bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supramolecular Design of Unsymmetric Reverse Bolaamphiphiles for Cell‐Sensitive Hydrogel Degradation and Drug Release
Authors: Chakroun Rami W. , Sneider Alexandra , Anderson Caleb F. , Wang Feihu , Wu Pei‐Hsun , Wirtz Denis , Cui Honggang 
Published: January 2020

AbstractSelf‐assembly of peptide‐based building units into supramolecular nanostructures creates an important class of biomaterials with robust mechanical properties and improved resistance to premature degradation. Yet, upon aggregation, substrate–enzyme interactions are often compromised because of the limited access of macromolecular proteins to the peptide substrate, leading to either a reduction or loss of responsiveness to biomolecular cues. Reported here is the supramolecular design of unsymmetric reverse bolaamphiphiles (RBA) capable of exposing a matrix metalloproteinase (MMP) substrate on the surface of their filamentous assemblies. Upon addition of MMP‐2, these filaments rapidly break into fragments prior to reassembling into spherical micelles. Using 3D cell culture, it is shown that drug release is commensurate with cell density, revealing more effective cell killing when more cancer cells are present. This design platform could serve as a cell‐responsive therapeutic depot for local chemotherapy.
Effect of poly(D‐lactic acid) and cooling temperature on heat resistance and antibacterial performance of stereocomplex poly(L‐lactic acid)
Authors: Boonluksiri Yeiangchart , Prapagdee Benjaphorn , Sombatsompop Narongrit 
Published: January 2020

ABSTRACTStereocomplex nucleated polylactic acid was prepared by the addition of poly(D‐lactic acid) (PDLA) in poly(L‐lactic acid) (PLLA) under various cooling temperatures by monitoring the mechanical properties and heat resistance. Antibacterial performance against the growth of Escherichia coli on PLLA/PDLA doped with various contents of 2‐hydroxypropyl‐3‐piperazinyl‐quinoline carboxylic acid methacrylate (HPQM) was also evaluated. The results suggested that a small addition of PDLA generated stereocomplex crystals while increasing cooling temperature resulted in homo crystals formation in PLLA. The incorporation of PDLA with high cooling temperature increased the heat deflection temperature, impact resistance, and tensile modulus, but decreased the antibacterial performance against E. coli. The addition of PDLA at 2.0 wt% in PLLA at cooling temperature at 80°C showed a synergistic effect to obtain an exceptionally high heat deflection temperature up to 164°C. HPQM was, for the first time, introduced as antibacterial agent in PLLA with an optimum dosage of 1750 ppm. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48970.
Neuronal differentiation of dental pulp stem cells from human permanent and deciduous teeth following coculture with rat auditory brainstem slices
Authors: Gonmanee Thanasup , Sritanaudomchai Hathaitip , Vongsavan Kutkao , Faisaikarm Tassanee , Songsaad Anupong , White Kenneth L. , Thonabulsombat Charoensri 
Published: January 2020

AbstractSensorineural hearing loss is a common disability found worldwide which is associated with a degeneration of spiral ganglion neurons (SGN). It is a challenge to restore SGN due to the permanent degeneration and viability of SGN is requisite for patients to receive an advantage from hearing aid devices. Human dental pulp stem cells (DPSC) and stem cells from human exfoliated deciduous teeth (SHED) are self‐renewing stem cells that originate from the neural crest during development. These stem cells have a high potential for neuronal differentiation. This is primarily due to their multilineage differentiation potential and their relative ease of access. Previously, we have shown the ability of these stem cell types to differentiate into spiral ganglion neuron‐like cells. In this study, we induced the cells into neural precursor cells (NPC) and cocultured with auditory brainstem slice (ABS) encompassing cochlear nucleus by the Stoppini method. We also investigated their ability to differentiate after 2 weeks and 4 weeks in coculture. Neuronal differentiation of DPSC‐NPC and SHED‐NPC was higher expression of specific markers to SGN, TrkB, and Gata3, compared to monoculture. The cells also highly expressed synaptic vesicle protein (SV2A) and exhibited intracellular calcium oscillations. Our findings demonstrated the possibility of using DPSCs and SHEDs as an autologous stem cell‐based therapy for sensorineural hearing loss patients.
DNA Vaccination With Hsp70 Protects Against Systemic Lupus Erythematosus in (NZB × NZW)F1 Mice
Authors: Liu Aijing , Ferretti Concetta , Shi Fu‐Dong , Cohen Irun R. , Quintana Francisco J. , La Cava Antonio 
Published: January 2020

