bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process‐wide control and automation of an integrated continuous manufacturing platform for antibodies
Authors: Feidl Fabian , Vogg Sebastian , Wolf Moritz , Podobnik Matevz , Ruggeri Caterina , Ulmer Nicole , Wälchli Ruben , Souquet Jonathan , Broly Hervé , Butté Alessandro , Morbidelli Massimo 
Published: February 2020

AbstractIntegrated continuous manufacturing is entering the biopharmaceutical industry. The main drivers range from improved economics, manufacturing flexibility, and more consistent product quality. However, studies on fully integrated production platforms have been limited due to the higher degree of system complexity, limited process information, disturbance, and drift sensitivity, as well as difficulties in digital process integration. In this study, we present an automated end‐to‐end integrated process consisting of a perfusion bioreactor, CaptureSMB, virus inactivation (VI), and two polishing steps to produce an antibody from an instable cell line. A supervisory control and data acquisition (SCADA) system was developed, which digitally integrates unit operations and analyzers, collects and centrally stores all process data, and allows process‐wide monitoring and control. The integrated system consisting of bioreactor and capture step was operated initially for 4 days, after which the full end‐to‐end integrated run with no interruption lasted for 10 days. In response to decreasing cell‐specific productivity, the supervisory control adjusted the loading duration of the capture step to obtain high capacity utilization without yield loss and constant antibody quantity for subsequent operations. Moreover, the SCADA system coordinated VI neutralization and discharge to enable constant loading conditions on the polishing unit. Lastly, the polishing was sufficiently robust to cope with significantly increased aggregate levels induced on purpose during virus inactivation. It is demonstrated that despite significant process disturbances and drifts, a robust process design and the supervisory control enabled constant (optimum) process performance and consistent product quality.
Limited life cycle and cost assessment for the bioconversion of lignin‐derived aromatics into adipic acid
Authors: van Duuren Jozef B. J. H. , de Wild Paul J. , Starck Sören , Bradtmöller Christian , Selzer Mirjam , Mehlmann Kerstin , Schneider Roland , Kohlstedt Michael , Poblete‐Castro Ignacio , Stolzenberger Jessica , Barton Nadja , Fritz Michel , Scholl Stephan , Venus Joachim , Wittmann Christoph 
Published: February 2020

AbstractLignin is an abundant and heterogeneous waste byproduct of the cellulosic industry, which has the potential of being transformed into valuable biochemicals via microbial fermentation. In this study, we applied a fast‐pyrolysis process using softwood lignin resulting in a two‐phase bio‐oil containing monomeric and oligomeric aromatics without syringol. We demonstrated that an additional hydrodeoxygenation step within the process leads to an enhanced thermochemical conversion of guaiacol into catechol and phenol. After steam bath distillation, Pseudomonas putida KT2440‐BN6 achieved a percent yield of cis, cis‐muconic acid of up to 95 mol% from catechol derived from the aqueous phase. We next established a downstream process for purifying cis, cis‐muconic acid (39.9 g/L) produced in a 42.5 L fermenter using glucose and benzoate as carbon substrates. On the basis of the obtained values for each unit operation of the empirical processes, we next performed a limited life cycle and cost analysis of an integrated biotechnological and chemical process for producing adipic acid and then compared it with the conventional petrochemical route. The simulated scenarios estimate that by attaining a mixture of catechol, phenol, cresol, and guaiacol (1:0.34:0.18:0, mol ratio), a titer of 62.5 (g/L) cis, cis‐muconic acid in the bioreactor, and a controlled cooling of pyrolysis gases to concentrate monomeric aromatics in the aqueous phase, the bio‐based route results in a reduction of CO2‐eq emission by 58% and energy demand by 23% with a contribution margin for the aqueous phase of up to 88.05 euro/ton. We conclude that the bio‐based production of adipic acid from softwood lignins brings environmental benefits over the petrochemical procedure and is cost‐effective at an industrial scale. Further research is essential to achieve the proposed cis, cis‐muconic acid yield from true lignin‐derived aromatics using whole‐cell biocatalysts.
Impact of self‐perception of aging on mortality of older patients in oncology
Authors: Schroyen Sarah , Letenneur Luc , Missotten Pierre , Jérusalem Guy , Adam Stéphane 
Published: February 2020

