bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geophysical survey in archaeological context: A review from Cyprus
Authors: Vella Marc‐Antoine , Sarris Apostolos 
Published: January 2022

AbstractCyprus, the third largest Mediterranean island, is located at an exceptional crossroad in the eastern Mediterranean, where cultures from the Middle East, Africa and Europe have interacted for more than 10 000 years. The aim of this paper is to present an exhaustive review of the past archaeological geophysical surveys on the island. The result of our research indicates that to date, more than 30 archaeological sites spanning from the Pre‐Pottery Neolithic (ca. 10 000 BC) to the Venetian period (up to 1571 AD) have been investigated through noninvasive ground‐based techniques. The investigations concern the mapping of the extent of ancient occupation (settlements and cemeteries), the study of the internal organization of settlements (domestic architecture, palaces and fortifications), the investigation of funerary structures (tombs) and the use of space within buildings. The methods implemented are multiple and often used in combination. Emphasis has been given to ground penetrating radar (GPR), electromagnetic induction (EMI) and magnetic and electrical resistance techniques. Most surveys have been targeted towards the production of maps representing the spatial distribution of the subsurface architectural residues, and sometimes these have been accompanied by soundings, tomographies, as well as 3D reconstructions of the ancient structures. Very few sites have been subjected to the measurements of the chemical or magnetic properties of the soils in relation to the results of geophysical prospection. Further discussion concerns (i) the targets of the archaeo‐geophysical surveys in Cyprus, (ii) the limitations of the application of the specific techniques in relation to the Cypriot archaeological and geological context, (iii) the geophysical signatures of archaeological remains and (iv) the metadata accompanying the geophysical results.
Biogenesis and mechanisms of microRNA‐mediated gene regulation
Authors: Rani Varsha , Sengar Rakesh Singh 
Published: January 2022

AbstractEndogenous RNAs that control posttranscriptional gene expression are microRNAs (miRNAs). These small regulatory molecules play a crucial role in certain biological processes and their expression is often strictly regulated. They are small 21–24 nucleotide molecules that act as major regulators of gene expression at the posttranscriptional level. One of the mechanisms by which miRNAs control the gene expression is to interact the interaction of the seeds with the 3ʹ‐end and and more seldom the 5ʹ‐end of mRNA transcribed by the target genes. miRNAs have been identified as important cytoplasmic regulators of gene expression. miRNAs function as posttranscriptional regulators of their messenger RNA (mRNA) targets by mRNA degradation and/or translational repression. It is becoming evident, however, that miRNAs have nuclear functions as well. About the cell type, the physiological state of the body, and various external factors, the following explanation will summarize the complex multilevel regulation of miRNA expression. A better understanding of the molecular mechanisms controlling miRNA expression will provide clarification of the variations in the expression of protein‐coding genes.
A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids
Authors: Fukushima Takeshi , Umino Maho , Sakamoto Tatsuya , Onozato Mayu 
Published: January 2022

AbstractKynurenine (KYN) is synthesized from an essential amino acid, tryptophan, by tryptophan 2,3‐dioxygenase or indoleamine 2,3‐dioxygenase via N‐formyl‐KYN in vivo. Subsequently, KYN acts as a precursor of some neuroactive metabolites such as kynurenic acid, quinolinic acid, and an important enzyme co‐factor, nicotine adenine dinucleotide. These metabolites of tryptophan are a part of the ‘kynurenine pathway.’ In addition, KYN functions as an endogenous ligand for the aryl hydrocarbon receptor, which acts as a transcription factor. The levels of tryptophan metabolites are important for the assessment of the stage of neurological disorders, and therefore have garnered significant interest for clinical diagnosis. In this review, the detection of kynurenine, kynurenic acid, quinolinic acid, and other tryptophan metabolites performed via chromatographic methods such as HPLC using UV absorbance, fluorescence, and chromatographic‐mass spectrometric detection is summarized.
Flipped classroom model applications in computing courses: Peer‐assisted groups, collaborative group and individual learning
Authors: Yildiz Durak Hatice 
Published: January 2022

