bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed Administration of Angiotensin Receptor (AT2R) Agonist C21 Improves Survival and Preserves Sensorimotor Outcomes in Female Diabetic Rats Post-Stroke through Modulation of Microglial Activation
Authors: Jackson-Cowan LaDonya , Eldahshan Wael , Dumanli Selin , Dong Guangkuo , Jamil Sarah , Abdul Yasir , Althomali Waleed , Baban Babak , Fagan Susan C. , Ergul Adviye
Published: January 2021

About 70% of stroke victims present with comorbid diseases such as diabetes and hypertension. The integration of comorbidities in pre-clinical experimental design is important in understanding the mechanisms involved in the development of stroke injury and recovery. We recently showed that administration of compound C21, an angiotensin II type 2 receptor agonist, at day 3 post-stroke improved sensorimotor outcomes by lowering neuroinflammation in diabetic male animals. In the current study, we hypothesized that a delayed administration of C21 would also lower chronic inflammation post-stroke in diabetic female animals. Young female diabetic rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Three days post-stroke, rats were administered C21 or vehicle in drinking water at a dose of 0.12 mg/kg/day for 4 weeks. The impact of C21 on microglial polarization was analyzed by flow cytometry in vivo and in vitro. Compound 21 treatment improved fine motor skills after MCAO through modulation of the microglia/macrophage inflammatory properties. In addition, C21 increased M2 polarization and reduced the M1:M2 ratio in vitro. In conclusion, delayed administration of C21 downregulates post-stroke inflammation in female diabetic animals. C21 may be a useful therapeutic option to lower neuro-inflammation and improve the post-stroke recovery in diabetes.
Regulation of Seed Dormancy and Germination Mechanisms in a Changing Environment
Authors: Klupczyńska Ewelina A. , Pawłowski Tomasz A.
Published: January 2021

Environmental conditions are the basis of plant reproduction and are the critical factors controlling seed dormancy and germination. Global climate change is currently affecting environmental conditions and changing the reproduction of plants from seeds. Disturbances in germination will cause disturbances in the diversity of plant communities. Models developed for climate change scenarios show that some species will face a significant decrease in suitable habitat area. Dormancy is an adaptive mechanism that affects the probability of survival of a species. The ability of seeds of many plant species to survive until dormancy recedes and meet the requirements for germination is an adaptive strategy that can act as a buffer against the negative effects of environmental heterogeneity. The influence of temperature and humidity on seed dormancy status underlines the need to understand how changing environmental conditions will affect seed germination patterns. Knowledge of these processes is important for understanding plant evolution and adaptation to changes in the habitat. The network of genes controlling seed dormancy under the influence of environmental conditions is not fully characterized. Integrating research techniques from different disciplines of biology could aid understanding of the mechanisms of the processes controlling seed germination. Transcriptomics, proteomics, epigenetics, and other fields provide researchers with new opportunities to understand the many processes of plant life. This paper focuses on presenting the adaptation mechanism of seed dormancy and germination to the various environments, with emphasis on their prospective roles in adaptation to the changing climate.
Conformational Ensembles by NMR and MD Simulations in Model Heptapeptides with Select Tri-Peptide Motifs
Authors: Krishnan V. V. , Bentley Timothy , Xiong Alina , Maitra Kalyani
Published: January 2021

Both nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulations are routinely used in understanding the conformational space sampled by peptides in the solution state. To investigate the role of single-residue change in the ensemble of conformations sampled by a set of heptapeptides, AEVXEVG with X = L, F, A, or G, comprehensive NMR, and MD simulations were performed. The rationale for selecting the particular model peptides is based on the high variability in the occurrence of tri-peptide E*L between the transmembrane β-barrel (TMB) than in globular proteins. The ensemble of conformations sampled by E*L was compared between the three sets of ensembles derived from NMR spectroscopy, MD simulations with explicit solvent, and the random coil conformations. In addition to the estimation of global determinants such as the radius of gyration of a large sample of structures, the ensembles were analyzed using principal component analysis (PCA). In general, the results suggest that the -EVL- peptide indeed adopts a conformational preference that is distinctly different not only from a random distribution but also from other peptides studied here. The relatively straightforward approach presented herein could help understand the conformational preferences of small peptides in the solution state.
How Enzymes, Proteins, and Antibodies Recognize Extended DNAs; General Regularities
Authors: Nevinsky Georgy A.
Published: January 2021

