bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased S1P expression in osteoclasts enhances bone formation in an animal model of Paget's disease
Authors: Nagata Yuki , Miyagawa Kazuaki , Ohata Yasuhisa , Petrusca Daniela N. , Pagnotti Gabriel M. , Mohammad Khalid S. , Guise Theresa A. , Windle Jolene J. , David Roodman G. , Kurihara Noriyoshi 
Published: October 2020

AbstractPaget's disease (PD) is characterized by increased numbers of abnormal osteoclasts (OCLs) that drive exuberant bone formation, but the mechanisms responsible for the increased bone formation remain unclear. We previously reported that OCLs from 70% of PD patients express measles virus nucleocapsid protein (MVNP), and that transgenic mice with targeted expression of MVNP in OCLs (MVNP mice) develop bone lesions and abnormal OCLs characteristic of PD. In this report, we examined if OCL‐derived sphingosine‐1‐phosphate (S1P) contributed to the abnormal bone formation in PD, since OCL‐derived S1P can act as a coupling factor to increase normal bone formation via binding S1P‐receptor‐3 (S1PR3) on osteoblasts (OBs). We report that OCLs from MVNP mice and PD patients expressed high levels of sphingosine kinase‐1 (SphK‐1) compared with wild‐type (WT) mouse and normal donor OCLs. SphK‐1 production by MVNP‐OCLs was interleukin‐6 (IL‐6)‐dependent since OCLs from MVNP/IL‐6−/− mice expressed lower levels of SphK‐1. Immunohistochemistry of bone biopsies from a normal donor, a PD patient, WT and MVNP mice confirmed increased expression levels of SphK‐1 in OCLs and S1PR3 in OBs of the PD patient and MVNP mice compared with normal donor and WT mice. Further, MVNP‐OCLs cocultured with OBs from MVNP or WT mice increased OB‐S1PR3 expression and enhanced expression of OB differentiation markers in MVNP‐OBs precursors compared with WT‐OBs, which was mediated by IL‐6 and insulin‐like growth factor 1 secreted by MVNP‐OCLs. Finally, the addition of an S1PR3 antagonist (VPC23019) to WT or MVNP‐OBs treated with WT and MVNP‐OCL‐conditioned media (CM) blocked enhanced OB differentiation of MVNP‐OBs treated with MVNP‐OCL‐CM. In contrast, the addition of the SIPR3 agonist, VPC24191, to the cultures enhanced osterix and Col‐1A expression in MVNP‐OBs treated with MVNP‐OCL‐CM compared with WT‐OBs treated with WT‐OCL‐CM. These results suggest that IL‐6 produced by PD‐OCLs increases S1P in OCLs and S1PR3 on OBs, to increase bone formation in PD.
Functional aspects of primary cilium in signaling, assembly and microenvironment in cancer
Authors: Wang Bo , Liang Zheyong , Liu Peijun 
Published: October 2020

AbstractThe primary cilium is an antennae‐like structure extent outside the cell surface. It has an important role in regulating cell‐signaling transduction to affect proliferation, differentiation and migration. Evidence is accumulating that ciliary defects lead to ciliopathies and ciliary deregulation also play crucial roles in cancer formation and progression. Interestingly, restoring the cilia can suppress proliferation in some cancer cell. However, t	he role of primary cilia in cancer still be debated. In this article, we review the role of the primary cilium in cancer through architecture, signaling pathways, cilia assembly and disassembly regulators, and summarized the new findings of the primary cilium in tumor microenvironments and different cancers, highlighting novel possibilities for therapeutic target in cancer.
Carbon nanotube field effect transistor (CNTFET) operational transconductance amplifier (OTA) based design of high frequency memristor emulator
Authors: Khurshid Tabassum , Fatima Syed , Khanday Farooq Ahmad , Bashir Faisal , Zahoor Furqan , Hussin Fawnizu Azmadi 
Published: October 2020

