bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a Distance Estimator for a Wildlife Tracking System Based on 802.15.4
Authors: Cascado-Caballero Daniel , Duran-Lopez Lourdes , Dominguez-Morales Juan Pedro , Gutierrez-Galan Daniel , Amaya-Rodriguez Claudio , Dominguez-Morales Manuel
Published: December 2019

In this work, a novel distance estimation mechanism using received signal strength indication (RSSI) signals with ZigBee modules is designed, implemented and tested in several scenarios. This estimator was used for a research project focused on a wildlife behavioral classification system deployed in Doñana’s National Park. As a supporting feature for that project, this work was implemented for locating animal’s collars acting as wireless nodes in order to find those who went outside of the coverage area of the network or that were accidentally detached from animals. This work describes the system architecture and the implementation of a mobile assistant capable of recovering devices located beyond the coverage of the network. The analytical model needed for distance estimation and the signal filtering are described, as well as the difficulties that the researchers must deal when building robust location estimators. This theoretical model was applied to three different scenarios and tested with two validation experiments.
The Technical Challenges Facing the Integration of Small-Scale and Large-scale PV Systems into the Grid: A Critical Review
Authors: Alshahrani Abdullah , Omer Siddig , Su Yuehong , Mohamed Elamin , Alotaibi Saleh
Published: December 2019

Decarbonisation, energy security and expanding energy access are the main driving forces behind the worldwide increasing attention in renewable energy. This paper focuses on the solar photovoltaic (PV) technology because, currently, it has the most attention in the energy sector due to the sharp drop in the solar PV system cost, which was one of the main barriers of PV large-scale deployment. Firstly, this paper extensively reviews the technical challenges, potential technical solutions and the research carried out in integrating high shares of small-scale PV systems into the distribution network of the grid in order to give a clearer picture of the impact since most of the PV systems installations were at small scales and connected into the distribution network. The paper reviews the localised technical challenges, grid stability challenges and technical solutions on integrating large-scale PV systems into the transmission network of the grid. In addition, the current practices for managing the variability of large-scale PV systems by the grid operators are discussed. Finally, this paper concludes by summarising the critical technical aspects facing the integration of the PV system depending on their size into the grid, in which it provides a strong point of reference and a useful framework for the researchers planning to exploit this field further on.
Demosaicing of Bayer and CFA 2.0 Patterns for Low Lighting Images
Authors: Kwan Chiman , Larkin Jude
Published: December 2019

It is commonly believed that having more white pixels in a color filter array (CFA) will help the demosaicing performance for images collected in low lighting conditions. However, to the best of our knowledge, a systematic study to demonstrate the above statement does not exist. We present a comparative study to systematically and thoroughly evaluate the performance of demosaicing for low lighting images using two CFAs: the standard Bayer pattern (aka CFA 1.0) and the Kodak CFA 2.0 (RGBW pattern with 50% white pixels). Using the clean Kodak dataset containing 12 images, we first emulated low lighting images by injecting Poisson noise at two signal-to-noise (SNR) levels: 10 dBs and 20 dBs. We then created CFA 1.0 and CFA 2.0 images for the noisy images. After that, we applied more than 15 conventional and deep learning based demosaicing algorithms to demosaic the CFA patterns. Using both objectives with five performance metrics and subjective visualization, we observe that having more white pixels indeed helps the demosaicing performance in low lighting conditions. This thorough comparative study is our first contribution. With denoising, we observed that the demosaicing performance of both CFAs has been improved by several dBs. This can be considered as our second contribution. Moreover, we noticed that denoising before demosaicing is more effective than denoising after demosaicing. Answering the question of where denoising should be applied is our third contribution. We also noticed that denoising plays a slightly more important role in 10 dBs signal-to-noise ratio (SNR) as compared to 20 dBs SNR. Some discussions on the following phenomena are also included: (1) why CFA 2.0 performed better than CFA 1.0; (2) why denoising was more effective before demosaicing than after demosaicing; and (3) why denoising helped more at low SNRs than at high SNRs.
A Framework for Analyzing and Testing Cyber–Physical Interactions for Smart Grid Applications
Authors: El Hariri Mohamad , Youssef Tarek , Saleh Mahmoud , Faddel Samy , Habib Hany , Mohammed Osama A.
Published: December 2019

The reliable performance of the smart grid is a function of the configuration and cyber–physical nature of its constituting sub-systems. Therefore, the ability to capture the interactions between its cyber and physical domains is necessary to understand the effect that each one has on the other. As such, the work in this paper presents a co-simulation platform that formalizes the understanding of cyber information flow and the dynamic behavior of physical systems, and captures the interactions between them in smart grid applications. Power system simulation software packages, embedded microcontrollers, and a real communication infrastructure are combined together to provide a cohesive smart grid cyber–physical platform. A data-centric communication scheme, with automatic network discovery, was selected to provide an interoperability layer between multi-vendor devices and software packages, and to bridge different protocols. The effectiveness of the proposed framework was verified in three case studies: (1) hierarchical control of electric vehicles charging in microgrids, (2) International Electrotechnical Committee (IEC) 61850 protocol emulation for protection of active distribution networks, and (3) resiliency enhancement against fake data injection attacks. The results showed that the co-simulation platform provided a high-fidelity design, analysis, and testing environment for cyber information flow and their effect on the physical operation of the smart grid, as they were experimentally verified, down to the packet, over a real communication network.
Aging-Resilient Topology Synthesis of Heterogeneous Manycore Network-On-Chip Using Genetic Algorithm with Flexible Number of Routers
Authors: Lee Young Sik , Kim SoYoung , Han Tae Hee
Published: December 2019

