bluuebunny/crossref_metadata_2025 huggingface dataset:
NBTI-Aware Power Gating Design with Dynamically Varying Stress Probability Control on Sleep Transistor
Authors: Bhattacharjee Abhishek , Pradhan Sambhu Nath
Published: March 2021

With the aggressive scaling of the transistor, Negative Bias Temperature Instability (NBTI) has become the most dominant aging effect which causes the device parameter to degrade over its lifetime. This device parameter degradation of logic gates in nanometer technology is a major concern for the reliability of the digital circuit. It becomes even more critical when it comes to power gating structure, as small NBTI effect on PMOS sleep transistor used in header-based power gating structure would seriously affect the reliability, performance of the whole logic circuit. The conventional method of mitigating the NBTI effect is to oversize the sleep transistor, but it also gives rise to leakage overhead. In this work, a novel NBTI aware power gating architecture is presented to improve the lifetime of the circuit. Here, sleep transistors (STs) are switched ON/OFF periodically and a greater number of STs are turned ON, when NBTI related degradation reaches to its threshold value so that STs get more time to anneal NBTI degradation and improve its lifetime. Simulation result on ISCAS’85 benchmark circuits shows for 40% sleep signal, an average of 51.2% and 14% lifetime improvement with respect to the conventional over-sizing (OS) technique and normal stress probability control method, respectively with some power and area overhead.
THE BIFRACTAL STRATIFIED CHARACTERIZATION OF A PLATEAU HONING CYLINDER LINER SURFACE PROFILE DURING THE WEARING PROCESS
Authors: WEI CHUNLING , ZHU HUA , LANG SHIHUI
Published: March 2021

In the current study, we propose a bifractal stratified characterization method to evaluate the surface profile evolution of a plateau honing cylinder liner during the wear process. This method is suitable for the characterization of two-process and worn surface profiles with bifractal and stratified characteristics. We develop a bifractal truncated separation structure function method to calculate the characterization parameters of the proposed method. In particular, the upper- and lower-strata surface profiles are truncated and separated in order to calculate their fractal parameters. Experimental results demonstrate the ability of the proposed method to outperform the traditional fractal method in characterizing the evolution of the plateau honing cylinder liner surface profile during the wearing process.
DYNAMICS OF SIR MATHEMATICAL MODEL FOR COVID-19 OUTBREAK IN PAKISTAN UNDER FRACTAL-FRACTIONAL DERIVATIVE
Authors: ALI ZEESHAN , RABIEI FARANAK , SHAH KAMAL , MAJID ZANARIAH ABDUL
Published: March 2021

There are still mathematical predictions in the fight against epidemics. Speedy expansion, ways and procedures for the pandemic control require early understanding when solutions with better computer-based mathematical modeling and prognosis are developed. Despite high uncertainty in each of these models, one of the important tools for public health management system is epidemiology models. The fractional order is shown to be more effective in modeling epidemic diseases, in relation to the memory effects. Notably, recently founded calculus tools, called fractal-fractional calculus, having a fractional order and fractal dimension, enable us to study the behavior of a real-world problem under both fractal and fractional tools. This paper is about the dynamical behavior of a new mathematical model of novel corona disease (COVID-19) under the fractal-fractional Atangana–Baleanu derivative. The considered model has three compartments, namely, susceptible, infected and recovered or removed (SIR). The existence and uniqueness of the model’s solution will be proved via Krasnoselskii’s and Banach’s fixed point theorems, respectively. The stability of the solution in the sense of Hyers–Ulam (HU) will be built up by nonlinear functional analysis. Moreover, the numerical simulations for different values of isolation parameters corresponding to various fractal-fractional orders are analyzed using fractional Adams–Bashforth (AB) method with two-step Lagrange polynomial. Finally, the obtained simulation results are applied to the real data of disease spread from Pakistan. The graphical interpretations demonstrate that increasing the isolation parameters which is caused by strict precautionary measures will reduce the disease infection transmission in society.
CALCULATION OF FRACTAL DIMENSION BASED ON ARTIFICIAL NEURAL NETWORK AND ITS APPLICATION FOR MACHINED SURFACES
Authors: ZHOU GUO , WANG XIAOHAO , FENG FENG , FENG PINGFA , ZHANG MIN
Published: March 2021

Fractal dimension ([Formula: see text]) is a widely used quantity to represent the irregularity of surfaces or profiles, e.g. it is often applied together with surface roughness to evaluate the quality of machined surfaces objectively and precisely. There are some conventional algorithms to calculate [Formula: see text] values through the morphological images of measured surfaces. However, the accuracies or efficiencies of these algorithms sometimes might be insufficient to satisfy the requirement of high-precision machining technology. In this paper, an artificial neural network (ANN) model is proposed to evaluate the [Formula: see text] value based on a single morphological image. First, the artificial fractal surfaces with preset ideal [Formula: see text] values are generated via Weierstrass–Mandelbrot (W–M) function. Then these surfaces are divided into a training dataset and a test dataset, which are used to train the ANN model and compare the model against the conventional algorithms (including box counting, power spectral density, autocorrelation function, structural function, and roughness scaling extraction with flatten order of 1), respectively. The accuracy and efficiency of [Formula: see text] calculation by using the trained ANN model are much superior. The mean relative error of ANN model is just 0.25%, while those of conventional algorithms are in the range of 2.22–9.33%. The average time cost for [Formula: see text] calculation of ANN model is 1.87[Formula: see text]ms, while those of conventional algorithms are in the range of 46[Formula: see text]ms–8[Formula: see text]s. Based on the advantages verified above, the trained ANN model is utilized to calculate the [Formula: see text] values of machined surfaces and investigate the influences of different cutting parameters. It is found that the [Formula: see text] values of machined surfaces could be influenced significantly by the feed rate, while the cutting speed and depth are relatively irrelevant.
Frame-cyclic operators and their properties
Authors: Alizadeh Moghaddam Nastaran , Janfada Mohammad
Published: March 2021