X-ray analysis cannot provide quantitative estimates of the relative contribution of non-specific, specific, strong, and weak contacts of extended DNA molecules to their total affinity for enzymes and proteins. The interaction of different enzymes and proteins with long DNA and RNA at the quantitative molecular level can be successfully analyzed using the method of the stepwise increase in ligand complexity (SILC). The present review summarizes the data on stepwise increase in ligand complexity (SILC) analysis of nucleic acid recognition by various enzymes—replication, restriction, integration, topoisomerization, six different repair enzymes (uracil DNA glycosylase, Fpg protein from Escherichia coli, human 8-oxoguanine-DNA glycosylase, human apurinic/apyrimidinic endonuclease, RecA protein, and DNA-ligase), and five DNA-recognizing proteins (RNA helicase, human lactoferrin, alfa-lactalbumin, human blood albumin, and IgGs against DNA). The relative contributions of structural elements of DNA fragments “covered” by globules of enzymes and proteins to the total affinity of DNA have been evaluated. Thermodynamic and catalytic factors providing discrimination of unspecific and specific DNAs by these enzymes on the stages of primary complex formation following changes in enzymes and DNAs or RNAs conformations and direct processing of the catalysis of the reactions were found. General regularities of recognition of nucleic acid by DNA-dependent enzymes, proteins, and antibodies were established.
Ovarian Aging: Molecular Mechanisms and Medical Management
Authors: Tesarik Jan , Galán-Lázaro Maribel , Mendoza-Tesarik Raquel
Published: January 2021

This is a short review of the basic molecular mechanisms of ovarian aging, written with a particular focus on the use of this data to improve the diagnostic and therapeutic protocols both for women affected by physiological (age-related) ovarian decay and for those suffering premature ovarian insufficiency. Ovarian aging has a genetic basis that conditions the ovarian activity via a plethora of cell-signaling pathways that control the functions of different types of cells in the ovary. There are various factors that can influence these pathways so as to reduce their efficiency. Oxidative stress, often related to mitochondrial dysfunction, leading to the apoptosis of ovarian cells, can be at the origin of vicious circles in which the primary cause feeds back other abnormalities, resulting in an overall decline in the ovarian activity and in the quantity and quality of oocytes. The correct diagnosis of the molecular mechanisms involved in ovarian aging can serve to design treatment strategies that can slow down ovarian decay and increase the quantity and quality of oocytes that can be obtained for an in vitro fertilization attempt. The available treatment options include the use of antioxidants, melatonin, growth hormones, and mitochondrial therapies. All of these treatments have to be considered in the context of each couple’s history and current clinical condition, and a customized (patient-tailored) treatment protocol is to be elaborated.
Density Functional Theory-Based Calculation Shed New Light on the Bizarre Addition of Cysteine Thiol to Dopaquinone
Authors: Kishida Ryo , Ito Shosuke , Sugumaran Manickam , Arevalo Ryan Lacdao , Nakanishi Hiroshi , Kasai Hideaki
Published: January 2021

Two types of melanin pigments, brown to black eumelanin and yellow to reddish brown pheomelanin, are biosynthesized through a branched reaction, which is associated with the key intermediate dopaquinone (DQ). In the presence of l-cysteine, DQ immediately binds to the –SH group, resulting in the formation of cysteinyldopa necessary for the pheomelanin production. l-Cysteine prefers to bond with aromatic carbons adjacent to the carbonyl groups, namely C5 and C2. Surprisingly, this Michael addition takes place at 1,6-position of the C5 (and to some extent at C2) rather than usually expected 1,4-position. Such an anomaly on the reactivity necessitates an atomic-scale understanding of the binding mechanism. Using density functional theory-based calculations, we investigated the binding of l-cysteine thiolate (Cys–S−) to DQ. Interestingly, the C2–S bonded intermediate was less energetically stable than the C6–S bonded case. Furthermore, the most preferred Cys–S−-attacked intermediate is at the carbon-carbon bridge between the two carbonyls (C3–C4 bridge site) but not on the C5 site. This structure allows the Cys–S− to migrate onto the adjacent C5 or C2 with small activation energies. Further simulation demonstrated a possible conversion pathway of the C5–S (and C2–S) intermediate into 5-S-cysteinyldopa (and 2-S-cysteinyldopa), which is the experimentally identified major (and minor) product. Based on the results, we propose that the binding of Cys–S− to DQ proceeds via the following path: (i) coordination of Cys–S− to C3–C4 bridge, (ii) migration of Cys–S− to C5 (C2), (iii) proton rearrangement from cysteinyl –NH3+ to O4 (O3), and (iv) proton rearrangement from C5 (C2) to O3 (O4).
Salivary Immunoglobulin Gamma-3 Chain C Is a Promising Noninvasive Biomarker for Systemic Lupus Erythematosus
Authors: Jung Ju-Yang , Nam Jin-Young , Ryu Keun-Sil , Son In-Ok , Shin Joo-Ho , Baek Wook-Young , Kim Hyoun-Ah , Suh Chang-Hee
Published: January 2021

