bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot Spot Analysis of YAP-TEAD Protein-Protein Interaction Using the Fragment Molecular Orbital Method and Its Application for Inhibitor Discovery
Authors: Kim Jongwan , Lim Hocheol , Moon Sungho , Cho Seon Yeon , Kim Minhye , Park Jae Hyung , Park Hyun Woo , No Kyoung Tai
Published: August 2021

The Hippo pathway is an important signaling pathway modulating growth control and cancer cell proliferation. Dysregulation of the Hippo pathway is a common feature of several types of cancer cells. The modulation of the interaction between yes-associated protein (YAP) and transcriptional enhancer associated domain (TEAD) in the Hippo pathway is considered an attractive target for cancer therapeutic development, although the inhibition of PPI is a challenging task. In order to investigate the hot spots of the YAP and TEAD1 interacting complex, an ab initio Fragment Molecular Orbital (FMO) method was introduced. With the hot spots, pharmacophores for the inhibitor design were constructed, then virtual screening was performed to an in-house library. Next, we performed molecular docking simulations and FMO calculations for screening results to study the binding modes and affinities between PPI inhibitors and TEAD1. As a result of the virtual screening, three compounds were selected as virtual hit compounds. In order to confirm their biological activities, cellular (luciferase activity, proximity ligation assay and wound healing assay in A375 cells, qRT-PCR in HEK 293T cells) and biophysical assays (surface plasmon resonance assays) were performed. Based on the findings of the study, we propose a novel PPI inhibitor BY03 and demonstrate a profitable strategy to analyze YAP–TEAD PPI and discover novel PPI inhibitors.
Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts
Authors: Ayesha  , Bilal Muhammad , Rasool Nasir , Khan Samreen Gul , Rashid Umer , Altaf Humaira , Ali Imtiaz
Published: August 2021

As part of natural products or biologically active compounds, the synthesis of nitrogen-containing heterocycles is becoming incredibly valuable. Palladium is a transition metal that is widely utilized as a catalyst to facilitate carbon-carbon and carbon-heteroatom coupling; it is used in the synthesis of various heterocycles. This review includes the twelve years of successful indole synthesis using various palladium catalysts to establish carbon-carbon or carbon-nitrogen coupling, as well as the conditions that have been optimized.
Roles of IgE and Histamine in Mast Cell Maturation
Authors: Tanaka Satoshi , Furuta Kazuyuki
Published: August 2021

Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases.
Multiple Solutions for Stagnation-Point Flow of Unsteady Carreau Fluid along a Permeable Stretching/Shrinking Sheet with Non-Uniform Heat Generation
Authors: Yang Dezhi , Israr Ur Rehman Muhammad , Hamid Aamir , Ullah Saif
Published: August 2021

The aim of the present study was to explore the effect of a non-uniform heat source/sink on the unsteady stagnation point flow of Carreau fluid past a permeable stretching/shrinking sheet. The novelty of the flow model was enhanced with additional effects of magnetohydrodynamics, joule heating, and viscous dissipation. The nonlinear partial differential equations were converted into ordinary differential equations with the assistance of appropriate similarity relations and were then tackled by employing the Runge-Kutta-Fehlberg technique with the shooting method. The impacts of pertinent parameters on the dimensionless velocity and temperature profiles along with the friction factor and local Nusselt number were extensively discussed by means of graphical depictions and tables. The current results were compared to the previous findings under certain conditions to determine the precision and validity of the present study. The fluid flow velocity of Carreau fluid increased with the value of the magnetic parameter in the case of the first solution, and the opposite behavior was noticed for the second solution. It was seen that temperature of the Carreau fluid expanded with the higher values of unsteadiness and magnetic parameters. It was visualized from multiple branches that the local Nusselt number declined with the Eckert number parameter for both the upper and lower branch.
Crystallization Behavior in Bi2O3-B2O3-ZnO Glass Braze and Its Application for Joining Ferrite Ceramics at a Relatively Low Temperature
Authors: Guo Wei , Fu Li , He Peng
Published: August 2021

50Bi2O3-30B2O3-20ZnO (mol.%) glass was designed and prepared in our previous work. On the basis of preliminary work on DSC analysis, the crystallization behavior of the glass was further investigated in the present work. The results showed that Bi38ZnO58 and Bi45BO69 crystals were formed in the glass during the heating process. Subsequently, ferrite ceramics were then brazed at one of the peak temperatures, 551 °C. The results showed that Bi38ZnO58 and Bi45BO69 crystals were formed in the joint domain, and the joint possessed a shear strength value of 76.6 MPa.
Cost-Effective Design of IoT-Based Smart Household Distribution System
Authors: Ahmed Musse Mohamud , Qays Md Ohirul , Abu-Siada Ahmed , Muyeen S. M. , Hossain Md Liton
Published: August 2021