AbstractObjectiveSeveral studies show that self‐perception of aging (SPA) is a significant predictor of mental and physical health. In this study, we analyze the effect of SPA on mortality in the specific context of geriatric oncology.MethodsThe sample constituted of 140 individuals aged 65 years and older suffering from a recent nonmetastatic cancer (breast, lung, gynecological, or hematological), followed up to 6 years. We used Cox proportional hazards model to assess the effect of SPA at baseline on mortality. It was adjusted for age, gender, educational and cognitive level, oncological information (the site and kind of cancer), number of comorbidities, and physical and mental health at baseline.ResultsPatients were aged 73 years at diagnosis and were more often women (85.7%). Individuals with more negative SPA were 3.62 times more likely to die than those with a more positive SPA, with control of gender, age, education and cognitive level, mental and physical health, the category (breast, lung, gynecological, or hematological), and kind (initial or recurrence) of cancer.ConclusionsThese findings suggest that SPA influence the mortality of older people in the particular context of oncology. Therefore, the need to change our attitudes toward aging and older people implied indirectly by these results is discussed.
Upregulation of hsa_circ_0007874 suppresses the progression of ovarian cancer by regulating the miR‐760/SOCS3 pathway
Authors: Li Li , Yu Poling , Zhang Ping , Wu Huanmei , Chen Qizhen , Li Shuangdi , Wang Yanqiu 
Published: February 2020

AbstractOvarian cancer (OVA) is a fatal and common malignancy in women worldwide. Circular RNAs (circRNAs) consist of a family of circular endogenous RNAs generated by selective splicing, and they are involved in many diseases. Previous studies reported that hsa_circ_0007874 is aberrantly expressed in cancer and functions in tumorigenesis. While the hsa_circ_0007874 role in OVA is unclear. Here, we detected the hsa_circ_0007874 expression in OVA cell lines using Rt‐qPCR. Hsa_circ_0007874 subcellular localization was confirmed by fluorescence in situ hybridization. The relationship between hsa_circ_0007874, microRNAs (miRNAs), and relative protein levels was assessed using the luciferase reporter assays. Results verified that hsa_circ_0007874 is downregulated in OVA cell lines. hsa_circ_0007874 overexpression decreased the OVA cell migration and proliferation in vitro and in vivo. Bioinformatics and luciferase reporter assays confirmed that miR‐760 and SOCS3 are the downstream targets of hsa_circ_0007874. Downregulation of SOCS3 or miR‐760 overexpression restored the migration and proliferation ability of SKOV3 or A2780 cells overexpressing hsa_circ_0007874. Downregulation of SOCS3 restored the proliferation and migration in miR‐760 knockdown SKOV3 and A2780 cells. In summary, the data suggest that hsa_circ_0007874 acts as a tumor suppressor by regulating the miR‐760/SOCS3 axis, highlighting its potential as an effective therapeutic target for OVA.
Chemical Characterization and Phytotoxic Effects of the Aerial Parts of Ruzigrass (Urochloa ruziziensis)
Authors: Pereira Moreno Beatriz , Mantovanelli Gislaine Cristiane , Lopes Ricardo Letycia , Silva Adriano Antônio , Silvério De Oliveira Rubem , Ishii‐Iwamoto Emy Luiza , Sarragiotto Maria Helena , Baldoqui Debora Cristina 
Published: February 2020