As semiconductor processes enter the nanoscale, system-on-chip (SoC) interconnects suffer from link aging owing to negative bias temperature instability (NBTI), hot carrier injection (HCI), and electromigration. In network-on-chip (NoC) for heterogeneous manycore systems, there is a difference in the aging speed of links depending on the location and utilization of resources. In this paper, we propose a heterogeneous manycore NoC topology synthesis that predicts the aging effect of each link and deploys routers and error correction code (ECC) logic. Aging-aware ECC logic is added to each link to achieve the same link lifetime with less area and latency than the Bose-Chaudhuri-Hocquenghem (BCH) logic. Moreover, based on the modified genetic algorithm, we search for a solution that minimizes the average latency while ensuring the link lifetime by changing the number of routers, location, and network connectivity. Simulation results demonstrate that the aging-aware topology synthesis reduces the average latency of the network by up to 26.68% compared with the aging analysis and the addition of ECC logic on the link after the topology synthesis. Furthermore, topology synthesis with aging-aware ECC logic reduces the maximum average latency by up to 39.49% compared with added BCH logic.
Estimation of Impedance and Susceptance Parameters of a 3-Phase Cable System Using PMU Data
Authors: Singh Ravi Shankar , van den Brom Helko , Babaev Stanislav , Cobben Sjef , Ćuk Vladimir
Published: December 2019

This paper proposes a new regression-based method to estimate resistance, reactance, and susceptance parameters of a 3-phase cable segment using phasor measurement unit (PMU) data. The novelty of this method is that it gives accurate parameter estimates in the presence of unknown bias errors in the measurements. Bias errors are fixed errors present in the measurement equipment and have been neglected in previous such attempts of estimating parameters of a 3-phase line or cable segment. In power system networks, the sensors used for current and voltage measurements have inherent magnitude and phase errors whose measurements need to be corrected using calibrated correction coefficients. Neglecting or using wrong error correction coefficients causes fixed bias errors in the measured current and voltage signals. Measured current and voltage signals at different time instances are the variables in the regression model used to estimate the cable parameters. Thus, the bias errors in the sensors become fixed errors in the variables. This error in variables leads to inaccuracy in the estimated parameters. To avoid this, the proposed method uses a new regression model using extra parameters which facilitate the modeling of present but unknown bias errors in the measurement system. These added parameters account for the errors present in the non- or wrongly calibrated sensors. Apart from the measurement bias, random measurement errors also contribute to the total uncertainty of the estimated parameters. This paper also presents and compares methods to estimate the total uncertainty in the estimated parameters caused by the bias and random errors present in the measurement system. Results from simulation-based and laboratory experiments are presented to show the efficacy of the proposed method. A discussion about analyzing the obtained results is also presented.
Identification and Expression of NAC Transcription Factors of Vaccinium corymbosum L. in Response to Drought Stress
Authors: Liang Kehao , Wang Aibin , Sun Yongjiang , Yu Mingxin , Zhang Lingyun
Published: December 2019

Research Highlights: Phenotypic changes and expression profiles, phylogeny, conserved motifs, and expression correlations of NAC (NAM, ATAF1, ATAF2 and CUC2) transcription factors (TFs) in blueberry genome were detected under drought stress, and the expression patterns and functions of 12 NACs were analyzed. Background and Objectives: Blueberry is an important shrub species with a high level of flavonoids in fruit, which are implicated in a broad range of health benefits. However, the molecular mechanism of this shrub species in response to drought stress still remains elusive. NAC TFs widely participate in stress tolerance in many plant species. The characterization and expression profiles of NAC TFs were analyzed on the basis of genome data in blueberry when subjected to drought stress. Materials and Methods: Combined with the analysis of chlorophyll a fluorescence and endogenous phytohormones, the phenotypic changes of blueberry under drought stress were observed. The phylogenetic tree, conserved motifs, differently expressed genes, and expression correlation were determined by means of multiple bioinformatics analysis. The expression profiles of NACs in different organs were examined and compared through RNA-seq and qRT-PCR assay. Results: The chlorophyll a fluorescence parameters φPo, φEo, φRo, and PIabs of leaves were significantly inhibited under drought stress. ABA (abscisic acid) content noticeably increased over the duration of drought, whereas GA3 (gibberellic acid) and IAA (indole acetic acid) content decreased continuously. A total of 158 NACs were identified in blueberry genome and 62 NACs were differently expressed in leaf and root of blueberry under drought stress. Among them, 14 NACs were significantly correlated with the expression of other NAC genes. Conclusions: Our results revealed the phenotypic changes of this shrub under drought stress and linked them with NAC TFs, which are potentially involved in the process of response to drought stress.
Sub-Genome Polyploidization Effects on Metabolomic Signatures in Triploid Hybrids of Populus
Authors: Cheng Shiping , Zong Yuxia , Wang Xuewen
Published: December 2019