We aimed to characterize the salivary protein components and identify biomarkers in patients with systemic lupus erythematosus (SLE). A proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry was performed to determine the alterations of salivary proteins between patients with SLE and healthy controls, and the concentrations of the candidate proteins were measured through Western blot analysis and the enzyme-linked immunosorbent assay. The 10 differentially expressed protein spots were immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region, protein S100A8, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels compared to patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively; p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively; p < 0.001 for both). The salivary IGHG3 levels correlated with the erythrocyte sedimentation rate (r = 0.26, p = 0.01), anti-double-stranded DNA (dsDNA) antibody levels (r = 0.25, p = 0.01), and nephritis (r = 0.28, p = 0.01). The proteomic analysis revealed that the salivary IGHG3 levels were associated with SLE and lupus disease activity, suggesting that salivary IGHG3 may be a promising noninvasive biomarker for SLE.
Late Pleistocene Boulder Slumps Eroded from a Basalt Shoreline at El Confital Beach on Gran Canaria (Canary Islands, Spain)
Authors: Galindo Inés , Johnson Markes E. , Martín-González Esther , Romero Carmen , Vegas Juana , Melo Carlos S. , Ávila Sérgio P. , Sánchez Nieves
Published: January 2021

This study examines the role of North Atlantic storms degrading a Late Pleistocene rocky shoreline formed by basaltic rocks overlying hyaloclastite rocks on a small volcanic peninsula connected to Gran Canaria in the central region of the Canary Archipelago. A conglomerate dominated by large, ellipsoidal to angular boulders eroded from an adjacent basalt flow was canvassed at six stations distributed along 800 m of the modern shore at El Confital, on the outskirts of Las Palmas de Gran Canaria. A total of 166 individual basalt cobbles and boulders were systematically measured in three dimensions, providing the database for analyses of variations in clast shape and size. The goal of this study was to apply mathematical equations elaborated after Nott (2003) and subsequent refinements in order to estimate individual wave heights necessary to lift basalt blocks from the layered and joint-bound sea cliffs at El Confital. On average, wave heights in the order of 4.2 to 4.5 m are calculated as having impacted the Late Pleistocene rocky coastline at El Confital, although the largest boulders in excess of 2 m in diameter would have required larger waves for extraction. A review of the fossil marine biota associated with the boulder beds confirms a littoral to very shallow water setting correlated in time with Marine Isotope Stage 5e (Eemian Stage) approximately 125,000 years ago. The historical record of major storms in the regions of the Canary and Azorean islands indicates that events of hurricane strength were likely to have struck El Confital in earlier times. Due to its high scientific value, the outcrop area featured in this study is included in the Spanish Inventory of Geosites and must be properly protected and managed to ensure conservation against the impact of climate change foreseen in coming years.
Prediction of Loss of Position during Dynamic Positioning Drilling Operations Using Binary Logistic Regression Modeling
Authors: Sanchez-Varela Zaloa , Boullosa-Falces David , Larrabe Barrena Juan Luis , Gomez-Solaeche Miguel A.
Published: January 2021

The prediction of loss of position in the offshore industry would allow optimization of dynamic positioning drilling operations, reducing the number and severity of potential accidents. In this paper, the probability of an excursion is determined by developing binary logistic regression models based on a database of 42 incidents which took place between 2011 and 2015. For each case, variables describing the configuration of the dynamic positioning system, weather conditions, and water depth are considered. We demonstrate that loss of position is significantly more likely to occur when there is a higher usage of generators, and the drilling takes place in shallower waters along with adverse weather conditions; this model has very good results when applied to the sample. The same method is then applied for obtaining a binary regression model for incidents not attributable to human error, showing that it is a function of the percentage of generators in use, wind force, and wave height. Applying these results to the risk management of drilling operations may help focus our attention on the factors that most strongly affect loss of position, thereby improving safety during these operations.
Hydrodynamic Model of Diver–DPV Coupled Multi-Body and Its Underwater Cruising Numerical Simulation
Authors: Li Hansheng , Han Fenglei , Zhu Haitao , Zhang Jiawei , Zhang Weipeng , Wu Yuliang
Published: January 2021

Diver propulsion vehicles (hereinafter referred to as DPV) are a kind of small vehicle with underwater high-speed used by divers, who are able to grasp or ride on, and operate the volume switch to change the speed. Different from unmanned underwater vehicles (UUVs), the interference caused by diver’s posture changing is a unique problem. In this paper, a Diver–DPV multi-body coupling hydrodynamic model considering rigid body dynamics and fluid disturbance is established by analyzing the existing DPV related equipment. The numerical simulation of multi-body articulated motion is realized by using Star-CCM+ overlapping grid and DFBI 6-DOF body motion method. Five cases of DPVs underwater cruising in a straight-line when restraining diver movement is simulated, and five cases with free diver movement are simulated too. Finally, the influence of the diver’s posture changing on the cruising speed resistance is analyzed, and the motion equation including the disturbance is solved. The final conclusion is that, the disturbance is favorable at high speed, which can reduce the cruising resistance, and unfavorable at low speed, which increases the cruising resistance. The friction resistance Ff always accounts for the main part in all speed cases.
In Vitro Comparison between Metal Sleeve-Free and Metal Sleeve-Incorporated 3D-Printed Computer-Assisted Implant Surgical Guides
Authors: Oh Kyung Chul , Shim June-Sung , Park Ji-Man
Published: January 2021

