bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations for a Trajectory Variation to Improve the Energy Conversion for a Four-Stroke Free-Piston Engine
Authors: Tempelhagen Robin , Gerlach Andreas , Benecke Sebastian , Klepatz Kevin , Leidhold Roberto , Rottengruber Hermann
Published: June 2021

Internal combustion engines with a crankshaft have been successfully developed for many years. They are lacking in the fact that the piston trajectory, i.e., position as a function of time, is limited by the crankshaft motion law. Position-controlled electric linear machines directly coupled to the piston allow to realize free-piston engines. Unlike the crankshaft-based engines, they allow for a higher degree of freedom in shaping the piston trajectory, including adaptive compression ratios, which enables optimal operation with alternative fuels. The possibility of adapting the stroke course results in new degrees of freedom with which the combustion process can be optimized. In this work, four-stroke trajectories with different amplitudes and piston dynamics have been proposed and analyzed regarding efficiency. A simulation model was created based on experimental measurements for testing the proposed trajectories. It could be proved that the variation of the trajectory resulted in an improvement of the overall efficiency. The trajectories were described analytically so that they can be used for a prototype in a future work.
The Effect of High-Pressure Treatment and Skimming on Caprine Milk Proteins
Authors: Kiełczewska Katarzyna , Dąbrowska Aneta , Jankowska Agnieszka , Wachowska Maria , Kowalik Jarosław
Published: June 2021

Background: Proteins are susceptible to HP-treatment and there is a need to determine the applicability of HP-treatment in dairy production. The aim of this study was to determine the effect of HP-treatment at 200–500 MPa (tconst. = 10 min; Tconst. = 20 °C) and skimming of HP-treated milk on the content of nitrogen compounds and protein composition of caprine milk. Methods: The content of nitrogen (total, non-casein, non-protein) was determined using the Kjeldahl method. Casein fractions and whey proteins were separated using SDS-PAGE electrophoresis. Color parameters were measured in the CIELAB color space. Results: HP-treatment decreased (p < 0.05) the content of non-casein nitrogen and soluble whey proteins. Skimming decreased the content of nitrogen compounds, and the noted decrease was more pronounced in HP-treated milk. Pressure and skimming had no influence on the proportions of α-, β-, κ-casein, β-lactoglobulin and α-lactalbumin. Total color difference (ΔE) increased with a rise in pressure, particularly in skim milk. Conclusion: HP-treatment led to a loss of protein solubility at pH 4.6 in caprine milk. In HP-treated milk, skimming did not induce changes in protein composition, despite a decrease in the content of nitrogen compounds after the separation of the cream layer. Higher values of ΔE in skim milk than in whole milk point to changes in colloidal phase components.
Discovering Intra-Urban Population Movement Pattern Using Taxis’ Origin and Destination Data and Modeling the Parameters Affecting Population Distribution
Authors: Rahimi Fatema , Sadeghi-Niaraki Abolghasem , Ghodousi Mostafa , Choi Soo-Mi
Published: June 2021

GPS-equipped vehicles are an effective approach for acquiring urban population movement patterns. Attempts have been made in the present study in order to identify the population displacement pattern of the study region using taxis’ origin and destination data, and then model the parameters affecting the population displacement pattern and provide an ultimate model in order to predict pick-up and drop-off locations. In this way, the passenger pick-up and drop-off locations have been identified in order to obtain the population movement pattern. In this study, Moran’s I index was used to measure the spatial autocorrelation, and hot spot analysis was used to analyze spatial patterns of pick-up and drop-off locations. Effective parameters modeling was performed using the Poisson regression. The results of the spatiotemporal distribution map for pick-up and drop-off locations indicated a similarity in patterns and equal results for some locations. Results also indicated different features of spatial distribution during different hours of the day. Spatial autocorrelation analysis results indicated a low probability of randomness in the general spatial distribution of the locations. The result of modeling the parameters shows the positive effect of the parameters on the pattern of population movement, and according to the p-value of 0.000, Poisson regression is significant for the pick-up and drop-off locations. The modeling results also highlighted the importance of movement patterns in recognizing urban hot spots, which is valuable for policymakers and urban planners.
Evaluation of Visual and Nonvisual Levels of Daylight from Spectral Power Distributions Considering Orientation and Seasonality
Authors: Ezpeleta Silvia , Orduna-Hospital Elvira , Aporta Justiniano , Luesma María José , Pinilla Isabel , Sánchez-Cano Ana
Published: June 2021

The evaluation of both visual and nonvisual effects from the spectral power distribution (SPD) of outdoor light is critical in lighting design. The dome-light SPD characteristically changes continuously depending on the seasonality, orientation, altitude of the sun or hour of the day. Traditional photopic parameters, such as the illuminance, luminance or correlated colour temperature (CCT), have been widely studied, but presently, there is no melanopic measurement or evaluation method. This article discusses the processes involved in establishing a simple method to determine the SPD of daylight and solar radiation over the skydome in a location to accurately account for the effects of both photopic and circadian levels around a location. Once per month for one year, natural daylight was spectrally measured in the city of Zaragoza (Spain); radiometric and photometric characteristics were analysed by season; and circadian effects were calculated in terms of standard parameters described by the Commission International de l’Eclairage (CIE), factors recommended by normative and scientific backgrounds. Finally, we suggest that the best parameter is the melanopic versus photopic irradiance ratio, which achieves reliable results at simplifying and correlating calculations.
Influence of Process Parameters on Cutting Width in CO2 Laser Processing of Hardox 400 Steel
Authors: Girdu Constantin Cristinel , Gheorghe Catalin , Radulescu Constanta , Cirtina Daniela
Published: June 2021