Allopolyploids are known to have superior advantages such as high growth speed. Triploids have even greater heterozygosity, explaining more phenotypic variance than 2n hybrid F1 and have therefore become new resources in breeding. To date, the metabolomic basis underlying polyploidization vigor remains unclear. Here, we identified and compared 235 metabolites in the shoot apical buds between multiple allo-triploid populations and parental 2n hybrid F1 in Populus via metabolome profiling using liquid chromatography–mass spectrometry (LC–MS) assays. Associations with growth vigor in three types of allo-triploid populations, namely first division restitution (FDR), second division restitution (SDR) and postmeiotic restitution (PMR) generated from doubled 2n female gametes and male gametes of 2n hybrid, were also investigated. Each allo-triploid population has different sub-genome duplicated. Major metabolomes were amino acids, secondary metabolism associated, and carbohydrates. We mapped 181 metabolites into known metabolism pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG). Ten compounds, i.e., fructose 1,6-diphosphate and xylulose, were more abundant in all allo-triploids than the 2n hybrid. Principal component analysis revealed the abundance of metabolites fell into distinct clusters corresponding to ploidy composition. Heterozygosity in triploids mainly effected the contents of carbohydrates and secondary metabolites rather than lipids. Comparisons between subgroups with different growth rates revealed some carbohydrates and secondary metabolites of flavonoids were positively associated with gene expression and the high growth vigor. The results provided an informative metabolomic basis for factors conferring growth vigor in polyploid Populus.
Dough Rheological Behavior and Microstructure Characterization of Composite Dough with Wheat and Tomato Seed Flours
Authors: Mironeasa Silvia , Codină Georgiana Gabriela
Published: December 2019

The rheological and microstructural aspects of the dough samples prepared from wheat flour and different levels of tomato seed flour (TSF) were investigated by rheology methods through the Mixolab device, dynamic rheology and epifluorescence light microscopy (EFLM). The Mixolab results indicated that replacing wheat flour with TSF increased dough development time, stability, and viscosity during the initial heating-cooling cycle and decreased alpha amylase activity. The dynamic rheological data showed that the storage modulus G’ and loss modulus G” increased with the level of TSF addition. Creep-recovery tests of the samples indicated that dough elastic recovery was in a high percentage after stress removal for all the samples in which TSF was incorporated in wheat flour. Using EFLM all the samples seemed homogeneous showing a compact dough matrix structure. The parameters measured with Mixolab during mixing were in agreement with the dynamic rheological data and in accordance with the EFLM structure images. These results are useful for bakery producers in order to develop new products in which tomato seed flour may be incorporated especially for wheat flours of a good quality for bread making and high wet gluten content. The addition of TSF may have a strength effect on the dough system and will increase the nutritional value of the bakery products.
Prediction of Terpenoid Toxicity Based on a Quantitative Structure–Activity Relationship Model
Authors: Perestrelo Rosa , Silva Catarina , Fernandes Miguel X. , Câmara José S.
Published: December 2019

Terpenoids, including monoterpenoids (C10), norisoprenoids (C13), and sesquiterpenoids (C15), constitute a large group of plant-derived naturally occurring secondary metabolites with highly diverse chemical structures. A quantitative structure–activity relationship (QSAR) model to predict terpenoid toxicity and to evaluate the influence of their chemical structures was developed in this study by assessing in real time the toxicity of 27 terpenoid standards using the Gram-negative bioluminescent Vibrio fischeri. Under the test conditions, at a concentration of 1 µM, the terpenoids showed a toxicity level lower than 5%, with the exception of geraniol, citral, (S)-citronellal, geranic acid, (±)-α-terpinyl acetate, and geranyl acetone. Moreover, the standards tested displayed a toxicity level higher than 30% at concentrations of 50–100 µM, with the exception of (+)-valencene, eucalyptol, (+)-borneol, guaiazulene, β-caryophellene, and linalool oxide. Regarding the functional group, terpenoid toxicity was observed in the following order: alcohol > aldehyde ~ ketone > ester > hydrocarbons. The CODESSA software was employed to develop QSAR models based on the correlation of terpenoid toxicity and a pool of descriptors related to each chemical structure. The QSAR models, based on t-test values, showed that terpenoid toxicity was mainly attributed to geometric (e.g., asphericity) and electronic (e.g., maximum partial charge for a carbon (C) atom (Zefirov’s partial charge (PC)) descriptors. Statistically, the most significant overall correlation was the four-parameter equation with a training coefficient and test coefficient correlation higher than 0.810 and 0.535, respectively, and a square coefficient of cross-validation (Q2) higher than 0.689. According to the obtained data, the QSAR models are suitable and rapid tools to predict terpenoid toxicity in a diversity of food products.
Influence of Feeding Substrates on the Presence of Toxic Metals (Cd, Pb, Ni, As, Hg) in Larvae of Tenebrio molitor: Risk Assessment for Human Consumption
Authors: Truzzi Cristina , Illuminati Silvia , Girolametti Federico , Antonucci Matteo , Scarponi Giuseppe , Ruschioni Sara , Riolo Paola , Annibaldi Anna
Published: December 2019