The present study aims to compare the accuracy of metal sleeve-free 3D-printed computer-assisted implant surgical guides (MSF group) (n = 10) with metal sleeve-incorporated 3D-printed computer-assisted implant surgical guides (MSI group) (n = 10). Implants of diameter 4.0 mm and 5.0 mm were placed in the left second premolars and bilateral first molars, respectively, using a fully guided system. Closed-form sleeves were used in teeth on the left and open-form sleeves on the right. The weight differences of the surgical guides before and after implant placement, and angular deviations before and after implant placement were measured. Weight differences were compared with Student’s t-tests and angular deviations with Mann–Whitney tests. Cross-sectional views of the insert parts were observed with a scanning electron microscope. Preoperative and postoperative weight differences between the two groups were not statistically significant (p = 0.821). In terms of angular deviations, those along the mesiodistal direction for the left second premolars were significantly lower in the MSF group (p = 0.006). However, those along the mesiodistal direction for the bilateral molars and those along the buccolingual direction for all teeth were not significantly different (p > 0.05). 3D-printed implant surgical guides without metal sleeve inserts enable accurate implant placement without exhausting the guide holes, rendering them feasible for fully guided implant placement.
Graphene Quantum Dots as Intracellular Imaging-Based Temperature Sensors
Authors: Lee Bong Han , McKinney Ryan Lee , Hasan Md. Tanvir , Naumov Anton V.
Published: January 2021

Non-invasive temperature sensing is necessary to analyze biological processes occurring in the human body, including cellular enzyme activity, protein expression, and ion regulation. To probe temperature-sensitive processes at the nanoscale, novel luminescence nanothermometers are developed based on graphene quantum dots (GQDs) synthesized via top-down (RGQDs) and bottom-up (N-GQDs) approaches from reduced graphene oxide and glucosamine precursors, respectively. Because of their small 3–6 nm size, non-invasive optical sensitivity to temperature change, and high biocompatibility, GQDs enable biologically safe sub-cellular resolution sensing. Both GQD types exhibit temperature-sensitive yet photostable fluorescence in the visible and near-infrared for RGQDs, utilized as a sensing mechanism in this work. Distinctive linear and reversible fluorescence quenching by up to 19.3% is observed for the visible and near-infrared GQD emission in aqueous suspension from 25 °C to 49 °C. A more pronounced trend is observed with GQD nanothermometers internalized into the cytoplasm of HeLa cells as they are tested in vitro from 25 °C to 45 °C with over 40% quenching response. Our findings suggest that the temperature-dependent fluorescence quenching of bottom-up and top-down-synthesized GQDs studied in this work can serve as non-invasive reversible/photostable deterministic mechanisms for temperature sensing in microscopic sub-cellular biological environments.
Refractory CrMoNbWV High-Entropy Alloy Manufactured by Mechanical Alloying and Spark Plasma Sintering: Evolution of Microstructure and Properties
Authors: Razumov Nikolay , Makhmutov Tagir , Kim Artem , Shemyakinsky Boris , Shakhmatov Aleksey , Popovich Vera , Popovich Anatoly
Published: January 2021

In this study, bulk samples of a CrMoNbWV high-entropy alloy (HEA) were obtained for the first time by spark plasma sintering (SPS) of mechanically alloyed (MA) powders at 1200 °C, 1300 °C, and 1400 °C. Microstructure evolution, phase formation as well as wear and corrosion behavior were investigated. The MA powders’ phase composition was found to be represented by body-centered-cubic (BCC) solid solution. The solid solution partially decomposed to Laves phases under the sintering, such as Cr2Nb and (Fe, Cr)Nb, and NbVO4-VO oxides mixture. The temperature increase to 1400 °C led to a grain coarsening of the BCC phase and decreased the Laves phase content accompanied by precipitation at the grain boundaries. The sintered samples showed high hardness and compressive strength (2700–2800 MPa) at room temperature. The wear tests demonstrated excellent results in comparison to conventional wear-resistant composites. The obtained samples also exhibited high corrosion resistance under electrochemical tests in H2SO4 solution. The CrMoNbWV HEA has comparable mechanical and corrosive properties with the WNbMoTaV type HEA, but at the same time has a reduced density: CrMoNbWV—10.55 g/cm3, WNbMoTaV—12.42 g/cm3.
Design of Concrete Mix Proportion Based on Particle Packing Voidage and Test Research on Compressive Strength and Elastic Modulus of Concrete
Authors: Cheng Yun-Hong , Zhu Bao-Long , Yang Si-Hui , Tong Bai-Qiang
Published: January 2021

