bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Satellite and UAV Data to Predict Peanut Maturity upon Artificial Neural Networks
Authors: Souza Jarlyson Brunno Costa , de Almeida Samira Luns Hatum , Freire de Oliveira Mailson , Santos Adão Felipe dos , Filho Armando Lopes de Brito , Meneses Mariana Dias , Silva Rouverson Pereira da
Published: June 2022

The monitoring and determination of peanut maturity are fundamental to reducing losses during digging operation. However, the methods currently used are laborious and subjective. To solve this problem, we developed models to access peanut maturity using images from unmanned aerial vehicles (UAV) and satellites. We evaluated an area of approximately 8 hectares in which a regular grid of 30 points was determined with weekly evaluations starting at 90 days after sowing. Two Artificial Neural Networking (ANN) were used with Radial Basis Function (RBF) and Multilayer Perceptron (MLP) to predict the Peanut Maturity Index (PMI) with the spectral bands available from each sensor. Several vegetation indices were used as input to the ANN, with the data being split 80/20 for training and validation, respectively. The vegetation index, Normalized Difference Red Edge Index (NDRE), was the most precise coefficient of determination (R2 = 0.88) and accurate mean absolute error (MAE = 0.06) for estimating PMI, regardless of the type of ANN used. The satellite with Normalized Difference Vegetation Index (NDVI) could also determine PMI with better accuracy (MAE = 0.05) than the NDRE. The performance evaluation indicates that the RBF and MLP networks are similar in predicting peanut maturity. We concluded that satellite and UAV images can predict the maturity index with good accuracy and precision.
A Preliminary Investigation of Myostatin Gene (MSTN) Variation in Red Deer (Cervus elaphus) and Its Implications for Venison Production in New Zealand
Authors: Cunningham Lily , Zhou Huitong , Fang Qian , Tapley Mark , Hickford Jonathan G. H.
Published: June 2022

Myostatin (MSTN), also known as growth differentiation factor 8 (GDF-8), is a negative regulator of lean muscle tissue growth. Variation in the gene has been studied in many domesticated species, because of its potential to dramatically increase muscle mass. It has, however, not been investigated in red deer (Cervus elaphus). In this study, variation in MSTN intron 1 was investigated in 211 male New Zealand red deer, for which phenotypic measurements of M. Longissimus dorsi (eye muscle) (width, depth, and area, together with 12-month weight) were recorded. Two sequence variants (named A and B) differing by one nucleotide (c.373 + 224) were identified in the intron 1 region of the gene resulting in three genotypes (AA, AB, and BB; frequencies of 63.5%, 30.8%, and 5.7%, respectively), but no association between this variation and any of the quantitative measurements was detected. These results suggest that the deer MSTN is less variable than for other livestock species and that its activity may be controlled to maintain a size–growth equilibrium.
Terpenoid-Rich Extract of Dillenia indica L. Bark Displays Antidiabetic Action in Insulin-Resistant C2C12 Cells and STZ-Induced Diabetic Mice by Attenuation of Oxidative Stress
Authors: Song Bo-Rim , Alam Md Badrul , Lee Sang-Han
Published: June 2022

Insulin resistance (IR) plays a key role in the pathogenesis and clinical outcome of patients with multiple diseases and diabetes. In this study, we examined the antidiabetic effects of a terpenoid-rich extract from Dillenia indica L. bark (TRDI) in palmitic acid-induced insulin resistance (PA-IR) in C2C12 myotube and a streptozotocin (STZ)-induced diabetic mice model and explored the possible underlying mechanism. TRDI showed potential DPPH- and ABTS-radical scavenging effects with a half-maximal inhibitory concentration (IC50) value of 9.76 ± 0.50 µg/mL and 17.47 ± 1.31 µg/mL, respectively. Furthermore, TRDI strongly mitigated α-glucosidase activity with an IC50 value of 3.03 ± 1.01 µg/mL, which was 92-fold higher than the positive control, acarbose (IC50 = 279.49 ± µg/mL). TRDI stimulated the insulin receptor substrarte-1 (INS-1), downregulated phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (Akt) in both normal and PA-IR C2C12 cells as well as in STZ-induced diabetic mice, enhanced glucose transporter 4 (GLUT4) translocation to the plasma membrane (PM), and increased glucose absorption. Furthermore, TRDI administration significantly reduced PA-induced reactive oxygen species (ROS) formation in C2C12 cells and increased the protein level of numerous antioxidant enzymes such as superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase-1 (GPx-1) and thioredoxin reductase (TrxR) both in vitro and in vivo. Furthermore, TRDI facilitated nuclear factor erythroid 2 related factor 2 (Nrf2) nuclear translocation and increased HO-1 expression in PA-IR C2C12 cells and STZ-induced diabetic mice. However, for the inhibition of Nrf2, TRDI failed to resist the effects of IR. Thus, this study provides new evidence to support the use of TRDI for diabetes treatment.
Daytime Lipid Metabolism Modulated by CLOCK Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma
Authors: Gubin Denis , Neroev Vladimir , Malishevskaya Tatyana , Kolomeichuk Sergey , Weinert Dietmar , Yuzhakova Natalya , Nelaeva Alsu , Filippova Yulia , Cornelissen Germaine
Published: June 2022