Larvae of Tenebrio molitor L. (Coleoptera: Tenebrionidae) are particularly suitable as novel food for the human consumption; nevertheless, there are some potential safety risks linked with insect consumption. In this study we investigated the presence of Cd, Pb, Ni, As, Hg in new feeding substrates coming from solid residues generated by olive fruits processing, called olive-pomace, and their influence on the metal content in larvae of T. molitor. Morover, bioaccumulation factor and the mercury-selenium balance were evaluated. Analyses were carried out via graphite furnace atomic absorption spectrophotometry for Cd, Pb, Ni, As and Se, and via Direct Mercury Analyzer for Hg. All metal concentrations found in feeding substrates were below the legal limit of undesirable substances in animal feed (2002/32/EC). Concentrations in larvae were in the range (mg kg−1 wet weight): Cd 0.008–0.016, Pb 0.063–0.079, Ni 0.03–0.63, As 0.021–0.023, Hg 0.12 × 10−3–0.49 × 10−3, and Se 0.057–0.085. Statistically significant correlation between metal content in feeding substrates and in larvae was evidenced only for Hg, which bioaccumulates. Se protects from mercury toxicity, with a Selenium Health Benefit Value (HVBSe) of > 0. Overall, our results indicate that the risk of exposure to metals from consumption of mealworm larvae is relatively low and in compliance with European Union regulations.
Sex/Gender Differences in the Association between Residential Green Space and Self-Rated Health—A Sex/Gender-Focused Systematic Review
Authors: Bolte Gabriele , Nanninga Sarah , Dandolo Lisa
Published: December 2019

Though sex/gender is an important social determinant of health, sex/gender inequalities have not been considered comprehensively in environmental health research thus far. The aim of this systematic review was to clarify whether sex/gender theoretical concepts were addressed in studies on the impact of residential green space on self-rated health and whether effect modification by sex/gender was observed. Three electronic databases were searched to identify epidemiological studies on perceived or objective residential green/blue space and self-rated health. Necessary for study inclusion was mentioning at least one keyword for sex/gender in title or abstract, adult study participants and data on self-rated health and on availability and/or use of green/blue spaces. Decisive for study inclusion was consideration of sex/gender differences in the impact of perceived or objective residential green/blue spaces on self-rated health in the analysis and presentation of results. Seven studies were included. They presented an overall positive impact of green space on self-rated health. No consistent sex/gender differences in the impact of green space on self-rated health were found in these studies. However, all studies used a binary operationalization male/female without further theoretical foundation. Research quality could be enhanced by integrating sex/gender-theoretical concepts into study design and interpretation of results.
Exposure to Indoor Ferromagnetic Particulate Matter Monitored by Strawberry Plants and the Occurrence of Acute Respiratory Events in Adults
Authors: Van Dyck Lieve , Bentouhami Hayat , Koch Kyra , Samson Roeland , Weyler Joost
Published: December 2019

Exposure assessment of air pollution in epidemiologic research remains a challenge. Previous studies showed that magnetic monitoring of strawberry leaves, based on Saturation Isothermal Remnant Magnetization (SIRM), is a valid tool for estimating the concentration of ambient particulate matter (PM). This study uses this assessment method for the first time in epidemiologic research to quantify indoor exposure to PM. In a nested case control study, we evaluated the association between ‘waking up by cough’ and indoor air pollution measured by SIRM of dust deposition on leaves of strawberry plants located in the bedroom in the general adult population. A multiple logistic regression was used to estimate the association between ‘waking up by cough’ and exposure to ferromagnetic particles of PM controlling for age, gender and smoking status. A cut-off of 10 µA was decided to define exposure status (high versus low). Using logistic regression, a crude odds ratio (OR) of 1.80 (95% CI: 0.90–3.60) for ‘waking up by cough’ was found. This association remained approximately the same after controlling for age, gender and smoking status (adjusted OR: 1.76; 95% CI: 0.60–5.30). We found an association between exposure to ferromagnetic particles and ‘waking up by cough’ in adults; however, it was not statistically significant. This environmental exposure assessment method could be a valuable alternative for expensive personal exposure measurement devices.
Association of Night Eating with Depression and Depressive Symptoms in Korean Women
Authors: Lee Kyung Won , Shin Dayeon
Published: December 2019