AbstractThe design and simulation of high frequency memristor emulator using carbon nanotube field effect transistor (CNTFET) based Operational Transconductance Amplifier (OTA) has been presented out in this paper. The proposed memristor emulator design consists of two CNTFET‐OTAs and one capacitor with both grounded and floating topologies available for applications. The proposed CNTFET memristor design emulator outperforms the conventional complementary metal oxide semiconductor (CMOS) based memristor emulator topologies. The performance comparison with the reported memristor emulator designs reveals that the proposed grounded and floating memristor design can work over a frequency range of 1 GHz and 10 MHz respectively in comparison to conventional CMOS based design, which works over a maximum range of 8 MHz and 0.4 MHz for grounded and floating memristor designs respectively. The proposed memristor emulator circuit also offers electronic tunability of the memristance which is important for digitally programmable application of memristors.
Circulating tumor cell analysis in locally advanced and metastatic squamous cell carcinoma of the head and neck
Authors: Harris Ethan J. , Huang Julian , Carroll Erin , Lowe Alarice C. , Chau Nicole G. , Rabinowits Guilherme , Haddad Robert , Hanna Glenn J. , Haddad Tyler , Sanborn Matthew , Kacew Alec , Lorch Jochen 
Published: October 2020

AbstractBackgroundCirculating tumors cells (CTCs) are considered an early step towards metastasis and have been linked to poor prognosis in several types of cancer. CTCs in squamous cell carcinoma of the head and neck (SCCHN) have an unclear role.MethodsIn this prospective study, patients with locally advanced or metastatic SCCHN had CTC counts assessed before starting systemic treatment using the CellSearch System. Select cases also had sequential CTC evaluation. Presence of CTCs was correlated with patient characteristics and outcomes.ResultsForty‐eight patients enrolled, and 36 had evaluable clinical data and baseline CTC counts. Twenty‐five patients had locally advanced disease (LAD) and 11 had metastatic disease. ≥1 CTCs were detected in six patients with LAD (24%) and four with metastatic disease (36%). On univariate analysis, smoking was associated with CTCs.ConclusionCTCs are not associated with prognosis in patients with LAD and metastatic disease; however, they are present in this patient population, and ≥1 CTCs is associated with a history of smoking.Level of evidence1b; individual prospective cohort study.
Polyethyleneimine‐CpG Nanocomplex as an In Situ Vaccine for Boosting Anticancer Immunity in Melanoma
Authors: Xu Yudi , Ma Sheng , Si Xinghui , Zhao Jiayu , Yu Haiyang , Ma Lili , Song Wantong , Tang Zhaohui 
Published: October 2020

AbstractCancer immunotherapy is redefining the field of cancer therapy. However, current cancer immunotherapies are limited by insufficient immune activation, which results in low response rate. Herein, polyethyleneimine‐CpG nanocomplex (CpG@PEI) is reported as an in situ vaccine for boosting anticancer immunity in melanoma. CpG, a Toll‐like receptor (TLR) 9 agonist, can activate antigen‐presenting cells and increase the expression of costimulatory molecules, while PEI can help to enhance the stability and cellular internalization of CpG. It is proved that PEI loading can significantly enhance the cellular internalization and immune stimulation ability of CpG, and the CpG@PEI nanocomplex can effectively inhibit murine B16F10 melanoma growth after intratumoral injection. Further analysis reveals that this CpG@PEI nanocomplex therapy elicits both innate and adaptive immunity, with much increased natural killer (NK) cells and T cells infiltration in the tumor, as well as CD80 expression on the dendritic cells (DCs). This study will inspire more attempts in directly using single nanoparticle‐loaded pattern recognition receptor (PRR) agonists for cancer immunotherapy.
Three‐dimensional whole‐brain simultaneous T1, T2, and T1ρquantification using MR Multitasking: Method and initial clinical experience in tissue characterization of multiple sclerosis
Authors: Ma Sen , Wang Nan , Fan Zhaoyang , Kaisey Marwa , Sicotte Nancy L. , Christodoulou Anthony G. , Li Debiao 
Published: October 2020

