bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovationen bei Betonbrücken
Authors: Haveresch Karlheinz 
Published: January 2021

AbstractNeue Anforderungen beim Ersatzneubau von Brücken haben starke Innovationen bei der Gestaltung, Bemessung und Bautechnik von Betonbrücken ausgelöst. Es ergeben sich sehr interessante neue Lösungsmöglichkeiten. Im Beitrag wird über den Bearbeitungsstand dieser Entwicklungen berichtet, insbesondere für den erweiterten Einsatz von Fertigteilen aus Beton, die Verwendung von Hochleistungsbeton, die Rahmenbedingungen für Spannglieder in Stegen von Überbauten mit Kastenquerschnitt und für Quervorspannung von Fahrbahnplatten sowie für die Bemessungsregeln bei Dekompressionsnachweis und Mindestbewehrung für beschleunigtes Bauen.
Prenatal exposure to atrazine induces cryptorchidism and hypospadias in F1 male mouse offspring
Authors: Tan Hongli , Wu Guohui , Wang Shanshan , Lawless John , Sinn Austin , Chen Da , Zheng Zhengui 
Published: January 2021

AbstractThe main objective of the present study was to determine whether prenatal exposure to atrazine could affect testicle descent and penile masculinization. Atrazine has been demonstrated with a variety of endocrine disrupting activities and reproductive toxicities. However, the effects of prenatal atrazine exposure on male offspring's genital malformation, such as hypospadias and cryptorchidism, remain poorly understood. In this study, pregnant ICR mice were gavaged from gestational day 12.5–16.5 with different doses of atrazine. Although no sign of systemic toxicity was observed in F1 male pups, prenatal exposure to 100 mg/kg/day atrazine affected penile morphology, urethral meatus position and descent of testis, and reduced anogenital distance and penile size in postnatal day 21 F1 male pups. The comparative study with an androgen receptor (AR) antagonist vinclozolin suggested that these effects of atrazine on male genital development may not be through antagonism of AR. The results also revealed that atrazine exposure significantly reduced maternal serum testosterone levels, decreased AR nuclear translocation, and altered the expression levels of developmental gene networks in developing penis of mice. Atrazine exposure also affected the expression of insulin‐like 3 (Insl3) and steroidogenic gene expression in developing reproductive tract. Therefore, our data indicate that prenatal atrazine exposure can induce hypospadias in F1 mice, likely through disruption of testosterone production, decreasing genomic androgen action, and then altering expression of developmental genes during sexual differentiation. Our data also suggest that prenatal atrazine exposure can induce cryptorchidism in F1 mice, possibly through down regulation of Insl3.
A high‐throughput predictive method for sequence‐similar fold switchers
Authors: Kim Allen K. , Looger Loren L. , Porter Lauren L. 
Published: January 2021

AbstractAlthough most experimentally characterized proteins with similar sequences assume the same folds and perform similar functions, an increasing number of exceptions is emerging. One class of exceptions comprises sequence‐similar fold switchers, whose secondary structures shift from α‐helix <‐> β‐sheet through a small number of mutations, a sequence insertion, or a deletion. Predictive methods for identifying sequence‐similar fold switchers are desirable because some are associated with disease and/or can perform different functions in cells. Here, we use homology‐based secondary structure predictions to identify sequence‐similar fold switchers from their amino acid sequences alone. To do this, we predicted the secondary structures of sequence‐similar fold switchers using three different homology‐based secondary structure predictors: PSIPRED, JPred4, and SPIDER3. We found that α‐helix <‐> β‐strand prediction discrepancies from JPred4 discriminated between the different conformations of sequence‐similar fold switchers with high statistical significance (P < 1.8*10−19). Thus, we used these discrepancies as a classifier and found that they can often robustly discriminate between sequence‐similar fold switchers and sequence‐similar proteins that maintain the same folds (Matthews Correlation Coefficient of 0.82). We found that JPred4 is a more robust predictor of sequence‐similar fold switchers because of (a) the curated sequence database it uses to produce multiple sequence alignments and (b) its use of sequence profiles based on Hidden Markov Models. Our results indicate that inconsistencies between JPred4 secondary structure predictions can be used to identify some sequence‐similar fold switchers from their sequences alone. Thus, the negative information from inconsistent secondary structure predictions can potentially be leveraged to identify sequence‐similar fold switchers from the broad base of genomic sequences.
Metabolic engineering of HEK293 cells to improve transient transfection and cell budding of HIV‐1 virus‐like particles
Authors: Lavado‐García Jesús , Díaz‐Maneh Andy , Canal‐Paulí Núria , Pérez‐Rubio Pol , Gòdia Francesc , Cervera Laura 
Published: January 2021