This study examined the associations of night eating with depression and depressive symptoms in Korean adults. The study used a nationally representative sample of 31,690 Korean adults (≥19 years old) from the Korea National Health and Nutrition Examination Survey from 2008 to 2013. The participants were divided into two groups based on status of night eating: night eaters (consuming ≥25% of total daily energy intake between 21:00 and 06:00) and non-night eaters. Depression was defined based on diagnosis by a doctor, whereas depressive symptoms were defined as feelings of sadness or desperation for more than two weeks in the last one year. Multivariable logistic regression analyses were performed to examine the relationship between night eating and odds of depression and depressive symptoms after controlling for age, education, income, marital status, drinking, smoking, day of recalled intake, physical activity, body mass index, menopausal status (women only), total energy intake, and sleep duration. A total of 14.3% of Korean adults were night eaters. Night eaters were more likely to be men, young, less educated, single, drinkers, current smokers, and not employed (all ps < 0.05). In women, night eaters had higher odds of depression (adjusted odds ratio [AOR], 1.33; 95% confidence interval [CI], 1.02–1.75; p for trend = 0.0389) and depressive symptoms (AOR, 1.20; 95% CI, 1.01–1.41; p for trend = 0.0382) compared with non-night eaters. However, no associations of night eating with depression and depressive symptoms were found in men. Night eaters had higher odds of depression and depressive symptoms only in Korean women. Future studies are warranted to elucidate the underlying psychological and behavioral mechanisms that in turn may shed light on the factors influencing both night eating and odds of depression and depressive symptoms.
Multi-Scale Validation of MODIS LAI Products Based on Crop Growth Period
Authors: Wang Ting , Qu Yonghua , Xia Ziqing , Peng Yiping , Liu Zhenhua
Published: December 2019

Leaf area index (LAI) is one of the most important canopy structure parameters utilized in process-based models of climate, hydrology, and biogeochemistry. In order to determine the reliability and applicability of satellite LAI products, it is critical to validate satellite LAI products. Due to surface heterogeneity and scale effects, it is difficult to validate the accuracy of LAI products. In order to improve the spatio-temporal accuracy of satellite LAI products, we propose a new multi-scale LAI product validation method based on a crop growth cycle. In this method, we used the PROSAIL model to derive Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) LAI data and Gaofen-1 (GF-1) for the study area. The Empirical Bayes Kriging (EBK) interpolation method was used to perform a spatial multi-scale transformation of Moderate Resolution Imaging Spectroradiometer (MODIS) LAI products, GF-1 LAI data, and ASTER LAI data. Finally, MODIS LAI satellite products were compared with field measured LAI data, GF-1 LAI data, and ASTER LAI data during the growing season of crop field. This study was conducted in the agricultural oasis area of the middle reaches of the Heihe River Basin in northwestern China and the Conghua District of Guangzhou in Guangdong Province. The results suggest that the validation accuracy of the multi-scale MODIS LAI products validated by ASTER LAI data were higher than those of the GF-1 LAI data and the reference field measured LAI data, showing a R2 of 0.758 and relative mean square error (RRMSE) of 28.73% for 15 m ASTER LAI and a R2 of 0.703 and RRMSE of 30.80% for 500 m ASTER LAI, which imply that the 15 m MODIS LAI product generated by the EBK method was more accurate than the 500 m and 8 m products. This study provides a new validation method for satellite remotely sensed products.
Heterogeneous Pattern of Dependence on Anti-Apoptotic BCL-2 Family Proteins upon CHOP Treatment in Diffuse Large B-Cell Lymphoma
Authors: de Jong Mathilde Rikje Willemijn , Langendonk Myra , Reitsma Bart , Nijland Marcel , van den Berg Anke , Ammatuna Emanuele , Visser Lydia , van Meerten Tom
Published: December 2019

Expression of the anti-apoptotic B-cell lymphoma 2 (BCL-2) protein in patients with diffuse large B-cell lymphoma (DLBCL) strongly correlates with resistance to standard therapy with cyclophosphamide, vincristine, doxorubicin, prednisolone, and rituximab (R-CHOP). Although studies focus mainly on the contribution of BCL-2, here we also investigate the contribution of other anti-apoptotic proteins to CHOP-therapy resistance in DLBCL. Functional dynamic BCL-2 homology (BH)3 profiling was applied to DLBCL cell lines upon CHOP treatment or single CHOP compounds. Cell-specific anti-apoptotic dependencies were validated with corresponding BH3-mimetics. We found high expression of anti-apoptotic BCL-2, MCL-1, and BCL-XL in DLBCL cell lines and patients. CHOP treatment resulted in both enhanced and altered anti-apoptotic dependency. Enhanced sensitivity to different BH3-mimetics after CHOP treatment was confirmed in specific cell lines, indicating heterogeneity of CHOP-induced resistance in DLBCL. Analysis of single CHOP compounds demonstrated that similar changes could also be induced by doxorubicin or vincristine, providing evidence for clinical combination therapies of doxorubicin or vincristine with BH3-mimetics in DLBCL. In conclusion, we show for the first time that CHOP treatment induces increased anti-apoptotic dependency on MCL-1 and BCL-XL, and not just BCL-2. These results provide new perspectives for the treatment of CHOP-resistant DLBCL and underline the potential of BH3 profiling in predicting therapy outcomes.
Dead Cas Systems: Types, Principles, and Applications
Authors: Brezgin Sergey , Kostyusheva Anastasiya , Kostyushev Dmitry , Chulanov Vladimir
Published: December 2019

