bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eotaxin-1/CCL11 is involved in cell migration in rheumatoid arthritis
Authors: Wakabayashi Kuninobu , Isozaki Takeo , Tsubokura Yumi , Fukuse Sayaka , Kasama Tsuyoshi 
Published: April 2021

AbstractEotaxin-1 (CCL11) induces the migration of different leukocyte types by interacting with CCR3. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are pathogenic effectors and a major CCR3-expressing cell. The aim of this study was to investigate the expression and function of CCL11 in RA FLS. The expression of CCL11 and CCR3 was evaluated by ELISA, immunofluorescence and quantitative PCR analysis. The CCL11 levels in serum and synovial fluids (SFs) from RA patients were significantly higher than those in serum from healthy controls and SFs from osteoarthritis patients. CCL11 and CCR3 were expressed in the RA synovial tissue lining layers. The secretion of CCL11 in RA FLS-conditioned medium and the mRNA expression of CCL11 and CCR3 were induced by TNF-α. Furthermore, CCL11 induced the mRNA expression of CCL11 and CCR3. Application of a CCR3 antagonist reduced TNF-α-induced CCL11 secretion from RA FLS. CCL11 induced the migration of RA FLS and monocytes. RA FLS migration was decreased by treatment with CCL11 siRNA. The migration of monocytes to medium conditioned with CCL11 siRNA-transfected and TNF-α-stimulated RA FLS was reduced. These data indicate that the self-amplification of CCL11 via CCR3 may play an important role in cell migration in RA.
Effects of interleukin-1 antagonism and corticosteroids on fibroblast growth factor-21 in patients with metabolic syndrome
Authors: Ebrahimi Fahim , Urwyler Sandrine Andrea , Betz Matthias Johannes , Christ Emanuel Remigius , Schuetz Philipp , Mueller Beat , Donath Marc Yves , Christ-Crain Mirjam 
Published: April 2021

AbstractFibroblast growth factor-21 (FGF21) is elevated in patients with the metabolic syndrome. Although the exact underlying mechanisms remain ill-defined, chronic low-grade inflammation with increased Interleukin-(IL)-1β expression may be responsible. The aim of this study was to investigate effects of two different anti-inflammatory treatments (IL-1 antagonism or high-dose corticosteroids) on FGF21 in patients with the metabolic syndrome. This is a secondary analysis of two interventional studies in patients with obesity and features of the metabolic syndrome. Trial A was an interventional trial (n = 73) investigating short-term effects of the IL-1 antagonist anakinra and of dexamethasone. Trial B was a randomized, placebo-controlled, double-blinded trial (n = 67) investigating longer-term effects of IL-1 antagonism. In total, 140 patients were included in both trials. Median age was 55 years (IQR 44–66), 26% were female and median BMI was 37 kg/m2 (IQR 34–39). Almost half of the patients were diabetic (45%) and had increased c-reactive protein levels of 3.4 mg/L. FGF21 levels correlated with fasting glucose levels, HOMA-index, C-peptide levels, HbA1c and BMI. Short-term treatment with anakinra led to a reduction of FGF21 levels by − 200 pg/mL (95%CI − 334 to − 66; p = 0.004). No effect was detectable after longer-term treatment (between-group difference: − 8.8 pg/mL (95%CI − 130.9 to 113.3; p = 0.89). Acute treatment with dexamethasone was associated with reductions of FGF21 by -175 pg/mL (95%CI − 236 to − 113; p < 0.001). Anti-inflammatory treatment with both, IL-1 antagonism and corticosteroids reduced FGF21 levels at short-term in individuals with the metabolic syndrome.Trial registration: ClinicalTrials.gov Identifiers NCT02672592 and NCT00757276.
Septal chondrocyte hypertrophy contributes to midface deformity in a mouse model of Apert syndrome
Authors: Kim Bong-Soo , Shin Hye-Rim , Kim Hyun-Jung , Yoon Heein , Cho Young-Dan , Choi Kang-Young , Choi Je-Yong , Kim Woo-Jin , Ryoo Hyun-Mo 
Published: April 2021