Lipid metabolism is intimately linked to circadian mechanisms and light signaling. Deteriorated photic transduction because of retinal ganglion cell (RGC) loss occurring with glaucoma progression reduces perceived light amplitude, causing circadian disruption. To investigate associations with RGCs, total cholesterol (TC), its low-density (LDL-C) and high-density (HDL-C) fractions, and triglycerides (TG) were measured, under a controlled meal regimen, during daytime hours in 114 patients diagnosed with primary open-angle glaucoma (POAG). RGC damage was assessed by high-definition optical coherence tomography (HD-OCT). Analysis of eight clock, clock-related, and melatonin receptor gene polymorphisms was performed on 19 patients. RGC loss was associated with changes in lipid metabolism in a time-dependent manner. Morning (08:00) values of HDL-C (r = 0.613, p < 0.0001) and TG (r = 0.568, p < 0.0001) correlated positively with RGC global loss, while LDL-C at 08:00 had a weak correlation (r = 0.235; p = 0.012) but showed a strong correlation in the evening (20:00) (r = 0.533, p < 0.0001). The morning–evening gradients (MEGs, changes at 20:00 versus 08:00) in TC and LDL-C changed sign from a negative to a positive association in patients exceeding the 15% two-eye mean GLV threshold. MEG (LDL-C higher in the evening than in the morning) was positive only in POAG patients with the CLOCK_3111 TT genotype.
Chemical Profiling of Limonium vulgare Mill. Using UHPLC-DAD-ESI/MS2 and GC-MS Analysis
Authors: Carius Benedict , Silva Helena , Silva Artur M. S. , Pinto Diana C. G. A.
Published: June 2022

Limonium vulgare Mill. is a plant growing widely in harsh environments, such as salt marshes, for which a chemical profile is still unknown, although some interesting bioactivities were already reported. So, this halophyte chemical profile must be established to find the possible bioactive compounds, valorize the species, and contribute to the salt marsh’s exploitation. This work set the chemical profile of L. vulgare’s aerial parts (leaves and inflorescences) using UHPLC-DAD-ESI/MS2 and GC-MS analysis. The lipophilic profile showed a richness in fatty acids, alkanes, and terpenoids, β-sitosterol being the major compound in inflorescences in the fruiting stage (0.822 ± 0.015 mg/g of the dry plant) and leaves (0.534 ± 0.017 mg/g of the dry plant). In contrast, in the inflorescences in the flowering stage, the major compound is nonacosane (0.228 ± 0.001 mg/g of the dry plant). The polyphenolic profile demonstrates that L. vulgare produces several flavonoids from which quercetin and myricetin can be highlighted; in particular, myricetin derivatives are prevalent in all extracts. Amongst the flavonoids, myricetin 3-rhamnoside is the most abundant in the inflorescences in the flowering stage (6.35 ± 0.05 mg/g of the dry plant), myricetin in leaves (9.69 ± 0.11 mg/g of the dry plant), and in the inflorescences in the fruiting stage baicalin presents the highest amount (5.15 ± 0.07 mg/g of the dry plant). This is the first report on L. vulgare’s chemical profile and the results indicate that this species is an exciting source of bioactive compounds, suggesting it has a use to produce nutraceuticals and/or pharmaceuticals.
Pain Perception during Orthodontic Treatment with Fixed Appliances
Authors: Olteanu Cristian Doru , Bucur Sorana-Maria , Chibelean Manuela , Bud Eugen Silviu , Păcurar Mariana , Feștilă Dana Gabriela
Published: June 2022

The present study aimed to determine the intensity of pain perception in patients undergoing fixed orthodontic treatment. We analyzed the severity of pain concerning four routine procedures: the placement of separating elastics, ring cementations, arch activations, and elastic tractions. Our study consisted of a sample of 100 patients between 12 and 35 years old during the initial months of orthodontic treatment with fixed appliances. The patients completed a questionnaire meant to assess their pain sensation perception. The study sample was divided according to age and sex. By determining the intensity of pain felt during the four orthodontic procedures, we found that the most painful one was the ring cementation in all four age groups. The therapeutic-arch-activation procedure ranked second, with a higher mean value (2.66) in the 18–24 age group; the least painful was considered the elastic traction procedure, with a higher value (1.33) in the group over 30 years old. The most painful period was during the first 3–4 days after procedures. Most patients showed moderate pain after following the studied orthodontic interventions and required analgesic medication, the most frequently used being Nurofen, ketonal or paracetamol. The level of pain felt was significantly higher in men than in women. Patients suffer differently from the intensity of perceived pain as they grow older.
Analysis and Design of Wireless Power Transfer System for Rotational Inertial Navigation Application
Authors: Niu Meng , Sun Xinglin , Ma Hongyu , Zhu Zhijuan , Huang Tiantian , Song Kaichen
Published: June 2022