The Internet of Things (IoT) plays an indispensable role in present-day household electricity management. Nevertheless, practical development of cost-effective intelligent condition monitoring, protection, and control techniques for household distribution systems is still a challenging task. This paper is taking one step forward into a practical implementation of such techniques by developing an IoT Smart Household Distribution Board (ISHDB) to monitor and control various household smart appliances. The main function of the developed ISHDB is collecting and storing voltage, current, and power data and presenting them in a user-friendly way. The performance of the developed system is investigated under various residential electrical loads of different energy consumption profiles. In this regard, an Arduino-based working prototype is employed to gather the collected data into the ThingSpeak cloud through a Wi-Fi medium. Blynk mobile application is also implemented to facilitate real-time monitoring by individual consumers. Microprocessor technology is adopted to automate the process, and reduce hardware size and cost. Experimental results show that the developed system can be used effectively for real-time home energy management. It can also be used to detect any abnormal performance of the electrical appliances in real-time through monitoring their individual current and voltage waveforms. A comparison of the developed system and other existing techniques reveals the superiority of the proposed method in terms of the implementation cost and execution time.
Polyprev: Randomized, Multicenter, Controlled Trial Comparing Fecal Immunochemical Test with Endoscopic Surveillance after Advanced Adenoma Resection in Colorectal Cancer Screening Programs: A Study Protocol
Authors: Regueiro Cristina , Almazán Raquel , Portillo Isabel , Besó María , Tourne-Garcia Carlos , Rodríguez-Camacho Elena , Ono Akiko , Gómez-Amorín Ángel , Cubiella Joaquín
Published: August 2021

Colorectal cancer (CRC) screening programs have been implemented to reduce the burden of the disease. When an advanced colonic lesion is detected, clinical practice guidelines recommend endoscopic surveillance with different intervals between explorations. Endoscopic surveillance is producing a considerable increase in the number of colonoscopies, with a limited effect on the CRC incidence. Instead, participation in CRC screening programs based on the fecal immunochemical test (FIT) could be a non-inferior alternative to endoscopic surveillance to reduce 10-year CRC incidence. Based on this hypothesis, we have designed a multicenter and randomized clinical trial within the Spanish population CRC screening programs to compare FIT surveillance with endoscopic surveillance. We will include individuals aged from 50 to 65 years with complete colonoscopy and advanced lesions resected within the CRC screening programs. Patients will be randomly allocated to perform an annual FIT and colonoscopy if fecal hemoglobin concentration is ≥10 µg/g, or to perform endoscopic surveillance. On the basis of the non-superior CRC incidence, we will recruit 1894 patients in each arm. The main endpoint is 10-year CRC incidence and the secondary endpoints are diagnostic yield, participation, adverse effects, mortality and cost-effectiveness. Our results may modify the clinical practice after advanced colonic resection in CRC screening programs.
Quantitative Evaluation Methods of Cluster Wind Power Output Volatility and Source-Load Timing Matching in Regional Power Grid
Authors: Liu Yongqian , Qiao Yanhui , Han Shuang , Xu Yanping , Geng Tianxiang , Ma Tiandong
Published: August 2021

The quantitative evaluation of cluster wind power output volatility and source-load timing matching is vital to the planning and operation of the future power system dominated by new energy. However, the existing volatility evaluation methods of cluster wind power output do not fully consider timing volatility, or are not suitable for small sample data scenarios. Meanwhile, the existing source-load timing matching evaluation indicator ignores the impact of wind power permeability on the timing matching degree between wind power output and load. Therefore, the authors propose quantitative evaluation methods of cluster wind power output volatility and source-load timing matching in regional power grid. Firstly, the volatility-based smoothing coefficient is defined to quantitatively evaluate the smoothing effect of wind-farm cluster power output. Then, the source-load timing matching coefficient considering wind power permeability is proposed to quantitatively evaluate the timing matching degree of regional wind power output and load, and the corresponding function model of volatility-based smoothing coefficient and source-load timing matching coefficient is established. Finally, the validity and applicability of the proposed methods are verified by MATLAB software based on the actual power output of 10 wind farms and actual grid load in a certain grid dispatching cross-section of northeast China. The results demonstrated that the proposed volatility-based smoothing coefficient can accurately represent the smoothing effect of wind farm cluster power output while maintaining the volatility continuity of wind power output time series and without affect from the data sample size. The source-load timing matching coefficient can accurately characterize the difference in the timing matching degree between wind power output and grid load under different wind power permeability and the influence degree on grid load.
MiRNAs and Cancer: Key Link in Diagnosis and Therapy
Authors: Shi Yu , Liu Zihao , Lin Qun , Luo Qing , Cen Yinghuan , Li Juanmei , Fang Xiaolin , Gong Chang
Published: August 2021

