bluuebunny/crossref_metadata_2025_split huggingface dataset:
X‐ray crystal structure localizes the mechanism of inhibition of an IL‐36R antagonist monoclonal antibody to interaction with Ig1 and Ig2 extra cellular domains
Authors: Larson Eric T. , Brennan Debra L. , Hickey Eugene R. , Ganesan Raj , Kroe‐Barrett Rachel , Farrow Neil A. 
Published: April 2020

AbstractCellular signaling via binding of the cytokines IL‐36α, β, and γ along with binding of the accessory protein IL‐36RAcP, to their cognate receptor IL‐36R is believed to play a major role in epithelial and immune cell‐mediated inflammation responses. Antagonizing the signaling cascade that results from these binding events via a directed monoclonal antibody provides an opportunity to suppress such immune responses. We report here the molecular structure of a complex between an extracellular portion of human IL‐36R and a Fab derived from a high affinity anti‐IL‐36R neutralizing monoclonal antibody at 2.3 Å resolution. This structure, the first of IL‐36R, reveals similarities with other structurally characterized IL‐1R family members and elucidates the molecular determinants leading to the high affinity binding of the monoclonal antibody. The structure of the complex reveals that the epitope recognized by the Fab is remote from both the putative ligand and accessory protein binding interfaces on IL‐36R, suggesting that the functional activity of the antibody is noncompetitive for these binding events.
Purification and crystal structure of human ODA16: Implications for ciliary import of outer dynein arms by the intraflagellar transport machinery
Authors: Wang Jiaolong , Taschner Michael , Petriman Narcis A. , Andersen Marie B. , Basquin Jerome , Bhogaraju Sagar , Vetter Melanie , Wachter Stefanie , Lorentzen Anna , Lorentzen Esben 
Published: April 2020

AbstractMotile cilia protrude from cell surfaces and are necessary to create movement of cells and fluids in the body. At the molecular level, cilia contain several dynein molecular motor complexes including outer dynein arms (ODAs) that are attached periodically to the ciliary axoneme, where they hydrolyse ATP to create the force required for bending and motility of the cilium. ODAs are preassembled in the cytoplasm and subsequently trafficked into the cilium by the intraflagellar transport (IFT) system. In the case of the green alga Chlamydomonas reinhardtii, the adaptor protein ODA16 binds to ODAs and directly to the IFT complex component IFT46 to facilitate the ciliary import of ODAs. Here, we purified recombinant human IFT46 and ODA16, determined the high‐resolution crystal structure of the ODA16 protein, and carried out direct interaction studies of IFT46 and ODA16. The human ODA16 C‐terminal 320 residues adopt the fold of an eight‐bladed β‐propeller with high overall structural similarity to the Chlamydomonas ODA16. However, the small 80 residue N‐terminal domain, which in Chlamydomonas ODA16 is located on top of the β‐propeller and is required to form the binding cleft for IFT46, has no visible electron density in case of the human ODA16 structure. Furthermore, size exclusion chromatography and pull‐down experiments failed to detect a direct interaction between human ODA16 and IFT46. These data suggest that additional factors may be required for the ciliary import of ODAs in human cells with motile cilia.
Anticancer properties and mechanism of action of the quassinoid ailanthone
Authors: Bailly Christian 
Published: April 2020

AbstractAilanthone (AIT) is a quassinoid natural product isolated from the worldwide‐distributed plant Ailanthus altissima. The drug displays multiple pharmacological properties, in particular significant antitumor effects against a variety of cancer cell lines in vitro. Potent in vivo activities have been evidenced in mice bearing hepatocellular carcinoma, nonsmall cell lung cancer and castration‐resistant prostate cancer. This review focusses on the mechanism of action of AIT, notably to highlight the capacity of the drug to activate DNA damage responses, to inhibit the Hsp90 co‐chaperone p23 and to modulate the expression of several microRNA. The interconnexion between these effects is discussed. The unique capacity of AIT to downregulate oncogenic miR‐21 and to upregulate the tumor suppressor miRNAs miR‐126, miR‐148a, miR‐195, and miR‐449a is presented. AIT exploits several microRNAs to exert its anticancer effects in distinct tumor types. AIT is one of the rare antitumor natural products that binds to and strongly inhibits cochaperone p23, opening interesting perspectives to treat cancers. However, the toxicity profile of the molecule may limit its development as an anticancer drug, unless it can be properly formulated to prevent AIT‐induced gastro‐intestinal damages in particular. The antitumor properties of AIT and analogs are underlined, with the aim to encourage further pharmacological studies with this underexplored natural product and related quassinoids.Highlights
Ailanthone (AIT) is an anticancer quassinoid isolated from Ailanthus altissima
It inhibits proliferation and induces cell death of many cancer cell types
The drug activates DNA damage response and targets p23 cochaperone
Up or downregulation of several microRNA by AIT contributes to the anticancer activity
Analogs or specific formulations must be developed to prevent the toxicity of AIT
Wood‐induced backwater effects in lowland streams
Authors: Geertsema Tjitske J. , Torfs Paul J. J. F. , Eekhout Joris P. C. , Teuling Adriaan J. , Hoitink Antonius J. F. 
Published: April 2020