AbstractMidface hypoplasia is a major manifestation of Apert syndrome. However, the tissue component responsible for midface hypoplasia has not been elucidated. We studied mice with a chondrocyte-specific Fgfr2S252W mutation (Col2a1-cre; Fgfr2S252W/+) to investigate the effect of cartilaginous components in midface hypoplasia of Apert syndrome. In Col2a1-cre; Fgfr2S252W/+ mice, skull shape was normal at birth, but hypoplastic phenotypes became evident with age. General dimensional changes of mutant mice were comparable with those of mice with mutations in EIIa-cre; Fgfr2S252W/+, a classic model of Apert syndrome in mice. Col2a1-cre; Fgfr2S252W/+ mice showed some unique facial phenotypes, such as elevated nasion, abnormal fusion of the suture between the premaxilla and the vomer, and decreased perpendicular plate of the ethmoid bone volume, which are related to the development of the nasal septal cartilage. Morphological and histological examination revealed that the presence of increased septal chondrocyte hypertrophy and abnormal thickening of nasal septum is causally related to midface deformities in nasal septum-associated structures. Our results suggest that careful examination and surgical correction of the nasal septal cartilage may improve the prognosis in the surgical treatment of midface hypoplasia and respiratory problems in patients with Apert syndrome.
Statistical characterization of airplane delays
Authors: Mitsokapas Evangelos , Schäfer Benjamin , Harris Rosemary J. , Beck Christian 
Published: April 2021

AbstractThe aviation industry is of great importance for a globally connected economy. Customer satisfaction with airlines and airport performance is considerably influenced by how much flights are delayed. But how should the delay be quantified with thousands of flights for each airport and airline? Here, we present a statistical analysis of arrival delays at several UK airports between 2018 and 2020. We establish a procedure to compare both mean delay and extreme events among airlines and airports, identifying a power-law decay of large delays. Furthermore, we note drastic changes in plane delay statistics during the COVID-19 pandemic. Finally, we find that delays are described by a superposition of simple distributions, leading to a superstatistics.
Introducing the tablet-based Oxford Cognitive Screen-Plus (OCS-Plus) as an assessment tool for subtle cognitive impairments
Authors: Demeyere Nele , Haupt Marleen , Webb Sam S. , Strobel Lea , Milosevich Elise T. , Moore Margaret J. , Wright Hayley , Finke Kathrin , Duta Mihaela D. 
Published: April 2021

AbstractHere, we present the Oxford Cognitive Screen-Plus, a computerised tablet-based screen designed to briefly assess domain-general cognition and provide more fine-grained measures of memory and executive function. The OCS-Plus was designed to sensitively screen for cognitive impairments and provide a differentiation between memory and executive deficits. The OCS-Plus contains 10 subtasks and requires on average 24 min to complete. In this study, 320 neurologically healthy ageing participants (age M = 62.66, SD = 13.75) from three sites completed the OCS-Plus. The convergent validity of this assessment was established in comparison to the ACE-R, CERAD and Rey–Osterrieth. Divergent validity was established through comparison with the BDI and tests measuring divergent cognitive domains. Internal consistency of each subtask was evaluated, and test–retest reliability was determined. We established the normative impairment cut-offs for each of the subtasks. Predicted convergent and divergent validity was found, high internal consistency for most measures was also found with the exception of restricted range tasks, as well as strong test–retest reliability, which provided evidence of test stability. Further research demonstrating the use and validity of the OCS-Plus in various clinical populations is required. The OCS-Plus is presented as a standardised cognitive assessment tool, normed and validated in a sample of neurologically healthy participants. The OCS-Plus will be available as an Android App and provides an automated report of domain-general cognitive impairments in executive attention and memory.
Copper-graphene heterostructure for back-end-of-line compatible high-performance interconnects
Authors: Son Myungwoo , Jang Jaewon , Lee Yongsu , Nam Jungtae , Hwang Jun Yeon , Kim In S. , Lee Byoung Hun , Ham Moon-Ho , Chee Sang-Soo 
Published: April 2021

AbstractHere, we demonstrate the fabrication of a Cu-graphene heterostructure interconnect by the direct synthesis of graphene on a Cu interconnect with an enhanced performance. Multilayer graphene films were synthesized on Cu interconnect patterns using a liquid benzene or pyridine source at 400 °C by atmospheric pressure chemical vapor deposition (APCVD). The graphene-capped Cu interconnects showed lower resistivity, higher breakdown current density, and improved reliability compared with those of pure Cu interconnects. In addition, an increase in the carrier density of graphene by doping drastically enhanced the reliability of the graphene-capped interconnect with a mean time to failure of >106 s at 100 °C under a continuous DC stress of 3 MA cm−2. Furthermore, the graphene-capped Cu heterostructure exhibited enhanced electrical properties and reliability even if it was a damascene-patterned structure, which indicates compatibility with practical applications such as next-generation interconnect materials in CMOS back-end-of-line (BEOL).
Dimensional crossover and band topology evolution in ultrathin semimetallic NiTe2 films
Authors: Hlevyack Joseph A. , Feng Liang-Ying , Lin Meng-Kai , Villaos Rovi Angelo B. , Liu Ro-Ya , Chen Peng , Li Yao , Mo Sung-Kwan , Chuang Feng-Chuan , Chiang T.-C. 
Published: April 2021

