bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Immune Activation by Pathologic α‐Synuclein in Parkinson's Disease
Authors: Grozdanov Veselin , Bousset Luc , Hoffmeister Meike , Bliederhaeuser Corinna , Meier Christoph , Madiona Karine , Pieri Laura , Kiechle Martin , McLean Pamela J. , Kassubek Jan , Behrends Christian , Ludolph Albert C. , Weishaupt Jochen H. , Melki Ronald , Danzer Karin M. 
Published: July 2019

ObjectiveExcessive inflammation in the central nervous system (CNS) and the periphery can result in neurodegeneration and parkinsonism. Recent evidence suggests that immune responses in Parkinson disease patients are dysregulated, leading to an increased inflammatory reaction to unspecific triggers. Although α‐synuclein pathology is the hallmark of Parkinson disease, it has not been investigated whether pathologic α‐synuclein is a specific trigger for excessive inflammatory responses in Parkinson disease.MethodsWe investigated the immune response of primary human monocytes and a microglial cell line to pathologic forms of α‐synuclein by assessing cytokine release upon exposure.ResultsWe show that pathologic α‐synuclein (mutations, aggregation) results in a robust inflammatory activation of human monocytes and microglial BV2 cells. The activation is conformation‐ dependent, with increasing fibrillation and early onset mutations having the strongest effect on immune activation. We also found that activation of immune cells by extracellular α‐synuclein is potentiated by extracellular vesicles, possibly by facilitating the uptake of α‐synuclein. Blood extracellular vesicles from Parkinson disease patients induce a stronger activation of monocytes than blood extracellular vesicles from healthy controls. Most importantly, monocytes from Parkinson disease patients are dysregulated and hyperactive in response to stimulation with pathologic α‐synuclein. Furthermore, we demonstrate that α‐synuclein pathology in the CNS is sufficient to induce the monocyte dysregulation in the periphery of a mouse model.InterpretationTaken together, our data suggest that α‐synuclein pathology and dysregulation of monocytes in Parkinson disease can act together to induce excessive inflammatory responses to α‐synuclein. ANN NEUROL 2019;86:593–606
Restriction of Access to the Dark State: A New Mechanistic Model for Heteroatom‐Containing AIE Systems
Authors: Tu Yujie , Liu Junkai , Zhang Haoke , Peng Qian , Lam Jacky W. Y. , Tang Ben Zhong 
Published: July 2019

AbstractRestriction of intramolecular motion (RIM), as the working mechanism of aggregation‐induced emission (AIE), cannot fully explain some heteroatom‐containing systems. Now, two excited states are taken into account and a mechanism, restriction of access to dark state (RADS), is specified to elaborate RIM and complete the picture of AIE mechanism. A nitrogen‐containing molecule named APA is chosen as a model compound; its weak fluorescence in solution is ascribed to the easy access from the bright (π,π*) state to the close‐lying dark (n,π*) state. By either metal complexation or aggregation, the dark state is less accessible due to restriction of the molecular motion leading to the dark state and elevation of the dark state energy, thus the bright state emission is restored. RADS is powerful in elucidating the AIE effect of molecules with excited states favoring non‐radiative decay, including overlap‐forbidden states such as (n,π*) and CT states, spin‐forbidden triplet states, and so on.
Mechanism of the Thermal Z⇌E Isomerization of a Stable Silene; Experiment and Theory
Authors: Zborovsky Lieby , Kostenko Arseni , Bravo‐Zhivotovskii Dmitry , Apeloig Yitzhak 
Published: July 2019

