bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR-Cas13a-Based Detection for Bovine Viral Diarrhea Virus
Authors: Yao Rui , Xu Yueren , Wang Lang , Wang Dawei , Ren Linchang , Ren Changling , Li Cunyuan , Li Xiaoyue , Ni Wei , He Yanhua , Hu Ruirui , Guo Tao , Li Yaxin , Li Lei , Wang Xiaokui , Hu Shengwei
Published: June 2021

Bovine Viral Diarrhea Virus (BVDV) is the main pathogen of bovine viral diarrhea disease (BVD), which leads to enormous economic losses in the cattle industry. A sensitive and specific detection for BVDV is advantageous to the control of BVDV. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have been used for detecting virus RNA. In this study, the expression and purification of LwCas13a protein was optimized and the RNase activity of LwCas13a in vitro was verified. CRISPR-LwCas13a system could detect BVDV virus and BVDV RNA with high specificity and simplicity. The detection limit of the LwCas13a system was 103 pM, and there were no cross-reactions with HEK293T and MDBK. In summary, a sensitive, specific, and simple nucleic acid detection method based on CRISPR-Cas13a was developed for BVDV. This method provides a new detection strategy for early diagnosis of BVDV.
Weed Spread and Caraway (Carum carvi L.) Crop Productivity in a Multi-Cropping System
Authors: Marcinkevičienė Aušra , Rudinskienė Aušra , Velička Rimantas , Kosteckas Robertas , Kriaučiūnienė Zita
Published: June 2021

The field experiment was carried out at the Experimental Station of Vytautas Magnus University Agriculture Academy (Lithuania) in 2017–2019. The aim of the study was to determine and to compare weed spread and caraway crop productivity in sole (spring barley, spring wheat, pea, caraway), binary (spring barley-caraway, spring wheat-caraway, pea-caraway) and trinary (spring barley-caraway-white clover, spring wheat-caraway-white clover, pea-caraway-white clover) crops. In the second and the third years of caraway cultivation, it was estimated that the abundance of perennial weeds in the crops increased. In the first year, significantly the highest dry matter mass of weeds was determined in non-sprayed with herbicides binary crops with undersown caraway and in trinary crops with undersown caraway and clover; in the second year—in the caraway binary crops, when they were grown after barley and wheat without clover; in the third year—in caraway binary and trinary crops when they were grown after barley, wheat and pea without clover and after barley and wheat with clover. In the second year, the highest yields of caraway seeds were obtained by growing them in peas, and in the third year by growing them in wheat together with clover. Caraway can be grown in trinary crops, including white clover, and harvested in the second or the third year of the vegetative season.
Proliferative and Apoptotic Pathways in the Testis of Quail Coturnix coturnix during the Seasonal Reproductive Cycle
Authors: Falvo Sara , Rosati Luigi , Di Fiore Maria Maddalena , Di Giacomo Russo Federica , Chieffi Baccari Gabriella , Santillo Alessandra
Published: June 2021

The quail Coturnix coturnix is a seasonal breeding species, with the annual reproductive cycle of its testes comprising an activation phase and a regression phase. Our previous results have proven that the testicular levels of both 17β-estradiol (E2) and androgens are higher during the reproductive period compared to the non-reproductive period, which led us to hypothesize that estrogens and androgens may act synergistically to initiate spermatogenesis. The present study was, therefore, aimed to investigate the estrogen responsive system in quail testis in relation to the reproduction seasonality, with a focus on the molecular pathways elicited in both active and regressive quail testes. Western blotting and immunohistochemistry analysis revealed that the expression of ERα, which is the predominant form of estrogen receptors in quail testis, was correlated with E2 concentration, suggesting that increased levels of E2-induced ERα could play a key role in the resumption of spermatogenesis during the reproductive period, when both PCNA and SYCP3, the mitotic and meiotic markers, respectively, were also increased. In the reproductive period we also found the activation of the ERK1/2 and Akt-1 kinase pathways and an increase in second messengers cAMP and cGMP levels. In the non-reproductive phase, when the E2/ERα levels were low, the inactivation of ERK1/2 and Akt-1 pathways favored apoptotic events due to an increase in the levels of Bax and cytochrome C, with a consequent regression of the gonad.
Spherical Polydopamine-Modified Carbon-Felt Cathode with an Active Indole Structure for Efficient Hydrogen Peroxide Electroproduction
Authors: Chen Lei , Yuan Sicheng , Wang Huaiyuan , Zhu Yanji , Fu Dengyu , Li Zhenggui
Published: June 2021

