bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperbranched poly(glycerol esteramide): A biocompatible drug carrier from glycerol feedstock and dicarboxylic acid
Authors: Muniandy Amala , Lee Choy Sin , Lim Wen Huei , Pichika Mallikarjuna Rao , Mak Kit Kay 
Published: October 2020

AbstractPolymer carrier with biodegradable, biocompatible as well as solubility enhancing properties are highly looked upon in the pharmaceutical industry to improve the drug delivery systems. A series of hyperbranched poly(glycerol esteramide) (HPGEA) with Mw of 5000–12,000 Da, degree of branching of 57%–62%, and hydroxyl values of 200–280 mg KOH/g sample were synthesized through polycondensation of N,N‐bis(2‐hydroxyethyl)stearamide (diethanolamide) and poly(glycerol ester) (PGE). The HPGEAs were characterized by ATR‐FTIR, GPC, 1H and 13C‐NMR, and DSC. The enthalpy of fusion of HPGEAs (43–84 J g−1) were lower than the commercial polymers (193–391 J g−1), indicating its potential as drug carrier for solid dispersion (SD). HPGEA‐based SDs showed substantial enhancement in solubility and release rate than pure drug, commercial polymer‐based SDs, as well as commercial formulation. The safety of HPGEAs and HPGEA‐based SDs were proven through MTT assay with IC50 of 2400–9800 and 1200–3500 μg ml−1, respectively.
Directed evolution of conformation‐specific antibodies for sensitive detection of polypeptide aggregates in therapeutic drug formulations
Authors: Lou Wenjia , Stimple Samuel D. , Desai Alec A. , Makowski Emily K. , Kalyoncu Sibel , Mogensen Jesper E. , Spang Lotte T. , Asgreen Désirée J. , Staby Arne , Duus Karen , Amstrup Jan , Zhang Yulei , Tessier Peter M. 
Published: October 2020

AbstractBiologics such as peptides and proteins possess a number of attractive attributes that make them particularly valuable as therapeutics, including their high activity, high specificity, and low toxicity. However, one of the key challenges associated with this class of drugs is their propensity to aggregate. Given the safety and immunogenicity concerns related to polypeptide aggregates, it is particularly important to sensitively detect aggregates in therapeutic drug formulations as part of the quality control process. Here, we report the development of conformation‐specific antibodies that recognize polypeptide aggregates composed of a GLP‐1 receptor agonist (liraglutide) and their integration into a sensitive immunoassay for detecting liraglutide amyloid fibrils. We sorted single‐chain antibody libraries against liraglutide fibrils using yeast surface display and magnetic‐activated cell sorting, and identified several antibodies with high conformational specificity. Interestingly, these antibodies cross‐react with amyloid fibrils formed by several other polypeptides, revealing that they recognize molecular features common to different types of fibrils. Moreover, we find that our immunoassay using these antibodies is >50‐fold more sensitive than the conventional method for detecting liraglutide aggregation (Thioflavin T fluorescence). We expect that our systematic approach for generating a sensitive, aggregate‐specific immunoassay can be readily extended to other biologics to improve the quality and safety of formulated drug products.
The role of MOOCs in engineering education: An exploratory systematic review of peer‐reviewed literature
Authors: Sezgin Sezan , Sevim Cirak Nese 
Published: October 2020

AbstractThe aim of the current study is to explore and evaluate the current status of massive open online courses (MOOCs) in the field of Engineering Education. In line with this aim, the study intends to identify and map the role of “MOOCs in engineering education research” through a review of empirical articles published in peer‐reviewed journals indexed in the “Web of Science,” “IEEE Xplore,” “Scopus,” “Science Direct,” and the “ACM Digital Library” databases. Social network analysis, content analysis, and inferential‐descriptive statistics were applied in the study. The study's findings indicate a growing trend in “MOOCs in engineering education research.” Online virtual labs, social networks, flipped classroom strategy, active learning, small private online courses, and motivation are the key lodestar topics in “MOOCs in engineering education research” and engineering education researchers mostly employ practice‐based and quantitative research approaches. Besides this, it was found that engineering education researchers use MOOCs for three main purposes: designing a domain‐specific MOOC with unique features; developing a system/model for e‐learning and MOOCs, or aiming to improve engineering education using interactive online technologies. The findings of the current study indicate that engineering education researchers primarily give importance to performance outcomes and motivation in learning, and try to increase the quality of engineering education through the use of MOOCs. Finally, the findings imply that the general discourse among the sampled articles is positive, and may be considered useful in the exploration of potential research into “MOOCs in engineering education research.”
Characterization of β‐Cryptoxanthin and Other Carotenoid Derivatives from Rhodotorula taiwanensis, A Novel Yeast Isolated from Traditional Starter Culture of Assam
Authors: Parasar Deep Prakash , Ramakrishnan Elancheran , Kabilan Senthamaraikannan , Kotoky Jibon , Sarma Hridip Kumar 
Published: October 2020