This paper presents an experimental research that proposes to determine the influence of process parameters on CO2 laser cutting of 8 mm thick Hardox 400 steel, for which Kerf has a minimum value. The experimental research was conducted according to a complete factorial plan with laser power, assistant gas pressure and cutting speed as the input parameters, and cutting width as the dependable variable. The Design of Experiment (DOE) consisted of 27 references and was completed with four replicas to determine the variation of the Kerf average. Functional, linear and quadratic relations were determined, which describe the Kerf dependence on the cutting parameters in order to establish the most influential parameter. The results show that the independent parameter with the most significant influence was the laser power, with minimum Kerf obtained if the laser power and the assistant gas pressure were adjusted to average values. The interaction between laser power and auxiliary gas pressure at constant cutting speed was investigated to improve Kerf and reduce the laser processing cost. The study offers the right combination of process parameters that leads to a minimum value of the cutting width.
Integrated Hydrological Analysis of Little Akaki Watershed Using SWAT-MODFLOW, Ethiopia
Authors: Tolera Mesfin Benti , Chung Il-Moon
Published: June 2021

In Ethiopia, groundwater is the main source of freshwater to support human consumption and socio-economic development. Little Akaki watershed is located in Upper Awash basin, known for its high annual rainfall and considered as the potential groundwater recharge zone. On the contrary, urbanization and industrial expansion are increasing at an alarming rate in the area. This became a concern threatening the groundwater resources’ sustainability. To address these challenges, integrated analysis of groundwater recharge and groundwater numerical simulations were made. For groundwater recharge estimation, SWAT model was used. The result indicated that recharge in the watershed mostly occurs from July to October with maximum values in August. On average, the estimated annual catchment recharge was 179 mm. For the numerical simulation and prediction of the groundwater flow system, MODFLOW 2005 was used. The model simulations indicated that the groundwater head converges towards the main river and, finally, to the outlet of the watershed. The study indicated areas of interactions between the river and groundwater. The scenario examination result reveals increasing the present pumping rate by over fifty percent (by 50%, 100%, and 200%) will surely cause visible groundwater head decline near the outlet of the watershed, and substantial river baseflow reduction. The recharge reduction scenario also indicates the huge risk of groundwater sustainability in the area.
Scenario-Based Techno-Economic Analysis of Steam Methane Reforming Process for Hydrogen Production
Authors: Lee Shinje , Kim Hyun Seung , Park Junhyung , Kang Boo Min , Cho Churl-Hee , Lim Hankwon , Won Wangyun
Published: June 2021

Steam methane reforming (SMR) process is regarded as a viable option to satisfy the growing demand for hydrogen, mainly because of its capability for the mass production of hydrogen and the maturity of the technology. In this study, an economically optimal process configuration of SMR is proposed by investigating six scenarios with different design and operating conditions, including CO2 emission permits and CO2 capture and sale. Of the six scenarios, the process configuration involving CO2 capture and sale is the most economical, with an H2 production cost of $1.80/kg-H2. A wide range of economic analyses is performed to identify the tradeoffs and cost drivers of the SMR process in the economically optimal scenario. Depending on the CO2 selling price and the CO2 capture cost, the economic feasibility of the SMR-based H2 production process can be further improved.
A Statistical Analysis of Daily Snow Depth Trends in North America
Authors: Woody Jonathan , Xu Yang , Dyer Jamie , Lund Robert , Hewaarachchi Anuradha P.
Published: June 2021

Several attempts to assess regional snow depth trends have been previously made. These studies estimate trends by applying various statistical methods to snow depths, new snowfalls, or their climatological proxies such as snow water equivalents. In most of these studies, inhomogeneities (changepoints) were not accounted for in the analysis. Changepoint features can dramatically influence trend inferences from climate time series. The purpose of this paper is to present a detailed statistical methodology to estimate trends of a time series of daily snow depths that account for changepoint features. The methods are illustrated in the analysis of a daily snow depth data set from North America.
Improving S-Band Polarimetric Radar Monsoon Rainfall Estimation with Two-Dimensional Video Disdrometer Observations in South China
Authors: Guo Zeyong , Hu Sheng , Liu Xiantong , Chen Xingdeng , Zhang Honghao , Qi Tao , Zeng Guangyu
Published: June 2021