According to the basic principle of dense packing of particles, and considering the interaction between particles, a dense packing model of granular materials in concrete was proposed. During the establishment of this model, binary particle packing tests of crushed stone and sand were carried out. The fitting analysis of the test results determines the relationship between the particle size ratio and the remaining volume fraction of the particle packing, and then the actual void fraction of the particle packing was obtained, based on which the water–binder ratio was combined to determine the amount of various materials in the concrete. The proposed concrete mix design method was used to prepare concrete, and its compressive strength and elastic modulus were tested experimentally. The test results show that the aggregate volume fraction of the prepared concrete increased, and the workability of the concrete mixture with the appropriate amount of water reducing agent meets the design requirements. When the water–binder ratio was 0.42, 0.47, or 0.52, the compressive strength of the concrete increased compared with the control concrete, and the degree of improvement in compressive strength increased with the decrease in water–binder ratio; when the water-binder ratio was 0.42, 0.47, or 0.52, the static elastic modulus of the concrete increased compared with the control concrete, and the degree of improvement in elastic modulus also increased with the decrease in water–binder ratio. The elastic modulus and compressive strength of the prepared concrete have a positive correlation. Findings show that the concrete mix design method proposed by this research is feasible and advanced in a sense.
Effect of Froude Number on Submerged Gas Blowing Characteristics
Authors: Svantesson Jonas , Ersson Mikael , Jönsson Pär
Published: January 2021

The flow behavior of gas in compressible and incompressible systems was investigated at an ambient temperature in an air–water system and at an operating process temperature in the IronArc system, using computational fluid dynamics. The simulation results were verified by experiments in the air–water system and established empirical equations to enable reliable predictions of the penetration length. The simulations in the air–water system were found to replicate the experimental behavior using both the incompressible and compressible models, with only small deviations of 7–8%. A lower requirement for the modified Froude number of the gas blowing to produce a jetting behavior was also found. For gas blowing below the required modified Froude number, the results illustrate that the gas will form large pulsating bubbles instead of a steady jet, which causes the empirical equation calculations to severely underpredict the penetration length. The lower modified Froude number limit was also found to be system dependent and to have an approximate value of 300 for the studied IronArc system. For submerged blowing applications, it was found that it is important to ensure sufficiently high modified Froude numbers of the gas blowing. Then, the gas penetration length will remain stable as a jet and it will be possible to predict the values using empirical equations.
Comparison of Structure and Adsorption Properties of Mesoporous Silica Functionalized with Aminopropyl Groups by the Co-Condensation and the Post Grafting Methods
Authors: Putz Ana-Maria , Ciopec Mihaela , Negrea Adina , Grad Oana , Ianăşi Cătălin , Ivankov Oleksandr I. , Milanović Marija , Stijepović Ivan , Almásy László
Published: January 2021

The adsorptive potential has been evaluated for the aminopropyl functionalized mesoporous silica materials obtained by co-condensation and post grafting methods. Nitrogen sorption, small angle neutron and X-ray scattering (SANS and SAXS) demonstrated high surface area and well-ordered hexagonal pore structure suitable for applications as adsorbents of metals from waste waters. A comparison of Cr(VI) adsorption properties of the materials prepared by different functionalization methods has been performed. The obtained results demonstrated the adsorption capacity due to the affinity of the chromium ions to the amino groups, and showed that co-condensation of tetraethoxysilane (TEOS) and 3-aminopropyl triethoxysilane (APTES) resulted in higher metal sorption capacity of the materials compared to post-synthesis grafting of aminopropyl groups onto the mesoporous silica particles.
Environmental Impact of Geosynthetics in Coastal Protection
Authors: Scholz Philipp , Putna-Nimane Ieva , Barda Ieva , Liepina-Leimane Ineta , Strode Evita , Kileso Alexandr , Esiukova Elena , Chubarenko Boris , Purina Ingrida , Simon Franz-Georg
Published: January 2021

Geosynthetic materials are applied in measures for coastal protection. Weathering or any damage of constructions, as shown by a field study in Kaliningrad Oblast (Russia), could lead to the littering of the beach or the sea (marine littering) and the discharge of possibly harmful additives into the marine environment. The ageing behavior of a widely used geotextile made of polypropylene was studied by artificial accelerated ageing in water-filled autoclaves at temperatures of 30 to 80 °C and pressures of 10 to 50 bar. Tensile strength tests were used to evaluate the progress of ageing, concluding that temperature rather than pressure was the main factor influencing the ageing of geotextiles. Using a modified Arrhenius equation, it was possible to calculate the half-life for the loss of 50% of the strain, which corresponds to approximately 330 years. Dynamic surface leaching and ecotoxicological tests were performed to determine the possible release of contaminants. No harmful effects on the test organisms were observed.
On a Class of Differential Variational Inequalities in Infinite-Dimensional Spaces
Authors: Treanţă Savin
Published: January 2021

A new class of differential variational inequalities (DVIs), governed by a variational inequality and an evolution equation formulated in infinite-dimensional spaces, is investigated in this paper. More precisely, based on Browder’s result, optimal control theory, measurability of set-valued mappings and the theory of semigroups, we establish that the solution set of DVI is nonempty and compact. In addition, the theoretical developments are accompanied by an application to differential Nash games.
Characterization of Probability Distributions via Functional Equations of Power-Mixture Type
Authors: Hu Chin-Yuan , Lin Gwo Dong , Stoyanov Jordan M.
Published: January 2021