AbstractThe E and Z geometric isomers of a stable silene (tBu2MeSi)(tBuMe2Si)Si=CH(1‐Ad) (1) were synthesized and characterized spectroscopically. The thermal Z to E isomerization of 1 was studied both experimentally and computationally using DFT methods. The measured activation parameters for the 1Z⇌1E isomerization are: Ea=24.4 kcal mol−1, ΔH≠=23.7 kcal mol−1, ΔS≠=−13.2 e.u. Based on comparison of the experimental and DFT calculated (at BP86‐D3BJ/def2‐TZVP(‐f)//BP86‐D3BJ/def2‐TZVP(‐f)) activation parameters, the Z⇌E isomerization of 1 proceeds through an unusual (unprecedented for alkenes) migration–rotation–migration mechanism (via a silylene intermediate), rather than through the classic rotation mechanism common for alkenes.
Quantitation of Femtomolar‐Level Protein Biomarkers Using a Simple Microbubbling Digital Assay and Bright‐Field Smartphone Imaging
Authors: Chen Hui , Li Zhao , Zhang Lingzhi , Sawaya Philippe , Shi Jianbo , Wang Ping 
Published: July 2019

AbstractQuantitating ultra‐low concentrations of protein biomarkers is critical for early disease diagnosis and treatment. However, most current point‐of‐care (POC) assays are limited in sensitivity. Herein, we introduce an ultra‐sensitive and facile microbubbling assay for the quantification of protein biomarkers with a digital‐readout method that requires only a smartphone camera. We used machine learning to develop a smartphone application for automated image analysis to facilitate accurate and robust counting. Using this method, post‐prostatectomy surveillance of prostate specific antigen (PSA) can be achieved with a detection limit (LOD) of 2.1 fm (0.060 pg mL−1), and early pregnancy detection using βhCG can be achieved with a of 0.034 mIU mL−1 (2.84 pg mL−1). This work provides the proof‐of‐principle of the microbubbling assay with a digital readout as an ultra‐sensitive technology with minimal requirement for power and accessories, facilitating future POC applications.
One‐pot green synthesis of Cu/bone nanocomposite and its catalytic activity in the synthesis of 1‐substituted 1H‐1,2,3,4‐tetrazoles and reduction of hazardous pollutants
Authors: Maham Mehdi , Nasrollahzadeh Mahmoud 
Published: July 2019

In this work, a simple and green method is reported for the biosynthesis of Cu/bone nanocomposite using Cordyline fruticosa extract as a stabilizer and reductant. Animal bone was used as a natural support to prevent the accumulation of Cu nanoparticles. The catalytic activity of Cu/bone nanocomposite was assessed in the synthesis of 1‐substituted 1H‐1,2,3,4‐tetrazoles and reduction of various organic dyes, including 4‐nitrophenol (4‐NP), nigrosin (NS), congo red (CR) and methylene blue (MB). The best catalytic performance in the synthesis of 1‐substituted tetrazoles was achieved using 0.05 g of Cu/bone nanocomposite at 120°C. In addition, under optimal conditions, the absorption bands corresponding to 4‐NP, CR, NS and MB completely disappeared after about 6 min, 3 min, 50 s and 7 s, respectively. The biosynthesis protocol used in the preparation of Cu/bone nanocomposite offers a very attractive area for further research.
Synthesis and characterization of nanocrystalline hydroxyapatite and its catalytic behavior towards synthesis of 3,4‐disubstituted isoxazole‐5(4H)‐ones in water
Authors: Maleki Behrooz , Chahkandi Mohammad , Tayebee Reza , Kahrobaei Sepideh , Alinezhad Heshmatollah , Hemmati Saba 
Published: July 2019

