bluuebunny/crossref_metadata_2025 huggingface dataset:
Cap Rates as a Function of Real Economic Growth
Authors: Larriva Matt
Published: July 2022

This study investigates the interactive effect of changes in the Gross Domestic Product (GDP) and the Consumer Price Index (CPI) on US multifamily cap rates. The data from the US and 20 of its metropolitan statistical areas (MSAs) was used from 2000 to 2021. The accompanying cap rate data is sourced to Green Street. A binary logistic regression model was specified by reducing the interaction between first-differenced GDP and CPI to a single binary variable and reducing the first-differenced cap rate series to a binary variable. Cap rate changes are forecasted, and the model is evaluated using standard goodness of fit methods, a confusion matrix, and a comparison to a buy-and-hold strategy. Overall, this study provides new evidence to explain and simplify the impact of inflation and economic growth on cap rates. The results show that the method of forecasting cap rates is highly robust in locations where growth is consistent with the national average (established cities), while it is less robust in fast-growing markets. It can be inferred that, in established cities and the US as a whole, cap rate growth can be modeled as a function of only the underlying GDP growth relative to CPI growth.
LSAP: A Machine Learning Method for Leaf-Senescence-Associated Genes Prediction
Authors: Li Zhidong , Tang Wei , You Xiong , Hou Xilin
Published: July 2022

Plant leaves, which convert light energy into chemical energy, serve as a major food source on Earth. The decrease in crop yield and quality is caused by plant leaf premature senescence. It is important to detect senescence-associated genes. In this study, we collected 5853 genes from a leaf senescence database and developed a leaf-senescence-associated genes (SAGs) prediction model using the support vector machine (SVM) and XGBoost algorithms. This is the first computational approach for predicting SAGs with the sequence dataset. The SVM-PCA-Kmer-PC-PseAAC model achieved the best performance (F1score = 0.866, accuracy = 0.862 and receiver operating characteristic = 0.922), and based on this model, we developed a SAGs prediction tool called “SAGs_Anno”. We identified a total of 1,398,277 SAGs from 3,165,746 gene sequences from 83 species, including 12 lower plants and 71 higher plants. Interestingly, leafy species showed a higher percentage of SAGs, while leafless species showed a lower percentage of SAGs. Finally, we constructed the Leaf SAGs Annotation Platform using these available datasets and the SAGs_Anno tool, which helps users to easily predict, download, and search for plant leaf SAGs of all species. Our study will provide rich resources for plant leaf-senescence-associated genes research.
Novel Nanoconjugate of Apamin and Ceftriaxone for Management of Diabetic Wounds
Authors: Alamoudi Abdullah A. , Alharbi Awaad S. , Abdel-Naim Ashraf B. , Badr-Eldin Shaimaa M. , Awan Zuhier A. , Okbazghi Solomon Z. , Ahmed Osama A. A. , Alhakamy Nabil A. , Fahmy Usama A. , Esmat Ahmed
Published: July 2022

Diabetic hyperglycemia delays wound healing, leading to serious consequences. Topical antibiotics can reduce the risk of a wound infection during healing; nevertheless, the microbial fight against antibiotics brings about public health challenges. Anti-microbial peptides (AMPs) belong to a novel class of drug that is used to prevent and treat systemic and topical infections. The aim of the current work was to achieve better wound healing in diabetic rats by conjugating the anti-microbial peptide “apamin” (APA) with the broad-spectrum antibiotic “ceftriaxone” (CTX) to form a nanocomplex. The CTX–APA nanoconjugate formulation was optimized using a Box–Behnken design. The optimized CTX–APA nanoconjugate formulation was evaluated for its size and zeta potential, and was then examined using transmission electron microscopy (TEM). The CTX–APA nanoconjugate was loaded onto a hydroxypropyl methylcellulose (2% w/v)-based hydrogel. It was observed that the application of the CTX–APA nanocomplex on the wounded skin of diabetic rats accelerated the regeneration of the epithelium, granulation tissue formation, epidermal proliferation, and keratinization. The nanocomplex was capable of significantly reducing the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), while increasing the expression of transforming growth factor beta-1 (TGF-β1) as well as the angiogenic markers: hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Conclusively, the application of an ion-paired CTX–APA nanocomplex enhances wound healing in diabetic rats.
Prediction and Classification of COVID-19 Admissions to Intensive Care Units (ICU) Using Weighted Radial Kernel SVM Coupled with Recursive Feature Elimination (RFE)
Authors: Alshanbari Huda M. , Mehmood Tahir , Sami Waqas , Alturaiki Wael , Hamza Mauawia A. , Alosaimi Bandar
Published: July 2022

