bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritage Management: Analytical Study of Tourism Impacts on the Archaeological Site of Umm Qais—Jordan
Authors: AlMasri Reem , Ababneh Abdelkader
Published: September 2021

The archaeological site of Umm Qais is a popular tourist destination for both local and foreign tourists who come to appreciate the site’s archaeological history, scenic landscape, and panoramic perspective. The site was the focus of tourism planning, which included the construction of amenities and infrastructure, the creation of tourist circuits, and archaeological management. This development was linked to a rise in visitor numbers as well as the provision of a high level of service, such as parking, tickets, kiosks, restaurants, and cafés, to welcome visitors. The purpose of this study was to examine the impacts of on-site tourist services and infrastructures, as well as those of visitors, and their geographical and temporal scope on the site. The study used a qualitative approach based on case study fieldwork as a research method to achieve this goal. Personal observation, interviews with site-related stakeholders, and a checklist were used to collect data during the fieldwork. Both tourism infrastructure and visitors were proven to have a detrimental influence on tourist attractions. The site’s aesthetic pollution and structural deterioration were caused by tourism services and infrastructure. Graffiti, vandalism, and trash left by visitors exerted strong negative impacts. Furthermore, spatial and temporal negative impacts were determined by the patterns of seasonal movement of visitors and the location of infrastructure. Thus, most of the impacts were concentrated in a small portion of the site, among the western theater, the panoramic view, and the traditional Ottoman village. This research sheds light on these challenges and makes recommendations in the areas of heritage management, tourism, and visitor impact management that may be of interest to on-the-ground decision makers as well as academics.
The Austronesian Advantage: Natural Selection and Linguistic Diversity
Authors: St. Clair Michael
Published: September 2021

The “Austronesian advantage” suggests that Austronesian-speaking populations in Melanesia are resistant to tropical splenomegaly syndrome, a medical condition linked to chronic exposure to malaria. This hypothesis was proposed by Kevin M. Kelly in his 1988 dissertation, a subsequent 1990 paper, and a 1993 paper co-published with Jeffrey Clark. I now update the Austronesian advantage hypothesis with additional linguistic, anthropological, and genetic data. I find that cultural adaptations cannot fully explain the Austronesian expansion. Rather, the Austronesian advantage, a classic example of natural selection, completes the picture by connecting the Austronesian expansion with greater reproductive success. I also strengthen the Austronesian advantage hypothesis with data from Tibet. The correlation between language expansion and natural selection extends well beyond the Austronesian world.
Small WORLD: Ancient Egyptian Architectural Replicas from the Tomb of Meketre
Authors: David Arlette
Published: September 2021

The paper presents a study of the context, functions, and rationale behind architectural replicas sealed off in ancient Egyptian tombs, the finest exemplars of which having been excavated in the Theban tomb of Meketre (ca. 2000 B.C.). The analysis is preceded by clarifications regarding the terminology used, the point of view from which they have to be considered, and the developments that led to their presence in the funerary assemblage. It is suggested that in the sealed ‘replicas chamber’ or burial chamber in which they were deposited, it was mainly the winged ba, a connective agent between the worlds of life, death, and eternity, that was meant to enter the imaginary realm of the replicas and feed the deceased in order to revivify him.
Eccentric Hamstring Muscle Strength during Home Confinement Due to the COVID-19 Pandemic, and Football Competition Resumption in Professional Football Referees: A Prospective Observational Study
Authors: Moreno-Pérez Víctor , Madruga-Parera Marc , Romero-Rodríguez Daniel , Sanchéz-Sanchéz Javier , Felipe José Luis , Marcè-Hernández Lluis , Recasens-Sarrà Eudald , Del Coso Juan
Published: September 2021

The COVID-19 pandemic has produced a major disruption for professional football leagues that has affected the physical preparation of both football players and referees. In Spain, health authorities decreed home confinement for eight weeks, supressing the normal training routines of professional referees. After home confinement, referees had four weeks to retrain as the national football league was set to resume matches to complete the 11 games remaining. The aim of the present investigation was to assess changes in eccentric hamstring muscle strength during football competition suspension/resumption due to the COVID-19 pandemic in 21 professional football referees (mean ± SD, age: 33.4 ± 5.1 years; height: 182.4 ± 5.0 cm; body mass: 75.1 ± 4.4 kg). Eccentric hamstring muscle strength was measured with the Nordic hamstring exercise at four time points. During home confinement, referees presented the lowest value of bilateral eccentric muscle strength (300 ± 14 N). Eccentric muscle strength increased by 13.2 ± 3.7% one week after the end of home confinement (339 ± 16 N; p = 0.001, effect size (ES) = 2.8) and remained stable before the first match (343 ± 17 N; p = 0.001, ES = 3.1) and after the end of the national league (328 ± 13 N; p = 0.001, ES = 2.0). In summary, home confinement produced detraining effects in professional football referees associated with hamstring muscle weakness. In this regard, strength-based activities with body loads may be insufficient to avoid muscle weakness and other means (e.g., weights) may be necessary to maintain muscle strength. However, the 4-weeks retraining period was sufficient to resolve hamstring muscle weakness induced by the restrictions of home confinement. This information may be helpful in the case of future sport competition suspension or home quarantine due to new waves of COVID-19 pandemic.
A Novel UPLC-MS/MS Method Identifies Organ-Specific Dipeptide Profiles
Authors: Heidenreich Elena , Pfeffer Tilman , Kracke Tamara , Mechtel Nils , Nawroth Peter , Hoffmann Georg F , Schmitt Claus Peter , Hell Rüdiger , Poschet Gernot , Peters Verena
Published: September 2021