Since the discovery of the first microRNA (miRNA), the exploration of miRNA biology has come to a new era in recent decades. Monumental studies have proven that miRNAs can be dysregulated in different types of cancers and the roles of miRNAs turn out to function to either tumor promoters or tumor suppressors. The interplay between miRNAs and the development of cancers has grabbed attention of miRNAs as novel tools and targets for therapeutic attempts. Moreover, the development of miRNA delivery system accelerates miRNA preclinical implications. In this review, we depict recent advances of miRNAs in cancer and discuss the potential diagnostic or therapeutic approaches of miRNAs.
Regional Specific Differentiation of Integumentary Organs: Regulation of Gene Clusters within the Avian Epidermal Differentiation Complex and Impacts of SATB2 Overexpression
Authors: Lin Gee-Way , Lai Yung-Chih , Liang Ya-Chen , Widelitz Randall B. , Wu Ping , Chuong Cheng-Ming
Published: August 2021

The epidermal differentiation complex (EDC) encodes a group of unique proteins expressed in late epidermal differentiation. The EDC gave integuments new physicochemical properties and is critical in evolution. Recently, we showed β-keratins, members of the EDC, undergo gene cluster switching with overexpression of SATB2 (Special AT-rich binding protein-2), considered a chromatin regulator. We wondered whether this unique regulatory mechanism is specific to β-keratins or may be derived from and common to EDC members. Here we explore (1) the systematic expression patterns of non-β-keratin EDC genes and their preferential expression in different skin appendages during development, (2) whether the expression of non-β-keratin EDC sub-clusters are also regulated in clusters by SATB2. We analyzed bulk RNA-seq and ChIP-seq data and also evaluated the disrupted expression patterns caused by overexpressing SATB2. The results show that the expression of whole EDDA and EDQM sub-clusters are possibly mediated by enhancers in E14-feathers. Overexpressing SATB2 down-regulates the enriched EDCRP sub-cluster in feathers and the EDCH sub-cluster in beaks. These results reveal the potential of complex epigenetic regulation activities within the avian EDC, implying transcriptional regulation of EDC members acting at the gene and/or gene cluster level in a temporal and skin regional-specific fashion, which may contribute to the evolution of diverse avian integuments.
Geochemical Study on the Annual Variation of Oxygen Isotope and Chemical Composition of Groundwater in the Sho River Alluvium Fan, Toyama, Japan, as an Investigation of Selected Qualitative Aspects of Efficient Utilization of Groundwater Heat
Authors: Iwatake Kaname , Ueda Akira
Published: August 2021

Seasonal variations of water temperature, electric conductivity, and oxygen isotope and chemical composition of shallow groundwaters and river waters were determined in the Sho River alluvial fan, western Toyama Prefecture, Japan, to examine groundwater heat utilization for indoor climate control. Samples were collected at 31 sites every 2 months for 1 year and at 11 representative sites monthly. In addition, the results of monthly precipitation amount and oxygen isotope composition of precipitation collected within the region during the same period were also taken into account. The sources of the shallow groundwaters are a mixture of river water and precipitation. The contribution of precipitation to groundwater is generally small along the Sho River but reaches as much as 80% along the Oyabe River and in the south and west of the alluvial fan. Though the origin of the groundwater differs regionally, water temperature is fixed at around 15 °C throughout the year in the northern part of the alluvial fan, and open-type ground source heat pump systems can be used for cooling and heating there, if adequate quantitative aquifer properties (exploitable groundwater amounts) are present.
New System for Measuring Cosmogenic Ne in Terrestrial and Extra-Terrestrial Rocks
Authors: Györe Domokos , Di Nicola Luigia , Currie David , M. Stuart Finlay
Published: August 2021

Cosmogenic Ne isotopes are used for constraining the timing and rate of cosmological and Earth surface processes. We combined an automated gas extraction (laser) and purification system with a Thermo Fisher ARGUS VI mass spectrometer for high through-put, high precision Ne isotope analysis. For extra-terrestrial material with high cosmogenic Ne concentrations, we used multi-collection on Faraday detectors. Multiple measurements (n = 26) of 1.67 × 10−8 cm3 air-derived 20Ne yielded an uncertainty of 0.32%, and 21Ne/20Ne = 0.17% and 22Ne/20Ne = 0.09%. We reproduced the isotope composition of cosmogenic Ne in the Bruderheim chondrite and Imilac pallasite in a sub-ten mg sample. For lower Ne amounts that are typical of terrestrial samples, an electron multiplier detector was used in peak jumping mode. Repeated analysis of 3.2 × 10−11 cm3 STP 20Ne from air reproduced 21Ne/20Ne and 22Ne/20Ne with 1.1% and 0.58%, respectively, and 20Ne intensity with 1.7% (n = 103) over a 4-month period. Multiple (n = 8) analysis of cosmogenic Ne in CREU-1 quartz yielded 3.25 ± 0.24 × 108 atoms/g (2 s), which overlaps with the global mean value. The repeatability is comparable to the best data reported in the international experiments performed so far on samples that are 2–5× smaller. The ability to make precise Ne isotope determinations in terrestrial and extra-terrestrial samples that are significantly smaller than previously analysed suggests that the new system holds great promise for studies with limited material.
Healthcare Warranty Policies Optimization for Chronic Diseases Based on Delay Time Concept
Authors: Zhao Heng , Liu Zixian , Li Mei , Liang Lijun
Published: August 2021