AbstractThe Flipped Classroom (FC) provides various opportunities to ensure active learning in a student‐based learning environment. In the literature, it is pointed out that the FC model provided a positive contribution to the teaching process when it was used for learning environments in past studies. Besides this, it is seen that FC was integrated into a learning method and the results were generally associated with only FC. From this point of view, it is thought that the methodological effect of FC needs to be examined. The aim of this study is to identify whether the use of different models (peer‐assisted group: PAL‐FC, collaborative group: SGCL‐FC, and individual learning: IL‐FC) in FC for computing courses of university students has an effect on academic performances, learning motivation, academic self‐efficacy, computer anxiety of the university students, and flipped learning readiness. This study is designed with a mixed method. The working group of the study is composed of 242 university students. The application lasted for 14 weeks. In this study, data have been collected by a Personal Information Form, semi‐structured interview form, information technologies achievement test, and four different data collection tools. As a result of the research, it is found out that different applications in the FC model have a significant effect on academic success, academic self‐efficacy, e‐learning readiness in FC. FC model application with PAL‐FC has proved more successful when compared to other methods in terms of developing performance and reducing technology anxiety. Also, it is seen that motivation and academic self‐efficacy in FC has improved positively for collaborative group work.
Engineered Bacterial Flavin‐Dependent Monooxygenases for the Regiospecific Hydroxylation of Polycyclic Phenols
Authors: Herrmann Susann , Dippe Martin , Pecher Pascal , Funke Evelyn , Pietzsch Markus , Wessjohann Ludger A. 
Published: January 2022

Abstract4‐Hydroxyphenylacetate 3‐hydroxylase (4HPA3H), a flavin‐dependent monooxygenase fromE. colithat catalyzes the hydroxylation of monophenols to catechols, was modified by rational redesign to convert also more bulky substrates, especially phenolic natural products like phenylpropanoids, flavones or coumarins. Selected amino acid positions in the binding pocket of 4HPA3H were exchanged with residues from the homologous protein fromPseudomonas aeruginosa, yielding variants with improved conversion of spacious substrates such as the flavonoid naringenin or the alkaloid mimetic 2‐hydroxycarbazole. Reactions were followed by an adapted Fe(III)‐catechol chromogenic assay selective for the products. Especially substitution of the residue Y301 facilitated modulation of substrate specificity: introduction of nonaromatic but hydrophobic (iso)leucine resulted in the preference of the substrate ferulic acid (having a guaiacyl (guajacyl) moiety, part of the vanilloid motif) over unsubstituted monophenols. Thein vivo(whole‐cell biocatalysts) andin vitro(three‐enzyme cascade) transformations of substrates by 4HPA3H and its optimized variants was strictly regiospecific and proceeded without generation of byproducts.
Engineering the Ligand Specificity of the Human Galectin‐1 by Incorporation of Tryptophan Analogues
Authors: Tobola Felix , Lepšík Martin , Zia Syeda Rehana , Leffler Hakon , Nilsson Ulf J. , Blixt Ola , Imberty Anne , Wiltschi Birgit 
Published: January 2022

AbstractGalectin‐1 is a β‐galactoside‐binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin‐1 specificity, we introduced several non‐canonical tryptophan analogues at this position of human galectin‐1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7‐azatryptophan and 7‐fluorotryptophan showed a reduced affinity for 3’‐sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin‐1 is an attractive approach for fine‐tuning its interactions with different ligands.
Trimetallic Catalyst Configuration for Syngas Production
Authors: Longo Alessandro , Theofanidis Stavros‐Alexandros , Poelman Hilde , Banerjee Dipanjan , Marin Guy B. , Galvita Vladimir V. 
Published: January 2022

AbstractDry reforming of methane (DRM) is a promising catalytic process for syngas production, utilizing and transforming CO2 to higher density compounds in view of circular economy. The performance of a bimetallic NiFe/MgAl2O4 strongly depends on the initial catalyst state – calcined, reduced or CO2‐reoxidized – that corresponds to different structures and is for each state significantly improved by the addition of a low Rh concentration (∼1 wt%). In the bimetallic catalyst, reduction is required to form the most active phase, a Ni3Fe alloy, showing a CH4 consumption rate of 0.9 mol s−1 kgcat−1. For the trimetallic NiFeRh, the effect of the initial state is less pronounced, yielding a CH4 consumption rate of 2.4 mol s−1 kgcat−1 after CO2‐reoxidation. Advanced characterization and modelling were used to gain insights in the trimetallic system and to systematically assess the role of each element. In NiFeRh, reduction leads to the formation of a trimetallic alloy. A subsequent CO2‐reoxidation induces partial Fe segregation from the trimetallic alloy, leading to separate Fe3O4. The latter structure represents the most active state due to the double role that the trimetallic catalyst takes up after H2‐reduction and CO2‐reoxidation: improved activity due to highly dispersed NiRh and NiFe alloy particles and carbon removal due to Fe3O4 particles.
Continuous Flow Bioconjugations of NIR‐AZA Fluorophores via Strained Alkyne Cycloadditions with Intra‐Chip Fluorogenic Monitoring**
Authors: Fitzgerald Sheila , O'Shea Donal F. 
Published: January 2022