As one of the most promising methods for H2O2 production, H2O2 electroproduction has received increasingly more attention. In this study, a spherical particle polydopamine (pDA) modified carbon felt (noted as ht-pDA/ACF) for H2O2 production was fabricated. At a constant potential of 2.0 V and pH of 1.0, the H2O2 production of the ht-pDA/ACF cathode reached 220 mg/L after 6 h of electrolyzing, compared to the 30 mg/L H2O2 production of raw carbon felt. Firstly, the spherical pDA exposes more active sites that are favorable to the 2e− ORR compared to pDA film. Secondly, the ring cleavage and re-cyclization of indole structure in the pDA during electrolyzing could form the radicals that act as the intermediate to the H2O2 formation. This research exhibits a low-cost method to modify carbon materials for effective H2O2 electroproduction. The ht-pDA/ACF cathode is promising for green H2O2 production and wastewater treatment.
Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Theory of Mind and Executive Function in Major Depressive Disorder and Its Correlation with Brain-Derived Neurotrophic Factor (BDNF): A Randomized, Double-Blind, Sham-Controlled Trial
Authors: Tong Jie , Zhang Jie , Jin Ying , Liu Weiqing , Wang Hao , Huang Ying , Shi Dianhong , Zhu Minhuan , Zhu Na , Zhang Tingting , Sun Xirong
Published: June 2021

Background: Studies have implicated hypofrontality in the pathogenesis of impaired theory of mind (ToM) and executive function (EF) in major depressive disorder (MDD). These symptoms are usually resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS) has been shown to reverse hypofrontality. Moreover, BDNF is an effective biomarker of antidepressant effects, but there have been very few studies on the correlation between BDNF and rTMS. We aimed to evaluate the efficacy of 20 sessions of a 10 Hz unilateral rTMS intervention over the left dorsolateral prefrontal cortex (DLPFC) in improving ToM and EF in patients with MDD and its correlation with BDNF. Methods: A total of 120 MDD patients were enrolled in this randomized, sham-controlled, double-blind trial. Each participant received 20 sessions of rTMS at 10 Hz frequency through the active or the sham coil over 4 weeks. ToM was assessed with the facial emotion identification test (FEIT) and hinting task (HT). EF was assessed with the Wisconsin card sorting test (WCST). BDNF assessments were carried out at baseline and 2-, 4-, 12-, and 24-week follow-ups. Results: The improvement in the ToM (FEIT, HT) in the active rTMS group was significantly different from that in the sham rTMS group (F = 18.09, p < 0.001; F = 5.02, p = 0.026). There were significant differences in the WCST (categories completed, response errors, response perseverative errors, non-response perseverative errors) after logarithmic transformation at different time points in the active rTMS group (F = 14.71, p < 0.001; F = 5.99, p = 0.046; F = 8.90, p = 0.031; F = 2.31, p = 0.048). However, there was no significant difference in log transformed BDNF concentration between the two groups (t = 0.07 to t = 1.29, p > 0.05). BDNF was negatively correlated with WCST categories completed at the 24th week (r = −0.258, p = 0.046). Conclusions: The results show that rTMS may improve the ToM and EF of patients with MDD and there was no significant correlation with serum BDNF concentration. RTMS can not only be used for treatment of patients with MDD but also has a positive effect on ToM and EF.
New Perspectives in Stroke Management: Old Issues and New Pathways
Authors: Pilato Fabio , Calandrelli Rosalinda , Capone Fioravante , Alessiani Michele , Ferrante Mario , Iaccarino Gianmarco , Di Lazzaro Vincenzo
Published: June 2021

Stroke is a leading cause of disability and death worldwide and social burden is huge in terms of disabilities, mortality and healthcare costs. Recently, in an acute stroke setting, renewed interest in disease-modifying therapies and novel approaches has led to enhanced recovery and the reduction of long-term disabilities of patients who suffered a stroke. In the last few years, the basic principle “time is brain” was overcome and better results came through the implementation of novel neuroimaging tools in acute clinical practice, allowing one to extend acute treatments to patients who were previously excluded on the basis of only a temporal selection. Recent studies about thrombectomy have allowed the time window to be extended up to 24 h after symptoms onset using advanced neuroradiological tools, such as computer tomography perfusion (CTP) and magnetic resonance imaging (MRI) to select stroke patients. Moreover, a more effective acute management of stroke patients in dedicated wards (stroke units) and the use of new drugs for stroke prevention, such as novel oral anticoagulants (NOACs) for atrial fibrillation, have allowed for significant clinical improvements. In this editorial paper, we summarize the current knowledge about the main stroke-related advances and perspectives and their relevance in stroke care, highlighting recent developments in the definition, management, treatment, and prevention of acute and chronic complications of stroke. Then, we present some papers published in the Special Issue “Clinical Research on Ischemic Stroke: Novel Approaches in Acute and Chronic Phase”.
Impact of Various Feed Properties on the Performance of a Control System for a Multiple Dividing Wall Column Pilot Plant
Authors: Preißinger Ulrich , Lukač Goran , Dejanović Igor , Grützner Thomas
Published: June 2021

Despite the attractive savings potential of multiple Dividing Wall Columns (mDWC), there are no reports in the open literature of an existing application so far. In this perspective, the control of mDWCs has been a rather little-investigated field. Pilot plants are a necessary step needed to further expand the application window of this sustainable distillation technology. This contribution aimed to show that mDWCs are sufficiently flexible, providing stable operation, even with suboptimal control structures arising from design limitations imposed by equipment. For this purpose, the pilot column design was assessed using dynamic simulation to evaluate its operability in case of different disturbances as well as different feed mixtures. The results showed that, in all cases, the column could be stabilized and product purities maintained. This suggests that even complex configurations such as mDWCs offer sufficient amount of flexibility to allow for the application of one design in different services.
Terbium(III) as a Fluorescent Probe for Molecular Detection of Ascorbic Acid
Authors: Selivanova Natalia , Galyametdinov Yuriy
Published: June 2021

