bluuebunny/crossref_metadata_2025_split huggingface dataset:
A methodology for creating thermostabilized mutants of G‐protein coupled receptors by combining statistical thermodynamics and evolutionary molecular engineering
Authors: Sugaya Kanna , Yasuda Satoshi , Sato Shingo , Sisi Chen , Yamamoto Taisei , Umeno Daisuke , Matsuura Tomoaki , Hayashi Tomohiko , Ogasawara Satoshi , Kinoshita Masahiro , Murata Takeshi 
Published: August 2022

AbstractWe constructed a methodology for thermostabilizing a G‐protein coupled receptor (GPCR) in the inactive state whose wild‐type (WT) structure is unknown solely by multiple amino‐acid mutations without the ligand binding. It is a combination of our recently developed theory based on statistical thermodynamics and site‐directed saturation mutagenesis, a method often employed in evolutionary molecular engineering. First, the WT structure is predicted using the homology modeling. Second, a key residue is determined by our statistical‐thermodynamics theory using suitably modeled mutant structures. Many of 19 different single mutations for the key residue are expected to produce significantly higher stabilization. Third, we undertake to mutate not only the key residue but also a few more residues whose side chains are close to the side chain of the key residue. The whole mutational space is then efficiently explored by introducing site‐directed saturation mutations, and a gene (mutant) library is constructed using the small‐intelligent and fully automatic single‐tube recombination methods. Each mutant is expressed in Escherichia coli cells, and highly stabilized mutants are sorted out using a fluorescence‐screening technique. The methodology was illustrated for the serotonin 2A receptor, 5‐HT2AR, for stabilizing its inactive state. We could identify a double mutant whose apparent midpoint temperature of thermal denaturation is higher than that of a thermostabilized double mutant previously reported by ~8.9°C and that of the WT by over 15°C. Moreover, it exhibits higher binding affinity for spiperone, an antagonist which was previously proved to stabilize 5‐HT2AR in the inactive state.
CHARMM‐GUIhigh‐throughput simulator for efficient evaluation of protein–ligand interactions with different force fields
Authors: Guterres Hugo , Park Sang‐Jun , Zhang Han , Perone Thomas , Kim Jongtaek , Im Wonpil 
Published: August 2022

AbstractMolecular docking is one of the most popular computational tools for the hit discovery step in drug design. However, there is ample room for improvement of docking's ability to identify correct binding modes and discriminate active from decoy compounds. Molecular dynamics (MD) simulations of protein–ligand docking structures have been shown to be effective in improving docking results. Here, we present CHARMM‐GUI high‐throughput simulator (HTS) that prepares MD simulation systems and inputs for multiple protein–ligand complex structures in a high‐throughput manner. HTS supports commonly used MD programs (NAMD, GROMACS, AMBER, OpenMM, GENESIS, Desmond, LAMMPS, and Tinker) along with various force field combinations for protein and ligand, including CHARMM36m, Amber (ff19SB/ff14SB), OPLS‐AA/M, CGenFF, GAFF2, and OpenFF. Validation tests using Miller and the directory of useful decoys‐enhanced (DUD‐E) datasets demonstrate that short MD simulations using HTS‐generated systems and simple ligand RMSD calculations consistently outperform docking results. Specifically, MD simulations can better identify correct ligand‐binding modes among top 10 binding poses as compared to docking scores. In addition, MD simulations can better discriminate active from decoy compounds in the DUD‐E dataset than docking scores for both soluble and membrane proteins. We expect that HTS can be a useful tool to facilitate the hit discovery process in drug design by improving docking results.
Asymptotic output tracking control with prescribed transient performance of nonlinear systems in the presence of unknown dynamics
Authors: Liu Yong‐Hua , Chen Lang‐Lei , Zhou Qi , Su Chun‐Yi 
Published: August 2022

