing Cone Beam Computed Tomography; An Observational Study
Authors: Kochhar Anuraj Singh , Sidhu Maninder Singh , Prabhakar Mona , Bhasin Ritasha , Kochhar Gulsheen Kaur , Dadlani Himanshu , Spagnuolo Gianrico
Published: October 2020

The current study was conducted to assess the extent of maxillary arch collapse on the cleft vis-a-vis non-cleft sides in the same individual presenting withunilateral cleft lip and palate (UCLP), using cone-beam computed tomography (CBCT). Thirty-one children (eighteen boys andthirteen girls) with surgically repaired UCLP, who met the inclusion criteria, were selected. Following the acquisition of CBCT scans, fourteen bilateral landmarks were selected. The distance of the bilateral landmark was calculated from the midsagittal plane on the cleft and non-cleft sides for both frontal and axial views. Tracings were done;the data obtained was subjected to statistical analysis;and intra-observer variability was checked with intraclass correlation coefficient (ICC) and two-way ANOVA. Subsequently, the measurements were subjected to paired t-tests at the 95% level of significance with Bonferroni correction. A significant reduction of pyriforme and an alveolar crest above the maxillary 1st molar were discerned in frontal analysis on the cleft side. In the axial view, the zygomatic arch, malar, porion and alveolar crest at the molar region were non-significant, but the alveolar crest at the premolar region (p < 0.004)) was significantly decreased. In the frontal analysis, pyriforme and the alveolar crest above the maxillary 1st molar, and, in the axial view, premolar widths, showed significant reduction when comparing the cleft vis-a-vis non-cleft sides.
New Insights into Mechanisms of Endocrine-Disrupting Chemicals in Thyroid Diseases: The Epigenetic Way
Authors: Pitto Letizia , Gorini Francesca , Bianchi Fabrizio , Guzzolino Elena
Published: October 2020

In recent years, the presence in the environment of chemical compounds with thyroid-disrupting effects is progressively increased. This phenomenon has risen concern for human health as the preservation of thyroid system homeostasis is essential for fetal development and for maintaining psychological and physiological wellbeing. An increasing number of studies explored the role of different classes of toxicants in the occurrence and severity of thyroid diseases, but large epidemiological studies are limited and only a few animal or in vitro studies have attempted to identify the mechanisms of chemical action. Recently, epigenetic changes such as alteration of methylation status or modification of non-coding RNAs have been suggested as correlated to possible deleterious effects leading to different thyroid disorders in susceptible individuals. This review aims to analyze the epigenetic alterations putatively induced by chemical exposures and involved in the onset of frequent thyroid diseases such as thyroid cancer, autoimmune thyroiditis and disruption of fetal thyroid homeostasis.
Community Education for a Dignified Last Phase of Life for Migrants: A Community Engagement, Mixed Methods Study among Moroccan, Surinamese and Turkish Migrants
Authors: de Voogd Xanthe , Willems Dick L. , Onwuteaka-Philipsen Bregje , Torensma Marieke , Suurmond Jeanine L.
Published: October 2020

Community engagement and -education are proposed to foster equity in access to care and to ensure dignity of migrant patients in the last phase of life, but evidence is lacking. We evaluated nine community educational interactive meetings about palliative care (136 participants totally)- co-created with educators from our target groups of Moroccan, Surinamese and Turkish migrants—with a mixed methods approach, including 114 questionnaires, nine observations, nine interviews with educators, and 18 pre- and post- group- and individual interviews with participants. Descriptive and thematic analysis was used. 88% of the participants experienced the meetings as good or excellent. Educators bridged an initial resistance toward talking about this sensitive topic with vivid real-life situations. The added value of the educational meetings were: (1) increased knowledge and awareness about palliative care and its services (2) increased comprehensiveness of participant’s wishes and needs regarding dignity in the last phase; (3) sharing experiences for relief and becoming aware of real-life situations. Community engagement and -education about palliative care for migrants effectively increases knowledge about palliative care and is a first step towards improved access to palliative care services, capacity building and a dignified last phase of life among migrants.
The Effects of Exogenous Lactate Administration on the IGF1/Akt/mTOR Pathway in Rat Skeletal Muscle
Authors: Kyun Sunghwan , Yoo Choongsung , Park Hun-Young , Kim Jisu , Lim Kiwon
Published: October 2020