AbstractThe importance of bioconjugation reactions continues to grow for cell specific targeting and dual therapeutic plus diagnostic medical applications. This necessitates the development of new bioconjugation chemistries, in‐flow synthetic and analytical methods. With this goal, continuous flow bioconjugations were readily achieved with short residence times for strained alkyne substituted carbohydrate and therapeutic peptide biomolecules in reaction with azide and tetrazine substituted fluorophores. The strained alkyne substrates included substituted 2‐amino‐2‐deoxy‐α‐D‐glucopyranose, and the linear and cyclic peptide sequences QIRQQPRDPPTETLELEVSPDPAS‐OH and c(RGDfK) respectively. The catalyst and reagent‐free inverse electron demand tetrazine cycloadditions proved more favourable than the azide 1,3‐dipolar cycloadditions. Reaction completion was achieved with residence times of 5 min at 40 °C for tetrazine versus 10 min at 80 °C for azide cycloadditions. The use of a fluorogenic tetrazine fluorophore, in a glass channelled reactor chip, allowed for intra‐chip reaction monitoring by recording fluorescence intensities at various positions throughout the chip. As the Diels‐Alder reactions proceeded through the chip, the fluorescence intensity increased accordingly in real‐time. The application of continuous flow fluorogenic bioconjugations could offer an efficient translational access to theranostic agents.
Synthesis of Chiral Hydantoins and Thiazolidinediones viaIridium‐Catalyzed Asymmetric Hydrogenation
Authors: Nie Yu , Li Jing , Yuan Qianjia , Zhang Wanbin 
Published: January 2022

Comprehensive SummaryHerein, we report an iridium‐catalyzed asymmetric hydrogenation of hydantoin and thiazolidinedione derived exocyclic alkenes using our developed BiphPHOX as a ligand. The transformation shows good functional group tolerance, and gives the hydrogenated products with excellent yields (up to 99%) and enantioselectivities (up to 98% ee). A gram‐scale reaction was also carried out, and provided the hydrogenated product in excellent yield with no erosion in enantioselectivity. Finally, the transformation of the hydrogenated product provided an efficient approach for the synthesis of the intermediate of a HIV protease inhibitor.
Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials
Authors: Wang Geqing , Mohanty Biswaranjan , Williams Martin L. , Doak Bradley C. , Dhouib Rabeb , Totsika Makrina , McMahon Róisín M. , Sharma Gaurav , Zheng Dan , Bentley Matthew R. , Ka‐Yan Chin Yanni , Horne James , Chalmers David K. , Heras Begoña , Scanlon Martin J. 
Published: January 2022