AbstractIn this article, we address the problem of asymptotic output tracking control with prescribed transient performance for a class of nonlinear systems in the presence of unknown dynamics. By fusing the funnel control approach and the tool of barrier Lyapunov function, a smooth adaptive tracking control strategy is developed in a recursive manner. In the proposed design, a new barrier Lyapunov function is adopted to eliminate the effects of unknown nonlinear dynamics, ensuring the prescribed transient behavior of the output tracking. The distinctive characteristic of the proposed method is that the designed control algorithm can guarantee not only prescribed output tracking performance but also global asymptotic stability without incorporating any prior knowledge of nonlinear dynamics or even corresponding bounding functions. Three illustrative examples are provided to testify the effectiveness of the proposed method.
Dual H2O2‐Amplified Nanofactory for Simultaneous Self‐Enhanced NIR‐II Fluorescence Activation Imaging and Synergistic Tumor Therapy
Authors: Zheng Ziliang , Chen Xuejiao , Ma Yanchun , Dai Rong , Wu Shutong , Wang Tong , Xing Jun , Gao Jinnan , Zhang Ruiping 
Published: August 2022

AbstractActivatable fluorescence imaging in the second near‐infrared window (NIR‐II FL, 1000–1700 nm) is of great significance for accurate tumor diagnosis and targeting therapy. However, the clinical translation of most stimulus‐activated nanoprobes is severely restricted by insufficient tumor response and out‐of‐synchronization theranostic process. Herein, an intelligent nanofactory AUC‐GOx/Cel that possesses the “external supply, internal promotion” dual H2O2‐amplification strategy for homologous activated tumor theranostic is designed. This nanofactory is constructed via a two‐step biomineralization method using Au‐doped Ag2S as a carrier for glucose oxidase (GOx) and celastrol, followed by the growing of CuS to “turn off” the NIR‐II FL signal. In the overexpressed H2O2 tumor‐microenvironment, the CuS featuring a responsive‐degradability behavior can effectively release Cu ions, resulting in the “ON” state of NIR‐II FL and Fenton‐like activity. The exposed GOx can realize the intratumoral H2O2 supply (external supply) via the effective conversion of glucose, and mediating tumor‐starvation therapy; the interaction of celastrol and mitochondria can offer a substantial increase in the endogenous H2O2 level (internal promotion), thereby significantly promoting the chemodynamic therapy (CDT) efficacy. Meanwhile, the dual H2O2‐enhancement performance will in turn accelerate the degradation of AUC‐GOx/Cel, and achieve a positive feedback mechanism for self‐reinforcing CDT.
Identification of late blight resistance quantitative trait loci in Solanum pimpinellifolium accession PI 270441
Authors: Sullenberger Matthew T. , Jia Mengyuan , Gao Sihui , Ashrafi Hamid , Foolad Majid R. 
Published: August 2022

AbstractLate blight (LB), caused by the oomycete Phytophthora infestans, is one of the most destructive diseases of the cultivated tomato (Solanum lycopersicum L.) and potato (Solanum tuberosum L.) worldwide. Genetic changes in the pathogen have resulted in the emergence of new genotypes, overcoming formerly effective fungicides or host resistance genes. We previously reported the identification of a LB‐resistant accession (PI 270441) of the wild tomato species S. pimpinellifolium L. and the high heritability of its resistance. In the present study, an F2 population (n = 1,209), derived from a cross between PI 270441 and a LB‐susceptible tomato breeding line (Fla. 8059), was screened for response to LB infection. Extreme resistant (n = 44) and susceptible (n = 39) F2 individuals were selected and used in a trait‐based marker analysis (TBA; a.k.a selective genotyping) to identify and map quantitative trait loci (QTLs) conferring LB resistance. Reduced representation libraries (RRLs) of Fla. 8059 and PI 270441 were constructed, sequenced, and mapped to the tomato genome. A total of 13,054 single‐nucleotide polymorphisms (SNPs) were identified, of which, 200 were used to construct a genetic linkage map and locate QTLs. Four LB resistance QTLs were identified on chromosomes 1, 10, and 11 of PI 270441. The markers associated with these QTLs can be used to transfer LB resistance from PI 270441 into new tomato cultivars and to develop near‐isogenic lines for fine mapping of the QTL.
Fostering Civic Reasoning Through Disciplinary Literacy
Authors: Zhang Jie , Lee Grace , Iluore Azizah Curry , Relyea Jackie Eunjung , Wui Ma. Glenda L. 
Published: August 2022