We investigated the effects of oral lactate administration on protein synthesis and degradation factors in rats over 2 h after intake. Seven-week-old male Sprague–Dawley rats were randomly divided into four groups (n = 8/group); their blood plasma levels of lactate, glucose, insulin, and insulin-like growth factor 1 (IGF1) were examined following sacrifice at 0, 30, 60, or 120 min after sodium lactate (2 g/kg) administration. We measured the mRNA expression levels of protein synthesis-related genes (IGF receptor, protein kinase B (Akt), mammalian target of rapamycin (mTOR)) or degradation-related genes (muscle RING-finger protein-1 (MuRF1), atrogin-1) and analyzed the protein expression and phosphorylation (activation) of Akt and mTOR. Post-administration, the plasma lactate concentration increased to 3.2 mmol/L after 60 min. Plasma glucose remained unchanged throughout, while insulin and IGF1 levels decreased after 30 min. The mRNA levels of IGF receptor and mTOR peaked after 60 min, and Akt expression was significantly upregulated from 30 to 120 min. However, MuRF1 and atrogin-1 expression levels were unaffected. Akt protein phosphorylation did not change significantly, whereas mTOR phosphorylation significantly increased after 30 min. Thus, lactate administration increased the mRNA and protein expression of protein-synthesis factors, suggesting that it can potentially promote skeletal muscle synthesis.
The Spanish Family Quality of Life Scales under and over 18 Years Old: Psychometric Properties and Families’ Perceptions
Authors: Balcells-Balcells Anna , Mas Joana M. , Baqués Natasha , Simón Cecilia , García-Ventura Simón
Published: October 2020

Background: Family quality of life (FQoL), just like individual quality of life, has become a priority outcome in the policies and services received by persons with intellectual and developmental disabilities (IDD) and their families. Conceptualizing, measuring, and theorizing FQoL has been the object of investigation in recent decades. The goal of this paper is to present a revision of the Spanish Family Quality of Life Scales, the CdVF-E < 18 and the CdVF-E >18, and describe the FQoL of Spanish families with a member with IDD. Methods: The sample included a total of 548 families with a member under 18 years old and 657 families with a member over 18. Based on an Exploratory Factor Analysis (EFA) firstly and a Confirmatory Factor Analysis (CFA) secondly, the two scales’ psychometric properties were explored. Results: The CdVF-ER < 18 and the CdVF-ER > 18 comprise 5 dimensions, containing 35 and 32 items, respectively, and they show good validity and reliability. The families obtained a high FQoL score, although some differences exist between the dimensions on which families with children under and over 18 score highest and lowest. Conclusion: The characteristics of the revised scales facilitate their use by professionals, administrations, and services.
Mixed and Multi-Methods Protocol to Evaluate Implementation Processes and Early Effects of the Pradhan Mantri Jan Arogya Yojana Scheme in Seven Indian States
Authors: Allegri Manuela De , Srivastava Swati , Strupat Christoph , Brenner Stephan , Parmar Divya , Parisi Diletta , Walsh Caitlin , Mahajan Sahil , Neogi Rupak , Ziegler Susanne , Basu Sharmishtha , Jain Nishant
Published: October 2020