Warranties for healthcare can be greatly beneficial for cost reductions and improvements in patient satisfaction. Under healthcare warranties, healthcare providers receive a lump sum payment for the entire care episode, which covers a bundle of healthcare services, including treatment decisions during initial hospitalization and subsequent readmissions, as well as disease-monitoring plans composed of periodic follow-ups. Higher treatment intensities and more radical monitoring strategies result in higher medical costs, but high treatment intensities reduce the baseline readmission rates. This study intends to provide a systematic optimization framework for healthcare warranty policies. In this paper, the proposed model allows healthcare providers to determine the optimal combination of treatment decisions and disease-monitoring policies to minimize the total expected healthcare warranty cost over the prespecified period. Given the nature of the disease progression, we introduced a delay time model to simulate the progression of chronic diseases. Based on this, we formulated an accumulated age model to measure the effect of follow-up on the patient’s readmission risk. By means of the proposed model, the optimal treatment intensity and the monitoring policy can be derived. A case study of pediatric type 1 diabetes mellitus is presented to illustrate the applicability of the proposed model. The findings could form the basis of developing effective healthcare warranty policies for patients with chronic diseases.
Trends in the Use of Naltrexone for Addiction Treatment among Alcohol Use Disorder Admissions in U.S. Substance Use Treatment Facilities
Authors: Qeadan Fares , Mensah Nana A. , Gu Lily Y. , Madden Erin F. , Venner Kamilla L. , English Kevin
Published: August 2021

Background: Naltrexone, a medication for addiction treatment (MAT), is an FDA-approved medication recommended for the treatment of alcohol use disorder (AUD). Despite the high prevalence of AUD and efficacy of naltrexone, only a small percentage of individuals with AUD receive treatment. Objectives: To identify trends for the prescription of naltrexone in AUD admissions in substance use treatment centers across the U.S. Methods: Data from the 2000–2018 U.S. Treatment Episode Data Set: Admissions (TEDS-A) were used in temporal trend analysis of naltrexone prescription in admissions that only used alcohol. Data from the 2019 National Survey of Substance Abuse Treatment Services (N-SSATS) were also used to characterize medication use among AUD clients across different treatment service settings. Results: Treatment of AUD with naltrexone was 0.49% in 2000 and tripled from 0.53% in 2015 to 1.64% in 2018 in AUD admissions (p < 0.0001 for the Cochran–Armitage trend test). Women, middle-aged adults, and admissions for clients living in the Northeast U.S. were more likely to be prescribed naltrexone than their respective counterparts, as were admissions with prior treatment episodes and referrals through alcohol/drug use care providers, who paid for treatment primarily through private insurance, used alcohol daily in the month prior to admission, and waited 1–7 days to enter treatment. Naltrexone was more commonly prescribed by AUD admissions compared to acamprosate and disulfiram and was more frequently prescribed in residential and outpatient services as opposed to hospital inpatient services. Conclusions: Naltrexone remains underutilized for AUD, and factors that influence prescription of medication are multifaceted. This study may contribute to the creation of effective interventions aimed at reducing naltrexone disparities for AUD.
Challenges and Controversies in the Surgical Treatment of Cervical Cancer: Open Radical Hysterectomy versus Minimally Invasive Radical Hysterectomy
Authors: Röseler Jona , Wolff Robert , Bauerschlag Dirk O. , Maass Nicolai , Hillemanns Peter , Ferreira Helder , Debrouwere Marie , Scheibler Fülöp , Geiger Friedemann , Elessawy Mohamed
Published: August 2021

Objective: The aim of the study was to perform a systematic assessment of disease-free survival (DFS), overall survival, and morbidity rates after open radical hysterectomy (ORH) and minimally invasive surgery (MIS) for early-stage cervical cancer and discuss with experts the consequences of the LACC trial (published by Ramirez et al. in 2018) on clinical routine. Methods: A total of 5428 records were retrieved. After exclusion based on text screening, four records were identified for inclusion. Five experts from three independent large-volume medical centers in Europe were interviewed for their interpretation of the LACC trial. Results: The LACC trial showed a significantly higher risk of disease progression with MIS compared to ORH (HR 3.74, 95% CI 1.63 to 8.58). This was not seen in one epidemiological study and was contradicted by one prospective cohort study reported by Greggi et al. A systematic review by Zhang et al. mentioned a similar DFS for robot-assisted radical hysterectomy (RRH) and LRH. Recurrence rates were significantly higher with MIS compared to ORH in the LACC trial (HR 4.26, 95% CI 1.44 to 12.60). In contrast, four studies presented by Greggi reported no significant difference in recurrence rates between LRH/RRH and ORH, which concurred with the systematic reviews of Zhang and Zhao. The experts mentioned various limitations of the LACC trial and stated that clinicians were obliged to provide patients with detailed information and ensure a shared decision-making process. Conclusions: The surgical treatment of early-stage cervical cancer remains a debated issue. More randomized controlled trials (RCT) will be needed to establish the most suitable treatment for this condition.
Fourth-Order Adjoint Sensitivity and Uncertainty Analysis of an OECD/NEA Reactor Physics Benchmark: I. Computed Sensitivities
Authors: Fang Ruixian , Cacuci Dan Gabriel
Published: August 2021