Motivated by frame-vector for a unitary system, we study a class of cyclic operators on a separable Hilbert space which is called frame-cyclic operators. The orbit of such an operator on some vector, namely frame-cyclic vector, is a frame. Some properties of these operators on finite- and infinite-dimensional Hilbert spaces and their relations with cyclic and hypercyclic operators are established. A lower and upper bound for the norm of a self-adjoint frame-cyclic operator is obtained. Also, construction of the set of frame-cyclic vectors is considered. Finally, we deal with Kato’s approximation of frame-cyclic operators and discuss their frame-cyclic properties.
Estimation of the Parameters of Generalized Inverse Weibull Geometric Distribution and its Application
Authors: Nasiri Parviz , Azarian Amir Abbas
Published: March 2021

Inverse Weibull distribution is one of the distributions having a wide use for modeling system reliability and survival analysis. Recently, some of the researchers have compounded these distributions with some others to improve their models. In this paper, we present the compounded generalized inverse Weibull with geometric distribution. To estimate the parameters, we discuss the maximum likelihood using EM algorithm and Bayesian estimation for compound parameter of distribution. Efficacy of estimators using EM algorithm and minimum distance method is compared using mean square error. Finally, this distribution is fitted to a real dataset.
Graph products and eccentric harmonic index
Authors: Azari Mahdieh
Published: March 2021

A graph invariant is any function on a graph that does not depend on a labeling of its vertices. One of the best known graph invariants successfully applied in chemical graph theory over the last decade is the harmonic index. It is defined for a graph [Formula: see text] as the sum of the terms [Formula: see text] over all edges [Formula: see text] of [Formula: see text], where [Formula: see text] and [Formula: see text] denote the degrees of the vertices [Formula: see text] and [Formula: see text] in [Formula: see text], respectively. The eccentric version of harmonic index has recently been proposed in an analogous way by replacing the vertex degrees with the vertex eccentricities. One of the main topics in chemical graph theory is to study how certain invariants of product graphs are related to the corresponding invariants of their components. Due to this, we investigate here the behavior of the eccentric version of harmonic index under various families of graph products and apply the derived results on some graphs of chemical and general interest.
Some algebraic and analytic properties of generalized tribonacci and generalized tribonacci-Lucas like polynomials
Authors: Badidja Salim , Hamdi Abdeldjabar
Published: March 2021

In this study, we give another formula to all the generalized tribonacci [Formula: see text] and generalized tribonacci-Lucas [Formula: see text] polynomials by using the combinatorial calculus and their sum. Then, we give the explicit formula of partial derivative of such polynomials [Formula: see text], [Formula: see text] with respect to one of those variables and describe some properties.
On existence and approximation of common fixed points in b-metric spaces
Authors: Ramesh Kumar D. , Prabavathy M. , Radenović S.
Published: March 2021

The purpose of this paper is to establish the uniqueness and existence of the common fixed point under generalized contractive conditions in [Formula: see text]-metric spaces with supportive examples. We also approximate the common fixed point by Jungck–Picard and Picard iteration procedures along with the [Formula: see text] property of the mappings. Further, [Formula: see text]-stability of Jungck–Picard iterative and [Formula: see text]-stability of Picard iterative schemes are proved.
Three-dimensional networked Na3V2(PO4)3/C composite as high-performance cathode for aqueous zinc-ion battery
Authors: Fan Xiaoyong , Sun Ruibo , Han Jiaxing , Wu Yan , Gou Lei , Li Donglin
Published: March 2021

Na3V2(PO[Formula: see text] (NVP) as one typical Na[Formula: see text] super ionic conductor (NASICON) is recognized as an ideal cathode material for ZIBs owing to its promising structural stability that facilitates long cycle, rich vacancies and channels facilitate storing metal ions, high operating potentials to ensure high energy density. However, it still faces poor cyclability and high-rate capacity. Here, three-dimensional networked Na3V2(PO[Formula: see text]/C composite is synthesized by a microemulsion strategy with cetyltrimethyl ammonium bromide (CTAB) as the soft template, and the effect of aging temperature of microemulsion on their morphology and electrochemical performance is investigated. The Na3V2(PO[Formula: see text]/C composite derived from the precursor reacted at 70[Formula: see text]C shows micrometer-size particles assembled by three-dimensional networked nanoplates, facilitating for ions transport and delivers the best electrochemical performance. It displays a high first capacity of 102.2 mAh g[Formula: see text] with 42.3 mAh g[Formula: see text] remained after 5000 stable cycles (capacity retention of 41.4%) at 5 C, a high capacity of 83.2 mAh g[Formula: see text] even the current density is as high as 20 C, which is better than most of the reports.
Skew cyclic codes over 𝔽q[u,v,w]/〈u2 − 1,v2 − 1,w2 − 1,uv − vu,vw − wv,wu − uw〉
Authors: Prakash Om , Patel Shikha
Published: March 2021