The capability to estimate monsoon rainfall is investigated by using S-band polarimetric radar (S-POL) and two-dimensional Video Disdrometer (2DVD) during 2017–2018 in South China. Based on 2 years of 2DVD raindrop size distribution (DSD) observations of monsoon precipitation systems, four different quantitative precipitation estimation (QPE) algorithms were obtained, including R(ZH), R(ZH, ZDR), R(KDP), and R(KDP, ZDR). In order to clearly demarcate the optimal ranges of the four QPE algorithms by considering the impact of the monsoon precipitation system of South China, the optimal ranges of the four QPE algorithms were integrated together according to the characteristics of different QPE algorithms in the reflectivity-differential reflectivity (ZH-ZDR) space distribution by reference to 8 monsoon rainfall events from 2016 to 2020 observed in Guangzhou and Yangjiang S-POL. Then, an optimal algorithm was proposed for the quantitative estimation of monsoon precipitation in South China (2DVD-SCM) using S-POL. The 2DVD-SCM was tested by comparing it with a traditional radar QPE algorithm PPS (WSR-88D Precipitation Processing System); a classical QPE algorithm CSU-HIDRO (Colorado State University-Hydrometeor Identification Rainfall Optimization) for the polarimetric radar; a piecewise fitting algorithm LPA-PFM (Piecewise Fitting Method) based on laser raindrop spectrum. The rainfall event one-by-one test results show that the 2DVD-SCM algorithm performs obviously better than the other three algorithms in most of the rainfall events. The hourly accumulated rainfalls estimated by the 2DVD-SCM algorithm are agreed well with rain gauge observations. The normalized errors (NE) and the root mean square errors (RMSE) values of 2DVD-SCM are remarkably less than the other three algorithms, and the correlation coefficient (CC) values are higher. The results of the classified rain rate test show that the NE and RMSE values of the 2DVD-SCM algorithm are the lowest in all classified rain rates. The overall evaluation results show that the 2DVD-SCM algorithm performs obviously better than the existing three algorithms and have the potential to apply in S-band polarimetric radar monsoon rainfall estimation operational system in South China.
K-Means and C4.5 Decision Tree Based Prediction of Long-Term Precipitation Variability in the Poyang Lake Basin, China
Authors: Lou Dan , Yang Mengxi , Shi Dawei , Wang Guojie , Ullah Waheed , Chai Yuanfang , Chen Yutian
Published: June 2021

The machine learning algorithms application in atmospheric sciences along the Earth System Models has the potential of improving prediction, forecast, and reconstruction of missing data. In the current study, a combination of two machine learning techniques namely K-means, and decision tree (C4.5) algorithms, are used to separate observed precipitation into clusters and classified the associated large-scale circulation indices. Observed precipitation from the Chinese Meteorological Agency (CMA) during 1961–2016 for 83 stations in the Poyang Lake basin (PLB) is used. The results from K-Means clusters show two precipitation clusters splitting the PLB precipitation into a northern and southern cluster, with a silhouette coefficient ~0.5. The PLB precipitation leading cluster (C1) contains 48 stations accounting for 58% of the regional station density, while Cluster 2 (C2) covers 35, accounting for 42% of the stations. The interannual variability in precipitation exhibited significant differences for both clusters. The decision tree (C4.5) is employed to explore the large-scale atmospheric indices from National Climate Center (NCC) associated with each cluster during the preceding spring season as a predictor. The C1 precipitation was linked with the location and intensity of subtropical ridgeline position over Northern Africa, whereas the C2 precipitation was suggested to be associated with the Atlantic-European Polar Vortex Area Index. The precipitation anomalies further validated the results of both algorithms. The findings are in accordance with previous studies conducted globally and hence recommend the applications of machine learning techniques in atmospheric science on a sub-regional and sub-seasonal scale. Future studies should explore the dynamics of the K-Means, and C4.5 derived indicators for a better assessment on a regional scale. This research based on machine learning methods may bring a new solution to climate forecast.
L-Fuzzy Rough Approximation Operators Based on Co-Implication and Their (Single) Axiomatic Characterizations
Authors: Jin Qiu , Li Lingqiang
Published: June 2021

For L a complete co-residuated lattice and R an L-fuzzy relation, an L-fuzzy upper approximation operator based on co-implication adjoint with L is constructed and discussed. It is proved that, when L is regular, the new approximation operator is the dual operator of the Qiao–Hu L-fuzzy lower approximation operator defined in 2018. Then, the new approximation operator is characterized by using an axiom set (in particular, by single axiom). Furthermore, the L-fuzzy upper approximation operators generated by serial, symmetric, reflexive, mediate, transitive, and Euclidean L-fuzzy relations and their compositions are characterize through axiom set (single axiom), respectively.
Two Inverse Problems Solution by Feedback Tracking Control
Authors: Turetsky Vladimir
Published: June 2021

Two inverse ill-posed problems are considered. The first problem is an input restoration of a linear system. The second one is a restoration of time-dependent coefficients of a linear ordinary differential equation. Both problems are reformulated as auxiliary optimal control problems with regularizing cost functional. For the coefficients restoration problem, two control models are proposed. In the first model, the control coefficients are approximated by the output and the estimates of its derivatives. This model yields an approximating linear-quadratic optimal control problem having a known explicit solution. The derivatives are also obtained as auxiliary linear-quadratic tracking controls. The second control model is accurate and leads to a bilinear-quadratic optimal control problem. The latter is tackled in two ways: by an iterative procedure and by a feedback linearization. Simulation results show that a bilinear model provides more accurate coefficients estimates.
Beverages Containing Plant-Derived Polyphenols Inhibit Growth and Biofilm Formation of Streptococcus mutans and Children’s Supragingival Plaque Bacteria
Authors: Wu Christine D. , Huang Ellen , Li Wei , White Mark , Jung Shawn , Xie Qian
Published: June 2021