Fluorescence analysis is a simple and a highly sensitive method for detection of small amounts of biologically active substances. In this study, a complexation of terbium(III) chelates with 1,10-phenanthroline and ascorbic acid (AA) and luminescent properties of complexes were investigated. The influence of pH and solubilization of complexes by micellar solutions of nonionic, cationic, and anionic surfactants on fluorescence was studied. The quenching effect of terbium ion fluorescence was detected upon an introduction of ascorbic acid. The quenching effect of the complex with mixed ligands Tb(1,10-phenanthroline)-AA allows for the detection of ascorbic acid with the limit of 7.4 × 10−5 mol·L−1.
Challenges and Opportunities for Climate Change Education (CCE) in East Africa: A Critical Review
Authors: Apollo Abigael , Mbah Marcellus Forh
Published: June 2021

It is undoubtedly clear that climate change is happening, and its adverse impacts could reverse the progress made toward meeting sustainable development goals. The global crisis poses one of the most severe challenges to reducing poverty and existing inequalities, especially in developing countries that are projected to be highly vulnerable to climate variability. However, the education sector provides an untapped opportunity for successful climate change adaptation and mitigation through knowledge and skill acquisitions, and consequently, positive behavioral change. Specifically, education can capacitate individuals and communities to make informed decisions and take practical actions for climate-resilient sustainable development. This study is focused on East Africa, a region whose economy heavily relies on climate-dependent activities. At present, East African governments are already embedding climate change in their school curriculum. However, they lack coherent approaches to leverage climate change education as a tool in their adaptation and mitigation strategies. Therefore, this review explores some of the critical barriers to climate change education and possible opportunities for leveraging learning to promote sustainable development in East Africa.
Immunohistochemistry for Prostate Biopsy—Impact on Histological Prostate Cancer Diagnoses and Clinical Decision Making
Authors: Mandel Philipp , Wenzel Mike , Hoeh Benedikt , Welte Maria N. , Preisser Felix , Inam Tahir , Wittler Clarissa , Humke Clara , Köllermann Jens , Wild Peter , Würnschimmel Christoph , Tilki Derya , Graefen Markus , Kluth Luis A. , Karakiewicz Pierre I. , Chun Felix K.-H. , Becker Andreas
Published: June 2021

Background: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making. Methods: Between January 2017–June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy. Results: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy (p < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7–10. Conclusions: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.
Caspase 9 and Caspase 3 Immunohistochemical Pattern in Skeletal and Cardiac Muscles at Different Times after Death: An Experimental Study on PMI Estimation
Authors: Mondello Cristina , Stassi Chiara , Minutoli Letteria , Baldino Gennaro , Alibrandi Angela , Spatola Giovanni Francesco , Uzzo Maria Laura , Micali Antonio , Puzzolo Domenico , Asmundo Alessio , Ventura Spagnolo Elvira
Published: June 2021

(1) Background: The estimation of the post mortem interval (PMI) is a challenge for forensic pathologists because data emerging from methods commonly applied are not always conclusive, since several conditions exist that may affect the reliability of these parameters. Thus, new approaches have been proposed to overcome such a limit. In recent years, several studies have been performed on proteins analyzing their expression/degradation patterns in relation to the progressing of the post mortem interval. (2) Methods: The immunoreactivity patterns of two apoptosis mediators—Caspase 9 and Caspase 3—have been tested in order to evaluate their potential role as markers of the post mortem interval. The immunohistochemical analysis was performed on samples of skeletal and cardiac muscles obtained from rats at 0, 4, 8, 12, 24 and 72 h after death. (3) Results: The observed immunoreactivity patterns of both Caspase 9 and Caspase 3 showed a significant correlation with increasing post mortem interval either in skeletal or cardiac muscles, while the comparison of the immunoreactivity patterns of the two apoptotic mediators within each tissue appeared consistent with a preliminary activation of the “initiator” Caspase 9, which, in turn, subsequently activates the “executioner” Caspase 3. (4) Conclusion: The different expressions and decrease immunohistochemically observed on both caspases with progressing PMI support the usefulness of the combined analysis for post mortem interval estimation.
Using Convolutional Neural Network and a Single Heartbeat for ECG Biometric Recognition
Authors: AlDuwaile Dalal A. , Islam Md Saiful
Published: June 2021