AbstractNickel ditelluride (NiTe2), a recently discovered Type-II Dirac semimetal with topological Dirac fermions near the Fermi energy, is expected to exhibit strong thickness-mediated electronic tunability and intrinsic two-gap superconductivity in the single-layer limit. Realizing such intriguing phenomena requires the fabrication of ultrathin NiTe2 films and an understanding of the underlying physics that is still under debate. By conducting experimental band mappings of ultrathin films prepared with molecular beam epitaxy, we reveal spectroscopic evidence for the dimensionality crossover of single-crystalline ultrathin NiTe2 films as a function of film thickness. As the film thickness increases from one to five layers, the gap in the conical topological surface states closes. Comparisons of experimental to first-principles results also highlight difficulties in fabricating atomically smooth single-layer NiTe2 films. Our results not only provide further impetus for studying emergent phenomena in NiTe2 but also underscore the limitations of fabricating NiTe2 films for device applications.
In-plane anisotropic optical and mechanical properties of two-dimensional MoO3
Authors: Puebla Sergio , D’Agosta Roberto , Sanchez-Santolino Gabriel , Frisenda Riccardo , Munuera Carmen , Castellanos-Gomez Andres 
Published: April 2021

AbstractMolybdenum trioxide (MoO3) in-plane anisotropy has increasingly attracted the attention of the scientific community in the last few years. Many of the observed in-plane anisotropic properties stem from the anisotropic refractive index and elastic constants of the material but a comprehensive analysis of these fundamental properties is still lacking. Here we employ Raman and micro-reflectance measurements, using polarized light, to determine the angular dependence of the refractive index of thin MoO3 flakes and we study the directional dependence of the MoO3 Young’s modulus using the buckling metrology method. We found that MoO3 displays one of the largest in-plane anisotropic mechanical properties reported for 2D materials so far.
Surface-tailored graphene channels
Authors: Lee Chung Won , Suh Jun Min , Choi Seokhoon , Jun Sang Eon , Lee Tae Hyung , Yang Jin Wook , Lee Sol A , Lee Bo Reum , Yoo Donghyeon , Kim Soo Young , Kim Dong Sung , Jang Ho Won 
Published: April 2021

AbstractThe detection of ions and molecules in liquids has been receiving considerable attention for the realization of the electronic tongue. Solution-gated field-effect transistors (SFETs) with high sensitivity are useful for detecting ions and molecules by reading electrical transconductance. However, to date, ionic and molecular sensors that employ SFETs have limitations, such as the lack of a dynamic on–off function and low selectivity. In this study, we evaluate rationally designed graphene SFETs as pH and glucose-selective sensors. The integration of the microfluidic channel to the graphene SFET exhibits dynamic on–off functions by controlling injection and withdrawal of solutions. The graphene SFET device exhibits high pH and glucose selectivity when coated with Nafion as a molecular sieve and Au-decorated nanoparticles as receptors, respectively. The dynamic on–off functions and high selectivity of SFETs with tailored graphene channels have a high potential for advancing as a platform for electronic tongues by integrating the separate SFETs as an array for simultaneous sensing of multiple targets.
Deletion of LBR N-terminal domains recapitulates Pelger-Huet anomaly phenotypes in mouse without disrupting X chromosome inactivation
Authors: Young Alexander Neil , Perlas Emerald , Ruiz-Blanes Nerea , Hierholzer Andreas , Pomella Nicola , Martin-Martin Belen , Liverziani Alessandra , Jachowicz Joanna W. , Giannakouros Thomas , Cerase Andrea 
Published: April 2021

AbstractMutations in the gene encoding Lamin B receptor (LBR), a nuclear-membrane protein with sterol reductase activity, have been linked to rare human disorders. Phenotypes range from a benign blood disorder, such as Pelger-Huet anomaly (PHA), affecting the morphology and chromatin organization of white blood cells, to embryonic lethality as for Greenberg dysplasia (GRBGD). Existing PHA mouse models do not fully recapitulate the human phenotypes, hindering efforts to understand the molecular etiology of this disorder. Here we show, using CRISPR/Cas-9 gene editing technology, that a 236bp N-terminal deletion in the mouse Lbr gene, generating a protein missing the N-terminal domains of LBR, presents a superior model of human PHA. Further, we address recent reports of a link between Lbr and defects in X chromosome inactivation (XCI) and show that our mouse mutant displays minor X chromosome inactivation defects that do not lead to any overt phenotypes in vivo. We suggest that our N-terminal deletion model provides a valuable pre-clinical tool to the research community and will aid in further understanding the etiology of PHA and the diverse functions of LBR.
An engineered channelrhodopsin optimized for axon terminal activation and circuit mapping
Authors: Hamada Shun , Nagase Masashi , Yoshizawa Tomohiko , Hagiwara Akari , Isomura Yoshikazu , Watabe Ayako M. , Ohtsuka Toshihisa 
Published: April 2021