AbstractDsbA enzymes catalyze oxidative folding of proteins that are secreted into the periplasm of Gram‐negative bacteria, and they are indispensable for the virulence of human pathogens such as Vibrio cholerae and Escherichia coli. Therefore, targeting DsbA represents an attractive approach to control bacterial virulence. X‐ray crystal structures reveal that DsbA enzymes share a similar fold, however, the hydrophobic groove adjacent to the active site, which is implicated in substrate binding, is shorter and flatter in the structure of V. cholerae DsbA (VcDsbA) compared to E. coli DsbA (EcDsbA). The flat and largely featureless nature of this hydrophobic groove is challenging for the development of small molecule inhibitors. Using fragment‐based screening approaches, we have identified a novel small molecule, based on the benzimidazole scaffold, that binds to the hydrophobic groove of oxidized VcDsbA with a KD of 446±10 μM. The same benzimidazole compound has ∼8‐fold selectivity for VcDsbA over EcDsbA and binds to oxidized EcDsbA, with KD>3.5 mM. We generated a model of the benzimidazole complex with VcDsbA using NMR data but were unable to determine the structure of the benzimidazole bound EcDsbA using either NMR or X‐ray crystallography. Therefore, a structural basis for the observed selectivity is unclear. To better understand ligand binding to these two enzymes we crystallized each of them in complex with a known ligand, the bile salt sodium taurocholate. The crystal structures show that taurocholate adopts different binding poses in complex with VcDsbA and EcDsbA, and reveal the protein‐ligand interactions that stabilize the different modes of binding. This work highlights the capacity of fragment‐based drug discovery to identify inhibitors of challenging protein targets. In addition, it provides a starting point for development of more potent and specific VcDsbA inhibitors that act through a novel anti‐virulence mechanism.
Population Pharmacokinetic Modeling and Exposure‐Response Analysis for Aripiprazole Once Monthly in Subjects With Schizophrenia
Authors: Wang Xiaofeng , Raoufinia Arash , Bihorel Sébastien , Passarell Julie , Mallikaarjun Suresh , Phillips Luann 
Published: January 2022

AbstractAn intramuscular formulation of aripiprazole monohydrate dosed once monthly (AOM) was developed to address nonadherence with the approved oral tablets. A 3‐compartment linear population pharmacokinetic model for oral and AOM doses was developed; relative bioavailability was estimated for AOM relative to oral dosing and body mass index and sex were significant predictors of AOM absorption rate constant (longer absorption half‐life for women and absorption half‐life increases with increasing body mass index). Aripiprazole apparent oral clearance for subjects with cytochrome P450 (CYP) 2D6 poor metabolizer status and in the presence of strong CYP2D6 inhibitors was approximately half that of subjects with CYP2D6 extensive metabolizer status and 24% lower in the presence of strong CYP3A4 inhibitors. Simulations of the population pharmacokinetics were conducted to evaluate the effect of different dose initiation strategies for AOM, the effects of CYP2D6 metabolizer status, coadministration of CYP2D6 and CYP3A4 inhibitors, and missed doses. An exposure‐response model with an exponential hazard function of the model‐predicted minimum concentration (Cmin) described the time to relapse. The hazard ratio (95% confidence interval) was 4.41 (2.89‐6.75). Thus, a subject with a diagnosis of schizophrenia and Cmin ≥ 95 ng/mL is 4.41 times less likely to relapse relative to a subject with Cmin < 95 ng/mL.
Pharmacokinetics and Bioequivalence Studies of Roxatidine Acetate Hydrochloride Sustained‐Release Capsule in Healthy Chinese Subjects
Authors: Li Xin , Yuan Fang , Xu Bing , Xiao Guiying , Fan Xingming , Li Yuan , Zhang Ping , Tu Shengqing 
Published: January 2022

AbstractThis study aimed to evaluate the bioequivalence between a generic roxatidine acetate hydrochloride (RAH) sustained‐release capsule and brand‐named formulation (ALTAT) under fasting and fed conditions. An open‐label, single‐center, randomized 2‐period crossover study with a 5‐day washout period was conducted. A single oral dose of 75‐mg generic RAH sustained‐release capsule (test drug) or a commercial capsule (reference drug) was given to healthy volunteers under fasting (n = 36) and fed conditions (n = 36). Blood samples were collected at baseline and during the 24 hours after dosing. The concentrations of roxatidine acetate (ROX) and bioactive metabolite roxatidine in plasma were detected using a validated high‐performance liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were analyzed with noncompartmental methods. As prodrug, RAH was dehydrochloric acid to ROX in body and further rapidly converted to roxatidine. Such a rapid metabolism resulted in ROX that was hardly detected in plasma. Active metabolism roxatidine was therefore used to evaluate the pharmacokinetic process. The major pharmacokinetic parameters of roxatidine including peak plasma concentration, area under the plasma concentration–time curve from time 0 to time t, and area under the plasma concentration–time curve from time 0 to infinity were similar between the 2 preparations under fasting and fed conditions. The generic RAH sustained‐release capsule is bioequivalent to the reference drug under fasting and fed conditions in healthy Chinese subjects.
The pH and Potential Dependence of Pb‐Catalyzed Electrochemical CO2 Reduction to Methyl Formate in a Dual Methanol/Water Electrolyte
Authors: Hofsommer Dillon T. , Liang Ying , Uttarwar Sandesh S. , Gautam Manu , Pishgar Sahar , Gulati Saumya , Grapperhaus Craig A. , Spurgeon Joshua M. 
Published: January 2022