This work extends the investigation of higher-order sensitivity and uncertainty analysis from 3rd-order to 4th-order for a polyethylene-reflected plutonium (PERP) OECD/NEA reactor physics benchmark. Specifically, by applying the 4th-order comprehensive adjoint sensitivity analysis methodology (4th-CASAM) to the PERP benchmark, this work presents the numerical results of the most important 4th-order sensitivities of the benchmark’s total leakage response with respect to the benchmark’s 180 microscopic total cross sections, which includes 180 4th-order unmixed sensitivities and 360 4th-order mixed sensitivities corresponding to the largest 3rd-order ones. The numerical results obtained in this work reveal that the number of 4th-order relative sensitivities that have large values (e.g., greater than 1.0) is far greater than the number of important 1st-, 2nd- and 3rd-order sensitivities. The majority of those large sensitivities involve isotopes 1H and 239Pu contained in the PERP benchmark. Furthermore, it is found that for most groups of isotopes 1H and 239Pu of the PERP benchmark, the values of the 4th-order relative sensitivities are significantly larger than the corresponding 1st-, 2nd- and 3rd-order sensitivities. The overall largest 4th-order relative sensitivity S(4)σt,6g=30,σt,6g=30,σt,6g=30,σt,6g=30=2.720×106 is around 291,000 times, 6350 times and 90 times larger than the corresponding largest 1st-order, 2nd-order and 3rd-order sensitivities, respectively, and the overall largest mixed 4th-order relative sensitivity S(4)σt,630,σt,630,σt,630,σt,530=2.279×105 is also much larger than the largest 2nd-order and 3rd-order mixed sensitivities. The results of the 4th-order sensitivities presented in this work have been independently verified with the results obtained using the well-known finite difference method, as well as with the values of the corresponding symmetric 4th-order sensitivities. The 4th-order sensitivity results obtained in this work will be subsequently used on the 4th-order uncertainty analysis to evaluate their impact on the uncertainties they induce in the PERP leakage response.
A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond
Authors: Matsumoto Yoshitaka , Fukumitsu Nobuyoshi , Ishikawa Hitoshi , Nakai Kei , Sakurai Hideyuki
Published: August 2021

In this paper, we discuss the role of particle therapy—a novel radiation therapy (RT) that has shown rapid progress and widespread use in recent years—in multidisciplinary treatment. Three types of particle therapies are currently used for cancer treatment: proton beam therapy (PBT), carbon-ion beam therapy (CIBT), and boron neutron capture therapy (BNCT). PBT and CIBT have been reported to have excellent therapeutic results owing to the physical characteristics of their Bragg peaks. Variable drug therapies, such as chemotherapy, hormone therapy, and immunotherapy, are combined in various treatment strategies, and treatment effects have been improved. BNCT has a high dose concentration for cancer in terms of nuclear reactions with boron. BNCT is a next-generation RT that can achieve cancer cell-selective therapeutic effects, and its effectiveness strongly depends on the selective 10B accumulation in cancer cells by concomitant boron preparation. Therefore, drug delivery research, including nanoparticles, is highly desirable. In this review, we introduce both clinical and basic aspects of particle beam therapy from the perspective of multidisciplinary treatment, which is expected to expand further in the future.
PTGDR2 Expression in Peripheral Blood as a Potential Biomarker in Adult Patients with Asthma
Authors: García-Sánchez Asunción , Estravís Miguel , Martin Maria J. , Pérez-Pazos Jacqueline , Martín-García Cristina , Gil-Melcón María , Ramos-González Jacinto , Eguiluz-Gracia Ibon , Triviño Juan Carlos , Isidoro-García María , Dávila Ignacio , Sanz Catalina
Published: August 2021

Background: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Methods: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. Results: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients’ peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.
Contrastive Feature Typologies of Arabic Consonant Reflexes
Authors: Youssef Islam
Published: August 2021