AbstractHIV‐1 Gag virus‐like particles (VLPs) are promising candidates for the development of future vaccines. Recent viral outbreaks have manifested the need of robust vaccine production platforms able to adapt to new challenges while achieving mass production capacity. For the rapid production of VLPs, the method of transient gene expression (TGE) have proved highly efficient. Based on a previous characterization of the HEK293 cell line upon transient transfection using multiplexed quantitative proteomics, molecular production bottlenecks and metabolic pathways likely to be optimized were identified. In this study, these molecular components and metabolic pathways have been explored and modulated via transient metabolic engineering using approaches like design of experiments to fully exploit and optimize VLP production, transfection and budding efficiency. Upon overexpression of endosomal sorting complex required for transport accessory proteins like NEDD4L and CIT, VLP production increased 3.3 and 2.9‐fold, respectively. Overexpression of glycosphingolipid precursor enzyme UGCG improved transfection efficiency by 17% and knocking‐down the Gag‐binding protein CNP improved 2.5‐fold VLP specific productivity. Combining CNP inhibition and UGCG overexpression further improved budding efficiency by 37.3%. Modulating VLP production and accessory pathways like intracellular budding, demonstrated the potential of metabolic engineering to optimize and intensify the development of robust production platforms for future vaccines.
Simultaneous quantification of cyclosporin, tacrolimus, sirolimus and everolimus in whole blood by UHPLC–MS/MS for therapeutic drug monitoring
Authors: Antunes Natalicia J. , Kipper Karin , Couchman Lewis , Duncan Marie‐Anne , Holt David W. , De Nucci Gilberto , Johnston Atholl 
Published: January 2021

AbstractThe aim of this study was to develop and validate a UHPLC–MS/MS assay to quantify cyclosporin (CYC), tacrolimus (TAC), sirolimus (SIR) and everolimus (EVE) in human whole blood for therapeutic drug monitoring. Analytes were extracted from 50 μL human whole blood by protein precipitation. The separation of the drugs was performed on an Acquity UPLC BEH C18 column. Analytes were eluted with a mobile phase consisting of 2 mM ammonium acetate with 0.1% formic acid (v/v) in deionised water and 2 mM ammonium acetate with 0.1% formic acid (v/v) in methanol at a flow rate of 300 μL/min in gradient elution. The method performance was evaluated by analysing patient blood samples and/or external quality control samples [proficiency testing (PT) scheme]. The method was linear from 23.75 to 1094.0, 1.3 to 42.4, 1.3 to 47.0 and 1.2–41.6 μg/mL for CYC, TAC, SIR and EVE, respectively. The within‐ and between‐assay reproducibility results were ˂ 11%. Results from PT and patient sample quantification were comparable to those obtained previously by an in‐house validated method using protein precipitation and liquid–liquid extraction. This method showed good analytical performance for quantifying CYC, TAC, SIR and EVE in whole blood over their respective calibration ranges.
Qualitatively driven mixed‐methods approaches to counselling and psychotherapy research
Authors: Bailey‐Rodriguez Deborah 
Published: January 2021

AbstractMany researchers and clinicians take an ‘either, or’ position regarding factors responsible for change when conducting research. Qualitatively driven mixed methods privilege the qualitative approach and offer the opportunity to generate multi‐dimensional material, permitting a more holistic insight into experiences that can be understood from a combination of epistemological and ontological stances. A qualitatively driven mixed‐methods approach apply a ‘both, and’ position when exploring the elements that produce change or that are under investigation, which can be of particular value to counselling and psychotherapy research. There are various ways of engaging with qualitatively driven mixed methods. Some designs include both qualitative and quantitative components, where the former is the core element. The secondary component may also be qualitative, known as a multimethod design. Yet, other designs mix different qualitative approaches, through the application of different qualitative analyses to the same data (pluralistic qualitative research). This paper discusses the application and value of qualitatively driven mixed methods in counselling and psychotherapy research through the presentation of two research case studies; one which mixes both qualitative and quantitative components to investigate the experiences of pain alleviation following a CBT pain management programme; and one which applies a pluralistic approach to a counselling psychology doctorate exploring the experiences and meanings attached to self‐harming. Through illustration and discussion of the case studies’ mixed‐methods approaches, this paper demonstrates that qualitatively driven mixed methods produce a more enhanced and holistic understanding into phenomena, and therefore a more balanced perspective to counselling and psychotherapy research.
In vitro Antioxidant and Cytotoxic Activities of Extracts of Endemic Tanacetum erzincanense Together with Phenolic Content by LC‐ESI‐QTOF‐MS
Authors: Yapıcı İsmail , Altay Ahmet , Öztürk Sarıkaya Beyza , Korkmaz Mustafa , Atila Alptuğ , Gülçin İlhami , Köksal Ekrem 
Published: January 2021