Healthcare systems have been under immense pressure since the beginning of the COVID-19 pandemic; hence, studies on using machine learning (ML) methods for classifying ICU admissions and resource allocation are urgently needed. We investigated whether ML can propose a useful classification model for predicting the ICU admissions of COVID-19 patients. In this retrospective study, the clinical characteristics and laboratory findings of 100 patients with laboratory-confirmed COVID-19 tests were retrieved between May 2020 and January 2021. Based on patients’ demographic and clinical data, we analyzed the capability of the proposed weighted radial kernel support vector machine (SVM), coupled with (RFE). The proposed method is compared with other reference methods such as linear discriminant analysis (LDA) and kernel-based SVM variants including the linear, polynomial, and radial kernels coupled with REF for predicting ICU admissions of COVID-19 patients. An initial performance assessment indicated that the SVM with weighted radial kernels coupled with REF outperformed the other classification methods in discriminating between ICU and non-ICU admissions in COVID-19 patients. Furthermore, applying the Recursive Feature Elimination (RFE) with weighted radial kernel SVM identified a significant set of variables that can predict and statistically distinguish ICU from non-ICU COVID-19 patients. The patients’ weight, PCR Ct Value, CCL19, INF-β, BLC, INR, PT, PTT, CKMB, HB, platelets, RBC, urea, creatinine and albumin results were found to be the significant predicting features. We believe that weighted radial kernel SVM can be used as an assisting ML approach to guide hospital decision makers in resource allocation and mobilization between intensive care and isolation units. We model the data retrospectively on a selected subset of patient-derived variables based on previous knowledge of ICU admission and this needs to be trained in order to forecast prospectively.
Differences in the Sensitivity of the Baroreflex of Heart Rate Regulation to Local Geomagnetic Field Variations in Normotensive and Hypertensive Humans
Authors: Poskotinova Liliya , Krivonogova Elena , Demin Denis , Zenchenko Tatyana
Published: July 2022

Synchronization between heart rate variability (HRV) in the low-frequency (LF) range (0.04–0.15 Hz) and 1-min variations in the components (X, Y, Z)and the total vector (F) of geomagnetic induction (nT) was studied in normotensive (blood pressure up to 140/90 mmHg) and hypertensive (blood pressure above 140/90 mmHg) individuals living in the Arkhangelsk region (60°51′52″ N 39°31′05″ E).The duration of registration of HRV for each person is 30 min in a sitting position. The most pronounced synchronization of the LF parameter, which reflects baroreflex activity, with variations in the GMF was found in normotensive individuals. The absence of a significant synchronization of the LF parameter with variations in the GMF components indicates a decrease in the sensitivity of the baroreflex mechanism and a risk of dysregulation of vascular tone, especially in people with arterial hypertension, under conditions of instability of the geomagnetic field.
Modeling the Truck Appointment System as a Multi-Player Game
Authors: Torkjazi Mohammad , Huynh Nathan , Asadabadi Ali
Published: July 2022

Background: Random truck arrivals at maritime container terminals are one of the primary reasons for gate congestion. Gate congestion negatively affects the terminal’s and drayage firms’ productivity and the surrounding communities in terms of air pollution and noise. To alleviate gate congestion, more and more terminals in the USA are utilizing a truck appointment system (TAS). Methods: This paper proposes a novel approach to modeling the truck appointment system problem. Unlike previous studies which largely treated this problem as a single-player game, this study explicitly models the interplay between the terminal and drayage firms with regard to appointments. A multi-player bi-level programming model is proposed, where the terminal functions as the leader at the upper-level and the drayage firms function as followers at the lower-level. The objective of the leader (the terminal) is to minimize the gate waiting cost of trucks by spreading out the truck arrivals, and the objective of the followers (drayage firms) is to minimize their own drayage cost. To make the model tractable, the bi-level model is transformed to a single-level problem by replacing the lower-level problem with its equivalent Karush–Kuhn–Tucker (KKT) conditions and the model is solved by finding the Stackelberg equilibrium in one-shot simultaneous-moves among players. For comparison purposes, a single-player version of the TAS model is also developed. Results: Experimental results indicate that the proposed multi-player model yields a lower gate-waiting cost compared to the single-player model, and that it yields higher cost savings for the drayage firms as the number of appointments per truck increases. Moreover, the solution of the multi-player model is not dependent on the objective function coefficients, unlike the single player model. Conclusions: This study demonstrates that a TAS is more effective if it considers how the assigned appointment slot affects a truck’s drayage cost. It is recommended that terminal operators and port authorities initiate conversations with their TAS providers about incorporating this element into their TAS.
Failure Mechanism of the Fire Control Computer CPU Board inside the Tank under Transient Shock: Finite Element Simulations and Experimental Studies
Authors: Li Xiangrong , Wang Guohui , Chen Yongkang , Zhao Bo , Xiao Jianguang
Published: July 2022

The electronic components inside a main battle tank (MBT) are the key components for the tank to exert its combat effectiveness. However, breakdown of the inner electronic components can easily occur inside the MBT due to the strong transient shock and large vibration during artillery fire. As a typical key electronic component inside an MBT, the fault mechanism and fault patterns of the CPU board of the fire control computer (FCC) are discussed through numerical simulation and experimental research. An explicit nonlinear dynamic analysis is performed to study the vibration features and fault mechanism under instantaneous shock load. By using finite element modal analysis, the first six nature frequencies of the CPU board are calculated. Meanwhile, curves of stress–frequency and strain–frequency of the CPU board under different harmonic loads are obtained, which are applied to further identify the peak response of the structure. Validation of the finite element model and simulation results are performed by comparing those obtained from the modal with experiments. Based on the dynamic simulation and experimental analysis, fault patterns of CPU board are discussed, and some optimization suggestions were proposed. The results shown in this work can provide a potential technical basis and reference for the optimization design of the electronic components that are commonly used in the modern weapon equipment and wartime support.
Comparative Analysis of the Influence of Chemical Composition and Microstructure on the Abrasive Wear of High-Strength Steels
Authors: Zemlik Martyna , Konat Łukasz , Napiórkowski Jerzy
Published: July 2022