AbstractStudies of the phytotoxic effects between plants can be a crucial tool in the discovery of innovative compounds with herbicide potential. In this sense, we can highlight ruzigrass (Urochloa ruziziensis), which is traditionally used in the crop rotation system in order to reduce weed emergence. The aim of this work was to characterize the secondary metabolites of ruzigrass and to evaluate its phytotoxic effects. In total, eight compounds were isolated: friedelin, oleanolic acid, α‐amyrin, 1‐dehydrodiosgenone, sitosterol and stigmasterol glycosides, tricin and p‐coumaric acid. Phytotoxic effects of the crude methanolic extract and fractions of ruzigrass were assessed using germination rate, initial seedling growth, and biomass of Bidens pilosa, Euphorbia heterophylla and Ipomoea grandifolia. Chemometric analysis discriminated the weed species into three groups, and B. pilosa was the most affected by fractions of ruzigrass. The phytotoxic activities of 1‐dehydrodiosgenone, tricin, and p‐coumaric acid are also reported, and p‐coumaric acid and 1‐dehydrodiosgenone were active against B. pilosa.
Identification of a Unique Azaphilone Produced by Chaetomium globosum Isolated from Polygonatum sibiricum
Authors: Song Chenggang , Ding Gang , Wu Gang , Yang Jian , Zhang Mingzhe , Wang Haoyu , Wei Dongsheng , Qin Jianchun , Guo Lanping 
Published: February 2020

AbstractA new azaphilone, chaephilone E, eight azaphilone derivatives, and three chaetoglobosins were isolated from endophytic fungi Chaetomium globosum. The structures of the compounds were elucidated by 1D and 2D NMR as well as HR‐ESI‐MS data, and the absolute configuration of chaephilone E was established on the basis of electronic circular dichroism and NOESY spectrum. The activity of chaephilone E was evaluated via the cytotoxic assay (human hepatoma cell lines HepG‐2) and brine shrimp (Artemia salina) bioassay.
Hijacking Translation Initiation for Synthetic Biology
Authors: Tharp Jeffery M. , Krahn Natalie , Varshney Umesh , Söll Dieter 
Published: February 2020

AbstractGenetic code expansion (GCE) has revolutionized the field of protein chemistry. Over the past several decades more than 150 different noncanonical amino acids (ncAAs) have been co‐translationally installed into proteins within various host organisms. The vast majority of these ncAAs have been incorporated between the start and stop codons within an open reading frame. This requires that the ncAA be able to form a peptide bond at the α‐amine, limiting the types of molecules that can be genetically encoded. In contrast, the α‐amine of the initiating amino acid is not required for peptide bond formation. Therefore, including the initiator position in GCE allows for co‐translational insertion of more diverse molecules that are modified, or completely lacking an α‐amine. This review explores various methods which have been used to initiate protein synthesis with diverse molecules both in vitro and in vivo.
Predicting the risk of late futile outcome after transcatheter aortic valve implantation
Authors: Zusman Oren , Barbash M. Israel , Guetta Victor , Finkelstein Ariel , Assali Abid , Segev Amit , Orvin Katia , Barsheshet Alon , Younis Arwa , Witberg Guy , Kornowski Ran , Danenberg Haim , Landes Uri 
Published: February 2020