Background: Amino acids have a central role in cell metabolism, and intracellular changes contribute to the pathogenesis of various diseases, while the role and specific organ distribution of dipeptides is largely unknown. Method: We established a sensitive, rapid and reliable UPLC-MS/MS method for quantification of 36 dipeptides. Dipeptide patterns were analyzed in brown and white adipose tissues, brain, eye, heart, kidney, liver, lung, muscle, sciatic nerve, pancreas, spleen and thymus, serum and urine of C57BL/6N wildtype mice and related to the corresponding amino acid profiles. Results: A total of 30 out of the 36 investigated dipeptides were detected with organ-specific distribution patterns. Carnosine and anserine were most abundant in all organs, with the highest concentrations in muscles. In liver, Asp-Gln and Ala-Gln concentrations were high, in the spleen and thymus, Glu-Ser and Gly-Asp. In serum, dipeptide concentrations were several magnitudes lower than in organ tissues. In all organs, dipeptides with C-terminal proline (Gly-Pro and Leu-Pro) were present at higher concentrations than dipeptides with N-terminal proline (Pro-Gly and Pro-Leu). Organ-specific amino acid profiles were related to the dipeptide profile with several amino acid concentrations being related to the isomeric form of the dipeptides. Aspartate, histidine, proline and serine tissue concentrations correlated with dipeptide concentrations, when the amino acids were present at the C- but not at the N-terminus. Conclusion: Our multi-dipeptide quantification approach demonstrates organ-specific dipeptide distribution. This method allows us to understand more about the dipeptide metabolism in disease or in healthy state.
Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy
Authors: Maiti Amit K.
Published: September 2021

Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.
The Effects of Three Chlorhexidine-Based Mouthwashes on Human Osteoblast-Like SaOS-2 Cells. An In Vitro Study
Authors: Brunello Giulia , Becker Kathrin , Scotti Luisa , Drescher Dieter , Becker Jürgen , John Gordon
Published: September 2021

Several decontamination methods for removing biofilm from implant surfaces during surgical peri-implantitis treatment have been reported, including the intraoperative usage of chlorhexidine (CHX)-based antiseptics. There is a lack of information on possible adverse effects on bone healing. The study aimed to examine the impact of three CHX-based mouthwashes on osteoblast-like cells (SaOS-2) in vitro. Cells were cultured for three days in 96-well binding plates. Each well was randomly treated for either 30, 60 or 120 s with 0.05% CHX combined with 0.05% cetylpyridinium chloride (CPC), 0.1% CHX, 0.2% CHX or sterile saline (NaCl) as control. Cell viability, cytotoxicity and apoptosis were assessed at day 0, 3 and 6. Cell viability resulted in being higher in the control group at all time points. At day 0, the CHX 0.2 group showed significantly higher cytotoxicity values compared to CHX 0.1 (30 s), CHX + CPC (30 s, 60 s and 120 s) and control (60 s and 120 s), while no significant differences were identified between CHX + CPC and both CHX 0.1 and NaCl groups. All test mouthwashes were found to induce apoptosis to a lower extent compared to control. Results indicate that 0.2% CHX presented the highest cytotoxic effect. Therefore, its intraoperative use should be carefully considered.
Insulin and Insulin Resistance in Alzheimer’s Disease
Authors: Sędzikowska Aleksandra , Szablewski Leszek
Published: September 2021

