bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practical notes on building molecular graph generative models
Authors: Mercado Rocío , Rastemo Tobias , Lindelöf Edvard , Klambauer Günter , Engkvist Ola , Chen Hongming , Bjerrum Esben Jannik 
Published: December 2020

AbstractHere are presented technical notes and tips on developing graph generative models for molecular design. Although this work stems from the development of GraphINVENT, a Python platform for iterative molecular generation using graph neural networks, this work is relevant to researchers studying other architectures for graph‐based molecular design. In this work, technical details that could be of interest to researchers developing their own molecular generative models are discussed, including an overview of previous work in graph‐based molecular design and strategies for designing new models. Advice on development and debugging tools which are helpful during code development is also provided. Finally, methods that were tested but which ultimately did not lead to promising results in the development of GraphINVENT are described here in the hope that this will help other researchers avoid pitfalls in development and instead focus their efforts on more promising strategies for graph‐based molecular generation.
Direct C(sp3)−H Sulfonylation and Sulfuration Reactions of Isoquinoline‐1,3(2H,4H)‐diones under Metal‐free Conditions
Authors: Wang Xing‐Lan , Bai Xue , Wu Chun‐Feng , Dong Yong‐Xi , Zhang Min , Fan Ling‐Ling , Tang Lei , Yang Yuan‐Yong , Zhang Ji‐Quan 
Published: December 2020

AbstractThe first direct C(sp3)−H bond sulfonylation and sulfuration reactions of isoquinoline‐1,3‐(2H,4H)‐diones have been developed under transition‐metal‐free conditions. Using air as the sole oxidant, the C‐4 sulfonylated products of isoquinolones were synthesized using sulfinates as the sulfonating agents and NaI as an iodine source in AcOH/DMSO. The sulfuration reaction was realized for the first time using disulfides as sulfurating partners in a t‐BuOK/DMF catalytic system. Both procedures undergo a free radical reaction process with the advantages of high atom economy, green reaction conditions, readily accessible materials and broad substrate scope.
Correspondence on “K2Sb(P2O7)F: Cairo Pentagonal Layer with Bifunctional Genes Reveal Optical Performance”
Authors: Krivovichev Sergey V. , Bindi Luca 
Published: December 2020

AbstractCompounds with the fresnoite structure type possess remarkable chemical diversity and a range of unique physical properties, including nonlinear optical (NLO) activity. K2Sb(P2O7)F, which was reported recently, belongs to this group and its structure is not novel in terms of either the topology or local coordination geometry around the Sb3+ cations. The crystallographic disorder observed in the fresnoite‐type structures can be explained by twinning, which is frequent for non‐centrosymmetric crystals.
Preparation of PdAuCu/C as a Highly Active Catalyst for the Reduction of 4‐Nitrophenol by Controlling the Deposition of Noble Metals
Authors: Duan Ying , Ma Yangyang , Xie Yanfu , Li Dongmi , Deng Dongsheng , Zhang Chi , Yang Yanliang 
Published: December 2020

AbstractThe reasonable control of the dispersion of noble metals is an important topic for heterogeneous catalysts. In this manuscript, PdCu/C, AuCu/C and PdAuCu/C were prepared by the galvanic reduction method to ensure that Pd and Au follow the distribution of Cu nanoparticles. The catalysts were characterized by X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), energy‐dispersive spectrometer elemental mappings and lines scans. Both the Pd and Au had very high dispersion no matter whether they were introduced individually or simultaneously. The Pd and Au were distributed mainly on the Cu nanoparticles as evidenced by the energy‐dispersive spectrometer elemental mappings and lines scans. The reduction of 4‐nitrophenol was used as a model reaction for the prepared catalysts. PdCu/C and AuCu/C showed high activity for this reaction compared to the literature, and the activity could be further increased by the introduction of Pd and Au in an appropriate ratio at the same time. The normalized reaction rate reached 2.005 s−1 mM−1 for the PdAuCu/C‐2.0, in which the mole ratio of Pd to Au was 2.0.
The Comorbidity of Schizophrenia Spectrum and Mood Disorders in Autism Spectrum Disorder
Authors: Chien Yi‐Ling , Wu Chi‐Shin , Tsai Hui‐Ju 
Published: December 2020