In this paper, we study skew cyclic codes over the ring [Formula: see text] where [Formula: see text]; [Formula: see text] is an odd prime. Here, the structural properties, generating polynomials and idempotent generators of the skew cyclic codes are obtained. Also, we show that the Gray images of skew cyclic codes of length [Formula: see text] over [Formula: see text] are skew 8-quasi-cyclic codes of length [Formula: see text].
On δ(k)-coloring of powers of helm and closed helm graphs
Authors: Ellumkalayil Merlin Thomas , Naduvath Sudev
Published: March 2021

If the availability of colors to color a graph [Formula: see text] is less than that of the chromatic number [Formula: see text] of the graph, then coloring the graph with available colors, say [Formula: see text] colors, where [Formula: see text], will cause the end vertices of at least one edge to be colored with same color. Such an edge whose end vertices receive a same color is called as a bad edge. A coloring that restricts few color classes to have adjacency between the elements in it so as to minimize the number of bad edges obtained from it in a graph [Formula: see text] is called as a near proper coloring and a near proper coloring that uses [Formula: see text] colors where [Formula: see text] to color a graph [Formula: see text] by permitting only one color class to have adjacency among the elements in it and thereby minimize the number of bad edges resulting from the permitted color class is called as a [Formula: see text]-coloring of the graph [Formula: see text]. In this paper, we determine the number of bad edges of powers of helm graphs [Formula: see text] and powers of closed helm graphs [Formula: see text].
Chapter 3 Thrusts, extensional faults and fold patterns of the major units
Authors: Scharf Andreas , Mattern Frank , Al-Wardi Mohammed , Frijia Gianluca , Moraetis Daniel , Pracejus Bernhard , Bauer Wilfried , Callegari Ivan
Published: March 2021

This chapter is concerned with the main faults and folds within the Southeastern Oman Mountains based on available literature. The main, best and most widely exposed thrusts are those related to the SW-directed late Cretaceous obduction of the allochthonous nappes onto the Arabian platform and margin. These thrusts are related to obduction of rocks, which had formed hundreds of kilometres offshore Oman. The thrusts were active from the Cenomanian to the Campanian. Obduction-related thrusts and folds are spectacularly exposed within the rocks of the Arabian platform in the eastern part of the Saih Hatat Dome, including large-scale recumbent cylindrical folds and sheath folds. At least six fold sets can be studied in the Southeastern Oman Mountains. At least two of them had formed prior to obduction and are exposed in the Pre-Permian formations of the Jabal Akhdar Dome. At least three fold sets formed in the course of obduction, while at least one fold set is postobductional in age. Besides the compressional structures, the Oman Mountains expose major post-obductional extensional faults, mostly at the margins of the Jabal Akhdar and Saih Hatat domes. The throw of these faults amounts to a few to several kilometres. Finally, this chapter provides an overview of the enigmatic Batinah Mélange which consists of slivers of Hawasina rocks, resting (unusually) structurally above the Semail Ophiolite.
Chapter 6 Conclusions, differences between the Jabal Akhdar and Saih Hatat domes and unanswered questions
Authors: Scharf Andreas , Mattern Frank , Al-Wardi Mohammed , Frijia Gianluca , Moraetis Daniel , Pracejus Bernhard , Bauer Wilfried , Callegari Ivan
Published: March 2021

This chapter provides the conclusions/outlines of the tectonics, affecting the Southeastern Oman Mountains, including the Jabal Akhdar and Saih Hatat domes. The main tectonic events include amongst others (1) Neoproterozoic rifting, (2) two distinct early Paleozoic compressive events, (3) large-scale open ‘Hercynian’ folding and formation of a pronounced unconformity during the late Paleozoic, (4) rifting preceding the opening of the Neo-Tethys Ocean during the late Paleozoic, (5) late Cretaceous obduction of the Semail Ophiolite and the response of the Arabian lithosphere as well as (6) post-obductional tectonics. Also of major geological significance are the three major glaciations (Sturtian, Marinoan and Late Paleozoic Gondwana glaciation) which have been recorded in the rocks of northern Oman. Moreover, major lithological, structural and metamorphic differences exist between the Jabal Akhdar and Saih Hatat domes. It appears likely that a major fault, striking parallel to the eastern margin of the Jabal Akhdar Dome, probably originating during Neoproterozoic terrain accretion, acted as a divide between both domes until present. This fault was multiple times reactivated and could explain the differences between the two domes. A catalogue of unanswered questions is included in chronological order to express that many geological aspects need further investigation and future research projects.
Cutting-Edge Single-Molecule Technologies Unveil New Mechanics in Cellular Biochemistry
Authors: Banerjee Souradeep , Chakraborty Soham , Sreepada Abhijit , Banerji Devshuvam , Goyal Shashwat , Khurana Yajushi , Haldar Shubhasis
Published: March 2021