We study power-mixture type functional equations in terms of Laplace–Stieltjes transforms of probability distributions on the right half-line [0,∞). These equations arise when studying distributional equations of the type Z=dX+TZ, where the random variable T≥0 has known distribution, while the distribution of the random variable Z≥0 is a transformation of that of X≥0, and we want to find the distribution of X. We provide necessary and sufficient conditions for such functional equations to have unique solutions. The uniqueness is equivalent to a characterization property of a probability distribution. We present results that are either new or extend and improve previous results about functional equations of compound-exponential and compound-Poisson types. In particular, we give another affirmative answer to a question posed by J. Pitman and M. Yor in 2003. We provide explicit illustrative examples and deal with related topics.
Dietary Chitosan Nanoparticles: Potential Role in Modulation of Rainbow Trout (Oncorhynchus mykiss) Antibacterial Defense and Intestinal Immunity against Enteric Redmouth Disease
Authors: Ahmed Fatma , Soliman Faiza M. , Adly Mohamed A. , Soliman Hamdy A. M. , El-Matbouli Mansour , Saleh Mona
Published: January 2021

Bio-nanotechnology employing bio-sourced nanomaterial is an emerging avenue serving the field of fish medicine. Marine-sourced chitosan nanoparticles (CSNPs) is a well-known antimicrobial and immunomodulatory reagent with low or no harm side effects on fish or their human consumers. In this study, in vitro skin mucus and serum antibacterial activity assays along with intestinal histology, histochemical, and gene expression analyses were performed to evaluate the impact of dietary CSNPs (5 g kg−1 dry feed) on rainbow trout resistance against ‘enteric redmouth’ disease. Two treatment conditions were included; short-term prophylactic-regimen for 21 days before the bacterial challenge, and long-term therapeutic-regimen for 21 days before the challenge and extended for 28 days after the challenge. Our results revealed higher antibacterial defense ability and positive intestinal histochemical and molecular traits of rainbow trout after dietary CSNPs. The prophylactic-regimen improved trout health while the therapeutic regimen improved their disease resistance and lowered their morbidity. Therefore, it is anticipated that CSNPs is an effective antibacterial and immunomodulatory fish feed supplement against the infectious threats. However, the CSNPs seem to be more effective in the therapeutic application rather than being used for short-term prophylactic applications.
Acute Clinical Syndromes and Suspicion of SARS-CoV-2 Infection: The Experience of a Single Romanian Center in the Early Pandemic Period
Authors: Haliga Raluca Ecaterina , Sorodoc Victorita , Lionte Catalina , Petris Ovidiu Rusalim , Bologa Cristina , Coman Adorata Elena , Vata Luminita Gina , Puha Gabriela , Dumitrescu Gabriela , Sirbu Oana , Stoica Alexandra , Ceasovschih Alexandr , Constantin Mihai , Nicoleta Catana Andreea , Jaba Elisabeta , Sorodoc Laurentiu
Published: January 2021

Background and Objectives: During the coronavirus disease 2019 (COVID-19) pandemic, patients with chronic diseases suffering exacerbations have required acute medical care. The purpose of our study was to determine useful criteria for the differentiation of patients with acute clinical syndromes and suspicion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Materials and Methods: This was an observational retrospective study, conducted in an internal medicine clinic from April to May 2020. We collected clinical, biological, and computed tomography (CT) data on patients with exacerbations of chronic diseases and clinical suspicion of SARS-CoV-2 infection. Patients with an already-positive real-time reverse-transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 on presentation at the emergency department were excluded from our study. Results: Of 253 suspected cases, 20 were laboratory-confirmed as having SARS-CoV-2 infection by RT-PCR, whereas COVID-19 diagnosis was ruled out in the remaining 233. Venous thromboembolism (VTE) correlated significantly with COVID-19 diagnosis in suspected patients, while laboratory markers were not significantly different between the two groups. Of the suspected patients, significantly higher percentages of dry cough, fever, myalgias, sore throat, loss of smell and appetite, and ground-glass opacities (GGOs) on CT were found in SARS-CoV-2-positive individuals. Conclusions: The study demonstrated that, until receiving the result of an RT-PCR test for SARS-CoV-2 (usually 12–24 h), association with VTE as a comorbidity, fever, dry cough, and myalgia as clinical features, and GGO on CT are the main markers for the identification of COVID-19 patients among those suspected with acute clinical syndromes. Our results also provide evidence for doctors not to rely solely on biological markers in the case of suspected SARS-CoV-2 infection in patients with exacerbations of chronic diseases. These data are useful for faster decision-making with regard to suspected COVID-19 patients before receiving RT-PCR test results, thus avoiding keeping patients in crowded emergency departments.
Potential Whole-Cell Biosensors for Detection of Metal Using MerR Family Proteins from Enterobacter sp. YSU and Stenotrophomonas maltophilia OR02
Authors: Baya Georgina , Muhindi Stephen , Ngendahimana Valentine , Caguiat Jonathan
Published: January 2021