AbstractIn this article, the authors introduce ways to use disciplinary literacy (DL) instructional strategies to foster civic engagement and reasoning for middle‐grade multilingual students. Four phases of DL strategies—framing, reading, discussion, and writing—are illustrated with examples from an intervention project with sixth‐grade multilingual students. The intervention features a 4‐week Space Exploration unit designed for students to address a contestable and relevant civic question: Should the government increase or decrease funding for space exploration? Teacher instructional moves, reading selections, student discussion excerpts, and writing samples are presented to highlight the language‐rich disciplinary teaching and learning in action and the benefits of multilingual students in their science, language, and literacy learning.
Nonwoven viscose fabric‐polyvinyl alcohol based flexible composite
Authors: Chatterjee Arobindo , Singh Harwinder , Chaudhary Khushboo 
Published: August 2022

AbstractDevelopment of ecofriendly packaging materials is still a challenging area. Researchers are continuously working to improve the mechanical and barrier properties of the different polymers which are used in the packaging industry. Selection of reinforcement and matrix for any composite are based upon end use applications. The novelty of the work is development of fully biodegradable, flexible, lightweight biocomposite by reinforcing needle punched flexible nonwoven viscose fabric to the PVA solution. The effect of PVA concentration and areal density of viscose fabric on the properties of prepared composite is examined. The composite thus prepared is assessed in terms of mechanical, thermal, breathability, and UV blocking properties. The nonwoven viscose‐PVA composite shows excellent improvement in tensile strength of 100% to 300% with respect to PVA film of equivalent concentration for two different areal densities of viscose fabric. The composite also exhibits improved thermal stability and UV blocking property with respect to parent components. However, a reduction in flexibility (with respect to PVA film) as well as breathability (with respect to viscose fabric) of the composite is observed. Based upon the improved performance of the viscose‐PVA composite in terms of mechanical properties, UV and water vapor permeability, it seems that the composite has a strong potential for application in the packaging sector as a flexible as well as biodegradable composite.
Metakaolin‐based geopolymer for mercury removal from model wastewater
Authors: Santos Ilídio Deocleciano Salomão Dos , Bao Shen Xu , Musah Baba Imoro 
Published: August 2022

AbstractMercury is recognized as a serious hazard, nature bioaccumulative and persistent to the environment. Developing a low‐cost, effective, eco‐friendly adsorbent for removing mercury constitutes an urgent task. In this study, metakaolin‐based geopolymer (MKG) was synthesized and applied to remove mercury from model wastewater by adsorption. The samples were characterized by X‐ray fluorescence (XRF), Brunauer–Emmett–Teller (BET), X‐ray diffraction (XRD) pattern, Fourier transform infrared (FTIR), and scanning electron microscope (SEM). They confirmed the synthesis of geopolymer due to the mass loss (LOI), crystallinity, peak changes, increase in surface area, and pore size. The highest removal efficiency recorded was 65.1%, with a corresponding adsorption capacity of 38.1 mg/g for MKG in 50 mg of dosage, 50 mg/L initial concentration, at a temperature of 25°C, contact time of 5 h and optimal pH of 3. The kinetic studies showed that mercury removal increased with the contact time until equilibrium after an hour. The adsorption equilibrium data were best described by Freundlich, whereas the pseudo‐second‐order model best fitted the adsorption kinetics. This may be indicative that chemisorption controlled the adsorption process. The stability studies of MKG adsorbent within the four reagents revealed that MKG has good stability in water, followed by 10% HCl, 3M NaCl, and 5% NaOH. In contrast, the desorption revealed the MKG represented the highest desorption efficiency in 10% HCl, followed by 3M NaCl, deionized water and 5% NaOH, respectively. The highest desorption efficiency was 96.83% for 10% HCl, followed by 91.83% for 3M NaCl, 82.55% for H2O, and 50.72% for 5% NaOH.Practitioner Points

A low‐cost metakaolin‐based geopolymer (MKG) was synthesized and applied as an adsorbent for removing Hg(II).
The most dominant mechanism involved in the removal process of Hg(II) was chemisorption.
The maximum adsorption capacity obtained in this study was 38.1 mg/g.
Hg(II) removal is influenced by pH zeta potential and temperature.
MKG shows good potential for the effective removal of mercury from modeled wastewater.
Introduction to the National Health Insurance of Taiwan
Authors: Po-Chang Lee  
Published: August 2022