The electrocardiogram (ECG) signal has become a popular biometric modality due to characteristics that make it suitable for developing reliable authentication systems. However, the long segment of signal required for recognition is still one of the limitations of existing ECG biometric recognition methods and affects its acceptability as a biometric modality. This paper investigates how a short segment of an ECG signal can be effectively used for biometric recognition, using deep-learning techniques. A small convolutional neural network (CNN) is designed to achieve better generalization capability by entropy enhancement of a short segment of a heartbeat signal. Additionally, it investigates how various blind and feature-dependent segments with different lengths affect the performance of the recognition system. Experiments were carried out on two databases for performance evaluation that included single and multisession records. In addition, a comparison was made between the performance of the proposed classifier and four well-known CNN models: GoogLeNet, ResNet, MobileNet and EfficientNet. Using a time–frequency domain representation of a short segment of an ECG signal around the R-peak, the proposed model achieved an accuracy of 99.90% for PTB, 98.20% for the ECG-ID mixed-session, and 94.18% for ECG-ID multisession datasets. Using the preprinted ResNet, we obtained 97.28% accuracy for 0.5-second segments around the R-peaks for ECG-ID multisession datasets, outperforming existing methods. It was found that the time–frequency domain representation of a short segment of an ECG signal can be feasible for biometric recognition by achieving better accuracy and acceptability of this modality.
Viability Assessment of Small-Scale On-Grid Wind Energy Generator for Households in Malaysia
Authors: Alkawsi Gamal , Baashar Yahia , Alkahtani Ammar Ahmed , Lim Chin Wai , Tiong Sieh Kiong , Khudari Mohammad
Published: June 2021

This study provides a techno-financial evaluation of two sites in Malaysia: Kudat, located on the coast of the northernmost part of Sabah, the state of East Malaysia with promising wind potential, and Putrajaya in the Klang Valley region with moderate wind potential at high elevations similar to the dominant cities in Malaysia. Three small-scale wind turbines were evaluated, taking into account a nominal electrical power generation below 100 kW. The research is focused on 220 residential households. The software used to perform the evaluation was Hybrid Optimization of Multiple Energy Resources (HOMER). The research novelty is the examination of the non-hybrid small-scale turbines at high elevations for regions with low wind speed, such as Malaysia. Regardless of the wind farms’ financial profit, this study used the net present cost (NPC) analysis in all cases. This research demonstrates the feasibility of small-scale wind turbines mounted at high elevations for generating sufficient energy. The results indicate that in both areas, the RX-20KH3 model is the best option, and the costs of the FH-5000 and RX-20KH3 farms are proportionate for a renewable project. Furthermore, with government support, the WES80 farm could be suitable.
Detection of Vegetation Encroachment in Power Transmission Line Corridor from Satellite Imagery Using Support Vector Machine: A Features Analysis Approach
Authors: Mahdi Elsiddig Haroun Fathi , Mohamed Deros Siti Noratiqah , Bin Baharuddin Mohd Zafri , Md Din Norashidah
Published: June 2021

Vegetation encroachment along electric power transmission lines is one of the major environmental challenges that can cause power interruption. Many technologies have been used to detect vegetation encroachment, such as light detection and ranging (LiDAR), synthetic aperture radar (SAR), and airborne photogrammetry. These methods are very effective in detecting vegetation encroachment. However, they are expensive with regard to the coverage area. Alternatively, satellite imagery can cover a wide area at a relatively lower cost. In this paper, we describe the statistical moments of the color spaces and the textural features of the satellite imagery to identify the most effective features that can increase the vegetation density classification accuracy of the support vector machine (SVM) algorithm. This method aims to distinguish between high- and low-density vegetation regions along the power line corridor right-of-way (ROW). The results of the study showed that the statistical moments of the color spaces contribute positively to the classification accuracy while some of the gray level co-occurrence matrix (GLCM) features contribute negatively to the classification accuracy. Therefore, a combination of the most effective features was used to achieve a recall accuracy of 98.272%.
Non-Equilibrium Thermodynamics-Based Convective Drying Model Applied to Oblate Spheroidal Porous Bodies: A Finite-Volume Analysis
Authors: Melo João C. S. , Delgado João M. P. Q. , Silva Wilton P. , B. Lima Antonio Gilson , Gomez Ricardo S. , Gomes Josivanda P. , Figueirêdo Rossana M. F. , Queiroz Alexandre J. M. , Santos Ivonete B. , Machado Maria C. N. , Lima Wanderson M. P. B. , Carmo João E. F.
Published: June 2021

Commonly based on the liquid diffusion theory, drying theoretical studies in porous materials has been directed to plate, cylinder, and sphere, and few works are applied to non-conventional geometries. In this sense, this work aims to study, theoretically, the drying of solids with oblate spheroidal geometry based on the thermodynamics of irreversible processes. Mathematical modeling is proposed to describe, simultaneously, the heat and mass transfer (liquid and vapor) during the drying process, considering the variability of the transport coefficients and the convective boundary conditions on the solid surface, with particular reference to convective drying of lentil grains at low temperature and moderate air relative humidity. All the governing equations were written in the oblate spheroidal coordinates system and solved numerically using the finite-volume technique and the iterative Gauss–Seidel method. Numerical results of moisture content, temperature, liquid, vapor, and heat fluxes during the drying process were obtained, analyzed, and compared with experimental data, with a suitable agreement. It was observed that the areas near the focal point of the lentil grain dry and heat up faster; consequently, these areas are more susceptible to the appearance of cracks that can compromise the quality of the product. In addition, it was found that the vapor flux was predominant during the drying process when compared to the liquid flux.
Analysis of Driving Dynamics Considering Driving Resistances in On-Road Driving
Authors: Song Jingeun , Cha Junepyo
Published: June 2021