Individuals with autism spectrum disorder are often diagnosed with at least one or more accompanying disorders. Most studies reported prevalence of the psychiatric comorbidities among these individuals; however, the incidence of developing comorbidities is unclear. This study used Taiwan's claims database and aimed to investigate the incidence of developing major psychiatric comorbidities in individuals with autism spectrum disorder and whether the incidence was moderated by gender, autism‐spectrum disorder subtypes, and autism‐associated neurodevelopmental conditions. A total of 3,837 individuals with autism spectrum disorder (2,929 autistic disorder, 447 Asperger syndrome, 461 pervasive developmental disorder‐not otherwise specified) and 38,370 comparison subjects, who were matched by age and gender, were included. The incidences of schizophrenia spectrum, bipolar, and major depressive disorders was examined. The results showed that the incidences of schizophrenia spectrum (9.7 per 1,000 person‐year), bipolar disorder (7.0 per 1,000 person‐year), and major depressive disorder (3.2 per 1,000 person‐year) were significantly higher than the comparison group across all three subtypes of autism‐spectrum disorder. Individuals with pervasive developmental disorder‐not otherwise specified had higher risk for major depressive disorder than autistic disorder. Females with Asperger syndrome had significant higher risk for schizophrenia spectrum than males. The comorbidity rate dramatically dropped when the autism‐associated neurodevelopmental conditions were taken into account. Our findings suggested that the incidences of major psychiatric comorbidities were higher in autism spectrum disorder and influenced by autism subtypes, gender, and autism‐associated neurodevelopmental conditions.Lay SummaryWe examined whether people with autism spectrum disorder (ASD) have higher incidence of schizophrenia, bipolar disorders, and major depression using a large claims database. The results showed the incidences of these mental illness among individual with ASD were significantly higher than those without ASD. In addition, the incidences were influenced by autism subtypes, gender, and comorbid neurodevelopmental conditions.
PAMAM G4.5 dendrimers for targeted delivery of ferulic acid and paclitaxel to overcome P‐glycoprotein‐mediated multidrug resistance
Authors: Anbazhagan Rajeshkumar , Muthusamy Ganesan , Krishnamoorthi Rajakumari , Kumaresan Swedha , Rajendra Prasad Nagarajan , Lai Juin‐Yih , Yang Jen‐Ming , Tsai Hsieh‐Chih 
Published: December 2020

AbstractIn this study, we prepared ferulic acid (FA) and paclitaxel (PTX) co‐loaded polyamidoamine (PAMAM) dendrimers conjugated with arginyl–glycyl–aspartic acid (RGD) to overcome P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR). FA was released in greater extent (80%) from the outer layer of the dendrimers compared with PTX (70%) from the interior of the dendrimers. FA improved intracellular availability of PTX via P‐gp modulation in drug‐resistant cells. In vitro drug uptake data show higher PTX delivery with RGD–PAMAM–FP than with PAMAM–FP in drug resistant KB CH‐R 8‐5 cell lines. This indicates that RGD facilitates intracellular PTX accumulation through active targeting in multidrug‐resistant KB CH‐R 8‐5 cells. The terminal deoxynucleotidyl transferase 2ʹ‐deoxyuridine 5ʹ‐triphosphate nick‐end labeling assay data and membrane potential analysis in mitochondria confirm the enhanced anticancer potential of RGD–PAMAM–FP nanoaggregates in drug‐resistant cells. We also confirmed by the increased protein levels of proapoptotic factors such as caspase 3, caspase 9, p53, and Bax after treatment with RGD–PAMAM–FP nanoaggregates and also downregulates antiapoptotic factors. Hence, FA–PTX co‐loaded, RGD‐functionalized PAMAM G4.5 dendrimers may be considered as an effective therapeutic strategy to induce apoptosis in P‐gp‐overexpressing, multidrug‐resistant cells.
Miniaturized electrochemical biosensor based on whole‐cell for heavy metal ions detection in water
Authors: Sciuto Emanuele L. , Petralia Salvatore , van der Meer Jan R. , Conoci Sabrina 
Published: December 2020