Cables or slip-rings are often used to power loads on a rotating unit in the rotation modulated inertial navigation system (RMINS). However, these power supply methods have the disadvantages of cable winding and slip ring friction and wear, which reduces the reliability and life of the RMINS. Therefore, this paper applies magnetic coupling resonant wireless power transfer (MCRWPT) technology to the RMINS to avoid the shortcomings of the above power supply methods. Furthermore, according to the structure and working characteristics of the RMINS, a simple design method of the MCRWPT system without any feedback control is proposed. Based on the ANSYS simulation, the magnetic shielding structure is designed to reduce magnetic leakage, and the efficiency of the MCRWPT system is optimized by designing the excitation frequency. Experiments verify the effectiveness of the proposed method. The experimental results show that the designed MCRWPT system can achieve an efficiency of 74.6% with an output power of 10 W and has been successfully applied to the uniaxial rotation module inertial navigation system. Finally, the design method of the MCRWPT system is simple, and it has guiding significance for the design of the wireless power transfer system in the RMINS.
Experimental Study on Repairing Corroded Cracks by Electrophoretic Deposition
Authors: Wang Yueming , Wang Changdan , Zhou Shunhua
Published: June 2022

The corrosion of reinforced concrete could reduce its mechanical properties and cause concrete cracking. Electrophoretic deposition is a new method for repairing rust-cracked reinforced concrete. In this study, we observed the crack surface morphology, mass growth, epoxy resin film thickness, ultrasonic rate, and epoxy resin filling depth of rust-cracked reinforced mortar specimens during the repair process and investigated internal microstructure and phase composition of the repaired mortar, and clarified the principle behind the electrophoretic deposition of cationic epoxy resin and curing agent molecules in the repair solution. The result of research shows that longer repair times decreased the carbonization depth and water absorption of the specimens. After repair, the porosity of the surface mortar decreased, owing to the filling of epoxy resin, and the newly generated epoxy resin film had a dense structure. Thus, the carbonization resistance and waterproof performance of the repaired specimens improved. The repair process of electrophoretic deposition can be divided into the immersion, repair, and curing stages, and the physical and chemical principles of each stage were explained.
A Conventional VOC-PID Sensor for a Rapid Discrimination among Aromatic Plant Varieties: Classification Models Fitted to a Rosemary Case-Study
Authors: Spadi Agnese , Angeloni Giulia , Guerrini Lorenzo , Corti Ferdinando , Maioli Francesco , Calamai Luca , Parenti Alessandro , Masella Piernicola
Published: June 2022

This study explores the use of a photoionization detector (PID) to distinguish varieties of rosemary plant, based on their volatile organic compound (VOC) emissions. The aim was to be able to distinguish plant varieties using a simple, quick, and inexpensive method. Two varieties were studied, Rosmarinus officinalis L. “Prostratus” and “Erectus”. First, the PID was used to detect VOCs emitted by leaves from each variety, and subsequently essential oil was extracted from the same leaves. Then, the well-established GC-MS method was used to characterize and differentiate the oil from each of the two varieties. The PID was able to capture different signals, and a ‘fingerprint’ for each of the two varieties was obtained. To validate the PID performance, the data set obtained was analyzed by means of advanced statistical models (principal component analysis, cluster and support vector machine and artificial neural network) which were able to discriminate the two varieties with high accuracy (over 80%). Therefore, the results confirm that the PID was able to detect differences in VOC emissions. In conclusion, PID proved be an interesting instrument for the classification of rosemary plants, and in this sense could be applied to other aromatic plants.
Risk Treatment for Energy-Oriented Production Plans through the Selection, Classification, and Integration of Suitable Measures
Authors: Roth Stefan , Huber Mirjam , Schilp Johannes , Reinhart Gunther
Published: June 2022

With rising electricity prices, industries are trying to exploit opportunities to reduce electricity costs. Adapting to fluctuating energy prices offers the possibility to save electricity costs without reducing the performance of the production system. Production planning and control play key roles in the implementation of the adjustments. By taking into account the price forecasts for the electricity markets in addition to machine utilization, work in process, and throughput time, an energy-oriented production plan is set up. The electrical energy is procured based on this plan and the associated load profile. Deviations from the forecast and the purchased amount of electricity lead to high penalties, as they can destabilize the energy system. For manufacturing companies, this means that machine failures and other unexpected events must be dealt with in a structured manner to avoid these penalty costs. This paper presents an approach to selecting, classifying, and integrating suitable measures from existing risk treatment paths into the production schedule. The selection of measures is based on a hybrid multi-criteria decision-making method in which the three relevant criteria, namely, cost, energy flexibility, and risk reduction, are weighted by applying both an analytic hierarchy process and entropy, and they are then prioritized according to multi-attribute utility theory. In the following, the subdivision into preventive and reactive measures is made in order to choose between the modification of the original plan or the creation of backup plans. With the help of mathematical optimization, the measures are integrated into the production schedule by minimizing the cost of balancing energy. The approach was implemented in MATLAB® and validated using a case study in the foundry industry.
Development of a Biotechnology Platform for the Fast-Growing Cyanobacterium Synechococcus sp. PCC 11901
Authors: Mills Lauren , Moreno-Cabezuelo José , Włodarczyk Artur , Victoria Angelo , Mejías Rebeca , Nenninger Anja , Moxon Simon , Bombelli Paolo , Selão Tiago , McCormick Alistair , Lea-Smith David
Published: June 2022