In the present work, the nanocrystalline particles of hydroxyapatite (HAp) using an easy alkoxide‐based sol–gel technique including triethyl phosphate [PO (OC2H5)3] and Ca (NO3)2·4H2O as P and Ca precursors have been synthesized. The sample characterization was performed by X‐ray diffraction, Fourier transform‐infrared analysis, scanning electron microscopy, thermal analysis (thermogravimetric analysis/differential thermal analysis), and elemental analysis of energy‐dispersive X‐ray analysis. It is interesting that single phase of HAp was obtained at a low firing temperature of 500°C. Modified Scherrer equation as the Williamson−Hall method was applied for the measurement of crystallite size distributions and micro‐strain of the sample. The determined crystallite size by complementary technique of transmission electron microscopy has good consistency with those obtained from the Scherrer formula. Moreover, we reported the one‐pot synthesis of 3,4‐disubstituted isoxazole‐5(4H)‐ones through the aqueous solution reaction of three components of ethyl acetoacetate, hydroxylamine hydrochloride and various aromatic aldehydes at room temperature. This protocol offers several advantages, including a simple work‐up procedure, very short reaction times (under 25 min), in accordance with the principles of green chemistry, recyclability, excellent yields (87–98%) and environmentally friendly.
Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator‐Initiated, Multicenter, Double‐Blind, Randomized, Placebo‐Controlled Trial
Authors: Khanna Dinesh , Spino Cathie , Johnson Sindhu , Chung Lorinda , Whitfield Michael L. , Denton Christopher P. , Berrocal Veronica , Franks Jennifer , Mehta Bhavan , Molitor Jerry , Steen Virginia D. , Lafyatis Robert , Simms Robert W. , Gill Anna , Kafaja Suzanne , Frech Tracy M. , Hsu Vivien , Domsic Robyn T. , Pope Janet E. , Gordon Jessica K. , Mayes Maureen D. , Schiopu Elena , Young Amber , Sandorfi Nora , Park Jane , Hant Faye N. , Bernstein Elana J. , Chatterjee Soumya , Castelino Flavia V. , Ajam Ali , Wang Yue , Wood Tammara , Allanore Yannick , Matucci‐Cerinic Marco , Distler Oliver , Singer Ora , Bush Erica , Fox David A. , Furst Daniel E. 
Published: July 2019

ObjectiveT cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsIn this 12‐month, randomized, double‐blind, placebo‐controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets.ResultsAmong 88 participants, the adjusted mean change in the MRSS at 12 months was −6.24 units for those receiving abatacept and −4.49 units for those receiving placebo, with an adjusted mean treatment difference of −1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal‐like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively.ConclusionIn this phase II trial, abatacept was well‐tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.
Continuous precipitation for monoclonal antibody capture using countercurrent washing by microfiltration
Authors: Li Zhao , Gu Qin , Coffman Jonathan L. , Przybycien Todd , Zydney Andrew L. 
Published: July 2019

AbstractThere is renewed interest in the possibility of using precipitation for initial capture of high‐value therapeutic proteins as part of an integrated continuous downstream process. Precipitation is greatly facilitated by the high product titers now achieved in most cell culture processes, in sharp contrast to chromatographic processes whose performance is reduced at high titers. The current study used a combination of reversible cross‐linking (zinc chloride, ZnCl2) and volume exclusion (polyethylene glycol) agents to precipitate a monoclonal antibody product directly from harvested cell culture fluid using a continuous tubular precipitation reactor. The precipitates were then dewatered and continuously washed using tangential flow filtration, with a countercurrent‐staged configuration used to reduce the amount of wash buffer required and increase host cell protein removal. Long‐term operation was achieved by operating the membrane modules below the critical filtrate flux to avoid fouling. Experimental results demonstrate the feasibility of this fully continuous integrated precipitation process at bench scale, with design calculations used to explore the key factors affecting the performance of this system for initial antibody capture.
Persistent Room‐Temperature Radicals from Anionic Naphthalimides: Spin Pairing and Supramolecular Chemistry
Authors: Huang Wenhuan , Chen Biao , Zhang Guoqing 
Published: July 2019

AbstractN‐Substituted naphthalimides (NNIs) have been shown to exhibit highly efficient and persistent room‐temperature phosphorescence from an NNI‐localized triplet excited state, when the N‐substitution is a sufficiently strong donor and mediates an intramolecular charge‐transfer (ICT) state upon photo‐excitation. This work shows that, when the electron‐donating ability of the N‐substitution is further increased in the presence of a carbanion or phenoxide, spontaneous electron transfer (ET) occurs and results in radical anions, verified with electron‐paramagnetic resonance (EPR) spectroscopy. However, the EPR‐active anion is surprisingly persistent and impervious to nucleophilic and radical reactions under anionic conditions. The stability is thought to originate from an intramolecular spin pairing between the N‐donor and the NI acceptor post ET, which is demonstrated in supramolecular chemistry.
Crystalline Anionic Germanate Covalent Organic Framework for High CO2 Selectivity and Fast Li Ion Conduction
Authors: Ashraf Shumaila , Zuo Yiming , Li Shuai , Liu Caixia , Wang Hang , Feng Xiao , Li Pengfei , Wang Bo 
Published: July 2019