AbstractThe heavy metals pollution represents one of the important issues in the environmental field since it is involved in many pathologies from cancer, neurodegenerative, and metabolic diseases. We propose an innovative portable biosensor for the determination of traces of trivalent arsenic (As(III)) and bivalent mercury (Hg(II)) in water. The system implements a strategy combining two advanced sensing modules consisting in (a) a whole cell based on engineered Escherichia coli as selective sensing element towards the metals and (b) an electrochemical miniaturised silicon device with three microelectrodes and a portable reading system. The sensing mechanism relies on the selective recognition from the bacterium of given metals producing the 4‐aminophenol redox active mediator detected through a cyclic voltammetry analysis. The miniaturized biosensor is able to operate a portable, robust, and high‐sensitivity detection of As(III) with a sensitivity of 0.122 µA ppb−1, LoD of 1.5 ppb, and a LoQ of 5 ppb. The LoD value is one order of magnitude below of the value indicated to WHO to be dangerous (10 μg/L). The system was proved to be fully versatile being effective in the detection of Hg(II) as well. A first study on Hg(II) showed sensitivity value of 2.11 µA/ppb a LOD value of 0.1 ppb and LoQ value of 0.34 ppb. Also in this case, the detected LOD was 10 times lower than that indicated by WHO (1 ppb). These results pave the way for advanced sensing strategies suitable for the environmental monitoring and the public safety.
A mechanistic model to account for the Donnan and volume exclusion effects in ultrafiltration/diafiltration process of protein formulations
Authors: Yu Zhao , Moomaw John F. , Thyagarajapuram Nagarajan R. , Geng Steven B. , Bent Colin James , Tang Yu 
Published: December 2020

AbstractUltrafiltration/diafiltration (UF/DF) is a typical step in protein drug manufacturing process to concentrate and exchange the protein solution into a desired formulation. However, significant offset of pH and composition from the target formulation have been frequently observed after UF/DF, posing challenges to the stability, performance, and consistency of the final drug product. Such shift can often be attributed to the Donnan and volume exclusion effects. In order to predict and compensate for those effects, a mechanistic model is developed based on the protein charge, mass and charge balances, as well as the equilibrium condition across the membrane. The integrated UF/DF model can be used to predict both the dynamic behavior and the final outcome of the process. Examples of the modeling results for the pH and composition variation during the UF/DF operations are presented for two monoclonal antibody proteins. The model predictions are in good agreement with a comprehensive experimental data set that covers different process steps, protein concentrations, solution matrices, and process scales. The results show that significant pH and excipient concentration shifts are more likely to occur for high protein concentration and low ionic strength matrices. As a special example, a self‐buffering protein formulation shows unique pH behavior during DF, which could also be captured with the dynamic model. The capability of the model in predicting the performance of UF/DF process as a function of protein characteristics and formulation conditions makes it a useful tool to improve process understanding and facilitate process development.
Two New Limonoids from the Fruits of Melia azedarach (Meliaceae)
Authors: Wang Wen‐Qi , Xia Zhen‐Zhen , Yu Shao‐Hua , Tian Zhen‐Hua , Yan Bin , Jiang Hai‐Qiang , Zhou Hong‐Lei 
Published: December 2020

AbstractTwo new limonoids, trichilinin M (1) and ohchinin benzoate (2), along with two known limonoids, 12‐hydroxyamoorastatone (3) and mesendanin H (4), were isolated from the fruits of Melia azedarach Linn. The structures of new limonoids were determined by analyses of HR‐ESI‐MS, 1D and 2D NMR (HSQC, HMBC and NOESY) data. All compounds were evaluated against human pancreatic cancer PANC1 cells and the results showed that compounds 3–4 exhibited substantial cytotoxic activity (3: IC50=4.55 μM; 4: IC50=7.54 μM), and compounds 1–2 exhibited moderate cytotoxicity (1: IC50=27.06 μM; 2: IC50=21.17 μM).
Synthesis of Bi‐functional Immobilized Polymer Catalysts via a Two‐step Radiation‐induced Graft Polymerization Process
Authors: Okuno Yoshinori , Shibata Takako , Ohyou Akie , Suzuki Rie , Takegami Mayuko , Kato Satoshi , Isomura Shigeki , Aoki Shoji , Kanno Junichi , Sato Yasuo 
Published: December 2020