Internal combustion engine emissions are a serious worldwide problem. To combat this, emission regulations have become stricter with the goal of reducing the proportion of transportation emissions in global air pollution. In addition, the European Commission passed the real driving emissions–light-duty vehicles (RDE-LDV) regulation that evaluates vehicle emissions by driving on real roads. The RDE test is significantly dependent on driving conditions such as traffic or drivers. Thus, the RDE regulation has the means to evaluate driving dynamics such as the vehicle speed per acceleration (v·apos) and the relative positive acceleration (RPA) to determine whether the driving during these tests is normal or abnormal. However, this is not an appropriate way to assess the driving dynamics because the v⋅apos and the RPA do not represent engine load, which is directly related to exhaust emissions. Therefore, in the present study, new driving dynamic variables are proposed. These variables use engine acceleration calculated from wheel force instead of the acceleration calculated from the vehicle speed, so they are proportional to the engine load. In addition, a variable of driving dynamics during braking is calculated using the negative wheel force. This variable can be used to improve the accuracy of the emission assessment by analyzing the braking pattern.
State-of-the-Art Review on the Energy Performance of Semi-Transparent Building Integrated Photovoltaic across a Range of Different Climatic and Environmental Conditions
Authors: Khalifeeh Reza , Alrashidi Hameed , Sellami Nazmi , Mallick Tapas , Issa Walid
Published: June 2021

Semi-transparent Building Integrated Photovoltaics provide a fresh approach to the renewable energy sector, combining the potential of energy generation with aesthetically pleasing, multi-functional building components. Employing a range of technologies, they can be integrated into the envelope of the building in different ways, for instance, as a key element of the roofing or façade in urban areas. Energy performance, measured by their ability to produce electrical power, at the same time as delivering thermal and optical efficiencies, is not only impacted by the system properties, but also by a variety of climatic and environmental factors. The analytical framework laid out in this paper can be employed to critically analyse the most efficient solution for a specific location; however, it is not always possible to mitigate energy losses, using commercially available materials. For this reason, a brief overview of new concept devices is provided, outlining the way in which they mitigate energy losses and providing innovative solutions for a sustainable energy future.
The Possibility of a High-Efficiency Wave Power Generation System Using Dielectric Elastomers
Authors: Chiba Seiki , Waki Mikio , Jiang Changqing , Takeshita Makoto , Uejima Mitsugu , Arakawa Kohei , Ohyama Kazuhiro
Published: June 2021

Power generation using dielectric elastomer (DE) artificial muscle is attracting attention because of its light weight, low cost, and high-efficiency. Since this method is a system that produces electricity without emitting carbon dioxide nor using rare earths, it would contribute to the goal of environmental sustainability. In this paper, the background of DEs, the associated high efficiency wave energy generation (WEG) systems that we developed using DEs, as well as the latest development of its material are summarized. By covering both the challenges and achievements, this paper discusses the opportunities to build the foundation of an energy recycling society through the usage of these WEGs. To make these possibilities commercially successful, the advantages of DEs need to be integrated with traditional technologies. To achieve this, the method of using DEs alone and a system used in combination with an oscillating water column were also considered. Finally, the current status and future of DE generators (DEGs) are discussed.
Differentiating the Physical Optimum from the Exergetic Evaluation of a Methane Combustion Process
Authors: Kerpen Lukas , Schmidt Achim , Sankol Bernd
Published: June 2021

Combustion processes continue to be essential for the energy supply sector. A reliable energetic evaluation of these processes is crucial, particularly since the pollutants resulting from combustion have a significant impact on global warming. This work evaluates a combustion using the exergetic evaluation and the Physical Optimum (PhO) as it is described in VDI-Guideline 4663. Differences between PhO and exergy are investigated, allowing a distinct differentiation and examining the PhO’s added value in combustion analysis. Based on the evaluation of a simulated methane combustion, this paper shows that the PhO-Factor may be used to evaluate combustion processes. However, it shows that the PhO of a combustion process is a simplification of this fuels exergy and does not provide advantages to the exergy evaluation. Nevertheless, an adaption of the PhO is not carried out in the context of this work since the minimal deviation of the simulated energy indicators currently cannot justify an adaptation. In addition, proposed adjustments of the reference value (PhO) could lead to the definition limits of the PhO-Factor being exceeded. The paper introduces the indirect PhO-Factor for a targeted process optimization. It is shown that in this case, the indirect PhO-Factor closely corresponds to the exergy efficiency.
Role of JAK/STAT in Interstitial Lung Diseases; Molecular and Cellular Mechanisms
Authors: Montero Paula , Milara Javier , Roger Inés , Cortijo Julio
Published: June 2021