AbstractPlacement of wood in streams has become a common method to increase ecological value in river and stream restoration and is widely used in natural environments. Water managers, however, are often hesitant to introduce wood in channels that drain agricultural and urban areas because of backwater effect concerns. This study aims to better understand the dependence of wood‐induced backwater effects on cross‐sectional area reduction and on discharge variation. A newly developed, one‐dimensional stationary model demonstrates how a reduction in water level over the wood patch significantly increases directly after wood insertion. The water level drop is found to increase with discharge, up to a maximum level. If the discharge increases beyond this maximum, the water level drop reduces to a value that may represent the situation without wood. This reduction predominately depends on the obstruction ratio, calculated as the area covered by wood in the channel cross section divided by the total cross‐sectional area. The model was calibrated with data from a field study in four lowland streams in the Netherlands. The field study showed that morphologic adjustments in the stream and reorientation of the woody material reduced the water level reduction over the patches in time. The backwater effects can thus be reduced by optimizing the location where wood patches are placed and by manipulating the obstruction ratio. The model can function as a generic tool to achieve a stream design with wood that optimizes the hydrological and ecological potential of streams.
Magnetically Separable Fe3O4@Au@Tb‐MOF Fluorescent Probe with Well‐Designed Sandwich Structure and Metal‐Enhanced Fluorescence
Authors: Li Yinghui , Wang Dandan , Li Shikuo , Zhang Hui , Zhang Lina , Huang Fangzhi 
Published: April 2020

AbstractExploiting a high‐performance magnetic separation probe is important for the detection of nitroaromatic compounds. Here, a novel Fe3O4@Au@Tb‐BTC metal–organic framework (MOF) fluorescent probe was synthesized and used for the determination of nitroaromatic hydrocarbons. Thanks to the fluorescence enhancement of the gold nanoparticle‐layer and the sheet structure of the outer Tb‐BTC, the Fe3O4@Au@Tb‐BTC with sandwich structure exhibits significantly higher sensitivity than Fe3O4@Tb‐BTC in quantitative detection of nitroaromatic explosives. The quenching constant (Ksv) toward picric acid in ethanol is up to 5.08×104 M−1 and the limit of detection (LOD) could reach to 3.14×10−6 M. Furthermore, it can be easily to recycle by applying an external magnetic field. The unique sandwich structure makes Fe3O4@Au@Tb‐MOF highly efficient and recoverable, offering broad opportunities in the field of promising probe synthesis and application.
Design, Synthesis and Biological Evaluation of 2‐(naphthoyl) iminothiazolidin‐4‐ones as Potential Anticancer Agents
Authors: Ashraf Saba , Saeed Aamer , Moon Seong‐Hee , Flörke Ulrich , Kim Seong Hwan , Ashraf Zaman , Yaseen Muhammad , Latif Muhammad 
Published: April 2020

AbstractA library of novel naphthyl bearing 2‐iminothiazolidin‐4‐ones (2‐ITZDs) (2 a–2 q) was designed and synthesized through a facile route involving regioselective heterocyclization of unsymmetrical thioureas (1 a–1 q). The synthesis was achieved at ambient temperature in good to excellent yields under catalyst free conditions. The molecular structures of 2‐ITZDs were elucidated by spectroscopic techniques such as FT‐IR, 1H‐NMR and 13C‐NMR. X‐ray structural data was used to establish the structure (2 o) unequivocally and to define the geometry of exo double bond. The in vitro anticancer activity of 2‐ITZDs (2 a–2 q) was investigated in several human cancer cell lines (A549, LNCap, PC‐3, MDA‐MB‐231, BxPC3, MIA PaCa2). All compounds showed cytotoxicity with IC50 values ranging from 6–23 μM in the tested cancer cell lines except MDA‐MB‐231. Compound 2 k (IC50=7 μM) and the homologous analog 2 q (IC50=6 μM) were found to be equipotent to 2 k and showed moderate cytotoxicity against human breast cell line (DA‐MB‐231). Furthermore, compound 2 k exhibited a medium permeability, enough metabolic stability and no significant inhibition of hERG channel. Compound 2 k inhibited cytochrome P450 activity below 50 % in 1 A2, 3 A4 and 2 C19, but not in 2 C9 and 2D6 at 10 μM. Structure‐activity relationships (SAR) provided useful insights towards this class of compounds and tiled a way to design novel analogues with increased potency.
The water‐energy nexus in the Middle East: Infrastructure, development, and conflict
Authors: Weinthal Erika , Sowers Jeannie 
Published: April 2020