In September 2018, India launched Pradhan Mantri Jan Arogya Yojana (PM-JAY), a nationally implemented government-funded health insurance scheme to improve access to quality inpatient care, increase financial protection, and reduce unmet need for the most vulnerable population groups. This protocol describes the methodology adopted to evaluate implementation processes and early effects of PM-JAY in seven Indian states. The study adopts a mixed and multi-methods concurrent triangulation design including three components: 1. demand-side household study, including a structured survey and qualitative elements, to quantify and understand PM-JAY reach and its effect on insurance awareness, health service utilization, and financial protection; 2. supply-side hospital-based survey encompassing both quantitative and qualitative elements to assess the effect of PM-JAY on quality of service delivery and to explore healthcare providers’ experiences with scheme implementation; and 3. process documentation to examine implementation processes in selected states transitioning from either no or prior health insurance to PM-JAY. Descriptive statistics and quasi-experimental methods will be used to analyze quantitative data, while thematic analysis will be used to analyze qualitative data. The study design presented represents the first effort to jointly evaluate implementation processes and early effects of the largest government-funded health insurance scheme ever launched in India.
Association between Psychological Factors and Evacuation Status and the Incidence of Cardiovascular Diseases after the Great East Japan Earthquake: A Prospective Study of the Fukushima Health Management Survey
Authors: Sanoh Toshiki , Eguchi Eri , Ohira Tetsuya , Hayashi Fumikazu , Maeda Masaharu , Yasumura Seiji , Suzuki Yuriko , Yabe Hirooki , Takahashi Atsushi , Takase Kanae , Harigane Mayumi , Hisamatsu Takashi , Ogino Keiki , Kanda Hideyuki , Kamiya Kenji
Published: October 2020

Evidence regarding the effect of psychological factors and evacuation on cardiovascular disease occurrence after large-scale disasters is limited. This prospective study followed up a total of 37,810 Japanese men and women aged 30–89 years from the Fukushima Prefecture with no history of stroke or heart disease at baseline (2012), until 2017. This period included 3000 cardiovascular events recorded through questionnaires and death certificates. The participants’ psychological distress, trauma reaction, and evacuation status were defined, and divided into four groups based on combinations of psychological factors and evacuation status. We calculated the hazard ratios and 95% confidence intervals for only psychological, only evacuation, or both of them compared with neither using Cox proportional hazard models. Psychological factors along with evacuation resulted in approximately 5% to 25% higher magnitude of stroke and heart disease risk than psychological factors only among men. Compared to neither, the multivariable hazard ratios of those with both psychological distress and evacuation were 1.75 for stroke and 1.49 for heart disease, and those of both trauma reaction and evacuation were 2.01 and 1.57, respectively, among men. Evacuation combined with psychological factors increased the risk of stroke and heart disease risks especially in men after the Great East Japan Earthquake.
Health and Diet among People Living in an Isolated Area: Case Study of Pingelap Island in Pohnpei State, the Federated States of Micronesia
Authors: Sakai Moeno , Nakazawa Minato , Abraham Delpihn
Published: October 2020

Pingelap Island in Pohnpei state is geographically isolated as the nearest island is 70 km away, and such geographical isolation is a challenge for public health due to the limited access to health services. This study aims to reveal the health situation on the island and investigate the influence of geographical isolation on health and diet. For that purpose, the result was compared with those who are living in a community on the main island of Pohnpei state (Mand) with the same ethnic background. Face-to-face interviews were conducted to collect data on demographics, diet, and behavior. Anthropometry and blood pressure measurements were also taken. A total of 98 (Pingelap = 50; Mand = 48) subjects participated in the study. The result showed that females, in particular, had a high prevalence of obesity (80.0% in Pingelap; 75.9% in Mand). However, no significant regional difference was found in both BMI and blood pressure, regardless of gender. Regarding diet, although the geographical location impacted food availability, the consumption of major imported foods did not show a significant regional difference. In conclusion, the geographical isolation did not significantly influence health and diet, but the majority of the study population displayed a high-risk burden of non-communicable diseases.
Activity–Inactivity Patterns, Screen Time, and Physical Activity: The Association with Overweight, Central Obesity and Muscle Strength in Polish Teenagers. Report from the ABC of Healthy Eating Study
Authors: Górnicka Magdalena , Hamulka Jadwiga , Wadolowska Lidia , Kowalkowska Joanna , Kostyra Eliza , Tomaszewska Marzena , Czeczelewski Jan , Bronkowska Monika
Published: October 2020