Interstitial lung diseases (ILDs) comprise different fibrotic lung disorders characterized by cellular proliferation, interstitial inflammation, and fibrosis. The JAK/STAT molecular pathway is activated under the interaction of a broad number of profibrotic/pro-inflammatory cytokines, such as IL-6, IL-11, and IL-13, among others, which are increased in different ILDs. Similarly, several growth factors over-expressed in ILDs, such as platelet-derived growth factor (PDGF), transforming growth factor β1 (TGF-β1), and fibroblast growth factor (FGF) activate JAK/STAT by canonical or non-canonical pathways, which indicates a predominant role of JAK/STAT in ILDs. Between the different JAK/STAT isoforms, it appears that JAK2/STAT3 are predominant, initiating cellular changes observed in ILDs. This review analyzes the expression and distribution of different JAK/STAT isoforms in ILDs lung tissue and different cell types related to ILDs, such as lung fibroblasts and alveolar epithelial type II cells and analyzes JAK/STAT activation. The effect of JAK/STAT phosphorylation on cellular fibrotic processes, such as proliferation, senescence, autophagy, endoplasmic reticulum stress, or epithelial/fibroblast to mesenchymal transition will be described. The small molecules directed to inhibit JAK/STAT activation were assayed in vitro and in in vivo models of pulmonary fibrosis, and different JAK inhibitors are currently approved for myeloproliferative disorders. Recent evidence indicates that JAK inhibitors or monoclonal antibodies directed to block IL-6 are used as compassionate use to attenuate the excessive inflammation and lung fibrosis related to SARS-CoV-2 virus. These altogether indicate that JAK/STAT pathway is an attractive target to be proven in future clinical trials of lung fibrotic disorders.
A New Presenilin 1 (Psen1) Mutation (p.Cys263Trp) as a Cause of Both Early and Late-Onset Alzheimer’s Disease in a Large Italian Family
Authors: Tortelli Rosanna , Seripa Davide , Zecca Chiara , Dell’Abate Maria Teresa , Bisceglia Paola , Barulli Maria Rosaria , De Blasi Roberto , Logroscino Giancarlo
Published: June 2021

Mutations in the PSEN1 gene are the most common cause of autosomal dominant Alzheimer’s disease, and are characterized by a high phenotype variability. This study describes a five-generation family, with a prevalent late-onset of the disease and a high frequency of depression, in which a new missense mutation (c.789T > G, p.Cys263Trp) in exon 8 of the PSEN1 gene was found. Only the proband presented an early onset at the age of 45 with attention deficit, followed by spatial disorientation, psychiatric symptoms and parkinsonian signs. The other two cases had a late onset of the disease and a typical presentation with memory loss. Both were characterized by a high level of anxiety and depression. The disease course was different with signs of Lewy body dementia for the proband’s mother, and pyramidal involvement and a shorter disease duration for the proband’s maternal aunt. The other eight cases with late-onset dementia and three cases with a long history of depression have been reported in the family pedigree, underlying the high phenotype variability of PSEN1 mutations.
Cinnamic Acid Derivatives as Cardioprotective Agents against Oxidative and Structural Damage Induced by Doxorubicin
Authors: Koczurkiewicz-Adamczyk Paulina , Klaś Katarzyna , Gunia-Krzyżak Agnieszka , Piska Kamil , Andrysiak Kalina , Stępniewski Jacek , Lasota Sławomir , Wójcik-Pszczoła Katarzyna , Dulak Józef , Madeja Zbigniew , Pękala Elżbieta
Published: June 2021

Doxorubicin (DOX) is a widely used anticancer drug. However, its clinical use is severely limited due to drug-induced cumulative cardiotoxicity, which leads to progressive cardiomyocyte dysfunction and heart failure. Enormous efforts have been made to identify potential strategies to alleviate DOX-induced cardiotoxicity; however, to date, no universal and highly effective therapy has been introduced. Here we reported that cinnamic acid (CA) derivatives exert a multitarget protective effect against DOX-induced cardiotoxicity. The experiments were performed on rat cardiomyocytes (H9c2) and human induced-pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs) as a well-established model for cardiac toxicity assessment. CA derivatives protected cardiomyocytes by ameliorating DOX-induced oxidative stress and viability reduction. Our data indicated that they attenuated the chemotherapeutic’s toxicity by downregulating levels of caspase-3 and -7. Pre-incubation of cardiomyocytes with CA derivatives prevented DOX-induced motility inhibition in a wound-healing assay and limited cytoskeleton rearrangement. Detailed safety analyses—including hepatotoxicity, mutagenic potential, and interaction with the hERG channel—were performed for the most promising compounds. We concluded that CA derivatives show a multidirectional protective effect against DOX-induced cardiotoxicity. The results should encourage further research to elucidate the exact molecular mechanism of the compounds’ activity. The lead structure of the analyzed CA derivatives may serve as a starting point for the development of novel therapeutics to support patients undergoing DOX therapy.
Degradation Products of Tryptophan in Cell Culture Media: Contribution to Color and Toxicity
Authors: Schnellbaecher Alisa , Lindig Anton , Le Mignon Maxime , Hofmann Tim , Pardon Brit , Bellmaine Stephanie , Zimmer Aline
Published: June 2021