AbstractThe metalloid‐centered covalent organic framework has attracted great interest from both its structure and application. Heavier elements have seldomly been incorporated in the covalent organic frameworks, even if they exhibit special structural features and properties. Herein, we reported the first crystalline germanate covalent organic framework with hexacoordinated germanate linked by an anthracene linker. The existence of counterion lithium ions in the framework provides a high CO2 uptake of 88.5 cm3 g−1 at 273 K and a high CO2/N2 selectivity of 101. A significantly improved lithium ion conductivity of 0.25 mS cm−1 at room temperature was observed due to the soft germanium center.
A Potts‐mixture spatiotemporal joint model for combined magnetoencephalography and electroencephalography data
Authors: Song Yin , Nathoo Farouk , Babul Arif 
Published: July 2019

AbstractWe develop a new methodology for determining the location and dynamics of brain activity from combined magnetoencephalography (MEG) and electroencephalography (EEG) data. The resulting inverse problem is ill‐posed and is one of the most difficult problems in neuroimaging data analysis. In our development we propose a solution that combines the data from three different modalities, magnetic resonance imaging (MRI), MEG and EEG, together. We propose a new Bayesian spatial finite mixture model that builds on the mesostate‐space model developed by Daunizeau & Friston [Daunizeau and Friston, NeuroImage 2007; 38, 67–81]. Our new model incorporates two major extensions: (i) We combine EEG and MEG data together and formulate a joint model for dealing with the two modalities simultaneously; (ii) we incorporate the Potts model to represent the spatial dependence in an allocation process that partitions the cortical surface into a small number of latent states termed mesostates. The cortical surface is obtained from MRI. We formulate the new spatiotemporal model and derive an efficient procedure for simultaneous point estimation and model selection based on the iterated conditional modes algorithm combined with local polynomial smoothing. The proposed method results in a novel estimator for the number of mixture components and is able to select active brain regions, which correspond to active variables in a high‐dimensional dynamic linear model. The methodology is investigated using synthetic data and simulation studies and then demonstrated on an application examining the neural response to the perception of scrambled faces. R software implementing the methodology along with several sample datasets are available at the following GitHub repository https://github.com/v2south/PottsMix. The Canadian Journal of Statistics 47: 688–711; 2019 © 2019 Statistical Society of Canada
Tyrosine hydroxylase immunolabeling reveals the distribution of catecholaminergic neurons in the central nervous systems of the spiders Hogna lenta (Araneae: Lycosidae) and Phidippus regius (Araneae: Salticidae)
Authors: Auletta Anthony , Rue Mara C. P. , Harley Cynthia M. , Mesce Karen A. 
Published: July 2019

AbstractWith over 48,000 species currently described, spiders (Arthropoda: Chelicerata: Araneae) comprise one of the most diverse groups of animals on our planet, and exhibit an equally wide array of fascinating behaviors. Studies of central nervous systems (CNSs) in spiders, however, are relatively sparse, and no reports have yet characterized catecholaminergic (dopamine [DA]‐ or norepinephrine‐synthesizing) neurons in any spider species. Because these neuromodulators are especially important for sensory and motor processing across animal taxa, we embarked on a study to identify catecholaminergic neurons in the CNS of the wolf spider Hogna lenta (Lycosidae) and the jumping spider Phidippus regius (Salticidae). These neurons were most effectively labeled with an antiserum raised against tyrosine hydroxylase (TH), the rate‐limiting enzyme in catecholamine synthesis. We found extensive catecholamine‐rich neuronal fibers in the first‐ and second‐order optic neuropils of the supraesophageal mass (brain), as well as in the arcuate body, a region of the brain thought to receive visual input and which may be involved in higher order sensorimotor integration. This structure likely shares evolutionary origins with the DA‐enriched central complex of the Mandibulata. In the subesophageal mass, we detected an extensive filigree of TH‐immunoreactive (TH‐ir) arborizations in the appendage neuromeres, as well as three prominent plurisegmental fiber tracts. A vast abundance of TH‐ir somata were located in the opisthosomal neuromeres, the largest of which appeared to project to the brain and decorate the appendage neuromeres. Our study underscores the important roles that the catecholamines likely play in modulating spider vision, higher order sensorimotor processing, and motor patterning.
Application health monitoring for extreme‐scale resiliency using cooperative fault management
Authors: Agarwal Pratul K. , Naughton Thomas , Park Byung H. , Bernholdt David E. , Hursey Joshua J. , Geist Al 
Published: July 2019