ObjectiveTo address whether a targeted modulation of the abnormal expression of Hsp70 and autoantibodies against this molecule in systemic lupus erythematosus can influence disease.MethodsLupus‐prone (NZB × NZW)F1 mice that had been DNA‐vaccinated with plasmids encoding Hsp70 and controls were monitored for lupus disease parameters including anti–double stranded DNA (anti‐dsDNA) autoantibodies and cytokines using enzyme‐linked immunosorbent assay, and for kidney function and pathology. The phenotypic and numerical changes in relevant immune cells were evaluated by flow cytometry, and cell function was assessed.ResultsMice that had been DNA‐vaccinated with Hsp70 displayed marked suppression of anti‐dsDNA antibody production, reduced renal disease, and antiinflammatory responses that are associated with a significantly extended survival, compared to controls. These protective effects in Hsp70‐vaccinated mice were associated with an induction of tolerogenic immune responses and an expansion of functional Treg cells.ConclusionDNA vaccination with Hsp70 suppresses murine lupus by inducing tolerogenic immune responses and antiinflammatory immune responses associated with reduced disease manifestations and increased mouse survival.
Black hole fueling and coalescence in galaxy mergers
Authors: del Valle Luciano , Prieto Joaquín , Escala Andrés 
Published: January 2020

AbstractWe study the gas accretion and orbital decay of super‐massive black hole (SMBH) pairs in the nuclear region of galaxy merger remnants, where a large amount of gas is expected to accumulate. For that purpose, we perform numerical simulations with both smooth particle hydro‐dynamics (SPH) (Gadget) and adaptive mesh refinement (AMR) (Ramses) techniques. We study the places of the highest SMBH gas accretion, finding that peaks of mass accretion rates are near pericenter passages. We also study the conditions for fast migration and coalescence of SMBHs in galactic nuclei, finding that, in the typical conditions of relatively wet mergers, the SMBHs will experience a fast shrinking, down to the scales where their final coalescence will be driven by the emission of gravitational waves, unless other processes strongly affect the distribution of the gas near the SMBH binary, such as active galactic nuclei (AGN) feedback.
Ultra‐compact objects in semiclassical gravity
Authors: Volkmer Guilherme L. , Hadjimichef Dimiter , Razeira Moises , Bodmann Benno , Zen Vasconcellos César A. 
Published: January 2020

AbstractIn this investigation, we study the structure of ultra‐compact stars in the framework of semiclassical gravity, an extension of Einstein's general relativity (GR), in which a classical spacetime metric is coupled to the quantum expectation value of the stress tensor and that incorporates the polarization of the quantum vacuum in the presence of a gravitational field. In this approach, a generalization of the classical Tolman–Oppenheimer–Volkoff (TOV) equations may be derived. Unlike most theoretical treatments based on GR, this formulation allows a wider range of consistent equation of state (EoS) solutions with enough compactness to produce a photon sphere without violating the Buchdahl limit, an upper bound on the compactness, thus motivating future studies to investigate if ultra‐compact stars could act as black hole mimickers. The main novelty of this extended formalism, when compared to the conventional form of the TOV equations, is the presence of an additional repulsive term—due to quantum corrections originated by the phenomenon of quantum vacuum polarization—that can withstand, under certain conditions, the gravitational collapse. Although the quantum corrections furnished by semiclassical gravity are negligible in most compact stars scenarios, for ultra‐compact configurations, where the star radius is not much larger than its gravitational radius, such effects may be relevant.
Birth weight and autism spectrum disorder: A population‐based nested case–control study
Authors: Talmi Ziv , Mankuta David , Raz Raanan 
Published: January 2020