Attempts to classify spoken Arabic dialects based on distinct reflexes of consonant phonemes are known to employ a mixture of parameters, which often conflate linguistic and non-linguistic facts. This article advances an alternative, theory-informed perspective of segmental typology, one that takes phonological properties as the object of investigation. Under this approach, various classificatory systems are legitimate; and I utilize a typological scheme within the framework of feature geometry. A minimalist model designed to account for segment-internal representations produces neat typologies of the Arabic consonants that vary across dialects, namely qāf,ǧīm,kāf, ḍād, the interdentals, the rhotic, and the pharyngeals. Cognates for each of these are analyzed in a typology based on a few monovalent contrastive features. A key benefit of the proposed typologies is that the featural compositions of the various cognates give grounds for their behavior, in terms of contrasts and phonological activity, and potentially in diachronic processes as well. At a more general level, property-based typology is a promising line of research that helps us understand and categorize purely linguistic facts across languages or language varieties.
Using an Improved Differential Evolution for Scheduling Optimization of Dual-Gantry Multi-Head Surface-Mount Placement Machine
Authors: Lin Cheng-Jian , Lin Chun-Hui
Published: August 2021

The difference between dual-gantry and single-gantry surface-mount placement (SMP) machines is that dual-gantry machines exhibit higher complexity and more problems due to their additional gantry robot, such as component allocation and collision. This paper presents algorithms to prescribe the assembly operations of a dual-gantry multi-head surface-mount placement machine. It considers five inter-related problems: (i) component allocation; (ii) automatic nozzle changer assignment; (iii) feeder arrangement; and (iv) pick-and-place sequence; it incorporates a practical restriction related to (v) component height. The paper proposes a solution to each problem: (i) equalizing “workloads” assigned to the gantries, (ii) using quantity ratio method, (iii) using two similarity measurement mechanisms in a modified differential evolution algorithm with a random-key encoding mapping method that addresses component height restriction, (iv) and a combination of nearest-neighbor search and 2-opt method to plan each placing operation. This study reports an experiment that involved the processing of 10 printed circuit boards and compared the performance of a modified differential evolution algorithm with well-known algorithms including differential evolution, particle swarm optimization, and genetic algorithm. The results reveal that the number of picks, moving distance of picking components, and total assembly time with the modified differential evolution algorithm are less than other algorithms.
Mathematical Modelling of Turbulent Combustion of Two-Phase Mixtures of Gas and Solid Particles with a Eulerian–Eulerian Approach: The Case of Hydrogen Combustion in the Presence of Graphite Particles
Authors: Nicolás-Pérez Francisco , Velasco F.J.S. , Otón-Martínez Ramón A. , García-Cascales José R. , Bentaib Ahmed , Chaumeix Nabiha
Published: August 2021

The numerical modelling of turbulent combustion of H2–air mixtures with solid graphite particles is a challenging and key issue in many industrial problems including nuclear safety. This study presents a Eulerian–Eulerian model based on the resolution of the Navier–Stokes equations via large eddy simulation (LES) coupled with a system of ordinary differential equations (ODEs) of the detailed chemical kinetics to simulate the combustion of mixtures of gases and particles. The model was applied to predict the transient evolution of turbulent combustion sequences of mixtures of hydrogen, air and graphite particles under low concentration conditions. When applied to simulate lab-scale combustion experiments, the results showed a good agreement between experimental and numerical data using a detailed chemical kinetic model. Moreover, the model was able to predict some key experimental tendencies and revealed that the presence of a low concentration of graphite particles (~96 g/m3) in the scenario influenced the hydrogen combustion dynamics for mixtures of 20% (in volume) of hydrogen in air. Under these conditions, pressure levels reached at the walls of the sphere were increased and the combustion time was shortened. The results also showed the viability of using this kind of a model for obtaining global combustion parameters such as wall pressure evolution with time.
On Various High-Order Newton-Like Power Flow Methods for Well and Ill-Conditioned Cases
Authors: Alharbi Talal , Tostado-Véliz Marcos , Alrumayh Omar , Jurado Francisco
Published: August 2021

Recently, the high-order Newton-like methods have gained popularity for solving power flow problems due to their simplicity, versatility and, in some cases, efficiency. In this context, recent research studied the applicability of the 4th order Jarrat’s method as applied to power flow calculation (PFC). Despite the 4th order of convergence of this technique, it is not competitive with the conventional solvers due to its very high computational cost. This paper addresses this issue by proposing two efficient modifications of the 4th order Jarrat’s method, which present the fourth and sixth order of convergence. In addition, continuous versions of the new proposals and the 4th order Jarrat’s method extend their applicability to ill-conditioned cases. Extensive results in multiple realistic power networks serve to sow the performance of the developed solvers. Results obtained in both well and ill-conditioned cases are promising.
Entropy-Driven Grain Boundary Segregation: Prediction of the Phenomenon
Authors: Lejček Pavel , Hofmann Siegfried
Published: August 2021

The question is formulated as to whether entropy-driven grain boundary segregation can exist. Such a phenomenon would be based on the assumption that a solute can segregate at the grain boundary sites that exhibit positive segregation energy (enthalpy) if the product of segregation entropy and temperature is larger than this energy (enthalpy). The possibility of entropy-driven grain boundary segregation is discussed for several model examples in iron-based systems, which can serve as indirect evidence of the phenomenon. It is shown that entropy-driven grain boundary segregation would be a further step beyond the recently proposed entropy-dominated grain boundary segregation as it represents solute segregation at “anti-segregation” sites.
PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma
Authors: Gutierrez Reyes Cristian D. , Huang Yifan , Atashi Mojgan , Zhang Jie , Zhu Jianhui , Liu Suyu , Parikh Neehar D. , Singal Amit G. , Dai Jianliang , Lubman David M. , Mechref Yehia
Published: August 2021