Synechococcus sp. PCC 11901 reportedly demonstrates the highest, most sustained growth of any known cyanobacterium under optimized conditions. Due to its recent discovery, our knowledge of its biology, including the factors underlying sustained, fast growth, is limited. Furthermore, tools specific for genetic manipulation of PCC 11901 are not established. Here, we demonstrate that PCC 11901 shows faster growth than other model cyanobacteria, including the fast-growing species Synechococcuselongatus UTEX 2973, under optimal growth conditions for UTEX 2973. Comparative genomics between PCC 11901 and Synechocystis sp. PCC 6803 reveal conservation of most metabolic pathways but PCC 11901 has a simplified electron transport chain and reduced light harvesting complex. This may underlie its superior light use, reduced photoinhibition, and higher photosynthetic and respiratory rates. To aid biotechnology applications, we developed a vitamin B12 auxotrophic mutant but were unable to generate unmarked knockouts using two negative selectable markers, suggesting that recombinase- or CRISPR-based approaches may be required for repeated genetic manipulation. Overall, this study establishes PCC 11901 as one of the most promising species currently available for cyanobacterial biotechnology and provides a useful set of bioinformatics tools and strains for advancing this field, in addition to insights into the factors underlying its fast growth phenotype.
Polyphenol and Tannin Nutraceuticals and Their Metabolites: How the Human Gut Microbiota Influences Their Properties
Authors: Fabbrini Marco , D’Amico Federica , Barone Monica , Conti Gabriele , Mengoli Mariachiara , Brigidi Patrizia , Turroni Silvia
Published: June 2022

Nutraceuticals have been receiving increasing attention in the last few years due to their potential role as adjuvants against non-communicable chronic diseases (cardiovascular disease, diabetes, cancer, etc.). However, a limited number of studies have been performed to evaluate the bioavailability of such compounds, and it is generally reported that a substantial elevation of their plasma concentration can only be achieved when they are consumed at pharmacological levels. Even so, positive effects have been reported associated with an average dietary consumption of several nutraceutical classes, meaning that the primary compound might not be solely responsible for all the biological effects. The in vivo activities of such biomolecules might be carried out by metabolites derived from gut microbiota fermentative transformation. This review discusses the structure and properties of phenolic nutraceuticals (i.e., polyphenols and tannins) and the putative role of the human gut microbiota in influencing the beneficial effects of such compounds.
Spark Desensitization of Nanothermites via the Addition of Highly Electro-Conductive Carbon Particles
Authors: Gibot Pierre
Published: June 2022

In the past decade, the formulation of spark-desensitized nanothermites has considerably advanced, making them safe to handle. When ignited, these materials reveal impressive properties such as high temperatures (>1000 °C), intense heat releases (>kJ/cm3), and sometimes gas generation. Unfortunately, these energetic systems are systematically characterized by an extreme sensitivity to electrostatic discharges, which can cause accidental ignitions during preparation, handling, and transport. The present study examines the electrostatic discharge sensitivity response of an Al/WO3 energetic formulation doped with highly conductive carbon nanoparticles (Ketjenblack EC600JD). The results showed an increased threshold from <0.14 mJ to almost 40 mJ with 18.80 vol. % of KB EC600JD in the energetic mixture. The energetic material was also desensitized to friction stress with a threshold greater than 360 N, in contrast to a value of <4.9 N for an un-doped Al/WO3 energetic composite material. The reactive performance of the system (w/o Ketjenblack additive) was verified in open medium by means of an optical igniter. The heat release was determined by a calorimetric bomb and a decrease of 50% was recorded for the carbon-doped energetic system compared to the pristine Al/WO3 composition.
BCG in Bladder Cancer Immunotherapy
Authors: Jiang Song , Redelman-Sidi Gil
Published: June 2022

BCG is a live attenuated strain of Mycobacterium bovis that is primarily used as a vaccine against tuberculosis. In the past four decades, BCG has also been used for the treatment of non-muscle invasive bladder cancer (NMIBC). In patients with NMIBC, BCG reduces the risk of tumor recurrence and decreases the likelihood of progression to more invasive disease. Despite the long-term clinical experience with BCG, its mechanism of action is still being elucidated. Data from animal models and from human studies suggests that BCG activates both the innate and adaptive arms of the immune system eventually leading to tumor destruction. Herein, we review the current data regarding the mechanism of BCG and summarize the evidence for its clinical efficacy and recommended indications and clinical practice.
The Potential Tumor-Suppressor DHRS7 Inversely Correlates with EGFR Expression in Prostate Cancer Cells and Tumor Samples
Authors: Stücheli Simon , Araya Selene , Ercan Caner , Moser Seraina O. , Gallon John , Jenö Paul , Piscuoglio Salvatore , Terracciano Luigi , Odermatt Alex
Published: June 2022