Insulin plays a range of roles as an anabolic hormone in peripheral tissues. It regulates glucose metabolism, stimulates glucose transport into cells and suppresses hepatic glucose production. Insulin influences cell growth, differentiation and protein synthesis, and inhibits catabolic processes such as glycolysis, lipolysis and proteolysis. Insulin and insulin-like growth factor-1 receptors are expressed on all cell types in the central nervous system. Widespread distribution in the brain confirms that insulin signaling plays important and diverse roles in this organ. Insulin is known to regulate glucose metabolism, support cognition, enhance the outgrowth of neurons, modulate the release and uptake of catecholamine, and regulate the expression and localization of gamma-aminobutyric acid (GABA). Insulin is also able to freely cross the blood–brain barrier from the circulation. In addition, changes in insulin signaling, caused inter alia insulin resistance, may accelerate brain aging, and affect plasticity and possibly neurodegeneration. There are two significant insulin signal transduction pathways: the PBK/AKT pathway which is responsible for metabolic effects, and the MAPK pathway which influences cell growth, survival and gene expression. The aim of this study is to describe the role played by insulin in the CNS, in both healthy people and those with pathologies such as insulin resistance and Alzheimer’s disease.
Aryl Hydrocarbon Receptor Defect Attenuates Mitogen-Activated Signaling through Leucine-Rich Repeats and Immunoglobulin-like Domains 1 (LRIG1)-Dependent EGFR Degradation
Authors: Hsu Han-Lin , Chen Hong-Kai , Tsai Chi-Hao , Liao Po-Lin , Chan Yen-Ju , Lee Yu-Cheng , Lee Chen-Chen , Li Ching-Hao
Published: September 2021

Aryl hydrocarbon receptor (AHR) genomic pathway has been well-characterized in a number of respiratory diseases. In addition, the cytoplasmic AHR protein may act as an adaptor of E3 ubiquitin ligase. In this study, the physiological functions of AHR that regulate cell proliferation were explored using the CRISPR/Cas9 system. The doubling-time of the AHR-KO clones of A549 and BEAS-2B was observed to be prolonged. The attenuation of proliferation potential was strongly associated with either the induction of p27Kip1 or the impairment in mitogenic signal transduction driven by the epidermal growth factor (EGF) and EGF receptor (EGFR). We found that the leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a repressor of EGFR, was induced in the absence of AHR in vitro and in vivo. The LRIG1 tends to degrade via a proteasome dependent manner by interacting with AHR in wild-type cells. Either LRIG1 or a disintegrin and metalloprotease 17 (ADAM17) were accumulated in AHR-defective cells, consequently accelerating the degradation of EGFR, and attenuating the response to mitogenic stimulation. We also affirmed low AHR but high LRIG1 levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients. This might partially elucidate the sluggish tissue repairment and developing inflammation in COPD patients.
Machine Learning Based Sensitivity Analysis of Aeroelastic Stability Parameters in a Compressor Cascade
Authors: Rauseo Marco , Vahdati Mehdi , Zhao Fanzhou
Published: September 2021

Aeroelastic instabilities such as flutter have a crucial role in limiting the operating range and reliability of turbomachinery. This paper offers an alternative approach to aeroelastic analysis, where the sensitivity of aerodynamic damping with respect to main flow and structural parameters is quantified through a surrogate-model-based investigation. The parameters are chosen based on previous studies and are represented by a uniform distribution within applicable intervals. The surrogate model is an artificial neural network, trained and tested to achieve an error within 1% of the test data. The quantity of interest is aerodynamic damping and the datasets are obtained from a linearised aeroelastic solver. The sensitivity of aerodynamic damping with respect to the input variables is obtained by calculating normalised gradients from the surrogate model at specific operating conditions. The results show a quantitative comparison of sensitivity across the different input parameters. The outcome of the sensitivity analysis is then used to decide the most appropriate action to take in order to induce stability in unstable operating conditions. The work is a preliminary study, carried out on a simplified two dimensional compressor cascade and it is aimed at proving the validity of a data-driven approach in studying the aeroelastic behaviour of turbomachinery. To the best of the authors’ knowledge, this is the first time a data-driven flutter model has been investigated. The initial results are encouraging, indicating that this approach is worth pursuing in the future. The presented framework can be used as a redesign tool to enhance the flutter stability of an existing blade.
Precise Underwater Gliders Pitch Control with the Presence of the Pycnocline
Authors: Zang Wenchuan , Chen Ming , Guo Tingting , Luan Xin , Song Dalei
Published: September 2021

Glider-based mobile currents observations are gaining increasing research attention. However, the quality of such observations is directly related to the pitch accuracy of the glider. As a buoyancy-driven robot, the glider will be strongly disturbed during the passage through the pycnocline. The pycnocline refers to the oceanic phenomenon where the density of the seawater changes abruptly with respect to depth. The presence of the pycnocline influences the pitch of the glider and consequently affects the quality of the observed currents data. In this work, we propose an actuator constrained active disturbance rejection controller (ACADRC) to improve the accuracy of the pitch angle control when gliders move across the pycnocline. For this purpose, the dynamical model of the glider is first derived. Then, the longitudinal plane motion model of the glider considering the density variation is analyzed. Based on that, we discuss three typical types of pycnocline encountered during glider profiling, which are the pycnocline, the inverted pycnocline and the multiple pycnocline. To alleviate the low accuracy of bang-bang control and proportion integration differentiation control, and furthermore, to mitigate the disturbance of pitch by sudden density changes, we propose the actuator constrained active disturbance rejection controller in conjunction with specific glider pitch actuator hardware constraints. Simulation results show that the proposed method has significant improvement in pitch control accuracy over the comparison methods.
Improving the Biological Value of Olive and Soybean Oil Blends with Olive Leaf Extract Obtained by Ultrasound-Assisted Extraction towards the Preparation of a Sauce Product
Authors: Aliyari Mohammad Amin , Rezaei Karamatollah
Published: September 2021