AbstractThe conversion of waste CO2 to value‐added chemicals through electrochemical reduction is a promising technology for mitigating climate change while simultaneously providing economic opportunities. The use of non‐aqueous solvents like methanol allows for higher CO2 availability and novel products. In this work, the electrochemistry of CO2 reduction in acidic methanol catholyte at a Pb working electrode was investigated while using a separate aqueous anolyte to promote a sustainable water oxidation half‐reaction. The selectivity among methyl formate (a product unique to reduction of CO2 in methanol), formic acid, and formate was critically dependent on the catholyte pH, with higher pH conditions leading to formate and low pH favoring methyl formate. The potential dependence of the product distribution in acidic catholyte was also investigated, with a faradaic efficiency for methyl formate as high as 75 % measured at −2.0 V vs. Ag/AgCl.
Hexafluoroisopropanol‐Promoted or Brønsted Acid‐Mediated Photochemical [2+2] Cycloadditions of Alkynes with Maleimides
Authors: Triandafillidi Ierasia , Nikitas Nikolaos F. , Gkizis Petros L. , Spiliopoulou Nikoleta , Kokotos Christoforos G. 
Published: January 2022

AbstractAlthough the use of light stimulating organic transformations has been known for more than a century, there is an increasing research interest on expanding the established knowledge. While [2+2] cycloadditions are promoted photochemically, literature precedent on the reaction between alkynes and maleimides is limited and only a handful of examples exist, focusing mainly on N‐aliphatic maleimides. Herein, the differences in reactivity between N‐alkyl and N‐aryl maleimides were identified, and the use of hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA) as viable solutions was proposed in order to achieve high yields. In the case of N‐alkyl maleimides, both HFIP‐mediated or TFA‐promoted reactions were established using LED 370 nm irradiation, without the use of an external photocatalyst. In the case of N‐aryl maleimides, thioxanthone (THX) was employed as the energy transfer photocatalyst along with LED 427 nm irradiation and HFIP. Mechanistic studies were performed, supporting the pivotal role of HFIP or TFA, in acquiring good to high yields in both classes of maleimides.
Insight into Hydrogenation Selectivity of the Electrocatalytic Nitrate‐to‐Ammonia Reduction Reaction via Enhancing the Proton Transport
Authors: Xu Yan‐Tong , Peng Zhigang , Han Ying , Zhong Huiqiong , Yang Jun , Cao Yan 
Published: January 2022

AbstractThe electrocatalytic nitrate‐to‐ammonia reduction reaction route (NARR) is one of the emerging routes toward green ammonia synthesis, and its conversion efficiency is controlled mainly by the hydrogenation selectivity. This study proposed a likely NARR route feasible and effective even in a neutral condition. Its high catalytic selectivity and efficiency were achieved by a switch of the sulfate solution to the phosphate buffer solution (PBS), while conditions of NO3− concentration, pH, and applied potential were maintained unchanged. Specifically, the faradaic efficiencies toward NH3 (FE
) in Na2SO4 were as low as 9.8, 19.8, and 11.4 % versus remarkably jumping to 82.8, 90.5, and 89.5 % in PBS under −0.75, −1.0, and −1.25 V, respectively. The corresponding faradaic efficiencies toward NO2− (FE
), 77.0, 69.2, and 73.7 % in Na2SO4, significantly dropped to10.8, 7.4, and 4.4 % in PBS, evidencing an unexpected selectivity reversal of the nitrate reduction from NO2− to NH3. This insight was further revealed by the visualization of the pH gradient near the electrode surface during NARR and confirmed by density functional theory calculations; PBS notably facilitated the proton transport and active mitigation over the proton transfer barrier. The use of PBS resulted in a maximal partial current density toward NH3 (J
) and NH3 formation rate (r
) up to 133.5 mA cm−2 and 1.74×10−7 mol s−1 cm−2 in 1.0 m KNO3 at −1.25 V.