The paper discusses the microstructural, chemical and tribological properties of the selected low-alloy, high-strength martensitic boron steels with a hardness of 500–600 HBW. These materials, due to their increased strength, and thus resistance to abrasive wear, are widely used in the mining, agricultural or building industries. Grades such as XAR, TBL and Creusabro were subjected to a comparative analysis. As a result of the conducted research, an attempt was made to determine the relation between the microstructural properties, chemical composition, hardness and abrasive wear resistance of the above-mentioned metallic materials belonging to the same material group. The scope of work involved a metallographic analysis, including the examination of the microstructure with an analysis of the prior austenite grain size. Tribological tests were carried out with the use of a T-07 tester, which is designed for testing abrasive wear resistance in the presence of a loose abrasive. As a result, it was found that the coefficient of relative abrasion resistance kbAV in relation to as-normalized C45 steel is equal to 0.9–1.25 and may even have the same value among materials of different hardness in the as-delivered state.
Numerical Simulation of Intelligent Fuzzy Closed-Loop Control Method for Radial–Axial Ring Rolling Process of Super-Large Rings
Authors: Zhang Ke , Wang Xiaokai , Hua Lin , Han Xinghui , Ning Xiangjin
Published: July 2022

During the radial–axial ring rolling (RARR) process of super-large rings, abnormal deformation states such as instability and out of circularity often lead to rolling termination and quality fluctuation of ring products. In this work, an intelligent fuzzy closed-loop control method for RARR process of super-large rings is proposed, i.e., the ring’s offset adaptive fuzzy control (ROAFC) based on the regulation of the axial roll’s rotational speed and the ring’s circularity fuzzy control (RCFC) based on the regulation of the mandrel’s feed speed. In addition, a recursive average filtering algorithm is added to smooth the axial roll’s rotational speed and the mandrel’s feed speed according to the actual situation. Using the ABAQUS/Explicit software and its subroutine VUAMP, the intelligent fuzzy controller of the ring’s offset and circularity in the RARR process is designed, and the finite element (FE) model for RARR process of a Φ10 m super-large ring with an integrated intelligent fuzzy control algorithm is established. The variation laws of the ring’s offset and circularity error in the RARR process are studied with regard to different control methods such as conventional planning control (CPC), ROAFC, RCFC, and comprehensive control of ROAFC combined with RCFC (ROAFC + RCFC). The results obtained show that, compared with the CPC, the ring’s offset is reduced by 84.6% and the circularity error is decreased by 51.9% in the RARR process utilizing comprehensive control of ROAFC + RCFC. The research results provide methodological guidance for realizing the intelligent forming of super-large rings.
Predicting the Tensile Behaviour of Ultra-High Performance Fibre-Reinforced Concrete from Single-Fibre Pull-Out Tests
Authors: Hauch Konstantin , Maryamh Kasem , Redenbach Claudia , Schnell Jürgen
Published: July 2022

In this paper, a prediction model for the tensile behaviour of ultra-high performance fibre-reinforced concrete is proposed. It is based on integrating force contributions of all fibres crossing the crack plane. Piecewise linear models for the force contributions depending on fibre orientation and embedded length are fitted to force–slip curves obtained in single-fibre pull-out tests. Fibre characteristics in the crack are analysed in a micro-computed tomography image of a concrete sample. For more general predictions, a stochastic fibre model with a one-parametric orientation distribution is introduced. Simple estimators for the orientation parameter are presented, which only require fibre orientations in the crack plane. Our prediction method is calibrated to fit experimental tensile curves.
Effect of Sn Grain Orientation on Reliability Issues of Sn-Rich Solder Joints
Authors: Shen Yu-An , Wu John A.
Published: July 2022

Sn-rich solder joints in three-dimensional integrated circuits and their reliability issues, such as the electromigration (EM), thermomigration (TM), and thermomechanical fatigue (TMF), have drawn attention related to their use in electronic packaging. The Sn grain orientation is recognized as playing an important role in reliability issues due to its anisotropic diffusivity, mechanical properties, and coefficient of thermal expansion. This study reviews the effects of the Sn grain orientation on the EM, TM, and TMF in Sn-rich solder joints. The findings indicate that in spite of the failure modes dominated by the Sn grain orientation, the size and shape of the solder joint, as well as the Sn microstructures, such as the cycling twining boundary (CTB), single crystals, and misorientations of the Sn grain boundary, should be considered in more detail. In addition, we show that two methods, involving a strong magnetic field and seed crystal layers, can control the Sn grain orientations during the solidification of Sn-rich solder joints.
Using Value-Based Potentials for Making Approximate Inference on Probabilistic Graphical Models
Authors: Bonilla-Nadal Pedro , Cano Andrés , Gómez-Olmedo Manuel , Moral Serafín , Retamero Ofelia Paula
Published: July 2022

The computerization of many everyday tasks generates vast amounts of data, and this has lead to the development of machine-learning methods which are capable of extracting useful information from the data so that the data can be used in future decision-making processes. For a long time now, a number of fields, such as medicine (and all healthcare-related areas) and education, have been particularly interested in obtaining relevant information from this stored data. This interest has resulted in the need to deal with increasingly complex problems which involve many different variables with a high degree of interdependency. This produces models (and in our case probabilistic graphical models) that are difficult to handle and that require very efficient techniques to store and use the information that quantifies the relationships between the problem variables. It has therefore been necessary to develop efficient structures, such as probability trees or value-based potentials, to represent the information. Even so, there are problems that must be treated using approximation since this is the only way that results can be obtained, despite the corresponding loss of information. The aim of this article is to show how the approximation can be performed with value-based potentials. Our experimental work is based on checking the behavior of this approximation technique on several Bayesian networks related to medical problems, and our experiments show that in some cases there are notable savings in memory space with limited information loss.
OMPEGAS: Optimized Relativistic Code for Multicore Architecture
Authors: Akimova Elena N. , Misilov Vladimir E. , Kulikov Igor M. , Chernykh Igor G.
Published: July 2022