Cell-based biosensors harness a cell’s ability to respond to the environment by repurposing its sensing mechanisms. MerR family proteins are activator/repressor switches that regulate the expression of bacterial metal resistance genes and have been used in metal biosensors. Upon metal binding, a conformational change switches gene expression from off to on. The genomes of the multimetal resistant bacterial strains, Stenotrophomonas maltophilia Oak Ridge strain 02 (S. maltophilia 02) and Enterobacter sp. YSU, were recently sequenced. Sequence analysis and gene cloning identified three mercury resistance operons and three MerR switches in these strains. Transposon mutagenesis and sequence analysis identified Enterobacter sp. YSU zinc and copper resistance operons, which appear to be regulated by the protein switches, ZntR and CueR, respectively. Sequence analysis and reverse transcriptase polymerase chain reaction (RT-PCR) showed that a CueR switch appears to activate a S. maltophilia 02 copper transport gene in the presence of CuSO4 and HAuCl4·3H2O. In previous studies, genetic engineering replaced metal resistance genes with the reporter genes for β-galactosidase, luciferase or the green fluorescence protein (GFP). These produce a color change of a reagent, produce light, or fluoresce in the presence of ultraviolet (UV) light, respectively. Coupling these discovered operons with reporter genes has the potential to create whole-cell biosensors for HgCl2, ZnCl2, CuSO4 and HAuCl4·3H2O.
Temperature Characteristics of a Contour Mode MEMS AlN Piezoelectric Ring Resonator on SOI Substrate
Authors: Fei Sitao , Ren Hao
Published: January 2021

As a result of their IC compatibility, high acoustic velocity, and high thermal conductivity, aluminum nitride (AlN) resonators have been studied extensively over the past two decades, and widely implemented for radio frequency (RF) and sensing applications. However, the temperature coefficient of frequency (TCF) of AlN is −25 ppm/°C, which is high and limits its RF and sensing application. In contrast, the TCF of heavily doped silicon is significantly lower than the TCF of AlN. As a result, this study uses an AlN contour mode ring type resonator with heavily doped silicon as its bottom electrode in order to reduce the TCF of an AlN resonator. A simple microfabrication process based on Silicon-on-Insulator (SOI) is presented. A thickness ratio of 20:1 was chosen for the silicon bottom electrode to the AlN layer in order to make the TCF of the resonator mainly dependent upon heavily doped silicon. A cryogenic cooling test down to 77 K and heating test up to 400 K showed that the resonant frequency of the AlN resonator changed linearly with temperature change; the TCF was shown to be −9.1 ppm/°C. The temperature hysteresis characteristic of the resonator was also measured, and the AlN resonator showed excellent temperature stability. The quality factor versus temperature characteristic was also studied between 77 K and 400 K. It was found that lower temperature resulted in a higher quality factor, and the quality factor increased by 56.43%, from 1291.4 at 300 K to 2020.2 at 77 K.
T-Cells and Interferon Gamma Are Necessary for Survival Following Crimean-Congo Hemorrhagic Fever Virus Infection in Mice
Authors: Hawman David W. , Meade-White Kimberly , Leventhal Shanna , Carmody Aaron , Haddock Elaine , Hasenkrug Kim , Feldmann Heinz
Published: January 2021

Crimean-Congo hemorrhagic fever (CCHF) is a severe tick-borne febrile illness with wide geographic distribution. In humans, the disease follows infection by the Crimean-Congo hemorrhagic fever virus (CCHFV) and begins as flu-like symptoms that can rapidly progress to hemorrhaging and death. Case fatality rates can be as high as 30%. An important gap in our understanding of CCHF are the host immune responses necessary to control the infection. A better understanding of these responses is needed to direct therapeutic strategies to limit the often-severe morbidity and mortality seen in humans. In this report, we have utilized a mouse model in which mice develop severe disease but ultimately recover. T-cells were robustly activated, differentiated to produce antiviral cytokines, and were critical for survival following CCHFV infection. We further identified a key role for interferon gamma (IFNγ) in survival following CCHFV infection. These results significantly improve our understanding of the host adaptive immune response to severe CCHFV infection.
Influence of Extremophiles on the Generation of Acid Mine Drainage at the Abandoned Pan de Azúcar Mine (Argentina)
Authors: Plaza-Cazón Josefina , Benítez Leonardo , Murray Jésica , Kirschbaum Pablo , Donati Edgardo
Published: January 2021

The risk of generation of acid drainages in the tailings of the Pan de Azúcar mine that closed its activities more than three decades ago, was evaluated through biooxidation studies using iron- and sulfur-oxidizing extremophilic leaching consortia. Most of tailings showed a high potential for generating acid drainage, in agreement with the results from net acid generation (NAG) assays. In addition, molecular analysis of the microbial consortia obtained by enrichment of the samples, demonstrated that native leaching microorganisms are ubiquitous in the area and they seemed to be more efficient in the biooxidation of the tailings than the collection microorganisms. The acid drainages detected at the site and those formed by oxidation of the tailings, produced a significant ecotoxicological effect demonstrated by a bioassay. These drainages, even at high dilutions, could seriously affect a nearby Ramsar site (Laguna de Pozuelos) that is connected to the Pan de Azúcar mine through a hydrological route (Cincel River).
Molecular Modelling Studies on Pyrazole Derivatives for the Design of Potent Rearranged during Transfection Kinase Inhibitors
Authors: Bhujbal Swapnil P. , Keretsu Seketoulie , Cho Seung Joo
Published: January 2021