Objectives: Polyphenols in edible berries and tea plant (Camellia sinensis) suppressed virulence factors of oral pathogens. We investigated if the commercially marketed plant polyphenols-containing beverages inhibited growth and biofilm formation of Streptococcus mutans and children’s dental plaque. Methods: Supragingival plaque collected from 16 children (7–11 years) were suspended in TSB for testing. Test beverages included 26 marketed packaged teas, ready-to-drink bottled raspberry flavored teas and cranberry juice cocktails with and without added sugars. Their effects on in vitro growth and biofilm formation of S. mutans and children’s plaque bacteria were determined after 24–48 h at 37 °C anaerobically in CDM with or without sucrose. Results: Brewed infusions from black, green and cinnamon or raspberry flavored teas bags inhibited growth and biofilm formation of children’s plaque bacteria. Compared to controls, bottled raspberry flavored teas and cranberry juice cocktails significantly inhibited growth and biofilm formation of test bacteria. Added sugar did not significantly impact the inhibition (p > 0.05). Biofilms formed in these beverages were loosely attached and easily dislodged from surfaces. Conclusions: Beverages rich in antimicrobial plant polyphenols reduce plaque adherence, may benefit oral health and are preferred over other sugary beverages. The concept of oral diseases prevention using natural foods/diet is innovative, practical and acceptable.
Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products
Authors: Bhat Irshad Ul Haq , Bhat Rajeev
Published: June 2021

Quercetin, a bioactive secondary metabolite, holds incredible importance in terms of bioactivities, which has been proved by in vivo and in vitro studies. The treatment of cardiovascular and neurological diseases by quercetin has been extensively investigated over the past decade. Quercetin is present naturally in appreciable amounts in fresh produce (fruits and vegetables). However, today, corresponding to the growing population and global demand for fresh fruits and vegetables, a paradigm shift and focus is laid towards exploring industrial food wastes and/or byproducts as a new resource to obtain bioactive compounds such as quercetin. Based on the available research reports over the last decade, quercetin has been suggested as a reliable therapeutic candidate for either treating or alleviating health issues, mainly those of cardiovascular and neurological diseases. In the present review, we have summarized some of the critical findings and hypotheses of quercetin from the available databases foreseeing its future use as a potential therapeutic agent to treat cardiovascular and neurological diseases. It is anticipated that this review will be a potential reference material for future research activities to be undertaken on quercetin obtained from fresh produce as well as their respective processing wastes/byproducts that rely on the circular concept.
Relationship between Fertility Traits and Kinematics in Clusters of Boar Ejaculates
Authors: Barquero Vinicio , Roldan Eduardo R. S. , Soler Carles , Vargas-Leitón Bernardo , Sevilla Francisco , Camacho Marlen , Valverde Anthony
Published: June 2021

The aim was to determine the relationship between kinematic parameters of boar spermatozoa and fertility rates of sow, as well as to assess the effect of sperm clusters on the fertility capacity of the ejaculate. Semen samples were collected from 11 sexually mature boars. Samples were analyzed by an ISAS®v1 CASA-Mot system for eight kinematic parameters. Ejaculate clusters were characterized using multivariate procedures, such as principal factors (PFs) analysis and clustering methods (the k-means model). Four different ejaculate clusters were identified from two kinematic PFs which involved linear trajectory and velocity. There were differences (p < 0.05) between the sperm kinematic variables by sire line. There was no statistical difference (p > 0.05) between dam lines and ejaculate clusters in fertility variables. The discriminant ability of the different kinematics of sperm variables to predict litter size fertility was analyzed using receiver operating characteristics (ROC) curve analysis. Curvilinear velocity (VCL), average path velocity (VAP), amplitude of lateral head displacement (ALH), and beat-cross frequency (BCF) showed significant, albeit limited, predictive capacity for litter size fertility variables (range: 0.55–0.58 area under curve, AUC). The kinematic analysis of the ejaculates in clusters did not have a predictive capacity for litter size variables.
Phylogenetic Diversity of Lhr Proteins and Biochemical Activities of the Thermococcales aLhr2 DNA/RNA Helicase
Authors: Hajj Mirna , Langendijk-Genevaux Petra , Batista Manon , Quentin Yves , Laurent Sébastien , Capeyrou Régine , Abdel-Razzak Ziad , Flament Didier , Chamieh Hala , Fichant Gwennaele , Clouet-d’Orval Béatrice , Bouvier Marie
Published: June 2021