The paper presents a new hydrodynamical code, OMPEGAS, for the 3D simulation of astrophysical flows on shared memory architectures. It provides a numerical method for solving the three-dimensional equations of the gravitational hydrodynamics based on Godunov’s method for solving the Riemann problem and the piecewise parabolic approximation with a local stencil. It obtains a high order of accuracy and low dissipation of the solution. The code is implemented for multicore processors with vector instructions using the OpenMP technology, Intel SDLT library, and compiler auto-vectorization tools. The model problem of simulating a star explosion was used to study the developed code. The experiments show that the presented code reproduces the behavior of the explosion correctly. Experiments for the model problem with a grid size of 128×128×128 were performed on an 16-core Intel Core i9-12900K CPU to study the efficiency and performance of the developed code. By using the autovectorization, we achieved a 3.3-fold increase in speed in comparison with the non-vectorized program on the processor with AVX2 support. By using multithreading with OpenMP, we achieved an increase in speed of 2.6 times on a 16-core processor in comparison with the vectorized single-threaded program. The total increase in speed was up to ninefold.
Effect of Q235 Hot-Dip Galvanized and Post-Casting T6 Heat Treatment on Microstructure and Mechanical Properties of Interfacial between AZ63 and Q235 by Solid-Liquid Compound Casting
Authors: Dai Jiahong , Xie Hongmei , Zhou Yangyang , Zou Qin , Tian Yuan , Yang Qingshan , Peng Cheng , Jiang Bin , Zhang Jianyue
Published: July 2022

AZ63 sacrificial anode is widely used to protect buried metal pipelines and reinforced concrete structures and so on. The interfacial metallurgical bonding between AZ63 sacrificial anode and Q235 wiring terminal directly affects its cathodic protection performance. Therefore, microstructure and mechanical properties of interfacial between AZ63 and Q235 by solid–liquid compound casting with hot-dip galvanized and post-casting solution-aging treatment (T6) were investigated. The results indicate that hot-dip galvanizing on the surface of Q235 is beneficial to the formation of intermetallic compounds at the interface. At the same time, it can promote the metallurgical bonding of the interface between AZ63 and Q235. After T6 heat treatment, the intermetallic compound at the interface between AZ63 and galvanized Q235 was refined. The electron-probe microanalyzer (EPMA) revealed that the intermetallic compounds at the interfaces between AZ63 and galvanized Q235 were Fe2Al5 before and after T6 treatment. Push-out testing and microhardness were used to investigate the mechanical properties of interface between AZ63 and Q235. It is shown that the hot-dip galvanization of the Q235 surface and T6 treatment were beneficial to improve the metallurgical bonding shear strength and microhardness of the interface. After T6 heat treatment, the highest shear strength at the interface between AZ63 and galvanized Q235 was up to 31.9 ± 1.9 MPa.
Demonstration of Ultra-High-Q Silicon Microring Resonators for Nonlinear Integrated Photonics
Authors: Zeng Desheng , Liu Qiang , Mei Chenyang , Li Hongwei , Huang Qingzhong , Zhang Xinliang
Published: July 2022

A reflowing photoresist and oxidation smoothing process is used to fabricate ultra-high-Q silicon microring resonators based on multimode rib waveguides. Over a wide range of wavelengths near 1550 nm, the average Q-factor of a ring with 1.2-μm-wide waveguides reaches up to 1.17 × 106, with a waveguide loss of approximately 0.28 dB/cm. For a resonator with 1.5-μm-wide waveguides, the average Q-factor reaches 1.20 × 106, and the waveguide loss is 0.27 dB/cm. Moreover, we theoretically and experimentally show that a reduction in the waveguide loss significantly improves the conversion efficiency of four-wave mixing. A high four-wave mixing conversion efficiency of −17.0 dB is achieved at a pump power of 6.50 dBm.
An AlGaN/GaN Lateral Bidirectional Current-Regulating Diode with Two Symmetrical Hybrid Ohmic-Schottky Structures
Authors: Shi Yijun , Cai Zongqi , Huang Yun , He Zhiyuan , Chen Yiqiang , Cheng Liye , Lu Guoguang
Published: July 2022

Bidirectional current-regulating ability is needed for AC light emitting diode (LED) drivers. In previous studies, various rectifier circuits have been used to provide constant bidirectional current. However, the usage of multiple electronic components can lead to additional costs and power consumption. In this work, a novel AlGaN/GaN lateral bidirectional current-regulating diode (B-CRD) featuring two symmetrical hybrid-trench electrodes is proposed and demonstrated by TCAD Sentaurus (California USA) from Synopsys corporation. Through shortly connecting the Ohmic contact and trench Schottky contact, the unidirectional invariant current can be obtained even with the applied voltage spanning a large range of 0–200 V. Furthermore, with the combination of two symmetrical hybrid-trench electrodes at each side of the device, the proposed B-CRD can deliver an excellent steady current in different directions. Through the TCAD simulation results, it was found that the device’s critical characteristics (namely knee voltage and current density) can be flexibly modulated by tailoring the depth and length of the trench Schottky contact. Meanwhile, it was also demonstrated through the device/circuit mixed-mode simulation that the proposed B-CRD can respond to the change in voltage in a few nanoseconds. Such a new functionality combined with excellent performance may make the proposed B-CRD attractive in some special fields where the bidirectional current-limiting function is needed.
Screening and Research on Skin Barrier Damage Protective Efficacy of Different Mannosylerythritol Lipids
Authors: Jing Chenxu , Guo Jiling , Li Zhenzhuo , Xu Xiaohao , Wang Jing , Zhai Lu , Liu Jianzeng , Sun Guang , Wang Fei , Xu Yangfen , Li Zhaolian , Zhao Daqing , Jiang Rui , Sun Liwei
Published: July 2022

