bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukemic stem cell signatures identify novel therapeutics targeting acute myeloid leukemia
Authors: Laverdière Isabelle , Boileau Meaghan , Neumann Andrea L. , Frison Héloïse , Mitchell Amanda , Ng Stanley W. K. , Wang Jean C. Y. , Minden Mark D. , Eppert Kolja 
Published: June 2018

AbstractTherapy for acute myeloid leukemia (AML) involves intense cytotoxic treatment and yet approximately 70% of AML are refractory to initial therapy or eventually relapse. This is at least partially driven by the chemo-resistant nature of the leukemic stem cells (LSCs) that sustain the disease, and therefore novel anti-LSC therapies could decrease relapses and improve survival. We performed in silico analysis of highly prognostic human AML LSC gene expression signatures using existing datasets of drug–gene interactions to identify compounds predicted to target LSC gene programs. Filtering against compounds that would inhibit a hematopoietic stem cell (HSC) gene signature resulted in a list of 151 anti-LSC candidates. Using a novel in vitro LSC assay, we screened 84 candidate compounds at multiple doses and confirmed 14 drugs that effectively eliminate human AML LSCs. Three drug families presenting with multiple hits, namely antihistamines (astemizole and terfenadine), cardiac glycosides (strophanthidin, digoxin and ouabain) and glucocorticoids (budesonide, halcinonide and mometasone), were validated for their activity against human primary AML samples. Our study demonstrates the efficacy of combining computational analysis of stem cell gene expression signatures with in vitro screening to identify novel compounds that target the therapy-resistant LSC at the root of relapse in AML.
Synergetic coordination and catecholamine chemistry for catalytic generation of nitric oxide on vascular stents
Authors: Li Xiangyang , Qiu Hua , Gao Peng , Yang Ying , Yang Zhilu , Huang Nan 
Published: June 2018

AbstractThe unique advantages of nitric oxide (NO) in cardiovascular disease therapy have driven the development of methods to functionalize cardiovascular stents for local generation of NO. However, current NO-generating materials used for surface engineering stents have limitations such as a complex fabrication process, poor stent adhesion strength, and low control of NO release. Herein, we apply synergetic coordination and catecholamine surface chemistry to develop an adhesive NO-generating coating with a copper-catecholamine framework through a simple, one-step molecule/ion co-assembly process. The copper-catecholic-selenocystamine framework provides glutathione peroxidase (GPx)-like interfacial catalytic activity, which results in long-term, stable, adjustable NO release rates from the coating. The resulting desirable therapeutic dose and release kinetics of NO endow the vascular stent with the ability to simultaneously inhibit platelet activation and smooth muscle cell (SMC) proliferation, and enhances endothelial cell (EC) adhesion, proliferation, and migration in vitro. Vascular stent functionalized by the optimized copper-catecholic-selenocystamine coating significantly suppresses thrombosis, promotes re-endothelialization, and reduces intimal hyperplasia in vivo, and may be promising to address the clinical complications associated with restenosis and late stent thrombosis.
Publisher Correction: Probing the strongly driven spin-boson model in a superconducting quantum circuit
Authors: Magazzù L. , Forn-Díaz P. , Belyansky R. , Orgiazzi J.-L. , Yurtalan M. A. , Otto M. R. , Lupascu A. , Wilson C. M. , Grifoni M. 
Published: June 2018

The original PDF and HTML versions of this Article omitted the ORCID ID of the authors L. Magazzù and P. Forn-Díaz. (L. Magazzù: 0000-0002-4377-8387; P. Forn-Diaz: 0000-0003-4365-5157).The original PDF version of this Article contained errors in Eqs. (2), (6), (13), (14), (25), (26). These equations were missing all instances of ‘Γ’ and ‘Δ’, which are correctly displayed in the HTML version.Similarly, the inline equation in the third sentence of the caption of Fig. 2 was missing the left hand term ‘Ω’.The original HTML version of this Article contained errors in Table 1. The correct version of the sixth row of the first column states ‘Figure 2’ instead of the original, incorrect ‘Figure’. And the correction version of the ninth row of the first column states ‘Figure 3’ instead of the original, incorrect ‘Figure’.This has been corrected in both the PDF and HTML versions of the Article.
α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease
Authors: Ludtmann Marthe H. R. , Angelova Plamena R. , Horrocks Mathew H. , Choi Minee L. , Rodrigues Margarida , Baev Artyom Y. , Berezhnov Alexey V. , Yao Zhi , Little Daniel , Banushi Blerida , Al-Menhali Afnan Saleh , Ranasinghe Rohan T. , Whiten Daniel R. , Yapom Ratsuda , Dolt Karamjit Singh , Devine Michael J. , Gissen Paul , Kunath Tilo , Jaganjac Morana , Pavlov Evgeny V. , Klenerman David , Abramov Andrey Y. , Gandhi Sonia 
Published: June 2018