Prostate cancer (PCa), one of the most common malignancies in men, typically responds to initial treatment, but resistance to therapy often leads to metastases and death. The dehydrogenase/reductase 7 (DHRS7, SDR34C1) is an “orphan” enzyme without known physiological function. DHRS7 was previously found to be decreased in higher-stage PCa, and siRNA-mediated knockdown increased the aggressiveness of LNCaP cells. To further explore the role of DHRS7 in PCa, we analyzed the proteome of LNCaP cells following DHRS7 knockdown to assess potentially altered pathways. Although DHRS7 is able to inactivate 5α-dihydrotestosterone, DHRS7 knockdown did not affect androgen receptor (AR) target gene expression, and its effect on PCa cells seems to be androgen-independent. Importantly, proteome analyses revealed increased expression of epidermal growth factor receptor (EGFR), which was confirmed by RT-qPCR and Western blotting. Comparison of AR-positive LNCaP with AR-negative PC-3 and DU145 PCa cell lines revealed a negative correlation between DHRS7 and EGFR expression. Conversely, EGFR knockdown enhanced DHRS7 expression in these cells. Importantly, analysis of patient samples revealed a negative correlation between DHRS7 and EGFR expression, both at the mRNA and protein levels, and DHRS7 expression correlated positively with patient survival rates. These results suggest a protective role for DHRS7 in PCa.
Molecular Basis of Beckwith–Wiedemann Syndrome Spectrum with Associated Tumors and Consequences for Clinical Practice
Authors: Eggermann Thomas , Maher Eamonn R. , Kratz Christian P. , Prawitt Dirk
Published: June 2022

Beckwith–Wiedemann syndrome (BWS, OMIM 130650) is a congenital imprinting condition with a heterogenous clinical presentation of overgrowth and an increased childhood cancer risk (mainly nephroblastoma, hepatoblastoma or neuroblastoma). Due to the varying clinical presentation encompassing classical, clinical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly, the syndromic entity was extended to the Beckwith–Wiedemann spectrum (BWSp). The tumor risk of up to 30% depends on the molecular subtype of BWSp with causative genetic or epigenetic alterations in the chromosomal region 11p15.5. The molecular diagnosis of BWSp can be challenging for several reasons, including the range of causative molecular mechanisms which are frequently mosaic. The molecular basis of tumor formation appears to relate to stalled cellular differentiation in certain organs that predisposes persisting embryonic cells to accumulate additional molecular defects, which then results in a range of embryonal tumors. The molecular subtype of BWSp not only influences the overall risk of neoplasia, but also the likelihood of specific embryonal tumors.
Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy
Authors: Herrero de la Parte Borja , Rodrigo Irati , Gutiérrez-Basoa Jon , Iturrizaga Correcher Sira , Mar Medina Carmen , Echevarría-Uraga Jose Javier , Garcia Jose Angel , Plazaola Fernando , García-Alonso Ignacio
Published: June 2022

Background: Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the magnetic field-frequency product (H × f = 4.85 × 108 Am−1s−1) proposed by Atkinson–Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects of overpassing this limit. Methods: Different combinations of field frequency and intensity exceeding the Atkinson–Brezovich limit (591–920 kHz, and 10.3–18 kA/m) have been applied for 21 min to WAG/RijHsd male rats, randomly distributed to groups of 12 animals; half of them were sacrificed after 12 h, and the others 10 days later. Biochemical serum analyses were performed to assess the general, hepatic, renal and/or pancreatic function. Results: MH raised liver temperature to 42.8 ± 0.4 °C. Although in five of the groups the exposure was relatively well tolerated, in the two of highest frequency (928 kHz) and intensity (18 kA/m), more than 50% of the animals died. A striking elevation in liver and systemic markers was observed after 12 h in the surviving animals, independently of the frequency and intensity used. Ten days later, liver markers were almost recovered in all of the animals. However, in those groups exposed to 591 kHz and 16 kA/m, and 700 kHz and 13.7 kA/m systemic markers remained altered. Conclusions: Exceeding the Atkinson–Brezovich limit up to 9.59 × 109 Am−1s−1 seems to be safe, though further research is needed to understand the impact of intensity and/or frequency on physiological conditions following MH.
In Vitro and In Vivo Models of CLL–T Cell Interactions: Implications for Drug Testing
Authors: Hoferkova Eva , Kadakova Sona , Mraz Marek
Published: June 2022

T cells are key components in environments that support chronic lymphocytic leukemia (CLL), activating CLL-cell proliferation and survival. Here, we review in vitro and in vivo model systems that mimic CLL–T-cell interactions, since these are critical for CLL-cell division and resistance to some types of therapy (such as DNA-damaging drugs or BH3-mimetic venetoclax). We discuss approaches for direct CLL-cell co-culture with autologous T cells, models utilizing supportive cell lines engineered to express T-cell factors (such as CD40L) or stimulating CLL cells with combinations of recombinant factors (CD40L, interleukins IL4 or IL21, INFγ) and additional B-cell receptor (BCR) activation with anti-IgM antibody. We also summarize strategies for CLL co-transplantation with autologous T cells into immunodeficient mice (NOD/SCID, NSG, NOG) to generate patient-derived xenografts (PDX) and the role of T cells in transgenic CLL mouse models based on TCL1 overexpression (Eµ-TCL1). We further discuss how these in vitro and in vivo models could be used to test drugs to uncover the effects of targeted therapies (such as inhibitors of BTK, PI3K, SYK, AKT, MEK, CDKs, BCL2, and proteasome) or chemotherapy (fludarabine and bendamustine) on CLL–T-cell interactions and CLL proliferation.
PD-1/PD-L1 Checkpoint Inhibitors Are Active in the Chicken Embryo Model and Show Antitumor Efficacy In Ovo
Authors: Wang Yan , Rousset Xavier , Prunier Chloé , Garcia Paul , Dosda Emilien , Leplus Estelle , Viallet Jean
Published: June 2022