AbstractOptogenetic tools such as channelrhodopsin-2 (ChR2) enable the manipulation and mapping of neural circuits. However, ChR2 variants selectively transported down a neuron’s long-range axonal projections for precise presynaptic activation remain lacking. As a result, ChR2 activation is often contaminated by the spurious activation of en passant fibers that compromise the accurate interpretation of functional effects. Here, we explored the engineering of a ChR2 variant specifically localized to presynaptic axon terminals. The metabotropic glutamate receptor 2 (mGluR2) C-terminal domain fused with a proteolytic motif and axon-targeting signal (mGluR2-PA tag) localized ChR2-YFP at axon terminals without disturbing normal transmission. mGluR2-PA-tagged ChR2 evoked transmitter release in distal projection areas enabling lower levels of photostimulation. Circuit connectivity mapping in vivo with the Spike Collision Test revealed that mGluR2-PA-tagged ChR2 is useful for identifying axonal projection with significant reduction in the polysynaptic excess noise. These results suggest that the mGluR2-PA tag helps actuate trafficking to the axon terminal, thereby providing abundant possibilities for optogenetic experiments.
A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications
Authors: Mett Vadim , Kurnasov Oleg V. , Bespalov Ivan A. , Molodtsov Ivan , Brackett Craig M. , Burdelya Lyudmila G. , Purmal Andrei A. , Gleiberman Anatoli S. , Toshkov Ilia A. , Burkhart Catherine A. , Kogan Yakov N. , Andrianova Ekaterina L. , Gudkov Andrei V. , Osterman Andrei L. 
Published: April 2021

AbstractThe Toll-like receptor 5 (TLR5) agonist entolimod, a derivative of Salmonella flagellin, has therapeutic potential for several indications including radioprotection and cancer immunotherapy. However, in Phase 1 human studies, entolimod induced a rapid neutralizing immune response, presumably due to immune memory from prior exposure to flagellated enterobacteria. To enable multi-dose applications, we used structure-guided reengineering to develop a next-generation, substantially deimmunized entolimod variant, GP532. GP532 induces TLR5-dependent NF-κB activation like entolimod but is smaller and has mutations eliminating an inflammasome-activating domain and key B- and T-cell epitopes. GP532 is resistant to human entolimod-neutralizing antibodies and shows reduced de novo immunogenicity. GP532 also has improved bioavailability, a stronger effect on key cytokine biomarkers, and a longer-lasting effect on NF-κB. Like entolimod, GP532 demonstrated potent prophylactic and therapeutic efficacy in mouse models of radiation-induced death and tissue damage. These results establish GP532 as an optimized TLR5 agonist suitable for multi-dose therapies and for patients with high titers of preexisting flagellin-neutralizing antibodies.
Divalent metal transporter-related protein restricts animals to marine habitats
Authors: Sassa Mieko , Takagi Toshiyuki , Kinjo Azusa , Yoshioka Yuki , Zayasu Yuna , Shinzato Chuya , Kanda Shinji , Murakami-Sugihara Naoko , Shirai Kotaro , Inoue Koji 
Published: April 2021

AbstractUtilization and regulation of metals from seawater by marine organisms are important physiological processes. To better understand metal regulation, we searched the crown-of-thorns starfish genome for the divalent metal transporter (DMT) gene, a membrane protein responsible for uptake of divalent cations. We found two DMT-like sequences. One is an ortholog of vertebrate DMT, but the other is an unknown protein, which we named DMT-related protein (DMTRP). Functional analysis using a yeast expression system demonstrated that DMT transports various metals, like known DMTs, but DMTRP does not. In contrast, DMTRP reduced the intracellular concentration of some metals, especially zinc, suggesting its involvement in negative regulation of metal uptake. Phylogenetic distribution of the DMTRP gene in various metazoans, including sponges, protostomes, and deuterostomes, indicates that it originated early in metazoan evolution. However, the DMTRP gene is only retained in marine species, and its loss seems to have occurred independently in ecdysozoan and vertebrate lineages from which major freshwater and land animals appeared. DMTRP may be an evolutionary and ecological limitation, restricting organisms that possess it to marine habitats, whereas its loss may have allowed other organisms to invade freshwater and terrestrial habitats.
Deconvolution of dissipative pathways for the interpretation of tapping-mode atomic force microscopy from phase-contrast
Authors: Phani Arindam , Jung Ho Sang , Kim Seonghwan 
Published: April 2021