French sauce from different blends of soybean and olive oils was prepared and the oxidative stability of the optimum sauce sample, enriched with various amounts of olive leaf polyphenolic extract (OLE) (obtained via ultrasound-assisted extraction), was investigated over 90 days of storage. The microbiological and sensory properties of the samples containing the optimum amounts of OLE, as a substitution for synthetic preservatives, were studied. According to the results, the addition of olive oil at higher levels (75% and 100%) could affect the physicochemical properties of the sauce as compared to the control sample. It was also found that the addition of olive oil (up to 50%) would not significantly impact the sauce properties. Regarding the OLE enrichment in the samples, it was found that high levels of OLE could improve the oxidative stability of the samples. It was also found that OLE could be used as a preservative instead of commercial ones. Overall, this study suggests the potential use of olive oil and olive leaf extract in the preparation of French sauce to boost its nutritional value and its stability.
Kinetics, Thermodynamics and Equilibrium Studies for Gold Recovery from Diluted Waste Solution
Authors: Negrea Adina , Ronka Sylwia , Ciopec Mihaela , Duteanu Narcis , Negrea Petru , Mihailescu Maria
Published: September 2021

2,2′-thiobisethanol dimethacrylate/ethylene glycol dimethacrylate copolymer (coP-TEDMA/EGDMA) was used as a sorbent for gold recovery from residual solutions resulting from the electroplating industry. Firstly, synthesized material was characterized by X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, and confocal laser scanning microscopy. The sorption process mechanism was evidenced on the basis of kinetic, thermodynamic and equilibrium studies. To highlight this, the influence of solution pH, temperature and gold initial concentration on maximum sorption capacity was studied. The obtained experimental data were modeled using Langmuir, Freundlich and Sips sorption isotherms, and it was observed that the Sips one was better for describing the studied sorption process. Kinetic data were fitted using pseudo-first-order and pseudo-second-order kinetic models. Of these models, the studied process was better described by the pseudo-second-order model. The thermodynamic parameters free Gibbs energy (ΔG0), enthalpy (ΔH0), and entropy (ΔS0) were evaluated on the basis of the van’t Hoff equation. On the basis of the thermodynamic study, it was concluded that gold recovery on coP-TEDMA/EGDMA is a spontaneous and endothermic process.
Experimental Study on Forged TC4 Titanium Alloy Fatigue Properties under Three-Point Bending and Life Prediction
Authors: Wang Bohan , Cheng Li , Li Dongchun
Published: September 2021

Ultrasonic fatigue tests of TC4 titanium alloy equiaxed I, II and bimodal I, II obtained by different forging processes were carried out in the range from 105 to 109 cycles using 20 kHz three-point bending. The results showed that the S-N curves had different shapes, there was no traditional fatigue limit, and the bimodal I had the best comprehensive fatigue performance. The fracture morphology was analyzed by SEM, and it was found that the fatigue cracks originated from the surface or subsurface facets, showing a transgranular quasi-cleavage fracture mechanism. EDS analysis showed that the facets were formed by the cleavage of primary α grains, and the fatigue cracks originated from the primary α grain preferred textures, rather than the primary α grain clusters. From the microstructure perspective, the reasons for better equiaxed high-cycle-fatigue properties and better bimodal ultra-high-cycle-fatigue properties were analyzed. The bimodal I fatigue life prediction based on energy was also completed, and the prediction curve was basically consistent with the experimental data.
Study of ZnO-CNT Nanocomposites in High-Pressure Conditions
Authors: Cursaru Laura-Madalina , Valsan Sorina Nicoleta , Puscasu Maria-Eliza , Tudor Ioan Albert , Zarnescu-Ivan Nicoleta , Vasile Bogdan Stefan , Piticescu Roxana Mioara
Published: September 2021