(1) Purpose: To assess the use of the chicken embryo (in ovo) model as an alternative in vivo model for immuno-oncology (IO) drug development, focusing on programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors. (2) Methods: First, the presence of immune cells in the model was detected through the immunophenotyping of chicken peripheral blood mononuclear cells (PBMCs) based on fluorescence activated cell sorting (FACS) analysis and the immunohistochemistry (IHC) analysis of in ovo tumor-infiltrating lymphocytes. Second, the cross-reactivity between one anti-human PD-1 Ab, pembrolizumab (KEYTRUDA®), and chicken PD-1 was verified through the labelling of chicken splenocytes with pembrolizumab by FACS analysis. Third, the blockade effect of pembrolizumab on chicken PBMCs was assessed in vitro through cytotoxicity assay based on MTT. Fourth, the CAM assay was used to estimate the anti-tumor performance of pembrolizumab through the analyses of tumor growth and chicken immune cell infiltration in tumors. Finally, the efficacy of several PD-1 or PD-L1 inhibitors (nivolumab, atezolizumab and avelumab) on tumor growth was further assessed using the CAM assay. (3) Results: The presence of CD3+, CD4+, CD8+ T lymphocytes and monocytes was confirmed by FACS and IHC analyses. During in vitro assays, pembrolizumab cross-reacted with chicken lymphocytes and induced PD-1/PD-L1 blockade, which permitted the restoration of chicken T-cell’s cytotoxicity against human lung cancer H460 tumor cells. All these in vitro results were correlated with in ovo findings based on the CAM assay: pembrolizumab inhibited H460 tumor growth and induced evident chicken immune cell infiltration (with significant chicken CD45, CD3, CD4, CD8 and CD56 markers) in tumors. Furthermore, the potency of the CAM assay was not limited to the application of pembrolizumab. Nivolumab, atezolizumab and avelumab also led to tumor growth inhibition in ovo, on different tumor models. (4) Conclusions: The chicken embryo affords a physiological, immune reactive, in vivo environment for IO research, which allows observation of how the immune system defense against tumor cells, as well as the different immune tolerance mechanisms leading to tumor immune escape. The encouraging results obtained with PD-1/PD-L1 inhibitors in this study reveal the potential use of the chicken embryo model as an alternative, fast, and reliable in vivo model in the different fields of IO drug discovery.
mGluR5 Is Substitutable for mGluR1 in Cerebellar Purkinje Cells for Motor Coordination, Developmental Synapse Elimination, and Motor Learning
Authors: Harbers Maria , Nakao Harumi , Watanabe Takaki , Matsuyama Kyoko , Tohyama Shoichi , Nakao Kazuki , Kishimoto Yasushi , Kano Masanobu , Aiba Atsu
Published: June 2022

Group I metabotropic glutamate receptors (mGluRs) include mGluR1 and mGluR5, which are coupled to the Gq family of heterotrimeric G-proteins and readily activated by their selective agonist 3,5-dihydroxyphenilglycine (DHPG). mGluR1 and mGluR5 exhibit nearly complementary distributions spatially or temporally in the central nervous system (CNS). In adult cerebellar Purkinje cells (PCs), mGluR1 is a dominant group I mGluR and mGluR5 is undetectable. mGluR1 expression increases substantially during the first three weeks of postnatal development and remains high throughout adulthood. On the other hand, mGluR5 expression is observed during the first two postnatal weeks and then decreases. However, functional differences between mGluR1 and mGluR5 in the CNS remains to be elucidated. To address this issue, we generated “mGluR5-rescue” mice in which mGluR5 is specifically expressed in PCs in global mGluR1-knockout (KO) mice. mGluR5-rescue mice exhibited apparently normal motor coordination, developmental elimination of redundant climbing fiber (CF)-PC synapses, and delay eyeblink conditioning, which were severely impaired in mGluR1-KO mice. We concluded that mGluR5 is functionally comparable with mGluR1 in cerebellar PCs.
Hematopoietic Stem and Progenitor Cell Maintenance and Multiple Lineage Differentiation Is an Integral Function of NFATc1
Authors: Barahona de Brito Carlotta , Klein-Hessling Stefan , Serfling Edgar , Patra Amiya Kumar
Published: June 2022

Hematopoietic stem and progenitor cell (HSPC) maintenance and the differentiation of various lineages is a highly complex but precisely regulated process. Multiple signaling pathways and an array of transcription factors influence HSPC maintenance and the differentiation of individual lineages to constitute a functional hematopoietic system. Nuclear factor of activated T cell (NFAT) family transcription factors have been studied in the context of development and function of multiple mature hematopoietic lineage cells. However, until now their contribution in HSPC physiology and HSPC differentiation to multiple hematopoietic lineages has remained poorly understood. Here, we show that NFAT proteins, specifically NFATc1, play an indispensable role in the maintenance of HSPCs. In the absence of NFATc1, very few HSPCs develop in the bone marrow, which are functionally defective. In addition to HSPC maintenance, NFATc1 also critically regulates differentiation of lymphoid, myeloid, and erythroid lineage cells from HSPCs. Deficiency of NFATc1 strongly impaired, while enhanced NFATc1 activity augmented, the differentiation of these lineages, which further attested to the vital involvement of NFATc1 in regulating hematopoiesis. Hematopoietic defects due to lack of NFATc1 activity can lead to severe pathologies such as lymphopenia, myelopenia, and a drastically reduced lifespan underlining the critical role NFATc1 plays in HSPC maintenance and in the differentaion of various lineages. Our findings suggest that NFATc1 is a critical component of the myriad signaling and transcriptional regulators that are essential to maintain normal hematopoiesis.
Synthesis and Properties of Self-Polishing Antifouling Coatings Based on BIT-Acrylate Resins
Authors: Dong Miao , Liu Liju , Wang Dazhuang , Li Mengting , Yang Jianxin , Chen Junhua
Published: June 2022