RET (rearranged during transfection) kinase, one of the receptor tyrosine kinases, plays a crucial role in the development of the human nervous system. It is also involved in various cell signaling networks responsible for the normal cell division, growth, migration, and survival. Previously reported clinical studies revealed that deregulation or aberrant activation of RET signaling can cause several types of human cancer. For example, medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia (MEN2A, MEN2B) occur due to sporadic mutation or germline RET mutation. A number of RET kinase inhibitors have been approved by the FDA for the treatment of cancer, such as cabozantinib, vandetanib, lenvatinib, and sorafenib. However, each of these drugs is a multikinase inhibitor. Hence, RET is an important therapeutic target for cancer drug design. In this work, we have performed various molecular modelling studies, such as molecular docking and dynamics simulation for the most active compound of the pyrazole series as RET kinase inhibitors. Furthermore, molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) free energy calculation and 3-dimensional quantitative structure–activity relationship (3D-QSAR) were performed using g_mmpbsa and SYBYL-X 2.1 package. The results of this study revealed the crucial binding site residues at the active site of RET kinase and contour map analysis showed important structural characteristics for the design of new highly active inhibitors. Therefore, we have designed ten RET kinase inhibitors, which showed higher inhibitory activity than the most active compound of the series. The results of our study provide insights to design more potent and selective RET kinase inhibitors.
Mechanistic Studies of the Antiallergic Activity of Phyllanthus amarus Schum. & Thonn. and Its Compounds
Authors: Abd Rani Nur Zahirah , Lam Kok Wai , Jalil Juriyati , Mohamad Hazni Falina , Mat Ali Mohd Shukri , Husain Khairana
Published: January 2021

Phyllanthus amarus Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of P. amarus extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, P. amarus did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (1), hypophyllanthin (2), niranthin (3), and corilagin (4). To gain insights into the binding interactions of the most active compound hypophyllanthin (2), molecular docking was conducted and found that hypophyllanthin (2) exhibited favorable binding in the H1R binding site. In conclusion, P. amarus and hypophyllanthin (2) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.
Recent Advances in the Development of Exogenous dsRNA for the Induction of RNA Interference in Cancer Therapy
Authors: Golubeva Tatiana S. , Cherenko Viktoria A. , Orishchenko Konstantin E.
Published: January 2021

Selective regulation of gene expression by means of RNA interference has revolutionized molecular biology. This approach is not only used in fundamental studies on the roles of particular genes in the functioning of various organisms, but also possesses practical applications. A variety of methods are being developed based on gene silencing using dsRNA—for protecting agricultural plants from various pathogens, controlling insect reproduction, and therapeutic techniques related to the oncological disease treatment. One of the main problems in this research area is the successful delivery of exogenous dsRNA into cells, as this can be greatly affected by the localization or origin of tumor. This overview is dedicated to describing the latest advances in the development of various transport agents for the delivery of dsRNA fragments for gene silencing, with an emphasis on cancer treatment.
Effects of 12 Weeks Cosmos caudatus Supplement among Older Adults with Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo-Controlled Trial
Authors: You Yee Xing , Shahar Suzana , Rajab Nor Fadilah , Haron Hasnah , Yahya Hanis Mastura , Mohamad Mazlyfarina , Din Normah Che , Maskat Mohamad Yusof
Published: January 2021

Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.
Bidirectional Interactions between the Menstrual Cycle, Exercise Training, and Macronutrient Intake in Women: A Review
Authors: Rocha-Rodrigues Sílvia , Sousa Mónica , Lourenço Reis Patrícia , Leão César , Cardoso-Marinho Beatriz , Massada Marta , Afonso José
Published: January 2021

Women have a number of specificities that differentiate them from men. In particular, the role of sex steroid hormones and the menstrual cycle (MC) significantly impact women’s physiology. The literature has shown nonlinear relationships between MC, exercise, and nutritional intake. Notably, these relationships are bidirectional and less straightforward than one would suppose. For example, the theoretical implications of the MC’s phases on exercise performance do not always translate into relevant practical effects. There is often a disconnect between internal measures (e.g., levels of hormone concentrations) and external performance. Furthermore, it is not entirely clear how nutritional intake varies across the MC’s phases and whether these variations impact on exercise performance. Therefore, a thorough review of the existing knowledge could help in framing these complex relationships and potentially contribute to the optimization of exercise prescription and nutritional intake according to the naturally occurring phases of the MC. Throughout this review, an emerging trend is the lack of generalizability and the need to individualize interventions, since the consequences of the MC’s phases and their relationships with exercise and nutritional intake seem to vary greatly from person to person. In this sense, average data are probably not relevant and could potentially be misleading.