AbstractBackgroundTranscatheter aortic valve implantation (TAVI) for aortic stenosis (AS) risk assessment is still developing and mostly concerned with mortality in the periprocedural period. We therefore sought to develop and then validate a score to predict 1‐year adverse outcome.MethodsPatients that underwent TAVI for severe AS in the Israeli registry. Patients with unsuccessful/suboptimal implantation were excluded. The cohort was split to derivation/validation cohorts by a ratio of 70:30. The outcome was defined as 1‐year composite of mortality, stroke, and no improvement in NYHA class (vs. baseline). Logistic regression was used to fit the prediction model.ResultsOut of 2,440 patients meeting inclusion criteria, 276 were excluded, leaving 2,160 patients for both cohorts. At 1 year, 299 (14%) patients experienced the adverse (“futile”) outcome. The derived prediction model included mean aortic valve (AV) gradient, previous pacemaker, previous oncological disease, need for diuretics, baseline NYHA class, hemoglobin and creatinine levels, and nonfemoral access site. The model's area under the curve (AUC) was 0.69 in the derivation and 0.70 in the validation cohort. Performance of other scores in the validation cohort were lower (0.60 for STS, 0.55 for Euroscore2, 0.56 for TVT score, and 0.53 for TAVI2‐score, p = .03). Based on three risk tiers, patients had a low risk (20/306, 7% futility), a medium risk (50/304, 17%), and high risk (18/37, 49%) for futility.ConclusionsThe TAVI futility risk model can be used to provide further insight regarding prediction measures and/or patients' outcomes outside of the periprocedural period (NCT02023060).
Antenatal diagnosis of absence of septum pellucidum
Authors: Ben M'Barek Imane , Tassin Mikael , Guët Agnes , Simon Isabelle , Mairovitz Valerie , Mandelbrot Laurent , Picone Olivier 
Published: February 2020

AbstractThe absence of septum pellucidum (ASP) is a rare disease, which affects the structure of the brain. It is either isolated or associated with various congenital brain malformations. The diagnosis of ASP can be performed by second‐trimester ultrasound. When the ASP is isolated, prenatal counseling is optimistic regarding neurological outcome, but there is a 20% risk of septo‐optic dysplasia in the neonate.
Much faster cross‐validation in PLSR‐modelling by avoiding redundant calculations
Authors: Liland Kristian Hovde , Stefansson Petter , Indahl Ulf Geir 
Published: February 2020

AbstractA novel formulation of the wide kernel algorithm for partial least squares regression (PLSR) is proposed. We show how the elimination of redundant calculations in the traditional applications of PLSR helps in speeding up any choice of cross‐validation strategy by utilizing precalculated lookup matrices.The proposed lookup approach is combined with some additional computational shortcuts resulting in highly effective and numerically accurate cross‐validation results. The computational advantages of the proposed method are demonstrated by comparisons to the classical NIPALS and the bidiag2 algorithms for calculating cross‐validated PLSR models. Problems including both one and several responses, double/nested cross‐validated, and one‐vs‐all classification are among the considered applications.
A chemometric study combined with spectroscopy for the quantification of secondary structure of flagellar‐associated protein 174 (FAP174)
Authors: M. Yogesha , Rao Venkatramanan G. , Devangad Praveen , D'Souza Jacinta S. , Chidangil Santhosh 
Published: February 2020

AbstractThe secondary structure analyses of proteins hold immense importance in the field of protein science because it plays a vital role in its hierarchical classification. It is the most important transitional step in the prediction of the three‐dimensional structure of any protein. The aim of the current study is to quantitatively determine the secondary structure of an important ciliary protein, viz, an MYC‐binding protein‐1 (MYCBP‐1) orthologue, viz, flagellar‐associated protein 174 (FAP174) from the green alga, Chlamydomonas reinhardtii. FAP174 binds to A‐kinase anchoring protein 240 (AKAP240) and has a crucial role to play in ciliary motility. Hence, the biochemical characterization of FAP174 becomes more vital in understanding its molecular function. The accurate secondary structure of FAP174 was investigated through circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) combined with partial least square regression (PLSR) methods. The far‐UV CD spectrum of FAP174 exhibited a positive band at 192 nm and negative bands at 208 and 221 nm, whereas quantification through BeStSel web server revealed 65% α‐helix, approximately 2% of antiparallel β‐sheets, 6% of β‐turns, and 27% of unordered structures. These results were further confirmed by FTIR spectrum of FAP174 that revealed amide I and II bands at 1654 and 1547 cm−1, respectively. And the PLSR calibration models led to the quantification of the secondary structure for FAP174 protein that fairly corroborated with the values obtained by quantifying CD spectrum, these being approximately 54% α‐helix, 0% β‐sheets, approximately 12% β‐turns, and approximately 34% other structures. The recombinant FAP174 protein is therefore considerably α‐helical and has negligible or no β‐sheets.
Synthesis and Characterization of Thiophene‐based Donor–Acceptor–Donor Heptameric Ligands for Spectral Assignment of Polymorphic Amyloid‐β Deposits
Authors: Lantz Linda , Shirani Hamid , Klingstedt Therése , Nilsson K. Peter R. 
Published: February 2020