Single-molecule technologies have expanded our ability to detect biological events individually, in contrast to ensemble biophysical technologies, where the result provides averaged information. Recent developments in atomic force microscopy have not only enabled us to distinguish the heterogeneous phenomena of individual molecules, but also allowed us to view up to the resolution of a single covalent bond. Similarly, optical tweezers, due to their versatility and precision, have emerged as a potent technique to dissect a diverse range of complex biological processes, from the nanomechanics of ClpXP protease–dependent degradation to force-dependent processivity of motor proteins. Despite the advantages of optical tweezers, the time scales used in this technology were inconsistent with physiological scenarios, which led to the development of magnetic tweezers, where proteins are covalently linked with the glass surface, which in turn increases the observation window of a single biomolecule from minutes to weeks. Unlike optical tweezers, magnetic tweezers use magnetic fields to impose torque, which makes them convenient for studying DNA topology and topoisomerase functioning. Using modified magnetic tweezers, researchers were able to discover the mechanical role of chaperones, which support their substrate proteinsby pulling them during translocation and assist their native folding as a mechanical foldase. In this article, we provide a focused review of many of these new roles of single-molecule technologies, ranging from single bond breaking to complex chaperone machinery, along with the potential to design mechanomedicine, which would be a breakthrough in pharmacological interventions against many diseases.
Amino acids differ in their capacity to stimulate GLP-1 release from the perfused rat small intestine and stimulate secretion by different sensing mechanisms
Authors: Modvig Ida Marie , Kuhre Rune Ehrenreich , Jepsen Sara Lind , Xu Stella Feng Sheng , Engelstoft Maja Storm , Egerod Kristoffer Lihme , Schwartz Thue Walther , Ørskov Cathrine , Rosenkilde Mette Marie , Holst Jens Juul
Published: March 2021

Using isolated perfused rat small intestines, we show that amino acids differ in their mechanisms and capacity of stimulating GLP-1 release. Furthermore, we demonstrate that sensing by GPR142, GPR35, GPR93, and the umami taste receptor (Tas1R1/Tas1R3) are not involved in amino acid stimulated GLP-1 release. In contrast to previous studies, this experimental model allows discrimination between the luminal and the vascular side of the intestine, which is essential when studying mechanisms of amino acid-stimulated GLP-1 secretion.
Disparate roles of retinoid acid signaling molecules in kidney disease
Authors: Chen Anqun , Liu Yu , Lu Yu , Lee Kyung , He John Cijiang
Published: March 2021

Retinoic acid (RA) exerts pleotropic cellular effects, including induction of cell differentiation while inhibiting proliferation and inflammation. These effects are mediated by both RA responsive element-dependent or -independent pathways. In kidneys, RA confers renoprotection by signaling through podocyte RA receptor (RAR)α and activation of cAMP/PKA/Kruppel-like factor 15 pathway to promote podocyte differentiation. Nevertheless, in kidney disease settings, RA can also promote podocyte apoptosis and loss through downstream expression of RAR responder protein 1, a recently described risk factor for glomerular disease progression. These disparate roles of RA underscore the complexity of its effects in kidney homeostasis and disease, and a need to target specific RA-mediated pathways for effective therapeutic treatments against kidney disease progression.
Applications of New Double Integral Transform (Laplace–Sumudu Transform) in Mathematical Physics
Authors: Ahmed Shams A.
Published: March 2021

The primary purpose of this research is to demonstrate an efficient replacement of double transform called the double Laplace–Sumudu transform (DLST) and prove some related theorems of the new double transform. Also, we will discuss the fundamental properties of the double Laplace–Sumudu transform of some basic functions. Then, by utilizing those outcomes, we will apply it to the partial differential equations to show its simplicity, efficiency, and high accuracy.
A Novel Ship-Ship Distance Model in Restricted Channel via Gaussian-TRR Identification
Authors: Zhang Jie , Zhang Yingjun
Published: March 2021

Very large ships are crucial cargo ships that are relatively difficult to manoeuvre, and ship-ship distance is a vital manoeuvring parameter in restricted channel. To ensure ship safety and improve scheduling efficiency, this study established a ship-ship distance model in restricted channel by ship manoeuvring motion simulation, collision detection, and identification modelling. Firstly, the ship manoeuvring model calculated the forces and moments of ship-ship interaction and ship-bank interaction. Then, the collision detection was applied to calculate the intersection area of ship collision. Secondly, the discrete numerical simulation approach was employed with varying speed and distance, and the intersection area was counted. Finally, the 3D Gaussian models of encountering and overtaking were identified by the trust-region-reflective (TRR) algorithm, and ship-ship distance and prohibited zone were proposed. The results show that the minimum ship-ship distance for encountering and overtaking is 1.50 and 2.4 ship beam, respectively, which is consistent with Japan’s standard. The numerical results revealed that the prohibited zone is an elliptical shape. The ship-ship distance and prohibited zone serve as ship safety domain for collision avoidance during harbor approaching.
Study of Zuojin Pill in Treating Chronic Atrophic Gastritis by UPLC-Q-TOF/MS Based on Serum and Urine Metabolomics Combined with Network Pharmacology
Authors: Wu Shihua , Chen Xing , Liu Honghong , Wang Ruilin , Li Jianyu , Wen Jianxia , Yang Tao , Wei Ying , Ren Sichen , Wei Shizhang , Jing Manyi , Li Haotian , Wang Min , Xia Houlin , Zhao Yanling
Published: March 2021