Helicase proteins are known to use the energy of ATP to unwind nucleic acids and to remodel protein-nucleic acid complexes. They are involved in almost every aspect of DNA and RNA metabolisms and participate in numerous repair mechanisms that maintain cellular integrity. The archaeal Lhr-type proteins are SF2 helicases that are mostly uncharacterized. They have been proposed to be DNA helicases that act in DNA recombination and repair processes in Sulfolobales and Methanothermobacter. In Thermococcales, a protein annotated as an Lhr2 protein was found in the network of proteins involved in RNA metabolism. To investigate this, we performed in-depth phylogenomic analyses to report the classification and taxonomic distribution of Lhr-type proteins in Archaea, and to better understand their relationship with bacterial Lhr. Furthermore, with the goal of envisioning the role(s) of aLhr2 in Thermococcales cells, we deciphered the enzymatic activities of aLhr2 from Thermococcus barophilus (Tbar). We showed that Tbar-aLhr2 is a DNA/RNA helicase with a significant annealing activity that is involved in processes dependent on DNA and RNA transactions.
Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience
Authors: Gragnaniello Vincenza , Burlina Alessandro P , Polo Giulia , Giuliani Antonella , Salviati Leonardo , Duro Giovanni , Cazzorla Chiara , Rubert Laura , Maines Evelina , Germain Dominique P , Burlina Alberto B
Published: June 2021

Fabry disease (FD) is a progressive multisystemic lysosomal storage disease. Early diagnosis by newborn screening (NBS) may allow for timely treatment, thus preventing future irreversible organ damage. We present the results of 5.5 years of NBS for FD by α-galactosidase A activity and globotriaosylsphingosine (lyso-Gb3) assays in dried blood spot through a multiplexed MS/MS assay. Furthermore, we report our experience with long-term follow-up of positive subjects. We screened more than 170,000 newborns and 22 males were confirmed to have a GLA gene variant, with an incidence of 1:7879 newborns. All patients were diagnosed with a variant previously associated with the later-onset phenotype of FD or carried an unclassified variant (four patients) or the likely benign p.Ala143Thr variant. All were asymptomatic at the last visit. Although lyso-Gb3 is not considered a reliable second tier test for newborn screening, it can simplify the screening algorithm when its levels are elevated at birth. After birth, plasma lyso-Gb3 is a useful marker for non-invasive monitoring of all positive patients. Our study is the largest reported to date in Europe, and presents data from long-term NBS for FD that reveals the current incidence of FD in northeastern Italy. Our follow-up data describe the early disease course and the trend of plasma lyso-Gb3 during early childhood.
Accumulated Knowledge of Activin Receptor-Like Kinase 2 (ALK2)/Activin A Receptor, Type 1 (ACVR1) as a Target for Human Disorders
Authors: Katagiri Takenobu , Tsukamoto Sho , Kuratani Mai
Published: June 2021

Activin receptor-like kinase 2 (ALK2), also known as Activin A receptor type 1 (ACVR1), is a transmembrane kinase receptor for members of the transforming growth factor-β family. Wild-type ALK2/ACVR1 transduces osteogenic signaling in response to ligand binding. Fifteen years ago, a gain-of-function mutation in the ALK2/ACVR1 gene was detected in patients with the genetic disorder fibro-dysplasia ossificans progressiva, which is characterized by heterotopic ossification in soft tissues. Additional disorders, such as diffuse intrinsic pontin glioma, diffuse idiopathic skeletal hyperostosis, primary focal hyperhidrosis, and congenital heart defects, have also been found to be associated with ALK2/ACVR1. These findings further expand in vitro and in vivo model system research and promote our understanding of the molecular mechanisms of the pathogenesis and development of novel therapeutics and diagnosis for disorders associated with ALK2/ACVR1. Through aggressive efforts, some of the disorders associated with ALK2/ACVR1 will be overcome in the near future.
Fine-Tuning the PI3K/Akt Signaling Pathway Intensity by Sex and Genotype-Load: Sex-Dependent Homozygotic Threshold for Somatic Growth but Feminization of Anxious Phenotype in Middle-Aged PDK1 K465E Knock-In and Heterozygous Mice
Authors: Santana-Santana Mikel , Bayascas José-Ramón , Giménez-Llort Lydia
Published: June 2021

According to the Research Domain Criteria (RDoC), phenotypic differences among disorders may be explained by variations in the nature and degree of neural circuitry disruptions and/or dysfunctions modulated by several biological and environmental factors. We recently demonstrated the in vivo behavioral translation of tweaking the PI3K/Akt signaling, an essential pathway for regulating cellular processes and physiology, and its modulation through aging. Here we describe, for the first time, the in vivo behavioral impact of the sex and genetic-load tweaking this pathway. The anxiety-like phenotypes of 61 mature (11–14-month-old) male and female PDK1 K465E knock-in, heterozygous, and WT mice were studied. Forced (open-field) anxiogenic environmental conditions were sensitive to detect sex and genetic-load differences at middle age. Despite similar neophobia and horizontal activity among the six groups, females exhibited faster ethograms than males, with increased thigmotaxis, increased wall and bizarre rearing. Genotype-load unveiled increased anxiety in males, resembling female performances. The performance of mutants in naturalistic conditions (marble test) was normal. Homozygotic-load was needed for reduced somatic growth only in males. Factor interactions indicated the complex interplay in the elicitation of different negative valence system’s items and the fine-tuning of PI3K/Akt signaling pathway intensity by genotype-load and sex.
ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD
Authors: Cervantes-Henriquez Martha L. , Acosta-López Johan E. , Ahmad Mostapha , Sánchez-Rojas Manuel , Jiménez-Figueroa Giomar , Pineda-Alhucema Wilmar , Martinez-Banfi Martha L. , Noguera-Machacón Luz M. , Mejía-Segura Elsy , De La Hoz Moisés , Arcos-Holzinger Mauricio , Pineda David A. , Puentes-Rozo Pedro J. , Arcos-Burgos Mauricio , Vélez Jorge I.
Published: June 2021