AbstractProtein deposits are associated with many devastating diseases and fluorescent ligands able to visualize these pathological entities are essential. Here, we report the synthesis of thiophene‐based donor–acceptor–donor heptameric ligands that can be utilized for spectral assignment of distinct amyloid‐β (Aβ) aggregates, one of the pathological hallmarks in Alzheimer's disease. The ability of the ligands to selectively distinguish Aβ deposits was abolished when the chemical composition of the ligands was altered. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species consisting of the same peptide or protein. In addition, such ligands might aid in interpreting the potential role of polymorphic Aβ deposits in the pathogenesis of Alzheimer's disease.
Boron–Nitrogen‐Doped Nanographenes: A Synthetic Tale from Borazine Precursors
Authors: Dosso Jacopo , Battisti Tommaso , Ward Benjamin D. , Demitri Nicola , Hughes Colan E. , Williams P. Andrew , Harris Kenneth D. M. , Bonifazi Davide 
Published: February 2020

AbstractIn this work, a comprehensive account of the authors’ synthetic efforts to prepare borazino‐doped hexabenzocoronenes by using the Friedel–Crafts‐type electrophilic aromatic substitution is reported. Hexafluoro‐functionalized aryl borazines, bearing anorthofluoride leaving group on each of the N‐ and B‐aryl rings, was shown to lead to cascade‐type electrophilic aromatic substitution events in the stepwise C−C bond formation, giving higher yields of borazinocoronenes than those obtained with borazine precursors bearing fluoride leaving groups at theorthopositions of the B‐aryl substituents. By using this pathway, an unprecedented boroxadizine‐doped PAH featuring a gulf‐type periphery could be isolated, and its structure proven by single‐crystal X‐ray diffraction analysis. Mechanistic studies on the stepwise Friedel–Crafts‐type cyclization suggest that the mechanism of the planarization reaction proceeds through extension of the π system. To appraise the doping effect of the boroxadizine unit on the optoelectronic properties of topology‐equivalent molecular graphenes, the all‐carbon and pyrylium PAH analogues, all featuring a gulf‐type periphery, were also prepared. As already shown for the borazino‐doped hexabenzocoronene, the replacement of the central benzene ring by its B3N2O congener widens the HOMO–LUMO gap and dramatically enhances the fluorescence quantum yield.
Feinstzerkleinerung von CFK‐Abfällen und Charakterisierung der Zerkleinerungsprodukte
Authors: Krampitz Thomas , Zöllner Mareen , Lieberwirth Holger , Kamptner Andre , Friedrich Jens 
Published: February 2020

AbstractDie Zerkleinerung von kohlenstofffaserverstärkten Kunststoffen (CFK) stellt für fast alle Recyclingprozesse einen zentralen Prozessschritt dar. Mit der Zerkleinerung wird spezifische Oberfläche geschaffen, die insbesondere bei Feingütern als Maß für den Zerkleinerungserfolg dient. Im Artikel wird die Zerkleinerung von 1 m Kantenlänge im Aufgabegut bis auf Zielproduktgröße von kleiner 100 µm mittels einer dreistufigen Zerkleinerung aufgezeigt. Dabei wird auf die Herausforderungen bei der granulometrischen Charakterisierung der Zerkleinerungsprodukte und die damit verbundene Bewertung des Zerkleinerungserfolges gezielt eingegangen.
High‐temperature CO2 adsorption over Li4SiO4 sorbents derived from different lithium sources
Authors: Fang Yuan , Zou Renjie , Chen Xiaoxiang 
Published: February 2020