AbstractThis chapter provides an overview of Taiwan’s National Health Insurance (NHI) system. In 1995, major social insurance programmes, such as labour insurance, government employee health insurance and farmers’ insurance, were merged and enlarged to form the NHI to deliver universal health coverage. Since its inception, the payment system of the NHI is the fee-for-service method. Moreover, most of the health care is provided by private sectors, and there are no restrictions on patients seeking medical care. Owing to the high medical accessibility, the volume of outpatient services is high, and the National Health Insurance Administration (NHIA) has to develop various measures to maintain its financial stability. Several strategies have been implemented by the NHIA for health equity, and the NHI MediCloud system, the NHI card and ‘My Health Bank’ were provided to ensure patients’ safety and enhance healthcare quality.
Coverage of Advanced Treatments and Medical Devices
Authors: (Mary) Tai Hsueh-Yung , Chang Yu-Pin 
Published: August 2022

AbstractThis chapter is primarily about the rationale and decision-making process of including advanced treatments (immuno-oncology therapy, hepatitis B and C medications), tests (next-generation sequencing, NGS) and medical devices in the benefits package of the National Health Insurance.Because of the high prevalence of hepatic cirrhosis and advancement in treatment, Taiwan aims to expand the coverage of hepatitis B treatment and eradicate hepatitis C by 2025. This chapter documents the history and achievements in the expansion of reimbursed indications. As for NGS, although it is recognized as essential for personalized oncology treatment, it requires regulation support to expand its coverage.The chapter ends with discussion in detail regarding why and how National Health Insurance Administration (NHIA) expanded its coverage for medical devices as well as strategies used to improve price transparency for out-of-pocket medical devices.
Kompetenzrahmen: Digitale Kompetenzen in der öffentlichen Verwaltung
Authors: Catakli Derya 
Published: August 2022

ZusammenfassungWie in den ersten Teilen der Ausarbeitung aufgezeigt werden konnte, sind im Umgang mit digitalen Technologien und Anwendungen zusätzliche digitale Kompetenzen erforderlich, die sich nicht in fachlichen Kompetenzen erschöpfen, sondern auch methodischer, sozialer oder personaler Art sein können. Durch die hauptsächlichrechtlichen, prozessualen und strukturellen Vorgaben, denen die Verwaltung unterworfen ist, bietet sich ein abgesteckter Rahmen, innerhalb dessen digitale Kompetenzen konkretisiert werden können.
Digitale Kompetenzen in der Personalakquise
Authors: Catakli Derya 
Published: August 2022

ZusammenfassungIn den vorigen Kapiteln wurden die Grundlagen digitaler Technologien und damit verknüpfter Kompetenzen erläutert. Die digitale Transformation der Verwaltung wurde unter v.a. rechtlichen und strategischen, strukturellen und personellen Aspekten untersucht. Die gefundenen Erkenntnisse wurden zu einem Kompetenzrahmen kondensiert, der digitale Kompetenzen in der Verwaltung in der Breite abdeckt.
Fazit
Authors: Catakli Derya 
Published: August 2022

ZusammenfassungNachdem die gesamte Ausarbeitung die aufgeworfenen Fragen jeweils punktuell beleuchtet hat, ist im folgenden letzten Teil ein Gesamtresümee zu ziehen. Zunächst werden die grundlegenden Forschungsfragen beantwortet und die gefundenen Ergebnisse beleuchtet, um sodann Schlüsse für die Verwaltung, insbesondere die vorherrschende Einstellungspraxis, und für die nachfolgende Forschung zu ziehen.
Skalierbarkeit von PROFINET over TSN für ressourcenbeschränkte Geräte
Authors: Leßmann Gunnar , Gamper Sergej , Albrecht Janis , Schriegel Sebastian 
Published: August 2022