Today, the time spent actively is increasingly being replaced by screen-based media, although in some teenagers, a high level of physical activity (PA) and longer time spent in front of a screen (screen time, ST) may coexist as a mixed behavioral pattern. This study aimed to examine the association of the pattern created as activity (low/high ST with high PA) and inactivity patterns (low/high ST with low PA) with overweight, central obesity, and muscle strength in Polish teenagers taking into consideration socioeconomic and demographic factors. Cross-sectional data were collected from elementary school children (n = 1567), aged 11–13 years. Height, weight, waist circumference, and handgrip strength were measured. Body mass index (BMI) was calculated as the overweight measure, and the waist-to-height ratio (WHtR) was calculated as the central obesity measure. Data on ST, PA, socioeconomic status, demographics, and nutrition knowledge were collected by a questionnaire. Activity–inactivity patterns were defined by an a priori approach. Multivariate logistic regression modelling was applied. The most active pattern (lowST-highPA) was found in 17% of the total sample. Teenagers with the most inactive pattern (highST-lowPA) had over four times higher chance of general overweight. No association between WHtR ≥0.5 and highST-highPA pattern was found. Higher muscle strength (>1 SD) was associated only with high physical activity. Urban residence or lower socioeconomic status increased adherence to the most inactive pattern. From a public health perspective, implementing interventions promoting active patterns in 11–13-year-old teenagers is important for obesity prevention and enhanced physical fitness, especially in girls, teenagers living in urban areas, and from families with lower socio-economic status.
New Insights into Therapy-Induced Progression of Cancer
Authors: Shnaider Polina V. , Ivanova Olga M. , Malyants Irina K. , Anufrieva Ksenia S. , Semenov Ilya A. , Pavlyukov Marat S. , Lagarkova Maria A. , Govorun Vadim M. , Shender Victoria O.
Published: October 2020

The malignant tumor is a complex heterogeneous set of cells functioning in a no less heterogeneous microenvironment. Like any dynamic system, cancerous tumors evolve and undergo changes in response to external influences, including therapy. Initially, most tumors are susceptible to treatment. However, remaining cancer cells may rapidly reestablish the tumor after a temporary remission. These new populations of malignant cells usually have increased resistance not only to the first-line agent, but also to the second- and third-line drugs, leading to a significant decrease in patient survival. Multiple studies describe the mechanism of acquired therapy resistance. In past decades, it became clear that, in addition to the simple selection of pre-existing resistant clones, therapy induces a highly complicated and tightly regulated molecular response that allows tumors to adapt to current and even subsequent therapeutic interventions. This review summarizes mechanisms of acquired resistance, such as secondary genetic alterations, impaired function of drug transporters, and autophagy. Moreover, we describe less obvious molecular aspects of therapy resistance in cancers, including epithelial-to-mesenchymal transition, cell cycle alterations, and the role of intercellular communication. Understanding these molecular mechanisms will be beneficial in finding novel therapeutic approaches for cancer therapy.
Balanced Xylan Acetylation is the Key Regulator of Plant Growth and Development, and Cell Wall Structure and for Industrial Utilization
Authors: Qaseem Mirza Faisal , Wu Ai-Min
Published: October 2020

Xylan is the most abundant hemicellulose, constitutes about 25–35% of the dry biomass of woody and lignified tissues, and occurs up to 50% in some cereal grains. The accurate degree and position of xylan acetylation is necessary for xylan function and for plant growth and development. The post synthetic acetylation of cell wall xylan, mainly regulated by Reduced Wall Acetylation (RWA), Trichome Birefringence-Like (TBL), and Altered Xyloglucan 9 (AXY9) genes, is essential for effective bonding of xylan with cellulose. Recent studies have proven that not only xylan acetylation but also its deacetylation is vital for various plant functions. Thus, the present review focuses on the latest advances in understanding xylan acetylation and deacetylation and explores their effects on plant growth and development. Baseline knowledge about precise regulation of xylan acetylation and deacetylation is pivotal to developing plant biomass better suited for second-generation liquid biofuel production.
Interaction of Cucurbit[7]uril with Oxime K027, Atropine, and Paraoxon: Risky or Advantageous Delivery System?
Authors: Zdarova Karasova Jana , Mzik Martin , Kucera Tomas , Vecera Zbynek , Kassa Jiri , Sestak Vit
Published: October 2020

Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood–brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC—pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks.
Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study
Authors: Moons Rani , van der Wekken-de Bruijne Renate , Maudsley Stuart , Lemière Filip , Lambeir Anne-Marie , Sobott Frank
Published: October 2020

The intrinsically disordered protein α-synuclein plays a major role in Parkinson’s disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how α-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of α-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to α-synuclein. Our data demonstrate that α-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor.
Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology
Authors: Samodelov Sophia L. , Kullak-Ublick Gerd A. , Gai Zhibo , Visentin Michele
Published: October 2020

Individual cells and epithelia control the chemical exchange with the surrounding environment by the fine-tuned expression, localization, and function of an array of transmembrane proteins that dictate the selective permeability of the lipid bilayer to small molecules, as actual gatekeepers to the interface with the extracellular space. Among the variety of channels, transporters, and pumps that localize to cell membrane, organic cation transporters (OCTs) are considered to be extremely relevant in the transport across the plasma membrane of the majority of the endogenous substances and drugs that are positively charged near or at physiological pH. In humans, the following six organic cation transporters have been characterized in regards to their respective substrates, all belonging to the solute carrier 22 (SLC22) family: the organic cation transporters 1, 2, and 3 (OCT1–3); the organic cation/carnitine transporter novel 1 and 2 (OCTN1 and N2); and the organic cation transporter 6 (OCT6). OCTs are highly expressed on the plasma membrane of polarized epithelia, thus, playing a key role in intestinal absorption and renal reabsorption of nutrients (e.g., choline and carnitine), in the elimination of waste products (e.g., trimethylamine and trimethylamine N-oxide), and in the kinetic profile and therapeutic index of several drugs (e.g., metformin and platinum derivatives). As part of the Special Issue Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations, this article critically presents the physio-pathological, pharmacological, and toxicological roles of OCTs in the tissues in which they are primarily expressed.
GasPhos: Protein Phosphorylation Site Prediction Using a New Feature Selection Approach with a GA-Aided Ant Colony System
Authors: Chen Chi-Wei , Huang Lan-Ying , Liao Chia-Feng , Chang Kai-Po , Chu Yen-Wei
Published: October 2020

Protein phosphorylation is one of the most important post-translational modifications, and many biological processes are related to phosphorylation, such as DNA repair, transcriptional regulation and signal transduction and, therefore, abnormal regulation of phosphorylation usually causes diseases. If we can accurately predict human phosphorylation sites, this could help to solve human diseases. Therefore, we developed a kinase-specific phosphorylation prediction system, GasPhos, and proposed a new feature selection approach, called Gas, based on the ant colony system and a genetic algorithm and used performance evaluation strategies focused on different kinases to choose the best learning model. Gas uses the mean decrease Gini index (MDGI) as a heuristic value for path selection and adopts binary transformation strategies and new state transition rules. GasPhos can predict phosphorylation sites for six kinases and showed better performance than other phosphorylation prediction tools. The disease-related phosphorylated proteins that were predicted with GasPhos are also discussed. Finally, Gas can be applied to other issues that require feature selection, which could help to improve prediction performance.
Advances on Plant Ubiquitylome—From Mechanism to Application
Authors: He Dongli , Damaris Rebecca Njeri , Li Ming , Khan Imran , Yang Pingfang
Published: October 2020