Mannosylerythritol lipids (MELs) may prevent skin barrier damage, although their protective mechanisms and active monomeric constituents remain unclear. Here, three MELs were extracted from Candida antarctica cultures containing fermented olive oil then purified using silica gel-based column chromatography and semipreparative HPLC. All three compounds (MEL-A, MEL-B, MEL-C) were well separated and stable, and reliable materials were used for NMR and HRESIMS chemical structure determinations and for assessing MELs’ protective effects against skin damage. Notably, MEL-B and MEL-C effectively protected HaCaT cells from UVB-induced damage by upregulating the contents of filaggrin (FLG) and transglutaminase-1 (TGM1), as determined via ELISA. Moreover, MEL-B treatment (20 μg/mL) of UVB-irradiated HaCaT cells led to the upregulation of both the expression of mRNA genes and the key proteins FLG, LOR, and TGM1, which are known to be decreased in damaged skin cells. Additionally, histopathological analysis results revealed a markedly reduced intracellular vacuolation and cell damage, reflecting improved skin function after MEL-B treatment. Furthermore, immunofluorescence results revealed that MEL-B protected EpiKutis® three-dimensional cultured human skin cells from sodium dodecyl sulfate-induced damage by up-regulating FLG, LOR, and TGM1 expression. Accordingly, MELs’ protection against skin barrier damage depended on MEL-B monomeric constituent activities, thus highlighting their promise as beneficial ingredients for use in skin-care products.
Succinimido–Ferrocidiphenol Complexed with Cyclodextrins Inhibits Glioblastoma Tumor Growth In Vitro and In Vivo without Noticeable Adverse Toxicity
Authors: Najlaoui Feten , Busser Benoit , Taïwe Germain Sotoing , Pigeon Pascal , Sturm Nathalie , Giovannini Diane , Marrakchi Naziha , Rhouma Ali , Jaouen Gérard , Gibaud Stéphane , De Waard Michel
Published: July 2022

SuccFerr (N-[4-ferrocenyl,5-5-bis (4-hydroxyphenyl)-pent-4-enyl]-succinimide) has remarkable antiproliferative effects in vitro, attributed to the formation of a stabilized quinone methide. The present article reports in vivo results for a possible preclinical study. SuccFerr is lipophilic and insoluble in water, so the development of a formulation to obviate this inconvenience was necessary. This was achieved by complexation with randomly methylated cyclodextrins (RAMEßCDs). This supramolecular water-soluble system allowed the in vivo experiments below to proceed. Application of SuccFerr on the glioblastoma cancer cell line U87 indicates that it affects the cellular cycle by inducing a blockade at G0/G1 phase, linked to apoptosis, and another one at the S phase, associated with senescence. Using healthy Fischer rats, we show that both intravenous and subcutaneous SuccFerr: RAMEßCD administration at 5 mg/kg lacks toxic effects on several organs. To reach lethality, doses higher than 200 mg/kg need to be administered. These results prompted us to perform an ectopic in vivo study at 1 mg/kg i.v. ferrocidiphenol SuccFerr using F98 cells xenografted in rats. Halting of cancer progression was observed after six days of injection, associated with an immunological defense response linked to the active principle. These results demonstrate that the properties of the selected ferrocidiphenol SuccFerr transfer successfully to in vivo conditions, leading to interesting therapeutic perspectives based on this chemistry.
Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis
Authors: Kopalli Spandana Rajendra , Annamneedi Venkata Prakash , Koppula Sushruta
Published: July 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by the dysregulation of cytokines and other immune mediators. JAK/STAT is a classical signal transduction pathway involved in various biological processes, and its dysregulation contributes to the key aspects of AD pathogenesis. Suppressor of cytokine signaling (SOCS) proteins negatively regulate the immune-related inflammatory responses mediated by the JAK/STAT pathway. JAK/STAT-mediated production of cytokines including IL-4, IL-13, IL-31, and TSLP inhibits the expression of important skin barrier proteins and triggers pruritus in AD. The expression of SOCS proteins regulates the JAK-mediated cytokines and facilitates maintaining the skin barrier disruptions seen in AD. STATs are crucial in dendritic-cell-activated Th2 cell differentiation in the skin, releasing inflammatory cytokines, indicating that AD is a Th2-mediated skin disorder. SOCS proteins aid in balancing Th1/Th2 cells and, moreover, regulate the onset and maintenance of Th2-mediated allergic responses by reducing the Th2 cell activation and differentiation. SOCS proteins play a pivotal role in inflammatory cytokine-signaling events that act via the JAK/STAT pathway. Therapies relying on natural products and derived biomolecules have proven beneficial in AD when compared with the synthetic regimen. In this review, we focused on the available literature on the potential natural-product-derived biomolecules targeting JAK/STAT/SOCS signaling, mainly emphasizing the SOCS family of proteins (SOCS1, SOCS3, and SOCS5) acting as negative regulators in modulating JAK/STAT-mediated responses in AD pathogenesis and other inflammatory disorders.
Andrographolide Inhibits Epstein–Barr Virus Lytic Reactivation in EBV-Positive Cancer Cell Lines through the Modulation of Epigenetic-Related Proteins
Authors: Malat Praphatson , Ekalaksananan Tipaya , Heawchaiyaphum Chukkris , Suebsasana Supawadee , Roytrakul Sittiruk , Yingchutrakul Yodying , Pientong Chamsai
Published: July 2022