AbstractProtein aggregation causes α-synuclein to switch from its physiological role to a pathological toxic gain of function. Under physiological conditions, monomeric α-synuclein improves ATP synthase efficiency. Here, we report that aggregation of monomers generates beta sheet-rich oligomers that localise to the mitochondria in close proximity to several mitochondrial proteins including ATP synthase. Oligomeric α-synuclein impairs complex I-dependent respiration. Oligomers induce selective oxidation of the ATP synthase beta subunit and mitochondrial lipid peroxidation. These oxidation events increase the probability of permeability transition pore (PTP) opening, triggering mitochondrial swelling, and ultimately cell death. Notably, inhibition of oligomer-induced oxidation prevents the pathological induction of PTP. Inducible pluripotent stem cells (iPSC)-derived neurons bearing SNCA triplication, generate α-synuclein aggregates that interact with the ATP synthase and induce PTP opening, leading to neuronal death. This study shows how the transition of α-synuclein from its monomeric to oligomeric structure alters its functional consequences in Parkinson’s disease.
Achieving high permeability and enhanced selectivity for Angstrom-scale separations using artificial water channel membranes
Authors: Shen Yue-xiao , Song Woochul , Barden D. Ryan , Ren Tingwei , Lang Chao , Feroz Hasin , Henderson Codey B. , Saboe Patrick O. , Tsai Daniel , Yan Hengjing , Butler Peter J. , Bazan Guillermo C. , Phillip William A. , Hickey Robert J. , Cremer Paul S. , Vashisth Harish , Kumar Manish 
Published: June 2018

AbstractSynthetic polymer membranes, critical to diverse energy-efficient separations, are subject to permeability-selectivity trade-offs that decrease their overall efficacy. These trade-offs are due to structural variations (e.g., broad pore size distributions) in both nonporous membranes used for Angstrom-scale separations and porous membranes used for nano to micron-scale separations. Biological membranes utilize well-defined Angstrom-scale pores to provide exceptional transport properties and can be used as inspiration to overcome this trade-off. Here, we present a comprehensive demonstration of such a bioinspired approach based on pillar[5]arene artificial water channels, resulting in artificial water channel-based block copolymer membranes. These membranes have a sharp selectivity profile with a molecular weight cutoff of ~ 500 Da, a size range challenging to achieve with current membranes, while achieving a large improvement in permeability (~65 L m−2 h−1 bar−1 compared with 4–7 L m−2 h−1 bar−1) over similarly rated commercial membranes.
Spatially confined lignin nanospheres for biocatalytic ester synthesis in aqueous media
Authors: Sipponen Mika Henrikki , Farooq Muhammad , Koivisto Jari , Pellis Alessandro , Seitsonen Jani , Österberg Monika 
Published: June 2018

AbstractDehydration reactions proceed readily in water-filled biological cells. Development of biocatalysts that mimic such compartmentalized reactions has been cumbersome due to the lack of low-cost nanomaterials and associated technologies. Here we show that cationic lignin nanospheres function as activating anchors for hydrolases, and enable aqueous ester synthesis by forming spatially confined biocatalysts upon self-assembly and drying-driven aggregation in calcium alginate hydrogel. Spatially confined microbial cutinase and lipase retain 97% and 70% of their respective synthetic activities when the volume ratio of water to hexane increases from 1:1 to 9:1 in the reaction medium. The activity retention of industrially most frequently used acrylic resin-immobilized Candida antarctica lipase B is only 51% under similar test conditions. Overall, our findings enable fabrication of robust renewable biocatalysts for aqueous ester synthesis, and provide insight into the compartmentalization of diverse heterogeneous catalysts.
A Dual-Modality Hybrid Imaging System Harnesses Radioluminescence and Sound to Reveal Molecular Pathology of Atherosclerotic Plaques
Authors: Zaman Raiyan T. , Yousefi Siavash , Long Steven R. , Saito Toshinobu , Mandella Michael , Qiu Zhen , Chen Ruimin , Contag Christopher H. , Gambhir Sanjiv S. , Chin Frederick T. , Khuri-Yakub Butras T. , McConnell Michael V. , Shung K. Kirk , Xing Lei 
Published: June 2018