Low birth weight (<2,500 g) and preterm birth (<37 weeks) were found to be associated with increased risk of autism spectrum disorder (ASD), however, the data regarding the entire birth weight (BW) and gestational age (GA) range are inconclusive. In this population nested case–control study, based on the Israeli National Insurance Institute records, we aimed to estimate the associations in the Israeli population. The study population included all children born between 2000 and 2012 and diagnosed with ASD (N = 12,635 cases), and a random 20% sample of children born in the same period who were not diagnosed with ASD (N = 369,548 controls). We used multiple logistic regression models to calculate the risk of ASD for each BW and GA category, adjusted for covariates (child sex, maternal age, paternal age, population group, maternal wage, paternal wage, having a sibling with ASD, multiple gestation and socioeconomic status). BW < 3,000 g and GA < 39 weeks were associated with higher risk of ASD, including BW of 2,500–3,000 g (adjusted odds ratio [AOR], 1.18; 95% CI, 1.12–1.24, in comparison to the 3,000–3,500 g category) and GA of 37 & 38 weeks (AOR, 1.35; 95% CI, 1.25–1.45 and AOR, 1.13; 95% CI 1.06–1.20, respectively; in comparison to GA of 40 weeks). To account for the high correlation between GA and BW, we modeled BW percentiles for gestational age and found that the BW < 20th percentile was associated with an increased risk of ASD (AOR, 1.10; 95% CI, 1.01–1.19). These results demonstrate that associations of ASD with BW and GA are not limited to commonly used clinical cutoffs. Autism Res 2020, 13: 655–665. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryAutism spectrum disorder (ASD) has been associated with low birth weight (<2,500 g) in prior research. Our study aims to describe the relationship between birth weight (BW) and ASD in the Israeli population. We found that BW <3,000 g was associated with a higher risk of ASD. These results demonstrate that an increased risk of ASD is not confined to clinically defined cutoffs such as BW < 2,500 g.
smartBridge Hamburg – prototypische Pilotierung eines digitalen Zwillings
Authors: Grabe Matthias , Ullerich Christof , Wenner Marc , Herbrand Martin 
Published: January 2020

AbstractZyklische, handnahe Inspektionen nach DIN 1076 bilden die Datenbasis für die Instandhaltungsplanung unserer Ingenieurbauwerke, die Berechnung von Zustandsnoten erfolgt dabei auf Grundlage erkannter Schäden. Die Dokumentation der Prüfung erfolgt überwiegend im Programmsystem SIB‐BW. Das System sorgt für einen vergleichsweise einheitlichen Bewertungsstandard und ermöglicht in begrenztem Umfang retrospektive und prospektive Betrachtungen für die Instandhaltungsplanung. Neuere Entwicklungen wie BIM oder die in anderen Wirtschaftszweigen etablierte kontinuierliche, sensorbasierte Zustandserfassung bleiben bislang konzeptionell unberücksichtigt.Vor dem Hintergrund der digitalen Transformation stellt sich die Frage, wie sich die etablierte manuelle und die digitale Zustandsbeurteilung sowie BIM‐generierte Daten in eine durchgängige digitale Prozesskette integrieren lassen und welcher Nutzen sich so generieren lässt. Die Hamburg Port Authority (HPA) hat daher das Projekt „smartBridge Hamburg“ initiiert, das prototypisch, anhand der Köhlbrandbrücke in Hamburg das Konzept des digitalen Zwillings pilotiert.Der digitale Zwilling dient dazu, BI‐Modell sowie analoge und elektronische Zustandserfassung konzeptionell zu vereinigen und die über mehrere Schichten aggregierten Daten unterschiedlichsten Nutzergruppen bedarfsgerecht bereitzustellen. Der Beitrag stellt Prämissen und Grundüberlegungen zur Projektinitiierung vor.
Side‐by‐side comparability of batch and continuous downstream for the production of monoclonal antibodies
Authors: David Laura , Schwan Peter , Lobedann Martin , Borchert Sven‐Oliver , Budde Bastian , Temming Maike , Kuerschner Mike , Alberti Aguilo Francisca Maria , Baumarth Kerstin , Thüte Tobias , Maiser Benjamin , Blank Andreas , Kistler Viktorija , Weber Nils , Brandt Heiko , Poggel Martin , Kaiser Klaus , Geisen Karl , Oehme Felix , Schembecker Gerhard 
Published: January 2020