Reactivation of Epstein–Barr virus (EBV) is associated with EBV-associated malignancies and is considered to be a benefit target for treatment. Andrographolide is claimed to have antiviral and anti-tumor activities. Therefore, this study aimed to investigate the effect of andrographolide on the inhibition of EBV lytic reactivation in EBV-positive cancer cells. The cytotoxicity of andrographolide was firstly evaluated in EBV-positive cancer cells; P3HR1, AGS-EBV and HONE1-EBV cells, using an MTT assay. Herein, the spontaneous expression of EBV lytic genes; BALF5, BRLF1 and BZLF1, was significantly inhibited in andrographolide-treated cells. Accordingly, andrographolide inhibited the expression of Zta and viral production in sodium butyrate (NaB)-induced EBV lytic reactivation. Additionally, proteomics and bioinformatics analysis revealed the differentially expressed proteins that inhibit EBV lytic reactivation in all treated cell lines were functionally related with the histone modifications and chromatin organization, such as histone H3-K9 modification and histone H3-K27 methylation. Taken together, andrographolide inhibits EBV reactivation in EBV-positive cancer cells by inhibiting EBV lytic genes, probably, through the histone modifications.
Effect of Ester Moiety on Structural Properties of Binary Mixed Monolayers of Alpha-Tocopherol Derivatives with DPPC
Authors: Neunert Grażyna , Hertmanowski Robert , Witkowski Stanislaw , Polewski Krzysztof
Published: July 2022

Phospholipid membranes are ubiquitous components of cells involved in physiological processes; thus, knowledge regarding their interactions with other molecules, including tocopherol ester derivatives, is of great importance. The surface pressure–area isotherms of pure α-tocopherol (Toc) and its derivatives (oxalate (OT), malonate (MT), succinate (ST), and carbo analog (CT)) were studied in Langmuir monolayers in order to evaluate phase formation, compressibility, packing, and ordering. The isotherms and compressibility results indicate that, under pressure, the ester derivatives and CT are able to form two-dimensional liquid-condensed (LC) ordered structures with collapse pressures ranging from 27 mN/m for CT to 44 mN/m for OT. Next, the effect of length of ester moiety on the surface behavior of DPPC/Toc derivatives’ binary monolayers at air–water interface was investigated. The average molecular area, elastic modulus, compressibility, and miscibility were calculated as a function of molar fraction of derivatives. Increasing the presence of Toc derivatives in DPPC monolayer induces expansion of isotherms, increased monolayer elasticity, interrupted packing, and lowered ordering in monolayer, leading to its fluidization. Decreasing collapse pressure with increasing molar ratio of derivatives indicates on the miscibility of Toc esters in DPPC monolayer. The interactions between components were analyzed using additivity rule and thermodynamic calculations of excess and total Gibbs energy of mixing. Calculated excess area and Gibbs energy indicated repulsion between components, confirming their partial mixing. In summary, the mechanism of the observed phenomena is mainly connected with interactions of ionized carboxyl groups of ester moieties with DPPC headgroup moieties where formed conformations perturb alignment of acyl chains, resulting in increasing mean area per molecule, leading to disordering and fluidization of mixed monolayer.
HDAC Inhibition Regulates Cardiac Function by Increasing Myofilament Calcium Sensitivity and Decreasing Diastolic Tension
Authors: Eaton Deborah M. , Martin Thomas G. , Kasa Michael , Djalinac Natasa , Ljubojevic-Holzer Senka , Von Lewinski Dirk , Pöttler Maria , Kampaengsri Theerachat , Krumphuber Andreas , Scharer Katharina , Maechler Heinrich , Zirlik Andreas , McKinsey Timothy A. , Kirk Jonathan A. , Houser Steven R. , Rainer Peter P. , Wallner Markus
Published: July 2022

We recently established a large animal model that recapitulates key clinical features of heart failure with preserved ejection fraction (HFpEF) and tested the effects of the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). SAHA reversed and prevented the development of cardiopulmonary impairment. This study evaluated the effects of SAHA at the level of cardiomyocyte and contractile protein function to understand how it modulates cardiac function. Both isolated adult feline ventricular cardiomyocytes (AFVM) and left ventricle (LV) trabeculae isolated from non-failing donors were treated with SAHA or vehicle before recording functional data. Skinned myocytes were isolated from AFVM and human trabeculae to assess myofilament function. SAHA-treated AFVM had increased contractility and improved relaxation kinetics but no difference in peak calcium transients, with increased calcium sensitivity and decreased passive stiffness of myofilaments. Mass spectrometry analysis revealed increased acetylation of the myosin regulatory light chain with SAHA treatment. SAHA-treated human trabeculae had decreased diastolic tension and increased developed force. Myofilaments isolated from human trabeculae had increased calcium sensitivity and decreased passive stiffness. These findings suggest that SAHA has an important role in the direct control of cardiac function at the level of the cardiomyocyte and myofilament by increasing myofilament calcium sensitivity and reducing diastolic tension.
Development of a Personalized Tumor Neoantigen Based Vaccine Formulation (FRAME-001) for Use in a Phase II Trial for the Treatment of Advanced Non-Small Cell Lung Cancer
Authors: Oosting Linette T. , Franke Katka , Martin Michael V. , Kloosterman Wigard P. , Jamieson Jennifer A. , Glenn Laura A. , de Jager Miranda W. , van Zanten Jacoba , Allersma Derk P. , Gareb Bahez
Published: July 2022