Biomanufacturing processes may be optimized by storing cell culture media at room temperature, but this is currently limited by their instability and change in color upon long-term storage. This study demonstrates that one of the critical contributing factors toward media browning is tryptophan. LC-MS technology was utilized to identify tryptophan degradation products, which are likely formed primarily from oxidation reactions. Several of the identified compounds were shown to contribute significantly to color in solutions but also to exhibit toxicity against CHO cells. A cell-culture-compatible antioxidant, a-ketoglutaric acid, was found to be an efficient cell culture media additive for stabilizing components against degradation, inhibiting the browning of media formulations, and decreasing ammonia production, thus providing a viable method for developing room-temperature stable cell culture media.
Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation
Authors: Somlapura Meghana , Gottschalk Benjamin , Lahiri Pooja , Kufferath Iris , Pabst Daniela , Rülicke Thomas , Graier Wolfgang F. , Denk Helmut , Zatloukal Kurt
Published: June 2021

p62/Sequestosome-1 (p62) is a multifunctional adaptor protein and is also a constant component of disease-associated protein aggregates, including Mallory–Denk bodies (MDBs), in steatohepatitis and hepatocellular carcinoma. We investigated the interaction of the two human p62 isoforms, p62-H1 (full-length isoform) and p62-H2 (partly devoid of PB1 domain), with keratins 8 and 18, the major components of MDBs. In human liver, p62-H2 is expressed two-fold higher compared to p62-H1 at the mRNA level and is present in slightly but not significantly higher concentrations at the protein level. Co-transfection studies in CHO-K1 cells, PLC/PRF/5 cells as well as p62− total-knockout and wild-type mouse fibroblasts revealed marked differences in the cytoplasmic distribution and aggregation behavior of the two p62 isoforms. Transfection-induced overexpression of p62-H2 generated large cytoplasmic aggregates in PLC/PRF/5 and CHO-K1 cells that mostly co-localized with transfected keratins resembling MDBs or (transfection without keratins) intracytoplasmic hyaline bodies. In fibroblasts, however, transfected p62-H2 was predominantly diffusely distributed in the cytoplasm. Aggregation of p62-H2 and p62ΔSH2 as well as the interaction with K8 (but not with K18) involves acquisition of cross-β-sheet conformation as revealed by staining with luminescent conjugated oligothiophenes. These results indicate the importance of considering p62 isoforms in protein aggregation disease.
Albumin-Coated Single-Core Iron Oxide Nanoparticles for Enhanced Molecular Magnetic Imaging (MRI/MPI)
Authors: Baki Abdulkader , Remmo Amani , Löwa Norbert , Wiekhorst Frank , Bleul Regina
Published: June 2021

Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI.
TNFα-Induced LDL Cholesterol Accumulation Involve Elevated LDLR Cell Surface Levels and SR-B1 Downregulation in Human Arterial Endothelial Cells
Authors: Okoro Emmanuel Ugochukwu
Published: June 2021

Excess lipid droplets are frequently observed in arterial endothelial cells at sites of advanced atherosclerotic plaques. Here, the role of tumor necrosis factor alpha (TNFα) in modulating the low-density lipoprotein (LDL) content in confluent primary human aortic endothelial cells (pHAECs) was investigated. TNFα promoted an up to 2 folds increase in cellular cholesterol, which was resistant to ACAT inhibition. The cholesterol increase was associated with increased 125I-LDL surface binding. Using the non-hydrolysable label, Dil, TNFα could induce a massive increase in Dil-LDL by over 200 folds. The elevated intracellular Dil-LDL was blocked with excess unlabeled LDL and PCSK9, but not oxidized LDL (oxLDL), or apolipoprotein (apoE) depletion. Moreover, the TNFα-induced increase of LDL-derived lipids was elevated through lysosome inhibition. Using specific LDLR antibody, the Dil-LDL accumulation was reduced by over 99%. The effects of TNFα included an LDLR cell surface increase of 138%, and very large increases in ICAM-1 total and surface proteins, respectively. In contrast, that of scavenger receptor B1 (SR-B1) was reduced. Additionally, LDLR antibody bound rapidly in TNFα-treated cells by about 30 folds, inducing a migrating shift in the LDLR protein. The effect of TNFα on Dil-LDL accumulation was inhibited by the antioxidant tetramethythiourea (TMTU) dose-dependently, but not by inhibitors against NF-κB, stress kinases, ASK1, JNK, p38, or apoptosis caspases. Grown on Transwell inserts, TNFα did not enhance apical to basolateral LDL cholesterol or Dil release. It is concluded that TNFα promotes LDLR functions through combined increase at the cell surface and SR-B1 downregulation.
Human Mesenchymal Stromal Cell-Derived Exosomes Promote In Vitro Wound Healing by Modulating the Biological Properties of Skin Keratinocytes and Fibroblasts and Stimulating Angiogenesis
Authors: Tutuianu Raluca , Rosca Ana-Maria , Iacomi Daniela Madalina , Simionescu Maya , Titorencu Irina
Published: June 2021