Recently, carbon nanotubes (CNTs) have been used extensively to develop new materials and devices due to their specific morphology and properties. The reinforcement of different metal oxides such as zinc oxide (ZnO) with CNT develops advanced multifunctional materials with improved properties. Our aim is to obtain ZnO-CNT nanocomposites by in situ hydrothermal method in high-pressure conditions. Various compositions were tested. The structure and morphology of ZnO-CNT nanocomposites were analyzed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry—thermogravimetry (DSC-TG), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). These analyses showed the formation of complex ZnO-CNT structures. FT-IR spectra suggest possible interactions between CNT and ZnO. DSC-TG analysis also reveals the formation of some physical bonds between ZnO and CNT, through the appearance of endothermic peaks which could be assigned to the decomposition of functional groups of the CNT chain and breaking of the ZnO-CNT bonds. XRD characterization demonstrated the existence of ZnO nanocrystallites with size around 60 nm. The best ZnO:CNT composition was further selected for preliminary investigations of the potential of these nanocomposite powders to be processed as pastes for extrusion-based 3D printing.
Lignosulfonate-Based Conducting Flexible Polymeric Membranes for Liquid Sensing Applications
Authors: Magina Sandra , Rudnitskaya Alisa , Soreto Sílvia , Costa Luís Cadillon , Barros-Timmons Ana , Evtuguin Dmitry V.
Published: September 2021

In this study, lignosulfonate (LS) from the acid sulfite pulping of eucalypt wood was used to synthesize LS-based polyurethanes (PUs) doped with multiwalled carbon nanotubes (MWCNTs) within the range of 0.1–1.4% w/w, yielding a unique conducting copolymer composite, which was employed as a sensitive material for all-solid-state potentiometric chemical sensors. LS-based PUs doped with 1.0% w/w MWCNTs exhibited relevant electrical conductivity suitable for sensor applications. The LS-based potentiometric sensor displayed a near-Nernstian or super-Nernstian response to a wide range of transition metals, including Cu(II), Zn(II), Cd(II), Cr(III), Cr(VI), Hg(II), and Ag(I) at pH 7 and Cr(VI) at pH 2. It also exhibited a redox response to the Fe(II)/(III) redox pair at pH 2. Unlike other lignin-based potentiometric sensors in similar composite materials, this LS-based flexible polymeric membrane did not show irreversible complexation with Hg(II). Only a weak response toward ionic liquids, [C2mim]Cl and ChCl, was registered. Unlike LS-based composites comprising MWCNTs, those doped with graphene oxide (GO), reduced GO (rGO), and graphite (Gr) did not reveal the same electrical conductivity, even with loads up to 10% (w/w), in the polymer composite. This fact is associated, at least partially, with the different filler dispersion abilities within the polymeric matrix.
Bond Properties of Carbon Fiber Reinforced Polymer and Corrosion-Cracked Reinforced Concrete Interface: Experimental Test and Nonlinear Degenerate Interface Law
Authors: Gong Yongzhi , Shan Yingjie , Wu Yuyuan , Wang Liping , Liu Xiaojie , Ding Faxing
Published: September 2021

Existing experimental research on bond properties of the interface between Carbon Fiber Reinforced Polymer (CFRP) and damaged concrete is limited, although CFRP strengthening technology has been widely used for corroded reinforced concrete structures. This work investigated the bond behavior of CFRP to the corrosion-cracked concrete interface, in which three factors were considered for experimentation, including corrosion degree, concrete strength and concrete cover thickness. The tests were conducted by developing a self-balancing double shear lap test device. In addition, a corrosion scene was provided simultaneously to simulate the external corrosion environment. The results showed that three peeling modes of CFRP sheets were observed with respect to corrosion degrees of the steel bars. The effects of the three factors on the stripping bearing capacity and effective bond length of CFRP sheets were discussed by systematic parametric analysis. Finally, a nonlinear degenerate law of CFRP-to-concrete interface considering the corrosion degree was improved and verified in this study.
Subungual Melanoma: A Single Institution Experience
Authors: LaRocca Christopher J. , Lai Lily , Nelson Rebecca A. , Modi Badri , Crawford Brooke
Published: September 2021

Despite the changing paradigms of melanoma treatment in recent years, there remains a relative paucity of data regarding subungual melanoma in the literature. From 2002–2018, 25 patients with subungual melanoma were surgically treated at our facility. A retrospective chart review was conducted to collect relevant demographic, clinical, pathologic, and outcomes data. The median age at diagnosis was 69 years. Most patients (60%) were male, and the melanoma lesion was most often located on the foot (68%). Acral-lentiginous was the most common histologic subtype (59%), and the median Breslow thickness was 3.4 mm. Fifteen patients (63%) underwent a sentinel lymph node biopsy as part of their surgical resection, and four of these patients (27%) had metastatic disease in the lymph nodes. In total, 10 patients underwent lymph node dissection of the involved basin. The median follow up was 21 months in this patient population. Age, gender, tumor location, ulceration, and lesion histology were not significantly associated with recurrence free survival (RFS). Increasing Breslow thickness was found to be significantly associated with shorter RFS (HR: 1.07, CI: 1.03–1.55). In total, 13 patients developed a disease recurrence, and RFS rates were 66% at 1 year and 40% at 3 years. Additionally, 91 and 37% of patients were alive at one year and three years, respectively. Subungual melanomas are rare lesions that often have a more advanced stage at diagnosis, which contributes to the poor prognosis of these cutaneous malignancies.
Palladium(0) Catalyzed Synthesis of (E)-4-Bromo-N-((3-bromothiophen-2-yl)methylene)-2-methylaniline Derivatives via Suzuki Cross-Coupling Reaction: An Exploration of Their Non-Linear Optical Properties, Reactivity and Structural Features
Authors: Rizwan Komal , Rasool Nasir , Hashmi Muhammad Ali , Noreen Sadia , Zubair Muhammad , Arshad Mahwish , Shah Syed Adnan Ali
Published: September 2021