Stage III–IV non-small cell lung cancer (NSCLC) is a devastating disease characterized by a poor prognosis. NSCLC tumors carry genetic mutations, which can lead to the expression of altered protein sequences. Peptides originating from mutated proteins and bound to MHC molecules on the tumor cell surface are referred to as neoantigens, as they are tumor-specific and not expressed in normal cells. Due to their tumor specificity, neoantigens have a strong potential to induce an anti-tumor immune response and have been investigated for development of personalized therapeutic cancer vaccines. The current study describes the development of a clinical grade neoantigen vaccine formulation (FRAME-001) intended as immunotherapy in advanced NSCLC in combination with the immune checkpoint inhibitor pembrolizumab. The detection of aberrant tumor-specific transcripts as well as an algorithm to select immunogenic neoantigen peptides are described. Subsequently, selected neoantigen peptides were synthesized with a high throughput synthesis platform and aseptically formulated under good manufacturing practice (GMP) conditions into four aqueous peptides mixtures that each contained six neoantigen peptides. A validated stability-indicating analytical method was developed in which we considered the personalized nature of the formulation. An extensive stability study performed either at −25 °C or −80 °C showed that the formulation was stable for up to 32 weeks. The formulation was mixed with the vaccine adjuvant Montanide ISA 51 VG, which yielded the final vaccine emulsion. The stability of the vaccine emulsion was demonstrated using microscopic examination, differential light scattering, and the water-drop test. The presented data show that FRAME-001 is a feasible personalized vaccine formulation for the treatment of stage III–IV NSCLC. The presented data may give guidance in the development of novel personalized therapeutic vaccines since this formulation strategy could be used for any cancer indication.
Manipulating Orbital Angular Momentum Entanglement in Three-Dimensional Spiral Nonlinear Photonic Crystals
Authors: Yu Qian , Xu Chuan , Chen Sixin , Chen Pengcheng , Nie Saiwei , Ke Shijie , Wei Dunzhao , Xiao Min , Zhang Yong
Published: July 2022

We propose and theoretically investigate two-photon orbital angular momentum (OAM) correlation through spontaneous parameter down-conversion (SPDC) processes in three-dimensional (3D) spiral nonlinear photonic crystals (NPCs). By properly designing the NPC structure, one can feasibly modulate the OAM-correlated photon pair, which provides a potential platform to realize high-dimensional entanglement for quantum information processing and quantum communications.
Genome Size Variation Assessment in Vitis vinifera L. Landraces in Ibiza and Formentera (Balearic Islands)
Authors: González Raquel , Vallès Joan , Garnatje Teresa
Published: July 2022

Plant genome size has many applications in different biological fields including ecology and plant breeding. The 2C value for Vitis vinifera L. has not been widely studied; furthermore, to date, no data from local landraces in the Pityusic Islands (the two smaller inhabited Balearic Islands, Ibiza, and Formentera) have been reported. This research aims to contribute to this knowledge and investigate whether there are variations between different grape landraces cultivated in Ibiza and Formentera and also among the same landraces on each island. To this end, 36 accessions of 15 cultivars and 6 landraces, identified with SSR markers, were assessed using flow cytometry. The results revealed that 2C values ranged from 1.09 pg to 1.28 pg. There were statistically significant differences in ‘AG1’ and ‘AG2’ landraces and ‘Santa Magdalena’, ‘Garnatxa’, ‘Danugue’, and ‘Valencí tinto/Grumier’ cultivars. No statistically significant differences were found in terms of the genome size content between islands. Statistically significant differences were found in accessions within ‘AG2’ landrace group and ‘Beba’ cultivar. The results presented here constitute the first-ever reported information on genome size in the genus Vitis vinifera in Pityusic, Balearic, and, in general, Spanish accessions, and they are one of the largest prospections in this field for this species anywhere. Further research should be conducted to explain the differences in nuclear DNA content found between landraces and cultivars studied here with others cultivated in different islands or countries to understand whether genome size varies in modern cultivars compared with local landraces. Additionally, it would be interesting to investigate whether there is a relationship between genome size and adaptations to diverse climatology conditions, crop management, and ripening characteristics.
Effects of Functional Coatings Containing Chitosan, Orange Peel and Olive Cake Extracts on the Quality Attributes of Cucumber during Cold Storage
Authors: Ghafoor Kashif , Al-Juhaimi Fahad Y. , Mohamed Ahmed Isam A. , Babiker Elfadil E. , Shahzad Syed Ali , Alsawmahi Omer N.
Published: July 2022