Post-translational modifications (PTMs) of proteins enable modulation of their structure, function, localization and turnover. To date, over 660 PTMs have been reported, among which, reversible PTMs are regarded as the key players in cellular signaling. Signaling mediated by PTMs is faster than re-initiation of gene expression, which may result in a faster response that is particularly crucial for plants due to their sessile nature. Ubiquitylation has been widely reported to be involved in many aspects of plant growth and development and it is largely determined by its target protein. It is therefore of high interest to explore new ubiquitylated proteins/sites to obtain new insights into its mechanism and functions. In the last decades, extensive protein profiling of ubiquitylation has been achieved in different plants due to the advancement in ubiquitylated proteins (or peptides) affinity and mass spectrometry techniques. This obtained information on a large number of ubiquitylated proteins/sites helps crack the mechanism of ubiquitylation in plants. In this review, we have summarized the latest advances in protein ubiquitylation to gain comprehensive and updated knowledge in this field. Besides, the current and future challenges and barriers are also reviewed and discussed.
Bacteria Residing at Root Canals Can Induce Cell Proliferation and Alter the Mechanical Properties of Gingival and Cancer Cells
Authors: Suprewicz Łukasz , Tokajuk Grażyna , Cieśluk Mateusz , Deptuła Piotr , Sierpińska Teresa , Wolak Przemysław , Wollny Tomasz , Tokajuk Joanna , Głuszek Stanisław , Piktel Ewelina , Bucki Robert
Published: October 2020

Understanding the importance of oral microbiota in human health and disease also leads to an expansion of the knowledge on functional, metabolic, and molecular alterations directly contributing to oral and systemic pathologies. To date, a compelling number of studies have documented the crucial role of some oral cavity-occurring microbes in the initiation and progression of cancers. Although this effect was noted primarily for Fusobacterium spp., the potential impact of other oral microbes is also worthy of investigation. In this study, we aimed to assess the effect of Enterococcus faecalis, Actinomyces odontolyticus, and Propionibacterium acnes on the proliferation capability and mechanical features of gingival cells and cell lines derived from lung, breast, and ovarian cancers. For this purpose, we incubated selected cell lines with heat-inactivated bacteria and supernatants collected from biofilms, cultured in both anaerobic and aerobic conditions, in the presence of surgically removed teeth and human saliva. The effect of oral bacteria on cell population growth is variable, with the highest growth-promoting abilities observed for E. faecalis in relation to human primary gingival fibroblasts (HGF) and lung cancer A549 cells, and P. acnes in relation to breast cancer MCF-7 and ovarian cancer SKOV-3 cells. Notably, this effect seems to depend on a delicate balance between the pro-stimulatory and toxic effects of bacterial-derived products. Regardless of the diverse effect of bacterial products on cellular proliferation capability, we observed significant alterations in stiffness of gingival and lung cancer cells stimulated with E. faecalis bacteria and corresponding biofilm supernatants, suggesting a novel molecular mechanism involved in the pathogenesis of diseases in oral cavities and tooth tissues. Accordingly, it is proposed that analysis of cancerogenic features of oral cavity bacteria should be multivariable and should include investigation of potential alterations in cell mechanical properties. These findings corroborate the important role of oral hygiene and root canal treatment to assure the healthy stage of oral microbiota.
Heterogeneity of Neuroinflammatory Responses in Amyotrophic Lateral Sclerosis: A Challenge or an Opportunity?
Authors: Cipollina Giada , Davari Serej Arash , Di Nolfi Gianluca , Gazzano Andrea , Marsala Andrea , Spatafora Mauro G. , Peviani Marco
Published: October 2020