AbstractIn this study, phenolic composition, and in vitro biological activities of ethyl acetate (EAE) and methanol (ME) extracts obtained from the aerial parts of endemic Tanacetum erzincanense were investigated. Total phenolic and flavonoid content of the extracts were determined by Folin‐Ciocalteu and aluminum chloride colorimetric methods, respectively. Antioxidant capacity of the extracts was evaluated over radical scavenging (DPPH and ABTS) and metal ion reducing power (FRAP and CUPRAC) tests. Individual phenolic compounds in ME was analyzed by high‐performance liquid chromatography coupled to electrospray ionization quadrupole time‐of‐flight mass spectrometry (LC‐ESI‐QTOF/MS). Cell inhibitory potential of the extracts was tested against colorectal adenocarcinoma (HT‐29), breast adenocarcinoma (MCF‐7), and hepatocarcinoma (HepG2) cells by 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide (XTT) assay. The results showed that ME contains higher TPC (64.4 mg GAE/g) and TFC (62.2 mg QE/g) than those of EAE (41.5 mg GAE/g and 40.0 mg QE/g). LC‐ESI‐QTOF/MS analysis revealed that ME is rich in phenolic compounds, namely, chlorogenic acid, apigenin, quercetin, luteolin, and diosmetin. Antioxidant assay results indicated that ME possess stronger activity than EAE and a power that competes with synthetic antioxidants. XTT assay results demonstrated that although both extracts displayed a considerable cytotoxicity against the tested cancer cell lines in a time and dose‐dependent manner, ME expressed its selective inhibitory action towards MCF‐7 cells with an IC50 value of 20.4 μg/mL for 72 h. These results may serve as a basis for further in vivo studies to examine the potential applications of T. erzincanense in food and pharmaceutical industries.
Platelet function and microvesicle generation in patients with hemophilia A
Authors: Melero‐Amor Antonia , Romecín Paola , Iyú David , García‐Bernal David , García‐Navaro Esther , Moraleda José M. , García‐Estañ Joaquín , García‐Candel Faustino , Atucha Noemí M. 
Published: January 2021

AbstractOur results do not support any effect of FVIII on platelet function in patients with severe HA treated under the regime of prophylaxis.
Histoplasma stomatitis unveiled: Not all opportunistic infections get better after initiation of antiretroviral therapy
Authors: Bansal Saurabh , Singhania Namrata , Nukala Chandra Mouli , Singh Anil Kumar , Al‐Rabadi Laith 
Published: January 2021

AbstractImmune reconstitution inflammatory syndrome in AIDS patients can lead to an initial worsening of underlying diseases due to body's ability to mount a strong immune response after recovery of CD4 counts.
A laceration of a wired silastic tracheostomy tube: A case report and review of the literature
Authors: Noda Kotaro , Nosaka Nobuyuki , Sai Youshun , Nagaoka Eiki , Nagashima Michio , Arai Hirokuni , Shigemitsu Hidenobu 
Published: January 2021

AbstractFractured tracheostomy tube is a rare, late complication. It typically occurs at the junction of metallic tube. We report an atypical case with laceration of the main trunk of a silastic tube after short period of use (10 days).
MODs vs. NPs: Vying for the Future of Printed Electronics
Authors: Douglas Samuel P. , Mrig Shreya , Knapp Caroline E. 
Published: January 2021

AbstractThis Minireview compares two distinct ink types, namely metal‐organic decomposition (MOD) and nanoparticle (NP) formulations, for use in the printing of some of the most conductive elements: silver, copper and aluminium. Printing of highly conductive features has found purpose across a broad array of electronics and as processing times and temperatures reduce, the avenues of application expand to low‐cost flexible substrates, materials for wearable devices and beyond. Printing techniques such as screen, aerosol jet and inkjet printing are scalable, solution‐based processes that historically have employed NP formulations to achieve low resistivity coatings printed at high resolution. Since the turn of the century, the rise in MOD inks has vastly extended the range of potentially applicable compounds that can be printed, whilst simultaneously addressing shelf life and sintering issues. A brief introduction to the field and requirements of an ink will be presented followed by a detailed discussion of a wide array of synthetic routes to both MOD and NP inks. Unindustrialized materials will be discussed, with the challenges and outlook considered for the market leaders: silver and copper, in comparison with the emerging field of aluminium inks.
Approaches to the Synthesis of Perfluoroalkyl‐Modified Carbohydrates and Derivatives: Thiosugars, Iminosugars, and Tetrahydro(thio)pyrans
Authors: Uhrig María Laura , Mora Flores Erwin W. , Postigo Al 
Published: January 2021