Zuojin Pill (ZJP) is widely used for the treatment of gastrointestinal diseases, while its specific mechanism has not been systematically investigated. The aim of this study was to explore the therapeutic effects and potential mechanism of ZJP in chronic atrophic gastritis (CAG) through UPLC-Q-TOF/MS-based metabolomics combined with network pharmacology. ZJP and omeprazole significantly reduce contents of IL-1β, IL-6, IL-10, and iNOS and improve pathological characteristics. Metabolomic results indicated that the therapeutic effects of ZJP were mainly related to ten metabolites, namely, choline, L-threonine, hydroxypyruvic acid, creatine, taurine, succinic acid, cis-aconitic acid, citric acid, succinic acid semialdehyde, and uric acid. Pathway analysis showed that the treatment of CAG by ZJP was associated with taurine and hypotaurine metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; citrate cycle (TCA cycle), alanine, aspartate, and glutamate metabolism; butanoate metabolism; and purine metabolism. Validation of metabolic markers and key targets of network pharmacology through RT-PCR analysis showed that ZJP significantly downregulated a series of inflammatory markers, such as MAPK1, PKIA, RB1, SCN5A, RXRA, E2F1, PTGS1, IGF2, ADRB1, ADRA1B, PTGS2, and GABRA1. This study was the first to use a combination of metabolomics and network pharmacology to clarify the therapeutic effects of ZJP on CAG and the regulation of multiple metabolic pathways.
Path Optimization along Buoys Based on the Shortest Path Tree with Uncertain Atmospheric and Oceanographic Data
Authors: Xue Han , Chai Tian
Published: March 2021

In order to design an optimized route for ships in line with economic benefits; avoid bad weather; reduce unnecessary detours; shorten the navigation time; and achieve the purpose of safety, fuel saving, and punctual arrival, this paper takes the navigation mark as the node of the tree, takes the connection of the adjacent navigation marks as the tree path, and divides the distance of the adjacent buoys by the ship’s speed as the path cost. The speed calculation collects the current hydrometeorological data such as wind and wave data, uses Aertssen’s deceleration formula to adjust the speed, and improves Dijkstra to find the shortest path. In the experiment, two routes from Dongdu to Xiamen Gang Kou are compared under bad weather conditions. Route 1 is with 5.877 m/s average wind speed, 0.860 m/s wave speed, and total distance 34717 m. Route 2 is with 8.503 m/s average wind speed, 1.429 m/s wave speed, and total distance 30223 m. The calculated ship speed travelling in route 1 is 12.243 km, and its travelling time is 1.53 h. The calculated ship speed travelling in route 2 is 10.523 km, and its travelling time is 1.55 h. Although the total distance of route 1 is longer, it takes less time for ships to travel in route 1. The experimental results verify the effectiveness of the navigation algorithm based on the shortest path tree of uncertain weather maps.
From Digital Divide to Information Availability: A Wi‐Fi‐Based Novel Solution for Information Dissemination
Authors: Majeed Muhammad Faran , Abbasi Irshad Ahmed , Ali Sikandar , Mustafa Elfatih Elmubarak , Hussain Ibrar , Saeed Khalid , Abrar Muhammad Faisal , No Mah E. , Khattak Muhammad Kashif
Published: March 2021

Digital divide means unequal access to the people for information and communication technology (ICT) facilities. The developed countries are comparatively less digitally divided as compared to developing countries. This study focuses on District Chitral considering its geographical conditions and high mountainous topography which plays a significant role in its isolation. Aside from the digital divide, the situation in Chitral is even more severe in terms of the absence of basic ICT infrastructure and electricity in the schools. To address this issue, especially in female secondary and higher secondary schools, we designed a project to bridge the digital divide via Wireless Local Area Network on Raspberry Pi3 for balancing the ICT facilities in the targeted area. The Wi‐Fi‐Based Content Distributors (Wi‐Fi‐BCDs) were provided to bridge the digital divide in rural area schools of Chitral. The Wi‐Fi‐BCD is a solar‐based system that is used to deliver quality educational contents directly to classroom, library, or other learning environments without electricity connection and Internet wire as these facilities are available by default in it. The close‐ended questionnaire was adopted to collect data from the students, teachers, and headmistresses of girl secondary and higher secondary schools in Chitral. The procedure of validity, reliability, regression, correlation, and exploratory factor analysis was used to analyze the obtained data. The technology acceptance model (TAM) was modified and adopted to examine the effects of Wi‐Fi‐BCD for bridging the digital divide. The relationship of the modified TAM model was examined through regression and correlation to verify the model fitness according to the data obtained. The result analysis of this study shows that the relationship of the modified TAM model with its variables is positively significant, while the analysis of path relationship between model variables and outcomes from the questionnaire shows that it motivates learners to use Wi‐Fi‐BCD.
Phytochemicals of Rhus spp. as Potential Inhibitors of the SARS-CoV-2 Main Protease: Molecular Docking and Drug-Likeness Study
Authors: Sherif Yousery E. , Gabr Sami A. , Hosny Nasser M. , Alghadir Ahmad H. , Alansari Rayan
Published: March 2021