AbstractLi4SiO4 is a promising sorbent for high temperature CO2 capture. It could be synthesized from three different Li sources (LiNO3, LiOH, and Li2CO3) by using the solid state reaction method. The effects of Li sources on the structure and CO2 adsorption/desorption properties of Li4SiO4 sorbents were analyzed in this work. The results showed that Li4SiO4 sorbents could be synthesized at a lower temperature by using LiNO3 and LiOH as the starting materials, which could reduce the sintering during the synthesis process and increase the surface area of synthesized Li4SiO4. During the CO2 adsorption/desorption cycles, Li4SiO4 sorbents derived from LiNO3 and LiOH presented higher initial CO2 adsorption capacities than those from Li2CO3. After 15 cycles, the adsorption efficiency of Li4SiO4 derived from LiNO3 showed no or slight decrease, while that from LiOH rapidly decreased to 20% of the initial value. This was because Li4SiO4 derived from LiNO3 had high surface area and porosity before CO2 adsorption/desorption cycles, and its surface area even increased after cycles. However, the surface area of Li4SiO4 derived from LiOH decreased greatly due to serious sintering. For Li4SiO4 derived from Li2CO3, its morphology and surface area were almost unchanged before and after CO2 adsorption/desorption cycles.
Biodegradable Periodic Mesoporous Organosilica (BPMO) Loaded with Daunorubicin: A Promising Nanoparticle‐Based Anticancer Drug
Authors: Mai Ngoc Xuan Dat , Birault Albane , Matsumoto Kotaro , Ta Hanh Kieu Thi , Intasa‐ard Soontaree Grace , Morrison Kendall , Thang Phan Bach , Doan Tan Le Hoang , Tamanoi Fuyuhiko 
Published: February 2020

AbstractBiodegradable periodic mesoporous organosilica (BPMO) nanoparticles have emerged as a promising type of nanocarrier for drug delivery, given the biodegradable feature is advantageous for clinical translation. In this paper, we report synthesis and characterization of daunorubicin (DNR) loaded BPMO. DNR was loaded onto rhodamine B‐labeled BPMO that contain tetrasulfide bonds. Tumor spheroids and chicken egg tumor models were used to characterize the activity in biological settings. In the first experiment we examined the uptake of BPMO into tumor spheroids prepared from ovarian cancer cells. BPMO were efficiently taken up into tumor spheroids and inhibited their growth. In the chicken egg tumor model, intravenous injection of DNR‐loaded BPMO led to the elimination of ovarian tumor. Lack of adverse effect on organs such as lung appears to be due to excellent tumor accumulation of BPMO. Thus, DNR‐loaded BPMO represents a promising nanodrug compared with free DNR currently used in cancer therapy. OK
Further Investigations into Rigidity‐Activity Relationships in BisQAC Amphiphilic Antiseptics
Authors: Leitgeb Austin J. , Feliciano Javier A. , Sanchez Hugo A. , Allen Ryan A. , Morrison Kelly R. , Sommers Kyle J. , Carden Robert G. , Wuest William M. , Minbiole Kevin P. C. 
Published: February 2020

AbstractThirty‐six biscationic quaternary ammonium compounds were efficiently synthesized in one step to examine the effect of molecular geometry of two‐carbon linkers on antimicrobial activity. The synthesized compounds showed strong antimicrobial activity against a panel of both Gram‐positive and Gram‐negative bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA). While the linker geometry showed only a modest correlation with antimicrobial activity, several of the synthesized bisQACs are promising potential antiseptics due to good antimicrobial activity (MIC≤2 μM) and their higher therapeutic indices compared to previously reported QACs.