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual–motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.
Electrophysiological Studies of Cognitive Reappraisal Success and Failure in aMCI
Authors: Xiao Shasha , Li Yingjie , Liu Meng , Li Yunxia
Published: June 2021

Background: Although successful reappraisal relies on cognitive resources, how cognitive impairment affects brain processes related to cognitive reappraisal is not yet clear. Methods: Forty-four amnestic mild cognitive impairment (aMCI) subjects and 72 healthy elderly controls (HECs) were divided into the MCI-Failure (n = 23), MCI-Success (n = 21), HEC-Failure (n = 26), and HEC-Success (n = 46) groups according to changes in self-reported affect using reappraisal. All participants viewed 30 negative and 30 neutral images preceded by straightforward descriptions of these images and 30 negative images preceded by more neutral descriptions. Results: Reappraisal failure was found to be more common in people with MCI. Reappraisal failure is associated with altered neurophysiological indices of negative-reappraisal stimuli processing that are reflected in smaller theta responsivity to negative-reappraisal stimuli between 350–550 ms. The MCI-Success group showed enhanced LPP for negative-reappraisal stimuli from 1200 to 3500 ms, reflecting compensatory effort to complete the reappraisal task, while subjects in other groups showed reduced LPP for negative-reappraisal stimuli from 550 to 1200 ms. Conclusions: These findings deepen our understanding of how cognitive decline impacts reappraisal and informs early diagnosis and interventions for MCI.
Carbons Formed in Methane Thermal and Thermocatalytic Decomposition Processes: Properties and Applications
Authors: Välimäki Emmi , Yli-Varo Lasse , Romar Henrik , Lassi Ulla
Published: June 2021

The hydrogen economy will play a key role in future energy systems. Several thermal and catalytic methods for hydrogen production have been presented. In this review, methane thermocatalytic and thermal decomposition into hydrogen gas and solid carbon are considered. These processes, known as the thermal decomposition of methane (TDM) and thermocatalytic decomposition (TCD) of methane, respectively, appear to have the greatest potential for hydrogen production. In particular, the focus is on the different types and properties of carbons formed during the decomposition processes. The applications for carbons are also investigated.
Protein Aggregation Patterns Inform about Breast Cancer Response to Antiestrogens and Reveal the RNA Ligase RTCB as Mediator of Acquired Tamoxifen Resistance
Authors: Direito Inês , Monteiro Liliana , Melo Tânia , Figueira Daniela , Lobo João , Enes Vera , Moura Gabriela , Henrique Rui , Santos Manuel A. S. , Jerónimo Carmen , Amado Francisco , Fardilha Margarida , Helguero Luisa A.
Published: June 2021

The protein quality control network, including autophagy, the proteasome and the unfolded protein response (UPR), is triggered by stress and is overactive in acquired antiestrogen therapy resistance. We show for the first time that the aggresome load correlates with apoptosis and is increased in antiestrogen-sensitive cells compared to endocrine-resistant variants. LC-MS/MS analysis of the aggregated proteins obtained after 4OH-tamoxifen and Fulvestrant treatment identified proteins with essential function in protein quality control in antiestrogen-sensitive cells, but not in resistant variants. These include the UPR modulators RTCB and PDIA6, as well as many proteasome proteins such as PSMC2 and PSMD11. RTCB is a tRNA and XBP1 ligase and its aggregation induced by antiestrogens correlated with impaired XBP1s expression in sensitive cells. Knock down of RTCB was sufficient to restore sensitivity to tamoxifen in endocrine-resistant cells and increased the formation of aggresomes, leading to apoptotic cell death. Analysis of primary human breast cancer samples and their metastases appearing after endocrine treatment showed that RTCB is only localized to aggresomes in the primary tumors, while total aggresomes, including aggregated RTCB, were significantly reduced in the metastases. Therefore, different protein aggregation patterns may indicate loss of function of essential proteins resulting in enhanced protein aggregation that can be used to identify antiestrogen-resistant breast cancer cells and improve the response to antiestrogenic therapy.
Organ Sparing for Locally Advanced Rectal Cancer after Neoadjuvant Treatment Followed by Electrochemotherapy
Authors: Rega Daniela , Granata Vincenza , Petrillo Antonella , Pace Ugo , Sassaroli Cinzia , Di Marzo Massimiliano , Cervone Carmela , Fusco Roberta , D’Alessio Valeria , Nasti Guglielmo , Romano Carmela , Avallone Antonio , Pecori Biagio , Botti Gerardo , Tatangelo Fabiana , Maiolino Piera , Delrio Paolo
Published: June 2021