Bone marrow-derived mesenchymal stromal cells (MSCs) are major players in regenerative therapies for wound healing via their paracrine activity, mediated partially by exosomes. Our purpose was to test if MSC-derived exosomes could accelerate wound healing by enhancing the biological properties of the main cell types involved in the key phases of this process. Thus, the effects of exosomes on (i) macrophage activation, (ii) angiogenesis, (iii) keratinocytes and dermal fibroblasts proliferation and migration, and (iv) the capacity of myofibroblasts to regulate the turnover of the extracellular matrix were evaluated. The results showed that, although exosomes did not exhibit anti-inflammatory properties, they stimulated angiogenesis. Exposure of keratinocytes and dermal (myo)fibroblasts to exosomes enhanced their proliferation and migratory capacity. Additionally, exosomes prevented the upregulation of gene expression for type I and III collagen, α-smooth muscle actin, and MMP2 and 14, and they increased MMP13 expression during the fibroblast–myofibroblast transition. The regenerative properties of exosomes were validated using a wound healing skin organotypic model, which exhibited full re-epithelialization upon exosomes exposure. In summary, these data indicate that exosomes enhance the biological properties of keratinocytes, fibroblasts, and endothelial cells, thus providing a reliable therapeutic tool for skin regeneration.
Decellularized Porcine Cartilage Scaffold; Validation of Decellularization and Evaluation of Biomarkers of Chondrogenesis
Authors: Stone Roxanne N. , Frahs Stephanie M. , Hardy Makenna J. , Fujimoto Akina , Pu Xinzhu , Keller-Peck Cynthia , Oxford Julia Thom
Published: June 2021

Osteoarthritis is a major concern in the United States and worldwide. Current non-surgical and surgical approaches alleviate pain but show little evidence of cartilage restoration. Cell-based treatments may hold promise for the regeneration of hyaline cartilage-like tissue at the site of injury or wear. Cell–cell and cell–matrix interactions have been shown to drive cell differentiation pathways. Biomaterials for clinically relevant applications can be generated from decellularized porcine auricular cartilage. This material may represent a suitable scaffold on which to seed and grow chondrocytes to create new cartilage. In this study, we used decellularization techniques to create an extracellular matrix scaffold that supports chondrocyte cell attachment and growth in tissue culture conditions. Results presented here evaluate the decellularization process histologically and molecularly. We identified new and novel biomarker profiles that may aid future cartilage decellularization efforts. Additionally, the resulting scaffold was characterized using scanning electron microscopy, fluorescence microscopy, and proteomics. Cellular response to the decellularized scaffold was evaluated by quantitative real-time PCR for gene expression analysis.
Surgical Management of Gastric Cancer: A Systematic Review
Authors: Mocan Lucian
Published: June 2021

Gastric cancer is the fifth most common cancer worldwide, and it is responsible for 7.7% of all cancer deaths. Despite advances in the field of oncology, where radiotherapy, neo and adjuvant chemotherapy may improve the outcome, the only treatment with curative intent is represented by surgery as part of a multimodal therapy. Two concepts may be adopted in appropriate cases, neoadjuvant treatment before gastrectomy (G) or primary surgical resection followed by chemotherapy. Such an approach, combined with early detection and better screening, has led to a decrease in the overall incidence of gastric cancer. Unfortunately, malignant tumors of the stomach are often diagnosed in locally advanced or metastatic stages when the median overall survival remains poor. Surgical care in these cases must be provided by a multidisciplinary team in a high-volume center. Important surgical aspects such as optimum resection margins, surgical technique, and number of harvested lymph nodes are important factors for patient outcomes. The standardization of surgical treatment of gastric cancer in accordance with the patient’s profile is of decisive importance for a better outcome. This review aims to summarize the current standards in the surgical treatment of gastric cancer.
Optimization of Power Generation Grids: A Case of Study in Eastern Mexico
Authors: López Esmeralda , Domínguez-Cruz René F. , Salgado-Tránsito Iván
Published: June 2021

Optimization of energy resources is a priority issue for our society. An improper imbalance between demand and power generation can lead to inefficient use of installed capacity, waste of fuels, worse effects on the environment, and higher costs. This paper presents the preliminary results of a study of seventeen interconnected power generation plants situated in eastern Mexico. The aim of the research is to apply a linear programming model to find the system-optimal solution by minimizing operating costs for this grid of power plants. The calculations were made taking into account the actual parameters of each plant; the demand and production of energy were analyzed in four time periods of 6 h during a day. The results show the cost-optimal configuration of the current power infrastructure obtained from a simple implementation model in MATLAB® software. The contribution of this paper is to adapt a lineal progamming model for an electrical distribution network formed with different types of power generation technology. The study shows that fossil fuel plants, besides emitting greenhouse gases that affect human health and the environment, incur maintenance expenses even without operation. The results are a helpful instrument for decision-making regarding the rational use of available installed capacity.