AbstractAtherosclerosis is a progressive inflammatory condition caused by an unstable lesion, called thin-cap fibro atheromata (TCFA) that underlies coronary artery disease (CAD)—one of the leading causes of death worldwide. Therefore, early clinical diagnosis and effective risk stratification is important for CAD management as well as preventing progression to catastrophic events. However, early detection could be difficult due to their small size, motion, obscuring 18F-FDG uptake by adjacent myocardium, and complex morphological/biological features. To overcome these limitations, we developed a catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system that can detect vulnerable plaques in coronary arteries and characterizes them with respect to pathology and biology. Our CIRPI system combined two imaging modalities: Circumferential Radioluminescence Imaging (CRI) and PhotoAcoustic Tomography (PAT) within a novel optical probe. The probe’s CaF2:Eu based scintillating imaging window provides a 360° view of human (n = 7) and murine carotid (n = 10) arterial plaques by converting β-particles into visible photons during 18F-FDG decay. A 60× and 63× higher radioluminescent signals were detected from the human and murine plaque inflammations, respectively, compared to the control. The system’s photoacoustic imaging provided a comprehensive analysis of the plaque compositions and its morphologic information. These results were further verified with IVIS-200, immunohistochemical analysis, and autoradiography.
Holocene forest dynamics in central and western Mediterranean: periodicity, spatio-temporal patterns and climate influence
Authors: Di Rita Federico , Fletcher William J. , Aranbarri Josu , Margaritelli Giulia , Lirer Fabrizio , Magri Donatella 
Published: June 2018

AbstractIt is well-known that the Holocene exhibits a millennial-scale climate variability. However, its periodicity, spatio-temporal patterns and underlying processes are not fully deciphered yet. Here we focus on the central and western Mediterranean. We show that recurrent forest declines from the Gulf of Gaeta (central Tyrrhenian Sea) reveal a 1860-yr periodicity, consistent with a ca. 1800-yr climate fluctuation induced by large-scale changes in climate modes, linked to solar activity and/or AMOC intensity. We show that recurrent forest declines and dry events are also recorded in several pollen and palaeohydrological proxy-records in the south-central Mediterranean. We found coeval events also in several palaeohydrological records from the south-western Mediterranean, which however show generally wet climate conditions, indicating a spatio-temporal hydrological pattern opposite to the south-central Mediterranean and suggesting that different expressions of climate modes occurred in the two regions at the same time. We propose that these opposite hydroclimate regimes point to a complex interplay of the prevailing or predominant phases of NAO-like circulation, East Atlantic pattern, and extension and location of the North African anticyclone. At a larger geographical scale, displacements of the ITCZ, modulated by solar activity and/or AMOC intensity, may have also indirectly influenced the observed pattern.
Analysis of the Co-existence of Long-range Transport Biomass Burning and Dust in the Subtropical West Pacific Region
Authors: Dong Xinyi , Fu Joshua S. , Huang Kan , Lin Neng-Huei , Wang Sheng-Hsiang , Yang Cheng-En 
Published: June 2018

AbstractBiomass burning and wind-blown dust has been well investigated during the past decade regarding their impacts on environment, but their co-existence hasn’t been recognized because they usually occur in different locations and episodes. In this study we reveal the unique co-existence condition that dust from the Taklamakan and Gobi Desert (TGD) and biomass burning from Peninsular Southeast Asia (PSEA) can reach to the west Pacific region simultaneously in boreal spring (March and April). The upper level trough at 700hPa along east coast of China favors the large scale subsidence of TGD dust while it travels southeastwards, and drives the PSEA biomass burning plume carried by the westerlies at 3–5 km to descend rapidly to around 1.5 km and mix with dust around southeast China and Taiwan. As compared to the monthly averages in March and April, surface observations suggested that concentrations of PM10, PM2.5, O3, and CO were 69%, 37%, 20%, and 18% higher respectively during the 10 identified co-existence events which usually lasted for 2–3 days. Co-existence also lowers the surface O3, NOx, and SO2 by 4–5% due to the heterogeneous chemistry between biomass burning and mineral dust as indicated by model simulations.
Evaluation of an artificial vertebral body fabricated by a tantalum-coated porous titanium scaffold for lumbar vertebral defect repair in rabbits
Authors: Wang Faqi , Wang Lin , Feng Yafei , Yang Xiaojiang , Ma Zhensheng , Shi Lei , Ma Xiangyu , Wang Jian , Ma Tiancheng , Yang Zhao , Wen Xinxin , Zhang Yang , Lei Wei 
Published: June 2018