Background: Currently, 45–55% of rectal cancer patients receive preoperative chemo- radio-therapy for Locally Advanced Rectal Cancer (LARC). The idea of our study is to use Electrochemotherapy (ECT) before surgery, in patients with major clinical response after neoadjuvant therapy, to allow for a more conservative surgical approach. Objective: To evaluate the increase of the complete response rate after neoadjuvant treatment in LARC and to spare organ function due to total mesorectal excision (TME). Patients and Methods: This is a Phase II randomized controlled trial enrolling 70 patients that will be developed in two stages. In the first step, 28 patients will be enrolled: 14 of these will receive ECT for four weeks after neo-adjuvant treatment and then local excision (treatment group) and 14 patients will receive neo-adjuvant treatment and then local excision (control group). If an increase of response rate is observed in the first stage, and/or feasibility/safety is demonstrated, the second stage of the trial will be performed, enrolling an additional 42 patients. The treatment response. in both the control arm and the treatment arm, will be assessed using the histopathological tumor regression grade on tissue specimens after local excision.
Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy—A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin
Authors: Deininger Susanne , Törzsök Peter , Oswald David , Lusuardi Lukas
Published: June 2021

Background: In the first and second-line therapy of metastatic urothelial carcinoma (mUC), checkpoint inhibitors (CPI) such as Pembrolizumab and Atezolizumab have been widely implemented. Little is currently known about what therapeutic options are effective after therapy with CPI. This article presents a systemic review of current treatment options in this setting. Methods: From August 2020 to 15 April 2021, a literature search was performed through the PubMed/Medline. Subsequently, a single-group meta-analysis of three studies testing Enfortumab vedotin (EV) was conducted. Results: Five therapy regimens tested in the post-CPI setting with adequate data were identified: Chemotherapy (CT), Ramucirumab plus Docetaxel, Erdafitinib (Erd), EV, and Sacituzumab govitecan (SG). In n = 74 + 125 + 288 patients, the single-group meta-analysis showed an objective response rate of 42.1% for EV compared to 17.9% for CT in a similar setting. EV was also ahead in progression free survival (5.9 months with EV vs. 3.7 months with CT) and overall survival (12.8 months with EV vs. 9.0 months with CT). Conclusion: Most data are currently available for EV. Further research is needed on the question of which patients’ subcollectives particularly benefit from which therapeutic approach.
Hydroxychloroquine (HCQ) Modulates Autophagy and Oxidative DNA Damage Stress in Hepatocellular Carcinoma to Overcome Sorafenib Resistance via TLR9/SOD1/hsa-miR-30a-5p/Beclin-1 Axis
Authors: Chen Ming-Yao , Yadav Vijesh Kumar , Chu Yi Cheng , Ong Jiann Ruey , Huang Ting-Yi , Lee Kwai-Fong , Lee Kuen-Haur , Yeh Chi-Tai , Lee Wei-Hwa
Published: June 2021

Sorafenib is used for treating advanced hepatocellular carcinoma (HCC), but some patients acquire sorafenib resistance. We investigated the mechanisms underlying acquired sorafenib resistance in HCC cells and targeted them to re-sensitize them to sorafenib. In silico analysis indicated that toll-like receptor (TLR)-9 was significantly overexpressed, and that miRNA (hsa-miR-30a-5p) was downregulated in sorafenib-resistant HCC cells, which modulated HCC cell proliferation, oxidative stress, and apoptosis. TLR9 overexpression increased HCC cell proliferation, whereas TLR9 inhibition from hydroxychloroquine (HCQ) decreased HCC cell proliferation, tumor growth, oxidative stress marker (SOD1), and the formation of autophagosome bodies (reduced ATG5 and Beclin-1 expression). Moreover, HCQ treatment reduced epithelial–mesenchymal transition, leading to decreased clonogenicity, migratory ability, and invasiveness. HCQ targeted and reduced the self-renewal capacity phenotype by inhibiting tumorsphere generation. Both in vitro and in vivo results demonstrated the synergistic effect of the HCQ–sorafenib combination on sorafenib-resistant HCC (Huh7-SR) cells, increasing their sensitivity to treatment by modulating TLR9, autophagy (ATG5 and Beclin-1), oxidative stress (SOD1), and apoptosis (c-caspase3) expression and thus overcoming the drug resistance. This study’s findings indicate that TLR9 overexpression occurs in sorafenib-resistant HCC cells and that its downregulation aids HCC suppression. Moreover, HCQ treatment significantly increases sorafenib’s effect on sorafenib-resistant HCC cells.
Integration of Salmonella into Combination Cancer Therapy
Authors: Al-Saafeen Besan H. , Fernandez-Cabezudo Maria J. , al-Ramadi Basel K.
Published: June 2021

Current modalities of cancer treatment have limitations related to poor target selectivity, resistance to treatment, and low response rates in patients. Accumulating evidence over the past few decades has demonstrated the capacity of several strains of bacteria to exert anti-tumor activities. Salmonella is the most extensively studied entity in bacterial-mediated cancer therapy, and has a good potential to induce direct tumor cell killing and manipulate the immune components of the tumor microenvironment in favor of tumor inhibition. In addition, Salmonella possesses some advantages over other approaches of cancer therapy, including high tumor specificity, deep tissue penetration, and engineering plasticity. These aspects underscore the potential of utilizing Salmonella in combination with other cancer therapeutics to improve treatment effectiveness. Herein, we describe the advantages that make Salmonella a good candidate for combination cancer therapy and summarize the findings of representative studies that aimed to investigate the therapeutic outcome of combination therapies involving Salmonella. We also highlight issues associated with their application in clinical use.
Special Issue “Biocatalysts: Design and Application”
Authors: Mateo Cesar , Palomo Jose M.
Published: June 2021