The gene editing tool CRISPR-Cas has become the foundation for developing numerous molecular systems used in research and, increasingly, in medical practice. In particular, Cas proteins devoid of nucleolytic activity (dead Cas proteins; dCas) can be used to deliver functional cargo to programmed sites in the genome. In this review, we describe current CRISPR systems used for developing different dCas-based molecular approaches and summarize their most significant applications. We conclude with comments on the state-of-art in the CRISPR field and future directions.
Estimation of Forces on Actin Filaments in Living Muscle from X-ray Diffraction Patterns and Mechanical Data
Authors: Mijailovich Srboljub M. , Prodanovic Momcilo , Irving Thomas C.
Published: December 2019

Many biological processes are triggered or driven by mechanical forces in the cytoskeletal network, but these transducing forces have rarely been assessed. Striated muscle, with its well-organized structure provides an opportunity to assess intracellular forces using small-angle X-ray fiber diffraction. We present a new methodology using Monte Carlo simulations of muscle contraction in an explicit 3D sarcomere lattice to predict the fiber deformations and length changes along thin filaments during contraction. Comparison of predicted diffraction patterns to experimental meridional X-ray reflection profiles allows assessment of the stepwise changes in intermonomer spacings and forces in the myofilaments within living muscle cells. These changes along the filament length reflect the effect of forces from randomly attached crossbridges. This approach enables correlation of the molecular events, such as the current number of attached crossbridges and the distributions of crossbridge forces to macroscopic measurements of force and length changes during muscle contraction. In addition, assessments of fluctuations in local forces in the myofilaments may reveal how variations in the filament forces acting on signaling proteins in the sarcomere M-bands and Z-discs modulate gene expression, protein synthesis and degradation, and as well to mechanisms of adaptation of muscle in response to changes in mechanical loading.
DeepMiR2GO: Inferring Functions of Human MicroRNAs Using a Deep Multi-Label Classification Model
Authors: Wang Jiacheng , Zhang Jingpu , Cai Yideng , Deng Lei
Published: December 2019

MicroRNAs (miRNAs) are a highly abundant collection of functional non-coding RNAs involved in cellular regulation and various complex human diseases. Although a large number of miRNAs have been identified, most of their physiological functions remain unknown. Computational methods play a vital role in exploring the potential functions of miRNAs. Here, we present DeepMiR2GO, a tool for integrating miRNAs, proteins and diseases, to predict the gene ontology (GO) functions based on multiple deep neuro-symbolic models. DeepMiR2GO starts by integrating the miRNA co-expression network, protein-protein interaction (PPI) network, disease phenotype similarity network, and interactions or associations among them into a global heterogeneous network. Then, it employs an efficient graph embedding strategy to learn potential network representations of the global heterogeneous network as the topological features. Finally, a deep multi-label classification network based on multiple neuro-symbolic models is built and used to annotate the GO terms of miRNAs. The predicted results demonstrate that DeepMiR2GO performs significantly better than other state-of-the-art approaches in terms of precision, recall, and maximum F-measure.
Colon Cancer and Perturbations of the Sphingolipid Metabolism
Authors: Machala Miroslav , Procházková Jiřina , Hofmanová Jiřina , Králiková Lucie , Slavík Josef , Tylichová Zuzana , Ovesná Petra , Kozubík Alois , Vondráček Jan
Published: December 2019

The development and progression of colorectal cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.
Interplay between MicroRNAs and Oxidative Stress in Neurodegenerative Diseases
Authors: Konovalova Julia , Gerasymchuk Dmytro , Parkkinen Ilmari , Chmielarz Piotr , Domanskyi Andrii
Published: December 2019

MicroRNAs are post-transcriptional regulators of gene expression, crucial for neuronal differentiation, survival, and activity. Age-related dysregulation of microRNA biogenesis increases neuronal vulnerability to cellular stress and may contribute to the development and progression of neurodegenerative diseases. All major neurodegenerative disorders are also associated with oxidative stress, which is widely recognized as a potential target for protective therapies. Albeit often considered separately, microRNA networks and oxidative stress are inextricably entwined in neurodegenerative processes. Oxidative stress affects expression levels of multiple microRNAs and, conversely, microRNAs regulate many genes involved in an oxidative stress response. Both oxidative stress and microRNA regulatory networks also influence other processes linked to neurodegeneration, such as mitochondrial dysfunction, deregulation of proteostasis, and increased neuroinflammation, which ultimately lead to neuronal death. Modulating the levels of a relatively small number of microRNAs may therefore alleviate pathological oxidative damage and have neuroprotective activity. Here, we review the role of individual microRNAs in oxidative stress and related pathways in four neurodegenerative conditions: Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD) disease, and amyotrophic lateral sclerosis (ALS). We also discuss the problems associated with the use of oversimplified cellular models and highlight perspectives of studying microRNA regulation and oxidative stress in human stem cell-derived neurons.
From Local to Global Modeling for Characterizing Calcium Dynamics and Their Effects on Electrical Activity and Exocytosis in Excitable Cells
Authors: Montefusco Francesco , Pedersen Morten
Published: December 2019