AbstractTantalum (Ta)-coated porous Ti-6A1-4V scaffolds have better bioactivity than Ti-6A1-4V scaffolds; however, their bioperformance as an artificial vertebral body (AVB) is unknown. In the present study, we combined a Ta-coated Ti-6A1-4V scaffold with rabbit bone marrow stromal cells (BMSCs) for tissue-engineered AVB (TEAVB) construction and evaluated the healing and fusion efficacy of this scaffold in lumbar vertebral defects after corpectomy in rabbits. The results showed that BMSCs on the surface of the Ta-coated Ti scaffolds proliferated better than BMSCs on Ti scaffolds. Histomorphometry showed better bone formation when using Ta-coated TEAVBs than that with Ti TEAVBs at both 8 and 12 weeks after implantation. In addition, the vertical and rotational stiffness results showed that, compared with uncoated TEAVBs, Ta-coated TEAVBs enhanced rabbit lumbar vertebral defect repair. Our findings demonstrate that Ta-coated TEAVBs have better healing and fusion efficacy than Ti TEAVBs in rabbit lumbar vertebral defects, which indicates their good prospects for clinical application.
Human influence on sub-regional surface air temperature change over India
Authors: Dileepkumar R. , AchutaRao Krishna , Arulalan T. 
Published: June 2018

AbstractHuman activities have been implicated in the observed increase in Global Mean Surface Temperature. Over regional scales where climatic changes determine societal impacts and drive adaptation related decisions, detection and attribution (D&A) of climate change can be challenging due to the greater contribution of internal variability, greater uncertainty in regionally important forcings, greater errors in climate models, and larger observational uncertainty in many regions of the world. We examine the causes of annual and seasonal surface air temperature (TAS) changes over sub-regions (based on a demarcation of homogeneous temperature zones) of India using two observational datasets together with results from a multimodel archive of forced and unforced simulations. Our D&A analysis examines sensitivity of the results to a variety of optimal fingerprint methods and temporal-averaging choices. We can robustly attribute TAS changes over India between 1956–2005 to anthropogenic forcing mostly by greenhouse gases and partially offset by other anthropogenic forcings including aerosols and land use land cover change.
Finite Element Stress Analysis of Keyhole Plate System in Sagittal Split Ramus Osteotomy
Authors: Kim Ju-Won , Park Kang-Nam , Lee Chang-Hyeon , Kim Yong-Su , Kim Young-Hee , Yang Byoung-Eun 
Published: June 2018

AbstractA new miniplate applied differently from conventional application method for bone fixation has been developed. The novel approach is the insertion of the screw into the bone before miniplate installation. This study aimed to assess the stress distribution of a newly designed Yang’s Keyhole (YK)- plate for segmental-bone fixation during sagittal split ramus osteotomy (SSO). Moreover, the effectiveness of the YK-plate system based on the clinical results was determined. The YK-plate system has a widened hole in the anterior region to permit a screw-head to be screwed through the system. The stress distribution using the finite-element analysis method was compared between in the case of the YK-plate system and the case of existing mini-plate fixation technique. Moreover, the clinical results of patients were evaluated during the follow-up examination periods. No critical complications in any of the six patients were reported during the four-month follow-up period. The result of the stress distribution using finite-element analysis showed a similar trend in all four fixation methods. The YK-plate system can be applied to fixation during SSO and allow for mechanically stable and convenient application.
Dropping anchor: attachment of peptidylarginine deiminase via A-LPS to secreted outer membrane vesicles of Porphyromonas gingivalis
Authors: Gabarrini Giorgio , Heida Rick , van Ieperen Nienke , Curtis Mike A. , van Winkelhoff Arie Jan , van Dijl Jan Maarten 
Published: June 2018