AbstractWater and energy are closely linked in the Middle East and North Africa (MENA) through coupled networks of infrastructure. This review explores the water‐energy nexus of infrastructure to explicate different patterns of development and de‐development in the MENA. First, the review highlights why states, donors, and firms have long built large‐scale coupled water‐energy infrastructures to provide urban services, expand irrigated agriculture, and foster development. Yet, too often the adverse social and environmental impacts from the construction of dams, water conveyance structures, groundwater mining, and desalination plants have been overlooked. We then examine the water‐energy nexus through infrastructure for the most important users of water and energy in the MENA region: urban populations and the agricultural sector. Third, the review illustrates that while investments in water and energy infrastructure generated significant gains in human development for much for of the region, the post‐2011 wars reversed many of these development gains in conflict‐affected countries through the destruction and deterioration of water‐energy infrastructures. The unprecedented displacement of populations within and across borders has also created new challenges for host communities, where infrastructures for providing water and energy services were already overstretched. The review further highlights the growing role of humanitarian assistance in providing water and energy services to refugees, internally displaced populations, and host communities. Overall, this review examines how the nexus of water and energy infrastructure shapes human security, livelihoods, and political economies in the MENA region.This article is categorized under:
Human Water > Water Governance
Engineering Water > Planning Water
Identification of Comparison Key Elements and Their Relationships for Cloud Service Selection
Authors: Nacer Anis Ahmed , Perrin Olivier , Charoy François 
Published: April 2020

Abstract
Nowadays, the cloud computing industry is enjoying an exponential growth, where several cloud service providers compete to be one of the market leaders. Usually, providers offering similar services use different non-functional attributes to describe them. Thus, given the heterogeneity and diversity of services descriptions, the selection process of the appropriate cloud service becomes challenging. Architects no longer know what criteria to use to make the suitable cloud services selection. In this paper, we highlight the challenge of identifying key elements of comparisons and their relationship for selecting cloud services. Further, we propose a methodology to solve this issue based on real data available from service providers and benchmark work. Our methodology is validated based on two case studies of cloud relational databases and cloud queuing services.
Technology-Agnostic Declarative Deployment Automation of Cloud Applications
Authors: Wurster Michael , Breitenbücher Uwe , Brogi Antonio , Harzenetter Lukas , Leymann Frank , Soldani Jacopo 
Published: April 2020

Abstract

Declarative approaches for automating the deployment and configuration management of multi-component applications are on the rise. Many deployment technologies exist, sharing the same baselines for enacting declarative deployments, even if based on different languages for specifying multi-component applications. The Essential Deployment Metamodel (EDMM) Modeling and Transformation Framework allows to specify multi-component applications in a technology-agnostic manner, and to automatically generate the technology-specific deployment artifacts allowing to deploy an IaaS-based application. In this paper, we propose an extension of the EDMM Modeling and Transformation Framework to PaaS and SaaS by allowing to deploy application components on PaaS platforms or to implement them by instrumenting SaaS services. Given that not all existing deployment technologies support PaaS and SaaS deployments, we also propose the new EDMM Decision Support Framework allowing us to determine which deployment technologies can be used to deploy an application specified with EDMM.
On a degenerate parabolic system describing the mean curvature flow of rotationally symmetric closed surfaces
Authors: Garcke Harald , Matioc Bogdan-Vasile 
Published: April 2020

AbstractWe show that the mean curvature flow for a closed and rotationally symmetric surface can be formulated as an evolution problem consisting of an evolution equation for the square of the function whose graph is rotated and two ODEs describing the evolution of the points of the evolving surface that lie on the rotation axis. For the fully nonlinear and degenerate parabolic problem we establish the well-posedness property in the setting of classical solutions. Besides we prove that the problem features the effect of parabolic smoothing.
Arthroscopic Bankart repair with an individualized capsular shift restores physiological capsular volume in patients with anterior shoulder instability
Authors: Eberbach Helge , Jaeger Martin , Bode Lisa , Izadpanah Kaywan , Hupperich Andreas , Ogon Peter , Südkamp Norbert P. , Maier Dirk 
Published: April 2020

Abstract
Purpose
Capsular volume reduction in the context of anterior arthroscopic shoulder stabilization represents an important but uncontrolled parameter. The aim of this study was to analyse capsular volume reduction by arthroscopic Bankart repair with an individualized capsular shift in patients with and without ligamentous hyperlaxity compared to a control group.