Electrical activity in neurons and other excitable cells is a result of complex interactions between the system of ion channels, involving both global coupling (e.g., via voltage or bulk cytosolic Ca2+ concentration) of the channels, and local coupling in ion channel complexes (e.g., via local Ca2+ concentration surrounding Ca2+ channels (CaVs), the so-called Ca2+ nanodomains). We recently devised a model of large-conductance BKCa potassium currents, and hence BKCa–CaV complexes controlled locally by CaVs via Ca2+ nanodomains. We showed how different CaV types and BKCa–CaV stoichiometries affect whole-cell electrical behavior. Ca2+ nanodomains are also important for triggering exocytosis of hormone-containing granules, and in this regard, we implemented a strategy to characterize the local interactions between granules and CaVs. In this study, we coupled electrical and exocytosis models respecting the local effects via Ca2+ nanodomains. By simulating scenarios with BKCa–CaV complexes with different stoichiometries in pituitary cells, we achieved two main electrophysiological responses (continuous spiking or bursting) and investigated their effects on the downstream exocytosis process. By varying the number and distance of CaVs coupled with the granules, we found that bursting promotes exocytosis with faster rates than spiking. However, by normalizing to Ca2+ influx, we found that bursting is only slightly more efficient than spiking when CaVs are far away from granules, whereas no difference in efficiency between bursting and spiking is observed with close granule-CaV coupling.
Assessment of Bones Deficient in Fibrillin-1 Microfibrils Reveals Pronounced Sex Differences
Authors: Altinbas Lukas , Bormann Nicole , Lehmann Daniel , Jeuthe Sarah , Wulsten Dag , Kornak Uwe , Robinson Peter N. , Wildemann Britt , Kararigas Georgios
Published: December 2019

Defects in the extracellular matrix protein fibrillin-1 that perturb transforming growth factor beta (TGFβ) bioavailability lead to Marfan syndrome (MFS). MFS is an autosomal-dominant disorder, which is associated with connective tissue and skeletal defects, among others. To date, it is unclear how biological sex impacts the structural and functional properties of bone in MFS. The aim of this study was to investigate the effects of sex on bone microarchitecture and mechanical properties in mice with deficient fibrillin-1, a model of human MFS. Bones of 11-week-old male and female Fbn1mgR/mgR mice were investigated. Three-dimensional micro-computed tomography of femora and vertebrae revealed a lower ratio of trabecular bone volume to tissue volume, reduced trabecular number and thickness, and greater trabecular separation in females vs. males. Three-point bending of femora revealed significantly lower post-yield displacement and work-to-fracture in females vs. males. Mechanistically, we found higher Smad2 and ERK1/2 phosphorylation in females vs. males, demonstrating a greater activation of TGFβ signaling in females. In summary, the present findings show pronounced sex differences in the matrix and function of bones deficient in fibrillin-1 microfibrils. Consequently, sex-specific analysis of bone characteristics in patients with MFS may prove useful in improving the clinical management and life quality of these patients, through the development of sex-specific therapeutic approaches.
Expression of Salivary and Serum Malondialdehyde and Lipid Profile of Patients with Periodontitis and Coronary Heart Disease
Authors: Isola Gaetano , Polizzi Alessandro , Santonocito Simona , Alibrandi Angela , Ferlito Sebastiano
Published: December 2019

Malondialdehyde (MAA) within a lipid pathway has been demonstrated to possess an important role in endothelial function that undergoes periodontitis and coronary heart disease (CHD) development. This study evaluated the impact of periodontitis, CHD, or a combination of both diseases (periodontitis + CHD) on salivary and serum MAA levels. The periodontal and clinical characteristics, serum, and saliva samples were collected from 32 healthy subjects, 34 patients with periodontitis, 33 patients with CHD, and 34 patients with periodontitis and CHD. Lipid profile and levels of MDA and C-reactive protein (CRP) were assessed. Patients in the periodontitis group (serum: 3.92 (3.7–4.4) µmol/L; salivary 1.81 (1–2.1) µmol/g protein, p < 0.01) and in the periodontitis + CHD (serum: 4.34 (3.7–4.8) µmol/L; salivary 1.96 (1.7–2.3) µmol/g protein, p < 0.001) group presented higher median concentrations of salivary and serum MAA compared to patients in the CHD (serum: 3.72 (3.5–4.1) µmol/L; salivary 1.59 (0.9–1.8) µmol/g protein, p < 0.01) and control group (serum: 3.14 (2.8–3.7) µmol/L; salivary 1.41 (0.8–1.6) µmol/g protein, p < 0.01). In univariate models, periodontitis (p = 0.034), CHD (p < 0.001), and CRP (p < 0.001) were significantly associated with MAA. In the multivariate model, only CRP remained a significant predictor of serum and salivary MAA (p < 0.001) MAA levels. Patients with periodontitis and with periodontitis + CHD presented higher levels of salivary and serum MAA compared to healthy subjects and CHD patients. CRP has been found to be a significant predictor of increased salivary and serum MAA levels.
Genetic Parameters and QTLs for Total Phenolic Content and Yield of Wheat Mapping Population of CSDH Lines under Drought Stress
Authors: Czyczyło-Mysza Ilona Mieczysława , Cyganek Katarzyna , Dziurka Kinga , Quarrie Steve , Skrzypek Edyta , Marcińska Izabela , Myśków Beata , Dziurka Michał , Warchoł Marzena , Kapłoniak Kamila , Bocianowski Jan
Published: December 2019