Currently, surveillance strategies have inadequate performance for cirrhosis and early detection of hepatocellular carcinoma (HCC). The glycosylation of serum haptoglobin has shown to have significant differences between cirrhosis and HCC, thus can be used for diagnosis. We performed a comprehensive liquid chromatography—parallel reaction monitoring—mass spectrometry (LC-PRM-MS) approach, where a targeted parallel reaction monitoring (PRM) strategy was coupled to a powerful LC system, to study the site-specific isomerism of haptoglobin (Hp) extracted from cirrhosis and HCC patients. We found that our strategy was able to identify a large number of isomeric N-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four N-glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples (p < 0.05). Strategic combinations of the significant N-glycopeptides, either with alpha-fetoprotein (AFP) or themselves, better estimate the areas under the curve (AUC) of their respective receiver operating characteristic (ROC) curves with respect to AFP. The combination of AFP with the isomeric sialylated fucosylated N-glycopeptides Asn207 + 5-6-1-2 and Asn207 + 5-6-1-3, resulted with an AUC value of 0.98, while the AUC value for AFP alone was 0.85. When comparing cirrhosis vs. early HCC, the isomeric N-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUCAFP = 0.81, and AUCAsn207 + 5-6-0-1 = 0.88, respectively).
Different Modes of Low-Frequency Focused Ultrasound-Mediated Attenuation of Epilepsy Based on the Topological Theory
Authors: Zhang Minjian , Li Bo , Liu Yafei , Tang Rongyu , Lang Yiran , Huang Qiang , He Jiping
Published: August 2021

Epilepsy is common brain dysfunction, where abnormal synchronized activities can be observed across multiple brain regions. Low-frequency focused pulsed ultrasound has been proven to modulate the epileptic brain network. In this study, we used two modes of low-intensity focused ultrasound (pulsed-wave and continuous-wave) to sonicate the brains of KA-induced epileptic rats, analyzed the EEG functional brain connections to explore their respective effect on the epileptic brain network, and discuss the mechanism of ultrasound neuromodulation. By comparing the brain network characteristics before and after sonication, we found that two modes of ultrasound both significantly affected the functional brain network, especially in the low-frequency band below 12 Hz. After two modes of sonication, the power spectral density of the EEG signals and the connection strength of the brain network were significantly reduced, but there was no significant difference between the two modes. Our results indicated that the ultrasound neuromodulation could effectively regulate the epileptic brain connections. The ultrasound-mediated attenuation of epilepsy was independent of modes of ultrasound.
Rational Design for Enhanced Acyltransferase Activity in Water Catalyzed by the Pyrobaculum calidifontis VA1 Esterase
Authors: Staudt Amanda , Terholsen Henrik , Kaur Jasmin , Müller Henrik , Godehard Simon P. , Itabaiana Ivaldo , Leal Ivana C. R. , Bornscheuer Uwe T.
Published: August 2021

Biocatalytic transesterification is commonly carried out employing lipases in anhydrous organic solvents since hydrolases usually prefer hydrolysis over acyl transfer in bulk water. However, some promiscuous acyltransferases can catalyze acylation in an aqueous solution. In this study, a rational design was performed to enhance the acyltransferase selectivity and substrate scope of the Pyrobaculum calidifontis VA1 esterase (PestE). PestE wild type and variants were applied for the acylation of monoterpene alcohols. The mutant PestE_I208A is selective for (–)-menthyl acetate (E-Value = 55). Highly active acyltransferases were designed, allowing for complete conversion of (–)-citronellol to citronellyl acetate. Additionally, carvacrol was acetylated but with lower conversions. To the best of our knowledge, this is the first example of the biocatalytic acylation of a phenolic alcohol in bulk water. In addition, a high citronellol conversion of 92% was achieved with the more environmentally friendly and inexpensive acyl donor ethyl acetate using PestE_N288F as a catalyst. PestE_N288F exhibits good acyl transfer activity in an aqueous medium and low hydrolysis activity at the same time. Thus, our study demonstrates an alternative synthetic strategy for acylation of compounds without organic solvents.
RNA Dynamics in Alzheimer’s Disease
Authors: Rybak-Wolf Agnieszka , Plass Mireya
Published: August 2021