AbstractFluoroalkyl‐substituted carbohydrates play relevant roles in diverse areas such as supramolecular chemistry, glycoconjugation, liquid crystals, and surfactants, with direct applications as wetting, antifreeze, and coating agents. In light of these promising applications, new methodologies for the late‐stage incorporation of fluoroalkyl RF groups into carbohydrates and derivatives are herein presented as they are relevant to the synthetic carbohydrate community. Previously reviewed protocols for the installation of RF groups onto carbohydrates and derivatives will be succinctly summarized in the light of the new achievements. Fluoroalkyl‐substituted iminosugars, on the other hand, are also interesting glycomimetic derivatives with prominent roles as glycosidases and glycosyltransferases inhibitors, as has recently been demonstrated. Also, they positively contribute to the study of sugar–protein interactions and enzyme mechanisms. New advances in the syntheses of fluoroalkyl‐substituted iminosugars will also be presented here.
Diagnostic mesothelioma biomarkers in effusion cytology
Authors: Eccher Albino , Girolami Ilaria , Lucenteforte Ersilia , Troncone Giancarlo , Scarpa Aldo , Pantanowitz Liron 
Published: January 2021

Malignant mesothelioma is a rare malignancy with a poor prognosis whose development is related to asbestos fiber exposure. An increasing role of genetic predisposition has been recognized recently. Pleural biopsy is the gold standard for diagnosis, in which the identification of pleural invasion by atypical mesothelial cell is a major criterion. Pleural effusion is usually the first sign of disease; therefore, a cytological specimen is often the initial or the only specimen available for diagnosis. Given that reactive mesothelial cells may show marked atypia, the diagnosis of mesothelioma on cytomorphology alone is challenging. Accordingly, cell block preparation is encouraged, as it permits immunohistochemical staining. Traditional markers of mesothelioma such as glucose transporter 1 (GLUT1) and insulin‐like growth factor 2 mRNA‐binding protein 3 (IMP3) are informative, but difficult to interpret when reactive proliferations aberrantly stain positive. BRCA1‐associated protein 1 (BAP1) nuclear staining loss is highly specific for mesothelioma, but sensitivity is low in sarcomatoid tumors. Cyclin‐dependent kinase inhibitor 2A (CDKN2A)/p16 homozygous deletion, assessed by fluorescence in situ hybridization, is more specific for mesothelioma with better sensitivity, even in the sarcomatoid variant. The surrogate marker methylthioadenosine phosphorylase (MTAP) has been found to demonstrate excellent diagnostic correlation with p16. The purpose of this review is to provide an essential appraisal of the literature regarding the diagnostic value of many of these emerging biomarkers for malignant mesothelioma in effusion cytology.
Safety, Tolerability, and Pharmacokinetics of Multiple Repeated Oral Doses of the α2/3/5‐Subtype Selective GABAA‐Positive Allosteric Modulator PF‐06372865 in Healthy Volunteers
Authors: Gurrell Rachel , Whitlock Mark , Wei Hua , Shen Zhongzhou , Ogden Adam 
Published: January 2021