AbstractThe periodontal pathogen Porphyromonas gingivalis has been invoked in the autoimmune disease rheumatoid arthritis (RA). This association relates to the peptidylarginine deiminase of P. gingivalis (PPAD), an enzyme capable of citrullinating human proteins and potentially contributing to loss of tolerance to citrullinated proteins in RA. PPAD is both retained in the outer membrane (OM) of P. gingivalis cells and secreted into the extracellular milieu, where it is detected in a soluble form and in association with outer membrane vesicles (OMVs). Recent studies showed that certain P. gingivalis proteins are retained in the OM through modification with an A-type lipopolysaccharide (A-LPS). Here, we investigated the possible involvement of A-LPS modification in the association of PPAD to the OM and OMVs. The results indicate that the OM- and OMV-associated PPAD is A-LPS-modified. The modified PPAD species is of low abundance in particular clinical isolates of P. gingivalis, which is not due to defects in the overall synthesis of A-LPS-modified proteins but, rather, to particular traits of the respective PPAD proteins. Lastly, we show that OMV association protects the A-LPS-modified PPAD from proteolytic degradation. Altogether, our observations show that A-LPS modification contributes to OM(V) sorting and ‘protective secretion’ of PPAD.
One-step hydrothermal synthesis of thioglycolic acid capped CdS quantum dots as fluorescence determination of cobalt ion
Authors: Wang Zhezhe , Xing Xinxin , Yang Yue , Zhao Rongjun , Zou Tong , Wang Zidong , Wang Yude 
Published: June 2018

AbstractHighly luminescent CdS quantum dots capped with thioglycolic acid (TGA@CdS QDs) were synthesized from cadmium chloride and thiourea as cadmium and sulfur sources via simple hydrothermal method. The room temperature photoluminescence (RTPL) properties of TGA@CdS QDs were investigated. The results indicate that the polarity of the solvent and the surface trap state resulted in the broadness Stokes shift between the maximum absorption wavelength and the emission wavelength of TGA@CdS QDs. The Co2+ sensing properties of fluorescence determination were investigated using TGA@CdS QDs. The as-synthesized CdS QDs exhibits the excellent selectivity and sensitivity of fluorescence quenching for cobalt ion (Co2+). The limit of detection (LOD) is as low as 0.05 μM which is much lower than maximum limit of cobalt ions in drinking water. The linear response range of Co2+ was from 0.5 to 80 μM. The sensing system revealed the advantages of low detection limit, excellent selectivity, high sensitivity, convenience and low cost. The color change of CdS QDs shows potential applications in the detection of Co2+.
Deciphering Clinicoradiologic Phenotype for Thymidylate Synthase Expression Status in Patients with Advanced Lung Adenocarcinoma Using a Radiomics Approach
Authors: Lee So Won , Park Hyunjin , Lee Ho Yun , Sohn Insuk , Lee Seung-Hak , Kang Jun , Sun Jong-Mu , Ahn Myung-Ju 
Published: June 2018

AbstractWe aimed to identify predictive clinicoradiologic characteristics of thymidylate synthase (TS) expression status in advanced non-squamous non-small cell lung cancer patients. We reviewed clinicoradiologic features of 169 patients stratified into TS-negative (n = 84) and TS-positive (n = 85) groups, including quantitative CT radiomic features of both primary lung and metastatic lesions from initial CT and PET. Clinical factors including age and smoking history were significantly associated with TS as well as radiomic features. The predictive performance for dichotomizing TS expression status was slightly higher when imaging features of primary lung lesions were added compared to the model based solely on the clinical features, but without statistical significance (10-fold cross-validated AUC = 0.619 and 0.581, respectively; P = 0.425). The predictive performance of clinicoradiologic parameters slightly increased with primary lung lesions only compared to the inclusion of metastatic lesions, but without statistical significance (10-fold cross-validated AUC = 0.619 and 0.554, respectively; P = 0.203). Overall survival was prolonged in the TS-negative group compared to the TS-positive group (P = 0.001). TS-negativity is a potential prognostic biomarker, and our study presents that although CT radiomic features have potential for predicting TS expression status, clinical significance is uncertain. The addition of radiomic features to clinical factors did not show significant improvement in predicting TS-negativity.