Amyotrophic Lateral Sclerosis (ALS) is a complex pathology: (i) the neurodegeneration is chronic and progressive; it starts focally in specific central nervous system (CNS) areas and spreads to different districts; (ii) multiple cell types further than motor neurons (i.e., glial/immune system cells) are actively involved in the disease; (iii) both neurosupportive and neurotoxic neuroinflammatory responses were identified. Microglia cells (a key player of neuroinflammation in the CNS) attracted great interest as potential target cell population that could be modulated to counteract disease progression, at least in preclinical ALS models. However, the heterogeneous/multifaceted microglia cell responses occurring in different CNS districts during the disease represent a hurdle for clinical translation of single-drug therapies. To address this issue, over the past ten years, several studies attempted to dissect the complexity of microglia responses in ALS. In this review, we shall summarize these results highlighting how the heterogeneous signature displayed by ALS microglia reflects not only the extent of neuronal demise in different regions of the CNS, but also variable engagement in the attempts to cope with the neuronal damage. We shall discuss novel avenues opened by the advent of single-cell and spatial transcriptomics technologies, underlining the potential for discovery of novel therapeutic targets, as well as more specific diagnostic/prognostic not-invasive markers of neuroinflammation.
Statins Stimulate New Myocyte Formation After Myocardial Infarction by Activating Growth and Differentiation of the Endogenous Cardiac Stem Cells
Authors: Cianflone Eleonora , Cappetta Donato , Mancuso Teresa , Sabatino Jolanda , Marino Fabiola , Scalise Mariangela , Albanese Michele , Salatino Alessandro , Parrotta Elvira Immacolata , Cuda Giovanni , De Angelis Antonella , Berrino Liberato , Rossi Francesco , Nadal-Ginard Bernardo , Torella Daniele , Urbanek Konrad
Published: October 2020

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert pleiotropic effects on cardiac cell biology which are not yet fully understood. Here we tested whether statin treatment affects resident endogenous cardiac stem/progenitor cell (CSC) activation in vitro and in vivo after myocardial infarction (MI). Statins (Rosuvastatin, Simvastatin and Pravastatin) significantly increased CSC expansion in vitro as measured by both BrdU incorporation and cell growth curve. Additionally, statins increased CSC clonal expansion and cardiosphere formation. The effects of statins on CSC growth and differentiation depended on Akt phosphorylation. Twenty-eight days after myocardial infarction by permanent coronary ligation in rats, the number of endogenous CSCs in the infarct border zone was significantly increased by Rosuvastatin-treatment as compared to untreated controls. Additionally, commitment of the activated CSCs into the myogenic lineage (c-kitpos/Gata4pos CSCs) was increased by Rosuvastatin administration. Accordingly, Rosuvastatin fostered new cardiomyocyte formation after MI. Finally, Rosuvastatin treatment reversed the cardiomyogenic defects of CSCs in c-kit haploinsufficient mice, increasing new cardiomyocyte formation by endogenous CSCs in these mice after myocardial infarction. In summary, statins, by sustaining Akt activation, foster CSC growth and differentiation in vitro and in vivo. The activation and differentiation of the endogenous CSC pool and consequent new myocyte formation by statins improve myocardial remodeling after coronary occlusion in rodents. Similar effects might contribute to the beneficial effects of statins on human cardiovascular diseases.
Prognostic Relevance of HJURP Expression in Patients with Surgically Resected Colorectal Cancer
Authors: Kang Dong Hyun , Woo Jongsoo , Kim Hyeongjoo , Kim Soo Youn , Ji Sanghee , Jaygal Gunn , Ahn Tae Sung , Kim Han Jo , Kwak Hyoung Jong , Kim Chang-Jin , Baek Moo-Jun , Jeong Dongjun
Published: October 2020

HJURP is a key factor for CENP-A deposition and maintenance in centromeres. The role of mis-regulation of histone chaperones in cancer initiation and progression has been studied. However, its role in colorectal cancer is still unclear. In this study, we aimed to evaluate the expression of HJURP in 162 colorectal cancer tissue. To investigate the function of HJURP in the colorectal cancer cell, we suppressed HJURP expression by siRNA and confirmed proliferation, migration, invasion, and anchorage independent of colony forming ability. The association between HJURP expression levels and clinicopathological factors was evaluated in 162 CRC tissues using immunohistochemistry. The overall survival rate in patients of HJURP high expression was higher than those in HJURP low expression in CRC. Suppressing HJURP expression decreased cellular proliferation, invasion, and migration in four CRC cell lines: HT29, HCT116, SW480, SW620 in vitro study. Our findings revealed that the knockdown of HJURP suppressed the proliferation, migration, invasion, and tumorigenicity in CRC cells. Due to its strong association with CRC, HJURP could be a potential prognostic biomarker and a novel target for drug discovery.