SummaryResiliency is and will be a critical factor in determining scientific productivity on current and exascale supercomputers, and beyond. Applications oblivious to and incapable of handling transient soft and hard errors could waste supercomputing resources or, worse, yield misleading scientific insights. We introduce a novel application‐driven silent error detection and recovery strategy based on application health monitoring. Our methodology uses application output that follows known patterns, as indicators of an application's health and knowledge that violation of these patterns could be indication of faults. Information from system monitors that report hardware and software health status is used to corroborate faults. Collectively, this information is used by a fault coordinator agent to take preventive and corrective measures by applying computational steering to an application between checkpoints. This cooperative fault management system uses the Fault Tolerance Backplane as a communication channel. The benefits of this framework are demonstrated with two real application case studies, molecular dynamics, and quantum chemistry simulations, on scalable clusters with simulated memory and I/O corruptions. The developed approach is general and can be easily applied to other applications.
Corrosion resistance of coupled sandblasted, large‐grit, acid‐etched (SLA) and anodized Ti implant surfaces in synthetic saliva
Authors: Al Otaibi Ala'a , Sherif El‐Sayed M. , Al‐Rifaiy Mohammed Q. , Zinelis Spiros , Al Jabbari Youssef S. 
Published: July 2019

AbstractPurposeThe purpose of this study was to investigate the corrosion resistance of galvanically coupled SLA and anodized implant surfaces with a Co‐Cr alloy.Materials and MethodsThree groups were included in this study. The first (SLA) was composed of SLA implants (Institut Straumann, Basel, Switzerland), the second (ANO) of NobelReplace® (Nobel Biocare, Göteborg, Sweden), and the third (MIX) of both implant systems combined. All groups were assembled with a single Co‐Cr superstructure. Electrochemical testing included open‐circuit potential, electrochemical impedance spectroscopy, cyclic potentiodynamic polarization, and chronoamperometric current‐time measurements. The quantitative results (EOCP, ECORR, ICORR, EPROT, RP, and ICA) were statistically analyzed by one‐way ANOVA and Tukey's post‐hoc multiple comparison test (α = 0.05)ResultsAll the aforementioned parameters showed statistically significant differences apart from ECORR and EPROT. The evaluation of qualitative and quantitative results showed that although SLA had higher corrosion resistance compared with ANO, it had less resistance to pitting corrosion. This means that SLA showed increased resistance to uniform corrosion but less resistance if pitting corrosion was initiated. In all cases, MIX showed intermediate behavior.ConclusionThe corrosion resistance of implant‐retained superstructures is dependent on the electrochemical properties of the implants involved, and thus different degrees of intraoral corrosion resistance among different implant systems are anticipated.
Social trust and corporate social responsibility: Evidence from China
Authors: Chen Xiangyu , Wan Peng 
Published: July 2019

AbstractBased on neo‐institutional theory, this paper examines whether social trust can influence corporate social responsibility (CSR). Using a sample of 4,209 observations selected from 788 firms listed in China between 2008 and 2015 and adopting an ordinary least square regression, we provide strong empirical evidence showing that social trust is positively associated with CSR. The result supports the view that social trust, as a kind of socially normative force, helps corporate managers safeguard stakeholders' interests by engaging in socially responsible activities. Our result holds after applying a series of robustness tests. We further find the positive relationship between social trust and CSR is more pronounced for state‐owned companies. This paper is one of the first to focus on and examine the relationship between social trust and CSR, and the findings contribute to our understanding of the determinants of CSR and highlight the influential role of social trust in improving CSR.