A doubled haploid population of 94 lines from the Chinese Spring × SQ1 wheat cross (CSDH) was used to evaluate additive and epistatic gene action effects on total phenolic content, grain yield of the main stem, grain number per plant, thousand grain weight, and dry weight per plant at harvest based on phenotypic and genotypic observations of CSDH lines. These traits were evaluated under moderate and severe drought stress and compared with well-watered plants. Plants were grown in pots in an open-sided greenhouse. Genetic parameters, such as additive and epistatic effects, affecting total phenolic content, were estimated for eight year-by-drought combinations. Twenty-one markers showed a significant additive effect on total phenolic content in all eight year-by-drought combinations. These markers were located on chromosomes: 1A, 1B, 2A, 2B, 2D, 3A, 3B, 3D, 4A, and 4D. A region on 4AL with a stable QTL controlling the phenolic content, confirmed by various statistical methods is particularly noteworthy. In all years and treatments, three markers significantly linked to QTLs have been identified for both phenols and yield. Thirteen markers were coincident with candidate genes. Our results indicated the importance of both additive and epistatic gene effects on total phenolic content in eight year-by-drought combinations.
Bioengineered Skin Substitutes: The Role of Extracellular Matrix and Vascularization in the Healing of Deep Wounds
Authors: Urciuolo Francesco , Casale Costantino , Imparato Giorgia , Netti Paolo A.
Published: December 2019

The formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although representing a valid alternative to autografting, induce skin cells in repairing the wound rather than guiding a regeneration process. Repaired skin differs from regenerated skin, showing high contracture, loss of sensitivity, impaired pigmentation and absence of cutaneous adnexa (i.e., hair follicles and sweat glands). This leads to significant mobility and aesthetic concerns, making the development of more effective bioengineered skin models a current need. The objective of this review is to determine the limitations of either commercially available or investigational bioengineered skin substitutes and how advanced skin tissue engineering strategies can be improved in order to completely restore skin functions after severe wounds.
Correlation between Hepatitis B Virus Infection and Colorectal Neoplasia
Authors: Jung Yoon Suk , Kim Nam Hee , Park Jung Ho , Park Dong Il , Sohn Chong Il
Published: December 2019

Background: Data about the association between hepatitis virus infection and colorectal neoplasia (CRN) are extremely limited. We examined the association between hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the risk of CRN. Methods: A cross-sectional study was performed on asymptomatic examinees who underwent a colonoscopy and serologic testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV Ab) between 2004 and 2015. Results: Of 155,674 participants who underwent serologic testing for HBsAg, 5476 (3.5%) were positive for HBsAg. The mean age of the study participants was 41.1 ± 9.1 years. The prevalence of CRN was higher in the HBsAg (+) than in HBsAg (-) participants (16.9% vs. 15.6%, p = 0.009). Even after adjusting for confounders, HBsAg positivity was correlated with an increased risk of CRN (odds ratio (OR), 1.10; 95% confidence interval (CI), 1.01–1.19; p = 0.025). Of 155,180 participants who underwent serologic testing for HCV Ab, only 240 (0.15%) were positive for HCV Ab. The prevalence of CRN was higher in HCV Ab (+) than in HCV Ab (-) participants (22.9% vs. 15.6%, p = 0.002). However, the association disappeared after adjusting for confounders (OR, 1.04; 95% CI, 0.72–1.50; p = 0.839). Conclusions: HBV infection was independently correlated with an increased risk of CRN. Our results indicate the possibility that HBV infection may contribute to colorectal carcinogenesis. Screening colonoscopy may have to be recommended more thoroughly for HBV-infected patients.
Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice
Authors: Sánchez-Garrido Ana I. , Prieto-Vicente Vanessa , Blanco-Gozalo Víctor , Arévalo Miguel , Quiros Yaremi , López-Montañés Daniel , López-Hernández Francisco J. , Rodríguez-Pérez Antonio , López-Novoa José M.
Published: December 2019

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.