Background. The outbreak of coronavirus disease 2019 (COVID-19) induced by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in China and spread to cover the entire world with an ongoing pandemic. The magnitude of the situation and the fast spread of the new and deadly virus, as well as the lack of specific treatment, led to a focus on research to discover new therapeutic agents. Aim. In this study, we explore the potential inhibitory effects of some active polyphenolic constituents of Rhus spp. (sumac) against the SARS-CoV-2 main protease enzyme (Mpro; 6LU7). Methods. 26 active polyphenolic compounds of Rhus spp. were studied for their antiviral activity by molecular docking, drug likeness, and synthetic accessibility score (SAS) as inhibitors against the SARS-CoV-2 Mpro. Results. The results show that all tested compounds of sumac provided good interaction with the main active site of SARS-CoV-2 Mpro, with better, lower molecular docking energy (kcal/mol) compared to the well-known drugs chloroquine and favipiravir (Avigan). Only six active polyphenolic compounds of Rhus spp. (sumac), methyl 3,4,5-trihydroxybenzoate, (Z)-1-(2,4-dihydroxyphenyl)-3-(3,4-dihydroxyphenyl)-2-hydroxyprop-2-en-1-one, (Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxybenzofuran-3(2H)-one, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chroman-4-one, 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxy-4H-chroman-4-one, and 3,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one, were proposed by drug likeness, solubility in water, and SAS analysis as potential inhibitors of Mpro that may be used for the treatment of COVID-19. Conclusion. Six phenolic compounds of Rhus spp. are proposed for synthesis as potential inhibitors against Mpro and have potential for the treatment of COVID-19. These results encourage further in vitro and in vivo investigations of the proposed ligands and research on the preventive use of Rhus spp. against SARS-CoV-2.
Chronic Serotonergic Overstimulation Mimicking Panic Attacks in a Patient with Parkinson’s Disease Receiving Additional Antidepressant Treatment with Moclobemide
Authors: Praetner Marc , Schiele Timo , Werle Lukas , Kuffer Janina , Nischwitz Sandra , Keck Martin E. , Kloiber Stefan
Published: March 2021

Background. The pharmacological treatment options of Parkinson’s disease (PD) have considerably evolved during the last decades. However, therapeutic regimes are complicated due to individual differences in disease progression as well as the occurrence of complex nonmotor impairments such as mood and anxiety disorders. Antidepressants in particular are commonly prescribed for the treatment of depressive symptoms and anxiety in PD. Case Presentation. In this case report, we describe a case of a 62-year-old female patient with PD and history of depressive symptoms for which she had been treated with moclobemide concurrent with anti-Parkinson medications pramipexole, rasagiline, and L-DOPA+benserazide retard. An increase in the dosage of moclobemide 12 months prior to admission progressively led to serotonergic overstimulation and psychovegetative exacerbations mimicking the clinical picture of an anxiety spectrum disorder. After moclobemide and rasagiline were discontinued based on the hypothesis of serotonergic overstimulation, the patient’s psychovegetative symptoms subsided. Conclusions. The specific pharmacological regime in this case probably caused drug-drug interactions resulting in a plethora of psychovegetative symptoms. Likely due to the delayed onset of adverse effects, physicians had difficulties in determining the pharmacologically induced serotonin toxicity. This case report emphasizes the complexity of pharmacological treatments and the importance of drug-drug interaction awareness in the treatment of PD patients with complicating nonmotor dysfunctions such as depression.
Abstract IA-09: Mapping cell structure across scales by fusing protein images and interactions
Authors: Ideker Trey
Published: March 2021

Cancer cells are multi-scale structures with modular organization across at least four orders of magnitude. Two central approaches for mapping this structure – protein fluorescent imaging and protein interaction – each generate extensive datasets but of distinct qualities and resolutions that are typically treated separately. Here, I will describe ongoing efforts to reconcile the large-scale data emerging from protein imaging and protein affinity purification interaction screens to create unified maps of cancer cells. The core concept is to use machine learning to compute a suitable embedding for each dataset, then to use these data embeddings to produce a general measure of protein distance calibrated against cellular components of known size. The evolving map, called the Multi-Scale Integrated Cell (MuSIC 1.0), currently resolves 69 subcellular systems of which approximately half are undocumented. Based on these findings we have performed 134 additional affinity purifications, validating close subunit associations for the majority of systems. I will also discuss how these cell maps can be used to identify protein complexes, and larger-scale systems such as organelles, that are under significant selective pressure for somatic mutations in different tumor types. In many of these cases, the mutation burden of the complex is far more substantial than the mutation frequency of any of the individual genes that encode it. By integration across scales, MuSIC substantially increases the mapping resolution obtained from imaging while giving protein interactions a spatial dimension, paving the way to incorporate many molecular data types in proteome-wide maps of cells. This work is a collaboration between the Cancer Cell Mapping Initiative (CCMI), the Human Protein Atlas (HPA), and the BioPlex Resource.

Citation Format: Trey Ideker. Mapping cell structure across scales by fusing protein images and interactions [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-09.
Abstract PO-054: Development of machine learning based early warning for rapid response system in a single cancer center
Authors: Kho Bo-Gun , Kim Min-Seok , Kim Tae-Ok , Park Cheol-Kyu , Kim Young-Chul , Kim Soo-Hyung , Oh In-Jae
Published: March 2021