AbstractContinuous processing is the future production method for monoclonal antibodies (mAbs). A fully continuous, fully automated downstream process based on disposable equipment was developed and implemented inside the MoBiDiK pilot plant. However, a study evaluating the comparability between batch and continuous processing based on product quality attributes was not conducted before. The work presented fills this gap comparing both process modes experimentally by purifying the same harvest material (side‐by‐side comparability). Samples were drawn at different time points and positions in the process for batch and continuous mode. Product quality attributes, product‐related impurities, as well as process‐related impurities were determined. The resulting polished material was processed to drug substance and further evaluated regarding storage stability and degradation behavior. The in‐process control data from the continuous process showed the high degree of accuracy in providing relevant process parameters such as pH, conductivity, and protein concentration during the entire process duration. Minor differences between batch and continuous samples are expected as different processing conditions are unavoidable due to the different nature of batch and continuous processing. All tests revealed no significant differences in the intermediates and comparability in the drug substance between the samples of both process modes. The stability study of the final product also showed no differences in the stability profile during storage and forced degradation. Finally, online data analysis is presented as a powerful tool for online‐monitoring of chromatography columns during continuous processing.
Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production
Authors: Henry Matthew N. , MacDonald Michael A. , Orellana Camila A. , Gray Peter P. , Gillard Marianne , Baker Kym , Nielsen Lars K. , Marcellin Esteban , Mahler Stephen , Martínez Verónica S. 
Published: January 2020

AbstractChinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by‐products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells.
The EU policy for a plastic economy: Reflections on a sectoral implementation strategy
Authors: Pazienza Pasquale , De Lucia Caterina 
Published: January 2020

AbstractAfter reviewing the main EU policy documents on the plastic waste issue, this work conceptualises an analysis framework to investigate farmers' attitudes to market‐based tools (i.e., subsidies, tax‐credits, and payback mechanisms in extended producer responsibility schemes) through which the introduction of an operational scheme for a better management of their plastic waste can be incentivised in line with the 2018 European Strategy for Plastics in a Circular Economy. A total number of 1,783 farmers responded to a purpose‐built questionnaire. Results show that most of the plastic waste they produce is piping and packaging and that tax credit represents their most favoured incentivising tool.
The aberrant expression of rhythm genes affects the genome instability and regulates the cancer immunity in pan‐cancer
Authors: Zhou Jian , Li Xinhui , Zhang Minghui , Gong Ji’nan , Li Qi , Shan Baocong , Wang Tianzhen , Zhang Lei , Zheng Tongsen , Li Xiaobo 
Published: January 2020

AbstractAlthough emerging studies showed that certain rhythm genes regulate cancer progression, the expression and roles of the vast majority of rhythm genes in human cancer are largely unknown, and the hallmarks of cancer regulated by rhythm genes have not been detected. In this study, we detected the expression changes of rhythm genes in pan‐cancer and found that almost all rhythm genes mutated in all cancer types, and their expression level was significantly altered partially due to abnormal methylation, and several rhythm genes regulate the expression of other rhythm genes in various cancer types. Furthermore, we revealed that rhythm genes are significantly enriched in genome instability and the expression of certain rhythm genes is correlated with the tumor mutation burden, microsatellite instability, and the expression of DNA damage repair genes in most of the detected cancer types. Moreover, rhythm genes are associated with the infiltration of immune cells and the efficiency of immune blockade therapy. This study provides a comprehensive understanding of the roles of rhythm genes in cancer immunity, which may provide a novel method for the diagnosis and treatment of cancer.
Learning and change within person‐centred therapy: Views of expert therapists
Authors: Renger Susan , Macaskill Ann , Naylor Bill 
Published: January 2020

AbstractAimsTraditionally in person‐centred therapy (PCT), clients are counselled for as long as required. It is a nondirective process. Recently, financial constraints have introduced time limits for therapy in health care, so it seemed appropriate to revisit the practice of PCT in the current UK context. The aim was to explore the concepts of learning and change within PCT and to consider whether learning is facilitated.MethodFive experienced person‐centred therapists, who were involved in educating therapists, participated in semi‐structured interviews. Questions explored their views on learning and change in therapy, whether learning processes can be facilitated in PCT—both philosophically and practically—and the outcomes of PCT. Therapists were not specifically asked about time pressure, but rather it was left to see if it emerged as an issue.ResultsTen major themes emerged: learning and change, goals, learning process, PCT process, issues on nondirectivity/directivity, questioning, outcomes, assessment and diagnosis, and other methods used. The issue of time pressure permeated many of these themes. Views were often contradictory reflecting the inconclusive views in the literature, particularly in relation to how clients learn and the relationship between change and learning.DiscussionThe issue of directivity seemed to cause cognitive dissonance, with participants wanting to be directive to deal with time pressures, but not wanting to be disloyal to Rogers' PCT principles. Processes of learning and change were acknowledged as important, but little clarity was obtained on their current application.
New Acetohydrazides Incorporating 2‐Oxoindoline and 4‐Oxoquinazoline: Synthesis and Evaluation of Cytotoxicity and Caspase Activation Activity
Authors: Huan Le Cong , Anh Duong Tien , Truong Bui Xuan , Duc Phan Huy , Hai Pham‐The , Duc‐Anh Lai , Huong Le‐Thi‐Thu , Park Eun Jae , Lee Hye Jin , Kang Jong Soon , Tran Phuong‐Thao , Thanh Hai Dinh Thi , Kim Oanh Dao Thi , Han Sang‐Bae , Nam Nguyen‐Hai 
Published: January 2020