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that heavily burdens healthcare systems worldwide. There is a significant requirement to understand the still unknown molecular mechanisms underlying AD. Current evidence shows that two of the major features of AD are transcriptome dysregulation and altered function of RNA binding proteins (RBPs), both of which lead to changes in the expression of different RNA species, including microRNAs (miRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs). In this review, we will conduct a comprehensive overview of how RNA dynamics are altered in AD and how this leads to the differential expression of both short and long RNA species. We will describe how RBP expression and function are altered in AD and how this impacts the expression of different RNA species. Furthermore, we will also show how changes in the abundance of specific RNA species are linked to the pathology of AD.
Enhanced Antibacterial Activity of CuS-BSA/Lysozyme under Near Infrared Light Irradiation
Authors: Swaidan Abir , Ghayyem Sena , Barras Alexandre , Addad Ahmed , Szunerits Sabine , Boukherroub Rabah
Published: August 2021

The synthesis of multifunctional photothermal nanoagents for antibiotic loading and release remains a challenging task in nanomedicine. Herein, we investigated a simple, low-cost strategy for the preparation of CuS-BSA nanoparticles (NPs) loaded with a natural enzyme, lysozyme, as an antibacterial drug model under physiological conditions. The successful development of CuS-BSA NPs was confirmed by various characterization tools such as transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Lysozyme loading onto CuS-BSA NPs was evaluated by UV/vis absorption spectroscopy, Fourier-transform infrared spectroscopy (FTIR), zeta potential, and dynamic light scattering measurements. The CuS-BSA/lysozyme nanocomposite was investigated as an effective means for bacterial elimination of B. subtilis (Gram-positive) and E. coli (Gram-negative), owing to the combined photothermal heating performance of CuS-BSA and lysozyme release under 980 nm (0.7 W cm−2) illumination, which enhances the antibiotic action of the enzyme. Besides the photothermal properties, CuS-BSA/lysozyme nanocomposite possesses photodynamic activity induced by NIR illumination, which further improves its bacterial killing efficiency. The biocompatibility of CuS-BSA and CuS-BSA/Lysozyme was elicited in vitro on HeLa and U-87 MG cancer cell lines, and immortalized human hepatocyte (IHH) cell line. Considering these advantages, CuS-BSA NPs can be used as a suitable drug carrier and hold promise to overcome the limitations of traditional antibiotic therapy.
Growth, Dietary Intake, and Vitamin D Receptor (VDR) Promoter Genotype in Indonesian School-Age Children
Authors: Angelin Tiffany Cornelia , Bardosono Saptawati , Shinta Dewi , Fahmida Umi
Published: August 2021

Nutrition has been known as a predominant factor associated with stunting. However, some studies have discovered a genetic contribution in calcium absorption that will affect growth, known as the VDR gene. The aim of this study was to assess the association between VDR gene polymorphism and dietary intake towards height-for-age z-score (HAZ) of elementary school children in Malang District, East Java. This study analyzed the baseline of a randomized trial in East Java, Indonesia. School children aged 8–10 years old (n = 142) were included in this study. Energy, protein, calcium, and vitamin D intakes were obtained using 4-day 24-h dietary recalls. Two SNPs located in the promoter region of VDR gene were selected (rs11568820 and rs4516035) and analyzed using Real-Time PCR. The result showed a significant correlation between energy and protein intake with HAZ of the children (p = 0.030 and p = 0.016, respectively). The association between VDR gene and HAZ was not found (p > 0.05). Adjusted by other factors, protein intake was significantly correlated with HAZ (β = 0.034, 95% CI 0.015–0.052, p < 0.001, adj. R2 = 0.089). The children in our study had a favorable VDR gene genotype, however the effect of VDR gene promoter activity might not be revealed due to very low vitamin D and calcium intake to stimulate intestinal calcium absorption which in turn affects HAZ.
Human Microbiota Network: Unveiling Potential Crosstalk between the Different Microbiota Ecosystems and Their Role in Health and Disease
Authors: Martínez Jose E. , Vargas Augusto , Pérez-Sánchez Tania , Encío Ignacio J. , Cabello-Olmo Miriam , Barajas Miguel
Published: August 2021

The human body is host to a large number of microorganisms which conform the human microbiota, that is known to play an important role in health and disease. Although most of the microorganisms that coexist with us are located in the gut, microbial cells present in other locations (like skin, respiratory tract, genitourinary tract, and the vaginal zone in women) also play a significant role regulating host health. The fact that there are different kinds of microbiota in different body areas does not mean they are independent. It is plausible that connection exist, and different studies have shown that the microbiota present in different zones of the human body has the capability of communicating through secondary metabolites. In this sense, dysbiosis in one body compartment may negatively affect distal areas and contribute to the development of diseases. Accordingly, it could be hypothesized that the whole set of microbial cells that inhabit the human body form a system, and the dialogue between the different host microbiotas may be a contributing factor for the susceptibility to developing diseased states. For this reason, the present review aims to integrate the available literature on the relationship between the different human microbiotas and understand how changes in the microbiota in one body region can influence other microbiota communities in a bidirectional process. The findings suggest that the different microbiotas may act in a coordinated way to decisively influence human well-being. This new integrative paradigm opens new insights in the microbiota field of research and its relationship with human health that should be taken into account in future studies.