Background: Rapid response systems identify deteriorating hospitalized patients and prevent unexpected mortality by providing immediate interventions. But there are also difficulties in costs and human resources for clinical implementation. Machine learning is an application of artificial intelligence that provides systems the ability to automatically learn and improve from experience without being explicitly programmed. We try to develop a machine learning based early warning system to predict intubation and cardiopulmonary resuscitation (CPR) using vital signs and laboratory values. Methods: The training set was composed of all patients admitted to a cancer hospital named Chonnam National University Hwasun Hospital for two years (event group 277 vs. non-event group 3576 cases), and the test set was made from all patients admitted to non-cancer hospital named Chonnam National University Hospital for four months (event group 61 vs. non-event group 2334 cases). The time point at which the patient's clinical deterioration was recognized in the ward was defined as ‘detection time’, and the time point at which the patient suffered airway intubation or CPR was defined as ‘event time’. The algorithm is developed using five vital signs (blood pressure, heart rate, body temperature, respiratory rate and oxygen saturation) and laboratory values. We compared the efficacy of developed models which were ensemble model, recurrent neural network (RNN), low gradient boosting (LGB), extreme gradient boosting (XGB) and random forest with established modified early warning score (MEWS) using receiver operating characteristic area under curve (ROC AUC) and precision recall AUC (PR AUC) analyses. Results: The ROC AUC value of the ensemble model using five vital signs was 0.9219 and the PR AUC was 0.0732. After adding laboratory values, the ROC AUC values of the ensemble, RNN, LGB, XGB, random forest improved to 0.9964, 0.9814, 0.9950, 0.9862 and 0.9962. The PR AUC values were also increased to 0.2326, 0.2140, 0.3252, 0.2095 and 0.1985, respectively. The developed models showed higher performance than MEWS (ROC AUC: 0.7253, PR AUC: 0.0468) Conclusion: Machine learning based early warning system using vital signs and laboratory results was feasible. And the performance was better than traditional MEWS model because the ensemble model showed highest value in ROC AUC and LGB showed highest value in PR AUC.

Citation Format: Bo-Gun Kho, Min-Seok Kim, Tae-Ok Kim, Cheol-Kyu Park, Young-Chul Kim, Soo-Hyung Kim, In-Jae Oh. Development of machine learning based early warning for rapid response system in a single cancer center [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-054.
Thinking Differently about Cancer Treatment Regimens
Authors: Settleman Jeff , Neto João M. Fernandes , Bernards René
Published: March 2021

Most experimental cancer drugs ultimately fail during the course of clinical development, contributing to the high cost of the few that are granted regulatory approval. Moreover, approved drugs often deliver only modest clinical benefit to patients with advanced disease due to the development of resistance. Here, we discuss opportunities we consider promising to overcome drug resistance associated with interactions between signaling pathways and the presence of multiple coexisting cell states within tumors with distinct vulnerabilities. We highlight how understanding drug-resistance mechanisms can enable innovative treatment regimens that deliver longer-lasting benefit to patients.
Calcitonin Gene-Related Peptide Protects Against Cardiovascular Dysfunction Independently of Nitric Oxide In Vivo
Authors: Argunhan Fulye , Thapa Dibesh , Aubdool Aisah Aniisah , Carlini Emanuele , Arkless Kate , Hendrikse Erica Ruth , de Sousa Valente Joao , Kodji Xenia , Barrett Brentton , Ricciardi Carlo Alberto , Gnudi Luigi , Lucy Hay Debbie , Brain Susan Diana
Published: March 2021

The neuropeptide CGRP (calcitonin gene-related peptide) is a potent vasodilator, with a cardioprotective role, although the precise mechanisms are unclear. Here we show the ability of endogenous and exogenous CGRP to restore blood pressure, when nitric oxide synthesis is blocked, in a model of cardiovascular disease associated with endothelial dysfunction and impaired nitric oxide production. Male wild-type and αCGRP knockout mice received L-nitro-arginine methyl ester (150 mg/kg in drinking water) to induce a sustained hypertension with evidence of cardiovascular remodeling. The hypertensive response was exacerbated in L-nitro-arginine methyl ester-treated αCGRP knockouts, indicating that endogenous αCGRP acts in a protective manner, when nitric oxide production is diminished. Exogenous CGRP rescued αCGRP knockout mice from both hypertension and cardiovascular remodeling. Further studies using a nonrecovery protocol with a CGRP receptor antagonist (BIBN4096 BS) revealed that CGRP acts via the canonical CGRP receptor (CLR [calcitonin-like receptor]/RAMP1 [receptor activity-modifying protein]); with no effect of an antagonist (AC187) of a second CGRP-responsive receptor (the amylin-1 receptor, CTR [calcitonin receptor]/RAMP1). Blood flow, in resistance vessels of the exteriorised mesentery, was investigated. Noradrenaline–induced vasoconstriction with recovery, in L-nitro-arginine methyl ester-treated wild-type mice. However, αCGRP knockout, or BIBN4096 BS-treated wild-type mice demonstrated a similar constrictor response to noradrenaline, but significantly impaired blood flow recovery. The combined findings highlight that αCGRP protects against cardiovascular dysfunction, signaling via the canonical CGRP receptor and acting when nitric oxide production is lost, such as in endothelial dysfunction associated with vascular disease. These in vivo results support the proposal that CGRP provides a novel treatment for cardiovascular disease.
Impact of Therapeutic Inertia on Long-Term Blood Pressure Control
Authors: Augustin Alexandry , Coutts Louise , Zanisi Lorenzo , Wierzbicki Anthony S. , Shankar Francesco , Chowienczyk Phil J. , Floyd Christopher N.
Published: March 2021