This study investigated the effect of functional coating using 2% chitosan and different concentrations of olive cake extract (OCE) and orange peel extract (OPE) on the physicochemical quality attributes of cucumber during cold storage at 4 °C for 21 days. Both coating and storage influenced (p ≤ 0.05) the physicochemical attributes of cucumber. The highest values of moisture content, total soluble solids (TSS), pH, total phenolic contents (TPC), DPPH radical scavenging activity, yellowness (b*), and hardness were found in coated samples, which also showed the lowest values of the lightness (L*), greenness (a*), total viable count (TVC), yeast and mold counts, and acidity (p ≤ 0.05). Uncoated cucumber samples showed the highest (p ≤ 0.05) levels of acidity, lightness, greenness, TVC, and yeast and mold count. During storage, concomitant (p ≤ 0.05) reduction in moisture, TSS, pH, TPC, DPPH radical scavenging activity, L*, a*, b*, and hardness along with concurrent (p ≤ 0.05) increment in acidity, TVC, and yeast and mold count were evident in all cucumber samples. Interestingly, the changes in the aforementioned attributes were minimal in functionally coated samples in comparison to uncoated ones, suggesting the potential of OCE and OPE to preserve quality attributes of cucumber during cold storage.
Estimation of Morphological Features and Essential Oil Content of Basils (Ocimum basilicum L.) Grown under Different Conditions
Authors: Juškevičienė Danguolė , Radzevičius Audrius , Viškelis Pranas , Maročkienė Nijolė , Karklelienė Rasa
Published: July 2022

This study was carried out in the experimental field and in unheated greenhouses of the Lithuanian Research Centre for Agriculture and Forestry Institute of Horticulture. The investigation aimed to evaluate the morphological features, amount of essential oil, and productivity of 10 basil (Ocimum basilicum L.) cultivars grown under different growing conditions. Studied cultivars were different according to morphological parameters, productivity, and the accumulation of essential oil. Most of the investigated parameters were influenced by growing conditions. Basil plants of cultivars Sweet Genovese and Toscano were determined to be the highest, and their height reached up to 70.5 cm. Cultivar Sweet Genovese was the most productive; its fresh herb mass per plant reached up to 0.71 kg under growing in the open field and greenhouse. Higher air temperature and constant watering of the soil in the greenhouse increased the accumulation of essential oils of basil. The biochemical analyses showed that the essential oil amount of 31% was higher when basils were grown in a greenhouse compared to an open field.
Heterologous Expression of Three Transcription Factors Differently Regulated Astragalosides Metabolic Biosynthesis in Astragalus membranaceus Hairy Roots
Authors: Li Xiao Hua , Kim Jae Kwang , Park Sang Un
Published: July 2022

Astragalus membranaceus has been used as a highly popular Chinese herbal medicine for centuries. Triterpenoids, namely astragalosides I, II, III, and IV, represent the main active compounds in this plant species. Transcription factors have a powerful effect on metabolite biosynthesis in plants. We investigated the effect of the Arabidopsis MYB12, production of anthocyanin pigment 1 (PAP1), and maize leaf color (LC) transcription factors in regulating the synthesis of astragaloside metabolites in A. membranaceus. Overexpression of these transcription factors in hairy roots differentially up-regulated these active compounds. Specifically, the overexpression of LC resulted in the accumulation of astragalosides I–IV. The content of astragalosides I and IV were, in particular, more highly accumulated. Overexpression of MYB12 increased the accumulation of astragaloside I in transgenic hairy roots, followed by astragaloside IV, and overexpression of PAP1 resulted in the increased synthesis of astragalosides I and IV. In addition, we found that overexpression of PAP1 together with LC increased astragaloside III levels. At the transcriptional level, several key genes of the mevalonate biosynthetic pathway, especially HMGR1, HMGR2, and HMGR3, were up-regulated differentially in response to these transcription factors, resulting in astragaloside synthesis in the hairy roots of A. membranaceus. Overall, our results indicated that heterologous expression of Arabidopsis MYB12, PAP1, and maize LC differentially affected triterpenoids biosynthesis, leading to the increased biosynthesis of active compounds in A. membranaceus.
Bioinformatics Study of Aux/IAA Family Genes and Their Expression in Response to Different Hormones Treatments during Japanese Apricot Fruit Development and Ripening
Authors: Iqbal Shahid , Hayat Faisal , Mushtaq Naveed , Khalil-ur-Rehman Muhammad , Khan Ummara , Yasoob Talat Bilal , Khan Muhammad Nawaz , Ni Zhaojun , Ting Shi , Gao Zhihong
Published: July 2022

Auxin/indole-3-acetic acid (Aux/IAA) is a transcriptional repressor in the auxin signaling pathway that plays a role in several plant growth and development as well as fruit and embryo development. However, it is unclear what role they play in Japanese apricot (Prunus mume) fruit development and maturity. To investigate the role of Aux/IAA genes in fruit texture, development, and maturity, we comprehensively identified and expressed 19 PmIAA genes, and demonstrated their conserved domains and homology across species. The majority of PmIAA genes are highly responsive and expressed in different hormone treatments. PmIAA2, PmIAA5, PmIAA7, PmIAA10, PmIAA13, PmIAA18, and PmIAA19 showed a substantial increase in expression, suggesting that these genes are involved in fruit growth and maturity. During fruit maturation, alteration in the expression of PmIAA genes in response to 1-Methylcyclopropene (1-MCP) treatment revealed an interaction between auxin and ethylene. The current study investigated the response of Aux/IAA development regulators to auxin during fruit ripening, with the goal of better understanding their potential application in functional genomics.