AbstractThe present investigation was intended to characterize pigments for the first time from Rhodotorula taiwanensis (LC011412) yeast isolated from the ethic fermentation starter culture source meant to evaluate its carotenoid contents for beneficial applications. The pigments were extracted by an optimized solvent system, purified by flash chromatography and were identified by TLC and UV/VIS spectroscopy. The absorbance spectra confirmed the presence of β‐carotene, β‐cryptoxanthin, torulene and torularhodin that showed maximum absorbance (λmax) within the ranges. The fractions were further characterized by LC/MS and analyzed through FT‐IR and NMR for structure elucidation. Spectral analyses also confirmed the presence of the compounds mentioned above. These compounds promise great commercial value and could be useful for large scale production anticipated for potential applications in food, nutraceutical, pharmaceutical and cosmetic sectors. It is pertinent that the characterized carotenoid pigments from the isolate have incredible prospects in industrial applications which require profound attention.
Pili Tree (Canarium ovatum) Resin's Antibacterial Essential Oil and Hydrosol as Rich Sources of (S)‐Phellandrenes Derivatives
Authors: Mercier Sylvain , Lorenzo Russell Y. , Pichette André , Côté Héloïse , Legault Jean , St‐Gelais Alexis 
Published: October 2020

AbstractFive batches of resin from the Pili tree (Canarium ovatum Engl.) were distilled, and their essential oils and hydrosols were analyzed by gas chromatography. The oils, obtained in yields of 13.4–19.7 % v/m, featured α‐phellandrene in high proportions (50–65 %), alongside limonene, β‐phellandrene and para‐cymene. Chiral GC analysis confirmed that both phellandrenes were in fact >95 % (S)‐(+) enantiomers, while the other monoterpenes featured less pronounced enantiomeric excesses. The hydrosols were rich in α‐phellandrene oxidation products including cis‐α‐phellandrene epoxide and a series of para‐menth‐5‐ene‐1,2‐diol isomers. Both essential oils and hydrosols were tested for their antibacterial activity against Escherichia coli and Staphylococcus aureus and exhibited MIC90 of less than 5 and 0.5 mg/mL of total volatiles, respectively. The essential oil features some potential as a source of readily available natural (S)‐(+)‐α‐phellandrene.
Machine Learning Enables Selection of Epistatic Enzyme Mutants for Stability Against Unfolding and Detrimental Aggregation
Authors: Li Guangyue , Qin Youcai , Fontaine Nicolas T. , Ng Fuk Chong Matthieu , Maria‐Solano Miguel A. , Feixas Ferran , Cadet Xavier F. , Pandjaitan Rudy , Garcia‐Borràs Marc , Cadet Frederic , Reetz Manfred T. 
Published: October 2020

AbstractMachine learning (ML) has pervaded most areas of protein engineering, including stability and stereoselectivity. Using limonene epoxide hydrolase as the model enzyme and innov'SAR as the ML platform, comprising a digital signal process, we achieved high protein robustness that can resist unfolding with concomitant detrimental aggregation. Fourier transform (FT) allows us to take into account the order of the protein sequence and the nonlinear interactions between positions, and thus to grasp epistatic phenomena. The innov'SAR approach is interpolative, extrapolative and makes outside‐the‐box, predictions not found in other state‐of‐the‐art ML or deep learning approaches. Equally significant is the finding that our approach to ML in the present context, flanked by advanced molecular dynamics simulations, uncovers the connection between epistatic mutational interactions and protein robustness.
Continuous Neutralization of NaOH Solution with CO2 in an Internal‐Loop Airlift Reactor
Authors: Pichler Thomas , Stoppacher Bernd , Kaufmann Alexander , Siebenhofer Matthäus , Kienberger Marlene 
Published: October 2020