AbstractHere, we designed and synthesized two types of bi‐functional immobilized polymer catalysts based on the prolineamide‐acid combination for direct enantioselective aldol reaction in flow systems. Conventional bi‐functional catalysts in which the two functions are present on the same graft polymer afforded up to 99 % yield and >99 % enantiomeric excess (ee) in a recirculating flow system. We also investigated bi‐functional catalysts in which the two functions are located on different graft polymers. We present a straightforward catalyst immobilization method that allows two different catalysts located on different graft polymers to be introduced separately onto the same polymer by conducting two successive steps of radiation‐induced graft polymerization process (RIGP). We confirmed that the graft polymers (grafted polycatalyst and polyacrylic acid chain) interact with each other to promote the aldol reaction with high conversion and ee. This design strategy may be superior to the conventional approach for synthesizing catalysts in which multiple functions interact.
Integrated Electro‐Biocatalysis for Amine Alkylation with Alcohols
Authors: Peñafiel Itziar , Dryfe Robert A. W. , Turner Nicholas J. , Greaney Michael F. 
Published: December 2020

AbstractThe integration of electro and bio‐catalysis offers new ways of making molecules under very mild, environmentally benign conditions. We show that TEMPO mediated electro‐catalytic oxidation of alcohols can be adapted to work in aqueous buffers, with minimal organic co‐solvent, enabling integration with biocatalytic reductive amination using the AdRedAm enzyme. The combined process offers a new approach to amine alkylation with native alcohols, a key bond formation in the chemical economy that is currently achieved via precious metal‐catalyzed hydrogen‐borrowing technologies. The electrobio transformation is effective for primary and secondary alcohols undergoing coupling with allyl, propargyl, benzyl, and cyclopropyl amines, and has been adapted for use with solid‐supported AdRedAm for ease of operation.
Sesquiterpenoids from the Whole Plants of Chloranthus holostegius and Their Anti‐inflammatory Activities
Authors: Zhan Zhao‐Chun , Wu Zhong‐Nan , Tang Qing , Li Can‐Jie , Wang Wen‐Zhi , Zhang Ji‐Hui , Zhuo Xue‐Fang , Zhang Yu‐Bo , Wang Guo‐Cai , Li Yao‐Lan 
Published: December 2020

Main observation and conclusionFive new sesquiterpenoids (1—5), chloranholides A—E, along with three known compounds (6—8), were isolated from the whole plants of Chloranthus holostegius. Their structures were elucidated using the spectroscopic methods (IR, UV, HR‐ESI‐MS, 1D and 2D NMR), and their absolute configurations were determined by the X‐ray crystallography and ECD calculation. Compounds 1—8 were evaluated for their anti‐inflammatory effects on LPS‐induced RAW 264.7 macrophage cells. Especially, compound 4 exhibited the most significant anti‐inflammatory activity with the secretion levels of TNF‐α and IL‐6 at 15.52% and 5.98%, respectively, better than that of dexamethasone.
Quality of Service‐aware matchmaking for adaptive microservice‐based applications
Authors: Štefanič Polona , Kochovski Petar , Rana Omer F. , Stankovski Vlado 
Published: December 2020

SummaryApplications that make use of Internet of Things (IoT) can capture an enormous amount of raw data from sensors and actuators, which is frequently transmitted to cloud data centers for processing and analysis. However, due to varying and unpredictable data generation rates and network latency, this can lead to a performance bottleneck for data processing. With the emergence of fog and edge computing hosted microservices, data processing could be moved towards the network edge. We propose a new method for continuous deployment and adaptation of multi‐tier applications along edge, fog, and cloud tiers by considering resource properties and non‐functional requirements (e.g., operational cost, response time and latency etc.). The proposed approach supports matchmaking of application and Cloud‐To‐Things infrastructure based on a subgraph pattern matching (P‐Match) technique. Results show that the proposed approach improves resource utilization and overall application Quality of Service. The approach can also be integrated into software engineering workbenches for the creation and deployment of cloud‐native applications, enabling partitioning of an application across the multiple infrastructure tiers outlined above.
Enzymatic Synthesis of Glucose‐ and Xylose Laurate Esters Using Different Acyl Donors, Higher Substrate Concentrations, and Membrane Assisted Solvent Recovery
Authors: Martinez‐Garcia Marta , Dejonghe Winnie , Cauwenberghs Lieve , Maesen Miranda , Vanbroekhoven Karolien , Satyawali Yamini 
Published: December 2020