Antihypertensive drug treatment is based on stepped titration in response to elevated blood pressure (BP) measurements. However, measurements do not necessarily represent an individual’s true BP (due to random error and biological variability), and medications are not always increased when measurements are above target (therapeutic inertia). We developed a Monte Carlo model with a 10-year horizon to investigate how measurement error impacted systolic BP (SBP) control in the presence of therapeutic inertia. When SBP measurements were in the range 140 to 159 mm Hg, the probability of escalating treatment was determined by a Bernoulli probability mass function parameterized by weighting functions exploring distinct inertia profiles. Simulating inertia with the weighting function that approximated to clinical practice resulted in ≈50% of individuals failing to achieve their SBP target within the 10-year time horizon. An inverse relationship was observed between measurement error and SBP control. This suggests that the value of accurate SBP measurement is only realized if it changes the underlying probability of inertia—that is, patients/clinicians believe a measurement to be accurate and so are more likely to act upon it. Removal of inertia during treatment initiation (ie, stepped titration until SBP measurement was below target) improved true SBP control for all simulations. Our simulations show that the impact of therapeutic inertia during treatment initiation persists during long-term follow-up. Strategies to remove therapeutic inertia during treatment initiation (ie, dual antihypertensive therapy) are likely to improve long-term BP control irrespective of BP measurement technique.
Plasma Leptin and Blood Pressure Progression in Blacks
Authors: Kaze Arnaud D. , Musani Solomon K. , Bidulescu Aurelian , Correa Adolfo , Bertoni Alain G. , Ahima Rexford S. , Golden Sherita H. , Abdalla Marwah , Echouffo-Tcheugui Justin B.
Published: March 2021

Data on the relation of plasma leptin with blood pressure (BP) progression among Blacks are scant. We evaluated the association of plasma leptin levels with BP progression and incident hypertension among Blacks. We analyzed a total of 1190 Jackson Heart Study participants without hypertension at baseline (2000–2004) who attended ≥1 follow-up visit (2005–2008 or 2009–2013). Modified Poisson regression was used to generate multivariable-adjusted risk ratios (RRs) and 95% CIs for BP progression (an increase by ≥1 BP category) and incident hypertension (BP ≥130/80 or use of antihypertensive medication). Of the 1190 participants, 64.1% were women (n=763), mean age was 48 (SD: 12) years. Over a median of 7 years, 71.3% progressed to a higher BP category (n=848) and 64.6% developed hypertension (n=769). After adjusting for confounders, each SD increment in log-leptin was associated with higher risks of BP progression (RR, 1.10 [95% CI, 1.03–1.18],
P
=0.007) and incident hypertension (RR, 1.14 [95% CI, 1.05–1.23],
P
=0.002). Compared with those in the lowest leptin quartile, participants in the highest quartile had significantly higher risks of BP progression (RR, 1.27 [95% CI, 1.05–1.54],
P
trend
=0.007) and incident hypertension (RR, 1.32 [95% CI, 1.07–1.64], Ptrend=0.010). These associations were consistent across multiple BP classifications. Our findings from a large cohort of Blacks support the notion that plasma leptin concentrations may help identify an at-risk population that could be targeted for hypertension prevention and management strategies in future studies.
Predictive Importance of Blood Pressure Characteristics With Increasing Age in Healthy Men and Women
Authors: Vishram-Nielsen Julie K.K. , Kristensen Anna M. Dyrvig , Pareek Manan , Laurent Stephane , Nilsson Peter M. , Linneberg Allan , Greve Sara V. , Palmieri Luigi , Giampaoli Simona , Donfrancesco Chiara , Kee Frank , Mancia Giuseppe , Cesana Giancarlo , Veronesi Giovanni , Grassi Guido , Kuulasmaa Kari , Salomaa Veikko , Palosaari Tarja , Sans Susana , Ferrieres Jean , Dallongeville Jean , Söderberg Stefan , Moitry Marie , Drygas Wojciech , Tamosiunas Abdonas , Peters Annette , Brenner Hermann , Grimsgaard Sameline , Savallampi Matti , Olsen Michael H. ,   On behalf of the MORGAM Project
Published: March 2021

It remains unclear which blood pressure (BP) characteristics best predict cardiovascular risk in different age groups and between sexes. We leveraged data from the MORGAM (MONICA [Monitoring of Trends and Determinants in Cardiovascular Disease], Risk, Genetics, Archiving and Monograph) Project to investigate determinants of BP characteristics and their prognostic importance, in younger and older (</≥50 years) men and women. The study population comprised 107 599 individuals (53% men) aged 19 to 97 years without established cardiovascular disease, not on antihypertensive treatment, recruited between 1982 and 2008 in 38 cohorts. Covariates of BP characteristics were explored using multivariable linear regression. Prognostic importance was examined using multivariable Cox proportional-hazards regression, area under the receiver operating characteristic curve, and net reclassification improvement. The primary end point was a composite cardiovascular end point (CEP), defined as fatal or nonfatal stroke, death from coronary heart disease or nonfatal myocardial infarction. The positive association between age and systolic BP was more pronounced among individuals ≥50 years while the same was true for diastolic BP in those <50 years (
P
interaction <0.001). Higher systolic BP and mean BP were significantly associated with cardiovascular end point, irrespective of age group (
P
<0.001), but diastolic BP only demonstrated an independent relationship in the younger group (
P
<0.001). Brachial pulse pressure was associated with cardiovascular end point in the older age group (
P
<0.001). In subjects <50 years, diastolic BP significantly improved area under the receiver operating characteristic curve compared with Systematic Coronary Risk Evaluation variables (including systolic BP) alone (0.842 versus 0.840,
P
=0.03), enhanced continuous net reclassification improvement (0.150 [95% CI, 0.087–0.215]) and improved the prognostic value of the European Society of Cardiology/European Society of Hypertension hypertension definition (categorical net reclassification improvement=0.0255,
P
=0.005). In conclusion, diastolic BP may provide additional prognostic utility beyond systolic BP, in predicting composite cardiovascular events among younger individuals.