AbstractThe neutralization of NaOH with CO2 in a continuously operated airlift reactor with gas flow rates up to 10 NL min−1 and gas phase recycle was investigated. Neutralization experiments were performed at 25 °C and the amount of absorbed CO2, as well as the NaOH feed rate, were recorded. The reaction rate was calculated based on the two‐film theory and empirical equations for several parameters. The calculations of the volumetric mass transfer coefficient, the liquid phase circulation velocity, and the gas holdup were experimentally validated. The reaction rate and the process efficiency were modeled with a deviation of 5 %.
Effect of rheology on mass transfer and bubble sizes in a bubble column operated in the heterogeneous regime
Authors: Augier Frédéric , Raimundo Pedro M. 
Published: October 2020

AbstractA recently developed measurement method has been applied for the first time to the characterization of a bubble column operated in the heterogeneous regime and in presence of non‐Newtonian fluids. The resulting measurements of bubble size are completed with local gas holdup and global mass transfer characterizations. A strong impact of rheology on both bubble size and mass transfer is observed, at any tested superficial gas velocity. A dissociation of the liquid side mass transfer kL and the specific interfacial area (a) is proposed. Results show that the kL model previously validated in stirred tanks filled with complex fluids is satisfyingly extended to bubble columns. The incoming databank will be of great help to develop and validate multiphase hydrodynamic models, especially in the scope of biotechnology and associated systems of complex rheology.
Recent Advances of Catalytic Enantioselective Heck Reactions and Reductive‐Heck Reactions
Authors: Xie Jia‐Qi , Liang Ren‐Xiao , Jia Yi‐Xia 
Published: October 2020

AbstractHeck reaction is one of the most important carbon‐carbon bond forming reactions with wide applications in organic synthesis. Considerable advances of enantioselective Heck reaction have been achieved in the past decades. This review focuses on recent development of catalytic asymmetric Heck reaction and reductive Heck reaction, which covers intermolecular and intramolecular versions since 2011. The article is organized in terms of the catalysts and olefin substrates.
A Gadolinium Metal‐Organic Framework Film as a Converter Layer for Neutron Detection
Authors: Canatelli Axel X. , Pérez Martín , Lipovetzky José , Marín Julio H. , Albornoz Cecilia A. , Tartaglione Aureliano , Roncaroli Federico 
Published: October 2020

AbstractMetal‐organic frameworks (MOFs) are known for their versatility in terms of their crystalline structure, porosity, resistance to temperature, radiation damage, and luminescence among others. Gadolinium (Gd) is one of the elements with the highest reported cross‐section for low energy neutron capture, producing internal conversion electrons and γ rays as a result of the neutron absorption. The development of Gd‐BTC films (BTC=1,3,5‐benzenetricarboxylate) is shown that were deposited on Si and Al substrates by airbrushing, and characterized by profilometry, Raman, EDX and X‐ray diffraction. Radiation damage, thermal decomposition and neutron absorption of these films were studied as well. Gd‐BTC films were attached to CMOS devices (Complementary Metal‐Oxide‐Semiconductor), which are sensible to the internal conversion electrons, in order to build a neutron detector. The devices Gd‐BTC/CMOS could selectively detect neutrons in the presence of γ rays with a thermal neutron detection efficiency of 3.3±0.1 %, a signal to noise ratio of 6 : 1, and were suitable to obtain images.
Nanocomposite‐Based Matrices in Laser Desorption/Ionization Mass Spectrometry for Small‐Molecule Analysis
Authors: Pei Congcong , Wan Jingjing 
Published: October 2020