The use of biocatalysts in chemical reactions is of great interest because reactions can be carried out under very mild and green conditions [...]
Bio-Catalytic Activity of Novel Mentha arvensis Intervened Biocompatible Magnesium Oxide Nanomaterials
Authors: Faisal Shah , Abdullah  , Jan Hasnain , Shah Sajjad Ali , Shah Sumaira , Rizwan Muhammad , Zaman Nasib , Hussain Zahid , Uddin Muhammad Nazir , Bibi Nadia , Khattak Aishma , Khan Wajid , Iqbal Arshad , Idrees Muhammad , Masood Rehana
Published: June 2021

In the present study Mentha arvensis medaited Magnesium oxide nanoparticles were synthesized by novel green route followed by advanced characterization via XRD, FTIR, UV, SEM, TEM, DLS and TGA. The mean grain size of 32.4 nm and crystallite fcc morphology were confirmed by X-ray diffractive analysis. Scanning and Transmission electron microscopy analysis revealed the spherical and elliptical morphologies of the biosynthesized nanoparticles. Particle surface charge of −16.1 mV were determined by zeta potential and zeta size of 30–120 nm via dynamic light scattering method. Fourier transform spectroscopic analysis revealed the possible involvement of functional groups in the plant extract in reduction of Mg2+ ions to Mg0. Furthermore, the antioxidant, anti-Alzheimer, anti-cancer, and anti-H. pylori activities were performed. The results revealed that MgO-NPs has significant anti-H. pyloric potential by giving ZOI of 17.19 ± 0.83 mm against Helicobacter felis followed by Helicobacter suis. MgO-NPs inhibited protein kinase enzyme up to 12.44 ± 0.72% at 5 mg/mL and thus showed eminent anticancer activity. Significant free radicals scavenging and hemocompatability was also shown by MgO-NPs. MgO-NPs also displayed good inhibition potential against Hela cell lines with maximum inhibition of 49.49 ± 1.18 at 400 µg/mL. Owing to ecofriendly synthesis, non-toxic and biocompatible nature, Mentha arvensis synthesized MgO-NPs can be used as potent antimicrobial agent in therapeutic applications.
Criteria for Engineering Cutinases: Bioinformatics Analysis of Catalophores
Authors: Fortuna Sara , Cespugli Marco , Todea Anamaria , Pellis Alessandro , Gardossi Lucia
Published: June 2021

Cutinases are bacterial and fungal enzymes that catalyze the hydrolysis of natural cutin, a three-dimensional inter-esterified polyester with epoxy-hydroxy fatty acids with chain lengths between 16 and 18 carbon atoms. Due to their ability to accept long chain substrates, cutinases are also effective in catalyzing in vitro both the degradation and synthesis of several synthetic polyesters and polyamides. Here, we present a bioinformatics study that intends to correlate the structural features of cutinases with their catalytic properties to provide rational basis for their effective exploitation, particularly in polymer synthesis and biodegradation. The bioinformatics study used the BioGPS method (Global Positioning System in Biological Space) that computed molecular descriptors based on Molecular Interaction Fields (MIFs) described in the GRID force field. The information was used to generate catalophores, spatial representations of the ability of each enzymatic active site to establish hydrophobic and electrostatic interactions. These tools were exploited for comparing cutinases to other serine-hydrolases enzymes, namely lipases, esterases, amidases and proteases, and for highlighting differences and similarities that might guide rational engineering strategies. Structural features of cutinases with their catalytic properties were correlated. The “catalophore” of cutinases indicate shared features with lipases and esterases.
Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals
Authors: Iarovaia Olga V. , Ioudinkova Elena S. , Velichko Artem K. , Razin Sergey V.
Published: June 2021

Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups. During infection, proteins of the nucleolus in association with viral components can be directly used for the processes of replication and transcription of viral nucleic acids and the assembly and transport of viral particles. In the course of a viral infection, the usurpation of the nucleolus functions occurs and the usurpation is accompanied by profound changes in ribosome biogenesis. Recent studies have demonstrated that the nucleolus is a multifunctional and dynamic compartment. In addition to the biogenesis of ribosomes, it is involved in regulating the cell cycle and apoptosis, responding to cellular stress, repairing DNA, and transcribing RNA polymerase II-dependent genes. A viral infection can be accompanied by targeted transport of viral proteins to the nucleolus, massive release of resident proteins of the nucleolus into the nucleoplasm and cytoplasm, the movement of non-nucleolar proteins into the nucleolar compartment, and the temporary localization of viral nucleic acids in the nucleolus. The interaction of viral and nucleolar proteins interferes with canonical and non-canonical functions of the nucleolus and results in a change in the physiology of the host cell: cell cycle arrest, intensification or arrest of ribosome biogenesis, induction or inhibition of apoptosis, and the modification of signaling cascades involved in the stress response. The nucleolus is, therefore, an important target during viral infection. In this review, we discuss the functional impact of viral proteins and nucleic acid interaction with the nucleolus during infection.