AbstractIn our search for new small molecules activating procaspase‐3, we have designed and synthesized a series of new acetohydrazides incorporating both 2‐oxoindoline and 4‐oxoquinazoline scaffolds. Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI−H23, lung cancer) in comparison to PAC‐1, a first procaspase‐3 activating compound, which was used as a positive control. One of those new compounds, 2‐(6‐chloro‐4‐oxoquinazolin‐3(4H)‐yl)‐N′‐[(3Z)‐5‐methyl‐2‐oxo‐1,2‐dihydro‐3H‐indol‐3‐ylidene]acetohydrazide activated the caspase‐3 activity in U937 human lymphoma cells by 5‐fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells.
pH‐Dependent Protonation of Surface Carboxylate Groups in PsbO Enables Local Buffering and Triggers Structural Changes
Authors: Gerland Lisa , Friedrich Daniel , Hopf Linus , Donovan Eavan J. , Wallmann Arndt , Erdmann Natalja , Diehl Anne , Bommer Martin , Buzar Krzysztof , Ibrahim Mohamed , Schmieder Peter , Dobbek Holger , Zouni Athina , Bondar Ana‐Nicoleta , Dau Holger , Oschkinat Hartmut 
Published: January 2020

AbstractPhotosystem II (PSII) catalyzes the splitting of water, releasing protons and dioxygen. Its highly conserved subunit PsbO extends from the oxygen‐evolving center (OEC) into the thylakoid lumen and stabilizes the catalytic Mn4CaO5 cluster. The high degree of conservation of accessible negatively charged surface residues in PsbO suggests additional functions, as local pH buffer or by affecting the flow of protons. For this discussion, we provide an experimental basis, through the determination of pKa values of water‐accessible aspartate and glutamate side‐chain carboxylate groups by means of NMR. Their distribution is strikingly uneven, with high pKa values around 4.9 clustered on the luminal PsbO side and values below 3.5 on the side facing PSII. pH‐dependent changes in backbone chemical shifts in the area of the lumen‐exposed loops are observed, indicating conformational changes. In conclusion, we present a site‐specific analysis of carboxylate group proton affinities in PsbO, providing a basis for further understanding of proton transport in photosynthesis.
Epiregulin promotes osteogenic differentiation and inhibits neurogenic trans‐differentiation of adipose‐derived mesenchymal stem cells via MAPKs pathway
Authors: Cao Yangyang , Shi Ruitang , Yang Haoqing , Zhang Jianpeng , Ge Lihua , Gao Runtao , Fan Zhipeng 
Published: January 2020

AbstractMesenchymal stem cells (MSCs) exists low efficiency to trans‐differentiate into other germinal layer cell types. One key issue is to discover the effect of important factor on MSCs differentiation abiltiy. In this study, we investigated the role and mechanism of epiregulin (EREG) on the osteogenic differentiation and neurogenic trans‐differentiation in adipose‐derived stem cells (ADSCs). We discovered that the depletion of EREG inhibited the osteogenic differentiation in vitro. And 25 ng/mL recombinant human epiregulin protein (rhEREG) effectively improved the osteogenic differentiation of EREG‐depleted‐ADSCs. Depletion of EREG promoted the formation of neural spheres, and increased the expressions of nestin, βIII‐tubulin, NeuroD, NCAM, TH, and NEF in ADSCs. Then, 25 ng/mL rhEREG significantly inhibited these neurogenic differentiation indicators. Inhibition of p38 MAPK, JNK, or Erk1/2 signaling pathway separately, blocked the rhEREG‐enhanced osteogenic differentiation ability and the rhEREG‐inhibited neurogenic trans‐differentiation ability of ADSCs. In conclusions, EREG promoted the osteogenic differentiation and inhibited the neurogenic trans‐differentiation potentials of ADSCs via MAPK signaling pathways.