AbstractMultiple‐dose pharmacokinetics (PK) and safety were investigated in this phase 1 study of PF‐06372865, a positive allosteric modulator of α2/3/5 subunit‐containing γ‐aminobutyric acid A receptors (NCT03351751). In 2 cohorts (7‐8 PF‐06372865 and 2 placebo in each cohort), healthy adult subjects received twice‐daily oral doses of PF‐06372865 for 21 days, which included titration in the first 7 days, followed by a maintenance dose of 25 mg twice daily (Cohort 1) and 42.5 mg twice daily (Cohort 2) for 14 days. Serial PK samples were collected on days 1 and 21. Nineteen subjects were assigned to study treatments; 18 completed the study. Approximate dose‐proportional increases in maximum plasma concentratin and area under the plasma concentration–time curve over the dosing interval were observed. PF‐06372865 was rapidly absorbed with a median time to maximum concentration of 1 to 2 hours following both single‐ and multiple‐dose administration. Mean terminal elimination half‐life on day 21 was approximately 11 hours in both cohorts. All adverse events were mild; the most frequently reported was dizziness. After titration, there were no reports of somnolence. There were no clinically significant safety findings, including a lack of withdrawal symptoms on discontinuation of treatment. These results demonstrate that PF‐06372865 is safe and well tolerated at doses estimated to achieve high receptor occupancy (>80%), a profile differentiated from nonselective benzodiazepines.
An Unsual Cys‐Glu‐Lys Catalytic Triad is Responsible for the Catalytic Mechanism of the Nitrilase Superfamily: A QM/MM Study on Nit2
Authors: Silva Teixeira Carla S. , Sousa Sérgio F. , Cerqueira Nuno M. F. S. A. 
Published: January 2021

AbstractNitrilase 2 (Nit2) is a representative member of the nitrilase superfamily that catalyzes the hydrolysis of α‐ketosuccinamate into oxaloacetate. It has been associated with the metabolism of rapidly dividing cells like cancer cells. The catalytic mechanism of Nit2 employs a catalytic triad formed by Cys191, Glu81 and Lys150. The Cys191 and Glu81 play an active role during the catalytic process while the Lys150 is shown to play only a secondary role. The results demonstrate that the catalytic mechanism of Nit2 involves four steps. The nucleophilic attack of Cys191 to the α‐ketosuccinamate, the formation of two tetrahedral enzyme adducts and the hydrolysis of a thioacyl‐enzyme intermediate, from which results the formation of oxaloacetate and enzymatic turnover. The rate limiting step of the catalytic process is the formation of the first tetrahedral intermediate with a calculated activation free energy of 18.4 kcal/mol, which agrees very well with the experimental kcat (17.67 kcal/mol).
Recycling of Primary Lithium Batteries Production Residues
Authors: Kahl M. , Pavón S. , Bertau M. 
Published: January 2021

AbstractProduction waste of primary lithium batteries constitutes a considerable secondary lithium feedstock. Although the recycling of lithium batteries is a widely studied field of research, the metallic residues of non‐rechargeable lithium battery production are disposed of as waste without further recycling. The risks of handling metallic Li on a large scale typically prevent the metal from being recycled. A way out of this situation is to handle Li in an aqueous solution, from where it can be isolated as Li2CO3. However, the challenge in hydrometallurgical treatment lies in the high energy release during dissolution and generation of H2. To reduce these process‐related risks, the Li sheet metal punching residues underwent oxidative thermal treatment from 300 to 400 °C prior to dissolution in water. Converting Li metal to Li2O in this initial process step results in an energy release reduction of ∼70 %. The optimal oxidation conditions have been determined by experimental design varying three factors: temperature, Li metal sheet thickness, and residence time. With 96.9±2.6 % almost the entire Li amount is converted to Li2O, after 2.5 h treatment at 400 °C for a Li sheet thickness of 1.99 mm. Final precipitation with CO2 yields 85.5±3.0 % Li2CO3. Using pure Li sheets, the product Li2CO3 is obtained in battery‐grade quality (>99.5 %). Non‐precipitated Li is recirculated into the process on the stage of dissolving Li2O, thus avoiding loss of material.
Spin‐projected QM/MM Free Energy Simulations for Oxidation Reaction of Guanine in B−DNA by Singlet Oxygen
Authors: Saito Toru , Takano Yu 
Published: January 2021

AbstractGuanine is the most susceptible base to oxidation damage induced by reactive oxygen species including singlet oxygen (1O2, 1Δg). We clarify whether the first step of guanine oxidation in B−DNA proceeds via either a zwitterionic or a diradical intermediate. The free energy profiles are calculated by means of a combined quantum mechanical and molecular mechanical (QM/MM) method coupled with the adaptive biasing force (ABF) method. To describe the open‐shell electronic structure of 1O2 correctly, the broken‐symmetry spin‐unrestricted density functional theory (BS−UDFT) with an approximate spin projection (AP) correction is applied to the QM region. We find that the effect of spin contamination on the activation and reaction free energies is up to ∼8 kcal mol−1, which is too large to be neglected. The QM(AP−ULC−BLYP)/MM‐based free energy calculations also reveal that the reaction proceeds through a diradical transition state, followed by a conversion to a zwitterionic intermediate. Our computed activation energy of 5.2 kcal mol−1 matches experimentally observed range (0∼6 kcal mol−1).