PurposeTo develop a 3D whole‐brain simultaneous T1/T2/T1ρquantification method with MR Multitasking that provides high quality, co‐registered multiparametric maps in 9 min.MethodsMR Multitasking conceptualizes T1/T2/T1ρrelaxations as different time dimensions, simultaneously resolving all three dimensions with a low‐rank tensor image model. The proposed method was validated on a phantom and in healthy volunteers, comparing quantitative measurements against corresponding reference methods and evaluating the scan‐rescan repeatability. Initial clinical validation was performed in age‐matched relapsing‐remitting multiple sclerosis (RRMS) patients to examine the feasibility of quantitative tissue characterization and to compare with the healthy control cohort. The feasibility of synthesizing six contrast‐weighted images was also examined.ResultsOur framework produced high quality, co‐registered T1/T2/T1ρmaps that closely resemble the reference maps. Multitasking T1/T2/T1ρmeasurements showed substantial agreement with reference measurements on the phantom and in healthy controls. Bland‐Altman analysis indicated good in vivo repeatability of all three parameters. In RRMS patients, lesions were conspicuously delineated on all three maps and on four synthetic weighted images (T2‐weighted, T2‐FLAIR, double inversion recovery, and a novel “T1ρ‐FLAIR” contrast). T1 and T2 showed significant differences for normal appearing white matter between patients and controls, while T1ρshowed significant differences for normal appearing white matter, cortical gray matter, and deep gray matter. The combination of three parameters significantly improved the differentiation between RRMS patients and healthy controls, compared to using any single parameter alone.ConclusionMR Multitasking simultaneously quantifies whole‐brain T1/T2/T1ρand is clinically promising for quantitative tissue characterization of neurological diseases, such as MS.
Results on approximate controllability results for second‐order Sobolev‐type impulsive neutral differential evolution inclusions with infinite delay
Authors: Vijayakumar V. , Panda Sumati Kumari , Nisar Kottakkaran Sooppy , Baskonus Haci Mehmet 
Published: October 2020

AbstractIn this article, we determine a set of appropriate conditions for approximate controllability of second‐order Sobolev‐type impulsive neutral differential evolution inclusions with infinite delay. We verify the main results by applying ideas about the cosine function, sine functions, and fixed point approach. Next, we continue the discussion to the nonlocal second‐order Sobolev‐type differential system. In the end, we provide a theoretical application to assist in the effectiveness of our discussion.
Proteomic Characterization of the Pseudomonas sp. Strain phDV1 Response to Monocyclic Aromatic Compounds
Authors: Lyratzakis Alexandros , Valsamidis Giannis , Kanavaki Iliana , Nikolaki Antigoni , Rupprecht Fiona , Langer Julian D. , Tsiotis Georgios 
Published: October 2020

AbstractThe degradation of aromatic compounds comprises an important step in the removal of pollutants and re‐utilization of plastics and other non‐biological polymers. Here, Pseudomonas sp. strain phDV1, a gram‐negative bacterium that is selected for its ability to degrade aromatic compounds is studied. In order to understand how the aromatic compounds and their degradation products are reintroduced in the metabolism of the bacteria and the systematic/metabolic response of the bacterium to the new carbon source, the proteome of this strain is analyzed in the presence of succinate, phenol, and o‐, m‐, and p‐cresol as the sole carbon source. As a reference proteome, the bacteria are grown in succinate and then compared with the respective proteomes of bacteria grown on phenol and different cresols. In total, 2295 proteins are identified; 1908 proteins are used for quantification between different growth conditions. The carbon source affects the synthesis of enzymes related to aromatic compound degradation and in particular the enzyme involved in the meta‐pathway of monocyclic aromatic compounds degradation. In addition, proteins involved in the production of polyhydroxyalkanoate (PHA), an attractive biomaterial, show higher abundance in the presence of monocyclic aromatic compounds. The results provide, for the first time, comprehensive information on the proteome response of this strain to monocyclic aromatic compounds.
The Weyl – Wigner – Moyal Formalism on a Discrete Phase Space. II. The Photon Wigner Function
Authors: Przanowski Maciej , Tosiek Jaromir , Turrubiates Francisco J. 
Published: October 2020

AbstractClassical model of light in helicity formalism is presented. Then quantum mechanical point of view at photons – construction and interpretation of two equivalent photon wave functions are proposed. Quantum mechanics of photon is investigated. The Białynicki – Birula scalar product and the generalized Hermitian conjugation of linear operator are discussed. Quantum description of light on a phase space based on the Weyl – Wigner – Moyal approach is developed. A photon Wigner function is built. Some explicit photon Wigner functions for different kernels are obtained.
Clinical prediction models to predict the risk of multiple binary outcomes: a comparison of approaches
Authors: Martin Glen P. , Sperrin Matthew , Snell Kym I. E. , Buchan Iain , Riley Richard D. 
Published: October 2020