AbstractPhase-contrast in tapping-mode atomic force microscopy (TM-AFM) results from dynamic tip-surface interaction losses which allow soft and hard nanoscale features to be distinguished. So far, phase-contrast in TM-AFM has been interpreted using homogeneous Boltzmann-like loss distributions that ignore fluctuations. Here, we revisit the origin of phase-contrast in TM-AFM by considering the role of fluctuation-driven transitions and heterogeneous loss. At ultra-light tapping amplitudes <3 nm, a unique amplitude dependent two-stage distribution response is revealed, alluding to metastable viscous relaxations that originate from tapping-induced surface perturbations. The elastic and viscous coefficients are also quantitatively estimated from the resulting strain rate at the fixed tapping frequency. The transitional heterogeneous losses emerge as the dominant loss mechanism outweighing homogeneous losses at smaller amplitudes for a soft-material. Analogous fluctuation mediated phase-contrast is also apparent in contact resonance enhanced AFM-IR (infrared), showing promise in decoupling competing thermal loss mechanisms via radiative and non-radiative pathways. Understanding the loss pathways can provide insights on the bio-physical origins of heterogeneities in soft-bio-matter e.g., single cancer cell, tumors, and soft-tissues.
Achieving high singlet-oxygen generation by applying the heavy-atom effect to thermally activated delayed fluorescent materials
Authors: Xiao Ya-Fang , Chen Jia-Xiong , Chen Wen-Cheng , Zheng Xiuli , Cao Chen , Tan Jihua , Cui Xiao , Yuan Zhanxiang , Ji Shaomin , Lu Guihong , Liu Weimin , Wang Pengfei , Li Shengliang , Lee Chun-Sing 
Published: April 2021

Applying the heavy-atom effect to TADF photosensitizers achieves ultra-high 1O2 generation (ФΔ = 0.91) by the synergetic effect of small ΔEST and considerable SOC.
Jacket temperature regulation allowing well-defined non-adiabatic lab-scale solution free radical polymerization of acrylates
Authors: Edeleva Mariya , Marien Yoshi W. , Van Steenberge Paul H. M. , D'hooge Dagmar R. 
Published: April 2021

Conventional batch solution free radical polymerization of n-butyl acrylate with thermal initiators such as AIBN is known to be strongly exothermic and influenced by highly activated side reactions such as backbiting and β-scission.
Paracrine interleukin-8 affects mesenchymal stem cells through the Akt pathway and enhances human umbilical vein endothelial cell proliferation and migration
Authors: Wang Lulu , Li Yongtao , Zhang Xiaodong , Liu Na , Shen Shiyang , Sun Shizhu , Jiang Yang , Li Penghui , Jin Haifeng , Shen Lei 
Published: April 2021

Abstract
Interleukin-8 (IL-8) promotes cell homing and angiogenesis, but its effects on activating human bone marrow mesenchymal stem cells (BMSCs) and promoting angiogenesis are unclear. We used bioinformatics to predict these processes. In vitro, BMSCs were stimulated in a high-glucose (HG) environment with 50 or 100 μg/ml IL-8 was used as the IL-8 group. A total of 5 μmol/l Triciribine was added to the two IL-8 groups as the Akt inhibitor group. Cultured human umbilical vein endothelial cells (HUVECs) were cultured in BMSCs conditioned medium (CM). The changes in proliferation, apoptosis, migration ability and levels of VEGF and IL-6 in HUVECs were observed in each group. Seventy processes and 26 pathways were involved in vascular development, through which IL-8 affected BMSCs. Compared with the HG control group, HUVEC proliferation absorbance value (A value), Gap closure rate, and Transwell cell migration rate in the IL-8 50 and IL-8 100 CM groups were significantly increased (P&lt;0.01, n=30). However, HUVEC apoptosis was significantly decreased (P&lt;0.01, n=30). Akt and phospho-Akt (P-Akt) protein contents in lysates of BMSCs treated with IL-8, as well as VEGF and IL-6 protein contents in the supernatant of BMSCs treated with IL-8, were all highly expressed (P&lt;0.01, n=15). These analyses confirmed that IL-8 promoted the expression of 41 core proteins in BMSCs through the PI3K Akt pathway, which could promote the proliferation and migration of vascular endothelial cells. Therefore, in an HG environment, IL-8 activated the Akt signaling pathway, promoted paracrine mechanisms of BMSCs, and improved the proliferation and migration of HUVECs.