Painting antifouling coatings is one of the most important methods to prevent marine biofouling. Acrylic resin is widely used in marine antifouling because of its excellent stickiness, water resistance, and film-forming capabilities. At present, the widely used acrylate antifouling coatings require a high concentration of cuprous oxide as antifoulant. The release and accumulation of copper ions are the main factors affecting the marine environment. In this study, BIT–allyl methacrylate (BM) and zinc acrylate (ZM) were selected as functional monomers copolymerized with methyl methacrylate (MMA) and butyl acrylate (BA) to prepare a series of BIT acrylate antifouling resins. The inhibitory effects of all resins against marine bacteria (S. aureus, V. coralliilyticus, and V. parahaemolyticus), marine algae (Chlorella, I. galbana, and C. curvisetus), and barnacle larvae were studied. Moreover, marine field tests on the BIT modified resin in coastal waters were conducted. The results demonstrate that the grafted BIT–zinc acrylate resin not only exhibits excellent antifouling properties but also a significant self-polishing performance, providing a novel strategy to design a long-term antifouling resin with stable antifoulant release.
Isorhodopsin: An Undervalued Visual Pigment Analog
Authors: de Grip Willem J. , Lugtenburg Johan
Published: June 2022

Rhodopsin, the first visual pigment identified in the animal retina, was shown to be a photosensitive membrane protein containing covalently bound retinal in the 11-cis configuration, as a chromophore. Upon photoexcitation the chromophore isomerizes in femtoseconds to all-trans, which drives the protein into the active state. Soon thereafter, another geometric isomer—9-cis retinal—was also shown to stably incorporate into the binding pocket, generating a slightly blue-shifted photosensitive protein. This pigment, coined isorhodopsin, was less photosensitive, but could also reach the active state. However, 9-cis retinal was not detected as a chromophore in any of the many animal visual pigments studied, and isorhodopsin was passed over as an exotic and little-relevant rhodopsin analog. Consequently, few in-depth studies of its photochemistry and activation mechanism have been performed. In this review, we aim to illustrate that it is unfortunate that isorhodopsin has received little attention in the visual research and literature. Elementary differences in photoexcitation of rhodopsin and isorhodopsin have already been reported. Further in-depth studies of the photochemical properties and pathways of isorhodopsin would be quite enlightening for the initial steps in vision, as well as being beneficial for biotechnological applications of retinal proteins.
An Improved Homogeneous Ensemble Technique for Early Accurate Detection of Type 2 Diabetes Mellitus (T2DM)
Authors: Faustin Umuhire Mucyo , Zou Beiji
Published: June 2022

The objective of the present study is to improve the genetic algorithm (GA) supremacy in selecting the most suitable and relevant features within a highly dimensional dataset. This results in cost reduction and improving classification performance. During text classification, employing terms such as features using vector space representation can result in a high dimensionality of future space. This condition presents some issues, including high computation cost in data analysis and deteriorating classification accuracy performance. Several computational feature selection techniques can be applied in eliminating the least significant features within a dataset, including a genetic algorithm. The present study improved the performance of the classifier in classifying Pima Indian diabetes data. Despite the popularity of GA in the feature selection area, it does not provide the most optimal features due to one of its underlying issues: premature convergence due to insufficient population diversity in the future generations. GA was improved in its crossover operator using two steps: define a variable slice point on the size of the gene to be interchanged for every offspring generation and apply feature frequency scores in deciding the interchanging of genes. The above obtained results to the proposed technique will be better results than the results for standard GA. Our proposed algorithm attained an accuracy of 97.5%, precision of 98, recall of 97% and F1-score of 97%.
Multiscale Price Lead-Lag Relationship between Steel Materials and Industry Chain Products Based on Network Analysis
Authors: Guo Sui , Wang Ze , Zhou Xing , Wang Yanan
Published: June 2022

As two main steelmaking materials, iron ore and scrap steel have different price lead-lag relationships (PLRs) on midstream and downstream steel products in China. The relationships also differ as the time scale varies. In this study, we compare the price influences of two important steel materials on midstream and downstream steel products at different time scales. First, we utilize the maximal overlap discrete wavelet transform (MODWT) method to decompose the original steel materials and products price series into short-term, midterm, and long-term time scale series. Then, we introduce the cross-correlation and Podobnik test method to calculate and test the price lead-lag relationships (PLRs) between two steel materials and 16 steel products. Finally, we construct 12 price lead-lag relationship networks and choose network indicators to present the price influence of the two materials at different time scales. We find that first, most scrap steel and steel products prices fluctuate at the same time lag order, while iron ore leads most steel products price for one day. Second, products that exist in the downstream industry chain usually lead to iron ore. Third, as the time scale becomes longer, the lead relationships from steel materials to steel products become closer.
An Improvement to Conformer-Based Model for High-Accuracy Speech Feature Extraction and Learning
Authors: Liu Mengzhuo , Wei Yangjie
Published: June 2022