A series of (E)-4-bromo-N-((3-bromothiophen-2-yl)methylene)-2-methylaniline analogs synthesized in considerable yields through Suzuki cross-coupling reactions. Various electron donating and withdrawing functional moieties were successfully incorporated under the employed reaction conditions. Reaction of 4-bromo-2-methylaniline (1) with 3-bromothiophene-2-carbaldehyde (2b) in the existence of glacial acetic acid, provided (E)-4-bromo-N-((3-bromothiophen-2-yl)methylene)-2-methylaniline (3b) in excellent yield (94%). Suzuki coupling of 3b with different boronic acids in the presence of Pd(PPh3)4/K3PO4 at 90 °C led to the synthesis of the monosubstituted and bisubstituted products 5a–5d and 6a–6d in moderate yields (33–40% and 31–46%, respectively). Density functional theory (DFT) investigations were performed on different synthesized analogues 5a–5d, 6a–6d to determine their structural characteristics. The calculations provide insight into the frontier molecular orbitals (FMOs) of the imine-based analogues and their molecular electrostatic potential (MESP). Reactivity descriptors like ionization energy (I), electron affinity (A), chemical hardness (ƞ) and index of nucleophilicity have been calculated for the first time for the synthesized molecules.
Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation
Authors: Márquez-Cantudo Laura , Ramos Ana , Coderch Claire , de Pascual-Teresa Beatriz
Published: September 2021

Protein degradation by the Ubiquitin-Proteasome System is one of the main mechanisms of the regulation of cellular proteostasis, and the E3 ligases are the key effectors for the protein recognition and degradation. Many E3 ligases have key roles in cell cycle regulation, acting as checkpoints and checkpoint regulators. One of the many important proteins involved in the regulation of the cell cycle are the members of the Histone Deacetylase (HDAC) family. The importance of zinc dependent HDACs in the regulation of chromatin packing and, therefore, gene expression, has made them targets for the design and synthesis of HDAC inhibitors. However, achieving potency and selectivity has proven to be a challenge due to the homology between the zinc dependent HDACs. PROteolysis TArgeting Chimaera (PROTAC) design has been demonstrated to be a useful strategy to inhibit and selectively degrade protein targets. In this review, we attempt to summarize the E3 ligases that naturally ubiquitinate HDACs, analyze their structure, and list the known ligands that can bind to these E3 ligases and be used for PROTAC design, as well as the already described HDAC-targeted PROTACs.
Designing Functional Fruit-Based Recovery Drinks in Powder Form That Contain Electrolytes, Peptides, Carbohydrates and Prebiotic Fiber Taking into Account Each Component’s Osmolality
Authors: Sadowska Anna , Świderski Franciszek , Kulik Klaudia , Waszkiewicz-Robak Bożena
Published: September 2021

High levels of osmolalities have been found in manufactured carbohydrate-based functional drinks that occasionally include added protein; however, fruit components rich in bioactive ingredients have been absent. It has proved difficult to obtain recovery drinks based on natural fruit components that deliver calories and nutrients to the body whilst simultaneously ensuring that the body is adequately hydrated after physical exertion; the problem being that it is difficult to ensure the drinks’ stability at low pH levels and maintain an appropriate sensory quality. This study aims to develop drinks based on natural fruit components that contain added electrolytes, carbohydrates, prebiotic fiber and protein; an improved water and electrolyte balance; the calories needed after intense physical exertion; a high content of nutrients; and a favorable sensory quality. Furthermore, the relationships between regressive osmolalities of beverage components are herein investigated. The study materials were raspberry powders (prepared via fluidized-bed jet milling, drying, freeze-drying and spray-drying) as well as citrated sodium, potassium, magnesium salts, isomaltulose, hydrolyzed collagen, whey protein isolate and prebiotic fiber. The drinks’ polyphenols and antioxidant properties were measured spectrophotometrically, whilst vitamin C content was determined using high-pressure liquid chromatography. The sensory qualities of each drink were assessed according to a scaling method. Six test versions of recovery drinks were prepared in which osmolalities ranged from 388 to 607 mOsm/kg water, total polyphenol content was 27–49 mg GAE/100 mL and vitamin C level was 8.1–20.6 mg/100 mL, following compositions defined by the study results. It is thus possible to obtain fruit-based recovery drinks of the recommended osmolality that contain added protein, prebiotics and fiber, as well as defined amounts of electrolytes and carbohydrates. All drinks were found to have a satisfactorily sensory quality. The design of appropriate recovery drink compositions was also greatly helped by investigating the relationships among the regressive osmolalities of beverage components (i.e., electrolytes, carbohydrates, fruit powders and protein).
Topical Nano Clove/Thyme Gel against Genetically Identified Clinical Skin Isolates: In Vivo Targeting Behavioral Alteration and IGF-1/pFOXO-1/PPAR γ Cues
Authors: Nazeam Jilan A. , Ragab Ghada M. , El-Gazar Amira A. , El-Mancy Shereen S. , Jamil Lina , Fayez Sahar M.
Published: September 2021

Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.
Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems
Authors: Mhambi Sinaye , Fisher David , Tchokonte Moise B. Tchoula , Dube Admire
Published: September 2021

The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.
Philosophic and Spiritual Conversion in Late Hellenism: Case Studies from the 3rd to the 5th Centuries AD
Authors: Alviz Fernández Marco
Published: September 2021

This paper aims to study the historic and sociological context of philosophic-spiritual conversions through several case studies from late Hellenism (2nd to 5th c. AD). In the History of Religion, spiritual initiatory experiences have been thought of as a key factor to understand the development of a belief; from Arthur D. Nock to modern times, there have been considerable attempts made at defining the concept of conversion as a part of the human psyche. This study will examine biographies of charismatic teachers of Greco-Roman higher education (παιδεία); specifically, some passages in which philosophic-spiritual initiatory experiences are described. In addition, they will be put in parallel with other passages in which the powerful charismatic personality of the teachers can be grasped, i.e., the main trigger of conversion. One of the more significant findings to emerge from this study is the importance of a charismatic master for a philosophic-spiritual experience to take place. In conclusion, late antique biographical sources must be re-examined in search for “the personal” without forgetting that, in this literary context, religious, philosophical, educational, and spiritual experiences can be encountered.
Metabolite-Specific Echo-Planar Imaging of Hyperpolarized [1-13C]Pyruvate at 4.7 T
Authors: Blazey Tyler , Reed Galen D , Garbow Joel R , von Morze Cornelius
Published: September 2021

Although hyperpolarization (HP) greatly increases the sensitivity of 13C MR, the usefulness of HP in vivo is limited by the short lifetime of HP agents. To address this limitation, we developed an echo-planar (EPI) sequence with spectral-spatial radiofrequency (SSRF) pulses for fast and efficient metabolite-specific imaging of HP [1-13C]pyruvate and [1-13C]lactate at 4.7 T. The spatial and spectral selectivity of each SSRF pulse was verified using simulations and phantom testing. EPI and CSI imaging of the rat abdomen were compared in the same rat after injecting HP [1-13C]pyruvate. A procedure was also developed to automatically set the SSRF excitation pulse frequencies based on real-time scanner feedback. The most significant results of this study are the demonstration that a greater spatial and temporal resolution is attainable by metabolite-specific EPI as compared with CSI, and the enhanced lifetime of the HP signal in EPI, which is attributable to the independent flip angle control between metabolites. Real-time center frequency adjustment was also highly effective for minimizing off-resonance effects. To the best of our knowledge, this is the first demonstration of metabolite-specific HP 13C EPI at 4.7 T. In conclusion, metabolite-specific EPI using SSRF pulses is an effective way to image HP [1-13C]pyruvate and [1-13C]lactate at 4.7 T.
Multicomponent Vaccines against Group A Streptococcus Can Effectively Target Broad Disease Presentations
Authors: Shaw Helen A. , Ozanne James , Burns Keira , Mawas Fatme
Published: September 2021