AbstractGlucose‐ and xylose laurate esters are enzymatically synthesized using equimolar substrate concentrations in 2‐methyl‐2‐butanol, comparing free lauric acid with methyl‐ and vinyl‐laurate as acyl donors. All reactions result in ≥70% acyl donor conversions after 72 h but the activated donors are also partially hydrolyzed to lauric acid, highlighting the difficulty in controlling water presence in this particular reaction system. The esterification of xylose generates a complex product profile, with several regioisomers of monoesters and diesters. The esterification of glucose is quite selective, forming mainly the 6‐O monoester (≥96%) with a small presence of two diester isomers (4%). Increasing substrate concentration up to 800 millimoles kg−1 results in lower conversion values (down to 58%) but shows that the reaction proceeds successfully even in the presence of high amounts of insoluble glucose. However, the reaction is less selective and the proportion of diester increases, becoming up to 46% (molar fraction) of the final product. Solvent recovery after esterification can be achieved by organic solvent nanofiltration through a polymeric membrane able to retain ≥80% of all reaction substrates and products.Practical Applications: The use of high substrate concentrations during the enzymatic synthesis of sugar ester biosurfactants leads to product titers that are more industrially appealing, without the need to find a solvent that can solubilize all initial substrate. The sustainability of the enzymatic conversion at mild temperatures can be enhanced by recycling of the reaction solvent through organic solvent nanofiltration, an energy efficient alternative to other traditional methods like distillation.
Hemin‐phytic Acid Functionalized Porous Conducting Polymer Hydrogel With Good Biocompatibility for Electrochemical Detection of H2O2 Released From Living Cells
Authors: Shang Xin , He Shaoying , Xu Zhiai , Lu Wei , Zhang Wen 
Published: December 2020

AbstractA novel hemin/phytic acid doped polyaniline (PA‐PANI) hydrogel composite was prepared through a simple chemical and self‐assembly method, which was modified onto electrode for electrochemical detection of H2O2 released from living cells. It showed good analytical performance with high sensitivity, selectivity and a rapid response for the analysis of H2O2 in the range of 2 to 102 μM, with the detection limit of 1.2 μM. The favorable results mainly originated from both the high conductivity of PA‐PANI hydrogel and its network structure preventing hemin from self‐dimerization to provide active catalytic species. Furthermore, PA‐PANI with good biocompatibility allowed living cells to adhere and resulted in a short diffusion distance between H2O2 released from cells and electrode.
Experimental and numerical studies of seismic fluid‐structure interaction in a base‐supported cylindrical vessel
Authors: Mir Faizan Ul Haq , Yu Ching‐Ching , Whittaker Andrew S. 
Published: December 2020

AbstractSeismic design and qualification of advanced reactors will rely heavily on the use of verified and validated numerical models capable of capturing the interaction of the vessel, its contained fluid, and the internal equipment: fluid‐structure interaction (FSI) analysis. Analytical solutions can be used for preliminary sizing and design of such vessels but their application is limited to simple geometries and boundary conditions, and small amplitude, translational (and rotational) inputs. To validate numerical models for seismic FSI analysis in finite element codes, a comprehensive set of experiments was performed on a liquid‐filled cylindrical vessel, using a 6 degree‐of‐freedom earthquake simulator. Results in terms of sloshing frequency, damping ratio in sloshing modes, and hydrodynamic responses (wave height, hydrodynamic pressure, base shear, and base moment) for multidirectional earthquake simulator inputs are reported and compared with analytical solutions for liquid‐filled vessels. The impact of seismic (base) isolation on hydrodynamic responses was studied using earthquake simulator inputs generated using a virtual isolation system. Data from the experiments are used to validate a numerical model of the fluid‐filled vessel using the Arbitrary Lagrangian Eulerian (ALE) solver in the commercial finite element program LS‐DYNA. Validation studies are presented for multidirectional seismic inputs, including rocking motions. Lagrangian modeling approaches using an elastic material formulation for the fluid are also investigated and their limitations and possible applications are identified. The results are broadly applicable to the seismic response of base supported, liquid‐filled vessels.