Owing to the loss of effective information and incomplete feature extraction caused by the convolution and pooling operations in a convolution subsampling network, the accuracy and speed of current speech processing architectures based on the conformer model are influenced because the shallow features of speech signals are not completely extracted. To solve these problems, in this study, we researched a method that used a capsule network to improve the accuracy of feature extraction in a conformer-based model, and then, we proposed a new end-to-end model architecture for speech recognition. First, to improve the accuracy of speech feature extraction, a capsule network with a dynamic routing mechanism was introduced into the conformer model; thus, the structural information in speech was preserved, and it was input to the conformer blocks via sequestered vectors; the learning ability of the conformed-based model was significantly enhanced using dynamic weight updating. Second, a residual network was added to the capsule blocks, thus, the mapping ability of our model was improved and the training difficulty was reduced. Furthermore, the bi-transformer model was adopted in the decoding network to promote the consistency of the hypotheses in different directions through bidirectional modeling. Finally, the effectiveness and robustness of the proposed model were verified against different types of recognition models by performing multiple sets of experiments. The experimental results demonstrated that our speech recognition model achieved a lower word error rate without a language model because of the higher accuracy of speech feature extraction and learning using our model architecture with a capsule network. Furthermore, our model architecture benefited from the advantage of the capsule network and the conformer encoder, and also has potential for other speech-related applications.
New Development in Quadratic L2 Performance of Switched Uncertain Stochastic Systems
Authors: Chang Yufang , Zhai Guisheng , Xiong Lianglin , Fu Bo
Published: June 2022

Global quadratic stability and L2 performance in probability (quadratic stability and L2 gain γ in probability: abbreviated as GQL2(γ)-P) is studied for switched systems consisting of linear stochastic subsystems with norm-bounded uncertainties. Under the assumption that there is no single subsystem achieving GQL2(γ)-P, it is shown that if there exists a convex combination of subsystems achieving GQL2(γ)-P, then a state-dependent switching law, based on the convex combination of subsystems, is proposed under which the switched system achieves GQL2(γ)-P. Then, the discussion is extended to the case involving state feedback controller gain. A numerical example and the application to DC–DC boost converters are provided to demonstrate the proposed design condition and the algorithm.
Multiple Ocular Disease Diagnosis Using Fundus Images Based on Multi-Label Deep Learning Classification
Authors: Ouda Osama , AbdelMaksoud Eman , Abd El-Aziz A. A. , Elmogy Mohammed
Published: June 2022

Designing computer-aided diagnosis (CAD) systems that can automatically detect ocular diseases (ODs) has become an active research field in the health domain. Although the human eye might have more than one OD simultaneously, most existing systems are designed to detect specific eye diseases. Therefore, it is crucial to develop new CAD systems that can detect multiple ODs simultaneously. This paper presents a novel multi-label convolutional neural network (ML-CNN) system based on ML classification (MLC) to diagnose various ODs from color fundus images. The proposed ML-CNN-based system consists of three main phases: the preprocessing phase, which includes normalization and augmentation using several transformation processes, the modeling phase, and the prediction phase. The proposed ML-CNN consists of three convolution (CONV) layers and one max pooling (MP) layer. Then, two CONV layers are performed, followed by one MP and dropout (DO). After that, one flatten layer is performed, followed by one fully connected (FC) layer. We added another DO once again, and finally, one FC layer with 45 nodes is performed. The system outputs the probabilities of all 45 diseases in each image. We validated the model by using cross-validation (CV) and measured the performance by five different metrics: accuracy (ACC), recall, precision, Dice similarity coefficient (DSC), and area under the curve (AUC). The results are 94.3%, 80%, 91.5%, 99%, and 96.7%, respectively. The comparisons with the existing built-in models, such as MobileNetV2, DenseNet201, SeResNext50, InceptionV3, and InceptionresNetv2, demonstrate the superiority of the proposed ML-CNN model.
Bibliometric Studies on Renewable Energy—Poland Compared to Other EU Countries
Authors: Brzozowska-Rup Katarzyna , Nowakowska Marzena
Published: June 2022

The necessity to use renewable energy sources (RES), especially in EU countries, is becoming more and more urgent in the face of environmental degradation. It is reflected not only in technological solutions for obtaining energy from renewable sources, but also in scientific research supporting RES technology development. There are an increasing number of papers on renewable energy. The aim of the study was to compare research areas concerning renewable energy in Poland and other EU countries by analyzing scientific works. A selected collection of publications available in the Scopus scientific databases was selected as the subject of the study. After cleaning the data and elaborating the thesaurus, the analysis of the article content was conducted applying text processing methods. Conceptual maps of keywords and keyword co-occurrences were created, which enables arranging and classifying knowledge from the subject area. Research hotspots and the directions of science development in the field of renewable energy were identified. The computer program VOSviewer was used in the investigation. Lorenz curves and Gini coefficients were used to identify quite a strong concentration of RES articles in leading journals on the publication market.