AbstractThe efficient detection of small molecules is of significance for environmental monitoring, pharmacology, metabolomics, and lipidomics. The laser desorption/ionization mass spectrometry (LDI MS) platform enables high sensitivity, accuracy, resolution, and throughput in molecular analysis, but its analytical capability with respect to small molecules is limited due to inherent drawbacks arising from conventional organic matrices. The selection of an appropriate matrix is thus a precondition for small molecule detection by LDI MS. To date, various inorganic matrices have been developed, with a growing interest in composite materials displaying synergetic effects. This Minireview highlights the development of nanocomposites as LDI matrices driven by numerous innovations in material science, and their emerging use in small‐molecule analysis.
A validated method for the simultaneous quantification of cannabidiol, Δ9‐tetrahydrocannabinol, and their metabolites in human plasma and application to plasma samples from an oral cannabidiol open‐label trial
Authors: Kevin Richard C. , Vogel Rebecca , Doohan Peter , Berger Maximus , Amminger G. Paul , McGregor Iain S. 
Published: October 2020

AbstractCannabidiol (CBD) and Δ9‐tetrahydrocannabinol (THC) are the two best known and most extensively studied phytocannabinoids within Cannabis sativa. An increasing number of preclinical studies and clinical trials have been conducted with one or both compounds, often probing their therapeutic effects in conditions such as paediatric epilepsy, anxiety disorders or chronic pain. Accurate monitoring of THC and CBD and their metabolites is essential for tracking treatment adherence and pharmacokinetics. However, fully validated methods for the comprehensive analysis of major Phase I CBD metabolites are yet to be developed due to a historical lack of commercially available reference material. In the present study, we developed, optimised and validated a method for the simultaneous quantification of CBD, THC and their major Phase I metabolites 6‐hydroxy‐CBD (6‐OH‐CBD), 7‐hydroxy‐CBD (7‐OH‐CBD), 7‐carboxy‐CBD (7‐COOH‐CBD), 11‐hydroxy‐tetrahydrocannabinol (11‐OH‐THC) and 11‐carboxy‐tetrahydrocannabinol (11‐COOH‐THC) as per Food and Drug Administration (FDA) guidelines for bioanalytical method validation. The method is accurate, reproducible, sensitive and can be carried out in high‐throughput 96‐well formats, ideal for larger scale clinical trials. Deuterated internal standards for each analyte were crucial to account for variable matrix effects between plasma lots. The application of the method to plasma samples, taken from people who had been administered oral CBD as part of an open‐label trial of CBD effects in anxiety disorders, demonstrated its immediate utility in ongoing and upcoming clinical trials. The method will prove useful for future studies involving CBD and/or THC and can likely accommodate the inclusion of additional metabolites as analytical reference materials become commercially available.
GDE2 expression in oligodendroglia regulates the pace of oligodendrocyte maturation
Authors: Choi Bo‐Ran , Dobrowolski Mateusz , Sockanathan Shanthini 
Published: October 2020

AbstractBackgroundOligodendrocytes generate specialized lipid‐rich sheaths called myelin that wrap axons and facilitate the rapid, saltatory transmission of action potentials. Extrinsic signals and surface‐mediated pathways coordinate oligodendrocyte development to ensure appropriate axonal myelination, but the mechanisms involved are not fully understood. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a six‐transmembrane enzyme that regulates the activity of surface glycosylphosphatidylinositol (GPI)‐anchored proteins by cleavage of the GPI‐anchor. GDE2 is expressed in neurons where it promotes oligodendrocyte maturation through the release of neuronally‐derived soluble factors. GDE2 is also expressed in oligodendrocytes but the function of oligodendroglial GDE2 is not known.ResultsUsing Cre‐lox technology, we generated mice that lack GDE2 expression in oligodendrocytes (O‐Gde2KO). O‐Gde2KOs show normal production and proliferation of oligodendrocyte precursor cells. However, oligodendrocyte maturation is accelerated leading to the robust increase of myelin proteins and increased myelination during development. These in vivo observations are recapitulated in vitro using purified primary oligodendrocytes, supporting cell‐autonomous functions for GDE2 in oligodendrocyte maturation.ConclusionsThese studies reveal that oligodendroglial GDE2 expression is required for controlling the pace of oligodendrocyte maturation. Thus, the cell‐type specific expression of GDE2 is important for the coordination of oligodendrocyte maturation and axonal myelination during neural development.
Cardiopoietic stem cell therapy in ischaemic heart failure: long‐term clinical outcomes
Authors: Bartunek Jozef , Terzic Andre , Davison Beth A. , Behfar Atta , Sanz‐Ruiz Ricardo , Wojakowski Wojciech , Sherman Warren , Heyndrickx Guy R. , Metra Marco , Filippatos Gerasimos S. , Waldman Scott A. , Teerlink John R. , Henry Timothy D. , Gersh Bernard J. , Hajjar Roger , Tendera Michal , Senger Stefanie , Cotter Gad , Povsic Thomas J. , Wijns William ,   for the CHART Program
Published: October 2020