Group A Streptococcus (GAS) is an important global human pathogen, with a wide range of disease presentations, from mild mucosal infections like pharyngitis to invasive diseases such as toxic shock syndrome. The effect on health and mortality from GAS infections is substantial worldwide, particularly from autoimmune sequelae-like rheumatic heart disease (RHD), and there is currently no licenced vaccine. We investigated protein antigens targeting a broad range of GAS disease presentations as vaccine components in individual and combination formulations. The potency and functional immunity generated were evaluated and compared between groups. Antibodies against all components were found in pooled human IgG (IVIG) and an immune response generated following the subcutaneous immunisation of mice. A combination immunisation showed a reduction in IgG response for SpyCEP but an increase for Cpa and Mac-1 (IdeS). An opsonophagocytosis assay (OPA) showed the killing of GAS with immune sera against M protein and combination groups, with a lower killing activity observed for immune sera against other individual antigens. Specific antigen assays showed functional immunity against SpyCEP and Mac-1 from both individual and combination immunisations, with the activity correlating with antibody titres. However, efficient blocking of the binding activity of Cpa to collagen I and fibronectin could not be demonstrated with immune sera or purified IgG. Our data indicate that combination immunisations, while effective at covering a broader range of virulence factors, can also affect the immune response generated. Further, our results showed that an OPA alone is inadequate for understanding protection from vaccination, particularly when considering protection from immune evasion factors and evaluation of the colonisation leading to pharyngitis.
Forest-Associated Fishes of the Conterminous United States
Authors: Bury Gwendolynn W. , Flitcroft Rebecca , Nelson Mark D. , Arismendi Ivan , Brooks Evan B.
Published: September 2021

Freshwaters are important, interconnected, and imperiled. Aquatic ecosystems, including freshwater fishes, are closely tied to the terrestrial ecosystems they are embedded within, yet available spatially explicit datasets have been underutilized to determine associations between freshwater fishes and forested areas. Here, we determined the spatial co-occurrence between freshwater fish distributions and forests within 2129 watersheds of the conterminous United States. We identified 21% of freshwater fishes as associated with forested areas, and 2% as strictly present only in highly forested areas (75–100% forested). The northern coasts and southeast regions, both heavily forested, showed the largest numbers of forest-associated fishes in highly forested areas and fish species richness. Fish associated with low-forested areas occurred in the southwest and central plains. Imperiled fishes were relatively evenly distributed among percent forest categories, which was distinctly different from patterns for all fishes. The identification of forest-associated fishes provides insights regarding species-specific landscape contexts. Determining these large-scale patterns of freshwater biodiversity is necessary for conservation planning at regional levels, especially in highly impacted freshwater ecosystems.
Global Isotopic Hydrograph Separation Research History and Trends: A Text Mining and Bibliometric Analysis Study
Authors: Yu Yunlong , Jin Zhao , Qiu Junping
Published: September 2021

Scientific research into isotope hydrograph separation (IHS) has rapidly increased in recent years. However, there is a lack of systematic and quantitative research to explore how this field has evolved over time. In this study, the methods of text mining and bibliometric analysis were combined to address this shortcoming. The results showed that there were clear periodical characteristics in IHS studies between 1986 and 2019. High-frequency words, e.g., catchment, stable isotope, runoff, groundwater, precipitation, runoff generation, and soil, were the basic topics in IHS studies. Forest and glacier/snow were the main landscapes in this research field. ‘Variation’, ‘spatial’, and ‘uncertainty’ are hot issues for future research. Today, studies involving the geographical source, flow path, and transit/residence time of streamflow components have enhanced our understanding of the hydrological processes by using hydrometeorological measurements, water chemistry, and stable isotope approaches. In the future, new methods, such as path analysis and ensemble hydrograph separation, should be verified and used in more regions, especially in remote and mountainous areas. Additionally, the understanding of the role of surface water in streamflow components remains limited and should be deeply studied in the future.
Variation Characteristics of Summer Water Vapor Budget and Its Relationship with the Precipitation over the Sichuan Basin
Authors: Qi Dongmei , Li Yueqing , Zhou Changyan
Published: September 2021

Based on the daily precipitation data from the meteorological stations in Sichuan and the monthly average ERA-Interim reanalysis data from 1979 to 2016, the variation characteristics of summer water vapor budget in the Sichuan Basin and its relationship with precipitation are discussed in this study. The results show that, in summer, the water vapor in the Sichuan Basin and its four sub-basins flows in from the southern and western boundaries and flows out through the eastern and northern boundaries, and the basin is obviously a water vapor sink. From 1979 to 2016, the water vapor inflow from the southern and western boundaries significantly decreased, as well as the water vapor outflow through the eastern boundary. The summer precipitation in the Sichuan Basin is significantly positively correlated with the water vapor inflow at the southern boundary and net water vapor budget of the basin in the same period, and it is negatively correlated with the water vapor outflow at the northern boundary. The southern and northern boundaries are the two most important boundaries for the summer precipitation in the Sichuan Basin. Additionally, this study reveals that, under the multi-scale topography on the east side of the Tibet Plateau, the spatio-temporal distribution of precipitation in the Sichuan Basin results from the interactions between the unique topography of the Sichuan Basin and the different modes of water-vapor transport from low latitudes. The atmospheric circulation over the key area of air–sea interaction in the tropical region and its accompanying systems, as well as the anomalies of regional circulations and water vapor transport over the eastern China and Sichuan Basin, are the main reasons for the variation in summer precipitation in the Sichuan Basin.