ZusammenfassungIndustrie 4.0 erfordert eine flexible und von der Feldebene (Sensoren und Aktoren) bis in das Internet durchgängige und skalierbare Kommunikationslösung. IEEE 802.1 Ethernet TSN (Time-Sensitive Networking) und Single Pair Ethernet werden als Netzwerktechnologien gesehen, welche dazu einen wichtigen Beitrag leisten können. Zu den Protokollen, die auf Basis dieser skalierbaren Ethernet-Netzwerke genutzt werden können oder genutzt werden, gehören Profinet und OPC UA. Ein SPE-fähiges Gerät sollte mit einem Prozessorsystem mit wenigen kByte Speicher auskommen, da ein solches System u. U. sehr preissensitiv ist und aufgrund der begrenzten Wärmeabgabemenge nur sehr wenig Energie aufnehmen darf. Entsprechend muss neben der Netzwerktechnologie auch das genutzte Protokoll skalierbar sein. Sowohl Profinet als auch OPC UA beinhalten bereits heute Skalierungsmöglichkeiten durch Profile. Die Grenzen dieser Profile und Vorschläge zur Erweiterung dieser Grenzen werden im Beitrag diskutiert.
Systematic Test Environment for Narrowband IoT Technologies
Authors: Sebastian Jubin E. , Sikora Axel 
Published: August 2022

AbstractSpatially Distributed Wireless Networks (SDWN) are one of the basic technologies for the Internet of Things (IoT) and (Industrial) Internet of Things (IIoT) applications. These SDWN for many of these applications has strict requirements such as low cost, simple installation and operations, and high potential flexibility and mobility. Among the different Narrowband Wireless Wide Area Networking (NBWWAN) technologies, which are introduced to address these categories of wireless networking requirements, Narrowband Internet of Things (NB-IoT) is getting more traction due to attractive system parameters, energy-saving mode of operation with low data rates and bandwidth, and its applicability in 5G use cases. Since several technologies are available and because the underlying use cases come with various requirements, it is essential to perform a systematic comparative analysis of competing technologies to choose the right technology. It is also important to perform testing during different phases of the system development life cycle. This paper describes the systematic test environment for automated testing of radio communication and systematic measurements of the performance of NB-IoT.
Concept for Rule-Based Information Aggregation in Modular Production Plants
Authors: Geng Christoph , Moriz Natalia , Bunte Andreas , Trsek Henning 
Published: August 2022

AbstractIn the context of Industrie 4.0, (Self-)adapting Cyber-Physical Production Systems (CPPS) offer a solution for production facilities to adapt to changing market requirements. The operation of a CPPS requires information of the entire plant at any time, which can usually be derived by aggregating the individual information of the production modules of a CPPS (information models). Even if the information models are designed following standardized guidelines, the aggregation of these individual information models often needs to be done manually, which requires a lot of effort and is error prone. To achieve an automated information aggregation, this paper presents a novel concept for modular production plants. The main aspect of the concept is the use of a Rule Engine for the processing of information models in order to create aggregated plant information. This Rule Engine uses a classification method for plant components in order to enable standardization. The challenge of this work is to design a Rule Engine that is suitable for different aspects of CPPS.
Automatische Bewertung und Überwachung von Safety & Security Eigenschaften: Strukturierung und Ausblick
Authors: Ehrlich Marco , Trsek Henning , Benk Stefan , Harder Dimitri , Kleen Philip , Schriegel Sebastian , Jasperneite Jürgen 
Published: August 2022

ZusammenfassungUm die Sicherheit von industriellen Fertigungsanlagen von der Entwicklung über den Betrieb bis zur Entsorgung zu gewährleisten, werden bestimmte regulative und normative Anforderungen gestellt. Durch die Vernetzung und die weiteren Entwicklungen im Rahmen der Industrie 4.0 wird der manuelle Aufwand zum Erreichen dieser Sicherheit immer größer und nahezu nicht mehr durchführbar, gerade für kleine und mittelständische Unternehmen. Deswegen untersucht diese Arbeit die vorhandenen Problemstellungen genauer und gibt einen Ausblick auf die möglichen Lösungen in diesem Bereich. Das Ziel ist eine (teil-)automatisierte Sicherheitsbetrachtung von modularen Fertigungsanlagen mit Bezug auf Safety und Security.
Stability Problem for the Nonlinear Functional Equation
Authors: Badora Roman 
Published: August 2022

AbstractWe discuss on the stability for functional equations in a single variable. We will prove the theorem about the stability of the nonlinear functional equation from which we can derive the result obtained by T. Trif (Publ Math Debrecen 60:47–61, 2002) on the stability of the linear functional equation.