AbstractClinical prediction models (CPMs) can predict clinically relevant outcomes or events. Typically, prognostic CPMs are derived to predict the risk of a single future outcome. However, there are many medical applications where two or more outcomes are of interest, meaning this should be more widely reflected in CPMs so they can accurately estimate the joint risk of multiple outcomes simultaneously. A potentially naïve approach to multi‐outcome risk prediction is to derive a CPM for each outcome separately, then multiply the predicted risks. This approach is only valid if the outcomes are conditionally independent given the covariates, and it fails to exploit the potential relationships between the outcomes. This paper outlines several approaches that could be used to develop CPMs for multiple binary outcomes. We consider four methods, ranging in complexity and conditional independence assumptions: namely, probabilistic classifier chain, multinomial logistic regression, multivariate logistic regression, and a Bayesian probit model. These are compared with methods that rely on conditional independence: separate univariate CPMs and stacked regression. Employing a simulation study and real‐world example, we illustrate that CPMs for joint risk prediction of multiple outcomes should only be derived using methods that model the residual correlation between outcomes. In such a situation, our results suggest that probabilistic classification chains, multinomial logistic regression or the Bayesian probit model are all appropriate choices. We call into question the development of CPMs for each outcome in isolation when multiple correlated or structurally related outcomes are of interest and recommend more multivariate approaches to risk prediction.
Three Decades of Research about the Corona Around Nanoparticles: Lessons Learned and Where to Go Now
Authors: Lundqvist Martin , Cedervall Tommy 
Published: October 2020

AbstractThe research about how a nanoparticle (NP) interacts with a complex biological solution has been conducted, according to the literature, for almost three decades. A significant amount of data has been generated, especially in the last one and a half decade. First, it became its own research field which was later divided into many subresearch fields. This outlook does not aim to be a comprehensive review of the field or any of its subresearch fields. There is too much data published to attempt that. Instead, here it has been tried to highlight what, in the opinion, is the main step taken during these three decades. Thereafter, the weaknesses and end are pointed out with what needs to be the main focus for the future to understand the protein corona formation in the bloodstream, which is a prerequisite for the developing of true target specific drug‐delivering nanoparticles.
Oxygen‐Deficient Bimetallic Oxide FeWOX Nanosheets as Peroxidase‐Like Nanozyme for Sensing Cancer via Photoacoustic Imaging
Authors: Gong Fei , Yang Nailin , Wang Yong , Zhuo Mingpeng , Zhao Qi , Wang Sheng , Li Yonggang , Liu Zhuang , Chen Qian , Cheng Liang 
Published: October 2020

AbstractNanozymes with high catalytic activity and great stability have attracted increasing interests as the promising alternative to natural enzymes for applications in various fields. In this study, a new type of highly efficient peroxidase‐like nanozymes based on FeWOX nanosheets (NSs) synthesized by a thermal‐decomposition method is reported. Owing to the sheet‐structure with maximized utilization of catalytic sites (Fe atoms and oxygen vacancies), such FeWOX NSs exert efficient enzyme activity to trigger catalytic decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). A nanozyme‐based ratio‐metric nanoprobe is then fabricated by co‐loading of 3,3,5,5‐tetramethylbenzidine (TMB) and IR780 dye on FeWOX NSs to enable ratio‐metric photoacoustic (PA) imaging of endogenous H2O2, as verified by imaging of the subcutaneous 4T1 xenograft tumor model and lipopolysaccharide (LPS)‐induced inflammation model. Moreover, FeWOX NSs could also be employed as promising nanoagents for multimodal computed tomography (CT) and magnetic resonance (MR) imaging of tumors, due to the strong X‐ray attenuation ability of W element and high MR contrast ability of Fe element, respectively. Importantly, FeWOX NSs with good biodegradability could be cleared out from the body without any significant biotoxicity. This work highlights bimetallic oxide FeWOX NSs as an enzyme‐mimetic nanoplatform for imaging of the tumor microenvironment.
Energetic damage analysis regarding the fatigue of concrete
Authors: Bode Matthias , Marx Steffen 
Published: October 2020

AbstractDue to the visco‐elasto‐plastic material behavior, the added energy to concrete specimens during fatigue tests is transformed into another form of energy. Besides the description of the energetic material behavior of concrete, the elastic and the plastic part of the energy as well as the dissipation energy are analyzed for different specimens. Especially the dissipation energy shows a correlation with the damage process as a result of the cyclic loading. Regarding this correlation, a new energetic damage model is introduced. With this model, a degree of damage during the tests and the development of the damage parameter over the load cycles can be determined. First tests with the developed model show good and plausible results.
Liquid‐Like Phases Preorder Peptides for Supramolecular Assembly
Authors: Rengifo Rolando F. , Sementilli Anthony , Kim Youngsun , Liang Chen , Xiang'An Li Noel , Mehta Anil K. , Lynn David G. 
Published: October 2020