AbstractAimsThis study aims to explore long‐term clinical outcomes of cardiopoiesis‐guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial.Methods and resultsCHART‐1 is a multinational, randomized, and double‐blind trial conducted in 39 centres in heart failure patients (n = 315) on standard‐of‐care therapy. The ‘active’ group received cardiopoietic stem cells delivered intramyocardially using a retention‐enhanced catheter. The ‘control’ group underwent patient‐level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow‐up, patients with left ventricular end‐diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years.ConclusionsLongitudinal follow‐up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long‐term clinical follow‐up thus offers guidance for future targeted trials.
A simplified transient technique for porosity and permeability determination in tight formations: Numerical simulation and experimental validation
Authors: Li Zequan , Feng Ruimin , Liu Jun , Pandey Rohit 
Published: October 2020

AbstractA simplified pulse decay method (PDM) with only a single downstream reservoir is proposed to replicate the in situ conditions for reservoir fluid flow, where the pore pressure at any location declines as production continues. The proposed PDM also allows determining the effective porosity and permeability for the core sample under replicated in situ conditions. A mathematical model is firstly established to closely represent the experimental design and verify the feasibility of the method. The analytical solutions of the model are derived to calculate the effective sample porosity and permeability. A series of experiments are then conducted under triaxial stress condition, and a detailed comparison is also made between the PDMs with a single upstream reservoir and a single downstream reservoir. The experimental results showed that accurate measurements on effective sample porosity and permeability can be achieved by the single downstream reservoir PDM due to its capability of better replicating the in situ fluid flow behavior, which extends the application of the transient technique. It is also found that the pore pressure along the sample changes linearly, and its gradient varies with time, indicating the applicability of the single‐reservoir PDMs in permeability determination. This method also lays a foundation for studying flow behavior when a second fluid phase evolves during pressure decline, which occurs in many reservoirs.
Ethanolic extract of okra has a potential gastroprotective effect on acute gastric lesions in Sprague Dawley rats
Authors: Yasin Hafsa , Tariq Farwa , Sameen Aysha , Ahmad Nazir , Manzoor Muhammad Faisal , Yasin Maria , Tariq Tayyaba , Iqbal Muhammad Waheed , Ishfaq Bushra , Mahmood Sana , Siddeeg Azhari 
Published: October 2020

AbstractOkra (Abelmoschus esculentus) has various bioactive components used for the treatment of different diseases such as gastritis and ulcers. This research aims to examine the anti‐inflammatory and anti‐ulcer attributes of okra extract against gastric lesions. Adult Sprague Dawley male albino rats were divided into five groups. The negative control (G1) received normal feed, positive control (G2) received ulcer‐inducing drug aspirin 150 mg/kg of body weight (b.w), G3 group received reference drug omeprazole 20 mg/kg of b.w, G4 group received okra extract 250 mg/kg of b.w, and G5 group received 500 mg/kg of b.w. Acute gastric damage was induced in G1, G2, G3, and G4 using aspirin 150 mg/kg of b.w, during 14‐day‐long efficacy trials after that all the animals were sacrificed. Anti‐ulcer parameters and histopathological analysis of stomachs were performed to evaluate the degree of recovery against tissue damage by the administration of okra extract. The obtained results indicated that the 500 mg/kg of b.w okra extract exerted a protective effect in aspirin‐induced gastric ulcers by significantly (p < .05) reducing ulcer score, ulcer area, total acidity, and gastric volume, and significantly (p < .05) increasing gastric pH. Moreover, histopathological observation revealed that gastric mucosa was normal in G1, G3, G4, and G5; however, disruptions in the gastric epithelium were observed in G2. Congestion was observed in all groups except G1 and G5. Gastric pits and gastric glands were increased in size in G2 and G4. A higher concentration of okra extract (500 mg/kg of b.w) showed almost similar results when compared to the reference drug omeprazole.