AbstractThe front cover artwork is provided by our research group at Emory University, Atlanta (USA). The image depicts the diverse array of single β‐sheets that we have identified spectroscopically existing within metastable solute‐rich peptide phases. As the particle phase grows in time, sheet‐sheet stacking appears to nucleate fibril assembly. Read the full text of the Communication at 10.1002/syst.202000007.
Catalytic Asymmetric Total Synthesis of Leucinostatin A
Authors: Watanabe Takumi , Abe Hikaru , Shibasaki Masakatsu 
Published: October 2020

AbstractThis review describes our efforts toward achieving catalytic asymmetric total synthesis of leucinostatin A, a compound that interferes with the tumor‐stroma interaction. The synthesis utilizes four catalytic asymmetric reactions, including direct‐type reactions exemplified by high atom‐economy, and three C−C bond forming reactions. Thorough analysis of the NMR data, HPLC profiles, and biologic activity led us to unambiguously revise the absolute configuration regarding the 6‐position of the AHMOD residue side chain from S (reported) to R. Other examples of previously reported important studies on the stereoselective synthesis of HyLeu and AHMOD are also described.
Establishing the allosteric mechanism in CRISPR‐Cas9
Authors: Nierzwicki Łukasz , Arantes Pablo Ricardo , Saha Aakash , Palermo Giulia 
Published: October 2020

AbstractAllostery is a fundamental property of proteins, which regulates biochemical information transfer between spatially distant sites. Here, we report on the critical role of molecular dynamics (MD) simulations in discovering the mechanism of allosteric communication within CRISPR‐Cas9, a leading genome editing machinery with enormous promises for medicine and biotechnology. MD revealed how allostery intervenes during at least three steps of the CRISPR‐Cas9 function: affecting DNA recognition, mediating the cleavage and interfering with the off‐target activity. An allosteric communication that activates concerted DNA cleavages was found to led through the L1/L2 loops, which connect the HNH and RuvC catalytic domains. The identification of these “allosteric transducers” inspired the development of novel variants of the Cas9 protein with improved specificity, opening a new avenue for controlling the CRISPR‐Cas9 activity. Discussed studies also highlight the critical role of the recognition lobe in the conformational activation of the catalytic HNH domain. Specifically, the REC3 region was found to modulate the dynamics of HNH by sensing the formation of the RNA:DNA hybrid. The role of REC3 was revealed to be particularly relevant in the presence of DNA mismatches. Indeed, interference of REC3 with the RNA:DNA hybrid containing mismatched pairs at specific positions resulted in locking HNH in an inactive “conformational checkpoint” conformation, thereby hampering off‐target cleavages. Overall, MD simulations established the fundamental mechanisms underlying the allosterism of CRISPR‐Cas9, aiding engineering strategies to develop new CRISPR‐Cas9 variants for improved genome editing.This article is categorized under:
Structure and Mechanism > Computational Biochemistry and Biophysics
Characterization of offshore vertical wind shear conditions in Southern New England
Authors: Borvarán Dager , Peña Alfredo , Gandoin Rémi 
Published: October 2020

AbstractVertical wind shears could have a significant effect on the energy produced by a wind turbine and on its loads. Although the development of several wind farms has been planned on the East Coast of the United States, there are no studies that characterize the vertical wind shear over this area. This study focuses on characterizing wind shears in the marine boundary layer in Southern New England and along the East Coast of the United States. The analysis looks at the statistical distribution of vertical wind shear values and at their associated meteorological conditions. The analysis relies on remote‐sensing wind measurements and other meteorological data recorded at the Woods Hole Oceanographic Institution Air–Sea Interaction Tower located 3 km to the South of Martha's Vineyard, together with buoy measurements and ERA5 reanalysis data. This work shows that large vertical wind shear values (>0.05 m/s/m) calculated using wind measurements at 60 and 53 m were often observed (≈25.3% of all the valid wind profiles analyzed) for South‐Westerly winds within a range of positive bulk Richardson numbers 0–0.1. These large‐shear values are the result of the presence of a strong high‐pressure system (Bermuda‐Azores High) over the North Atlantic basin and low pressures over land, which result in warm Southerly winds flowing over the cold waters of the Labrador current. The power density computed considering the vertical wind shear by means of the rotor equivalent wind speed is 5.5% smaller than that considering wind speed measurements at 110 m only.