Methods
In the context of a prospective controlled study, intraoperative capsular volume measurements were performed in 32 patients with anterior shoulder instability before and after arthroscopic Bankart repair with an individualized capsular shift. The results were compared to those of a control group of 50 patients without instability. Physiological shoulder joint volumes were calculated and correlated with biometric parameters (sex, age, height, weight and BMI).

Results
Patients with anterior shoulder instability showed a mean preinterventional capsular volume of 35.6 ± 10.6 mL, which was found to be significantly reduced to 19.3 ± 5.4 mL following arthroscopic Bankart repair with an individualized capsular shift (relative capsular volume reduction: 45.9 ± 21.9%; P < 0.01). Pre-interventional volumes were significantly greater in hyperlax than in non-hyperlax patients, while post-interventional volumes did not differ significantly. The average shoulder joint volume of the control group was 21.1 ± 7.0 mL, which was significantly correlated with sex, height and weight (P < 0.01). Postinterventional capsular volumes did not significantly differ from those of the controls (n.s.).

Conclusion
Arthroscopic Bankart repair with an individualized capsular shift enabled the restoration of physiological capsular volume conditions in hyperlax and non-hyperlax patients with anterior shoulder instability. Current findings allow for individual adjustment and intraoperative control of capsular volume reduction to avoid over- or under correction of the shoulder joint volume. Future clinical studies should evaluate, whether individualized approaches to arthroscopic shoulder stabilization are associated with superior clinical outcome.
Evaluation of lipid quantification accuracy using HILIC and RPLC MS on the example of NIST® SRM® 1950 metabolites in human plasma
Authors: Lange Mike , Fedorova Maria 
Published: April 2020

AbstractLipidomics analysis for large-scale studies aiming at the identification and quantification of natural lipidomes is often performed using LC–MS-based data acquisition. However, the choice of suitable LC–MS method for accurate lipid quantification remains a matter of debate. Here, we performed the systematic comparison between two HRAM-MS-based quantification workflows based on HILIC and RPLC MS by quantifying 191 lipids from five lipid classes in human blood plasma using deuterated standards in the “one ISTD-per-lipid class” approach. Lipid quantification was performed considering all necessary isotopic corrections, and obtained correction factors are illustrated. Concentrations of lipids in NIST® SRM® 1950 human blood plasma determined by the two methods were comparable for most of the studied lipid species except for highly unsaturated phosphatidylcholines (PC). A comparison of lipid concentrations to consensus values determined in a previously published multi-laboratory study illustrated possible “overestimation” of concentrations for these highly unsaturated lipids by HILIC MS. We evaluated the influence of lipid loading amounts as well as the difference between quantified lipid and internal standard concentrations on the HILIC MS quantification results. We conclude that both HILIC and RPLC HRAM-MS workflows can be equally used for accurate lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and sphingomyelin (SM) lipid quantification, despite significant differences in the concentration of highly unsaturated PC lipids which need to be addressed by establishing response factors to account for the differences in degree of lipid unsaturation.
The Sc-GAP makeover flap: eliminating the need for position changes in gluteal flap breast reconstruction
Authors: Bijkerk Ennie , van der Hulst René R. W. J. , Lataster Arno , Tuinder Stefania M. H. 
Published: April 2020

Abstract
Background
The gluteal region is one of the many alternative donor sites for autologous breast reconstruction. However, the harvest of the gluteal flap is rather difficult, and the major drawback of gluteal flaps has been the need for position changes for flap harvest and inset. A new approach of a gluteal flap is introduced, based on the septocutaneous perforators of the superior gluteal artery: the septocutaneous gluteal artery perforator (Sc-GAP) makeover flap.

Methods
A prospective study was performed in Maastricht University Medical Center between January 2018 and December 2019. Patients who underwent a Sc-GAP makeover flap breast reconstruction in the Maastricht University Medical Center and have had preoperative magnetic resonance angiography (MRA) of the abdomen between January 2018 and June 2019 were included.

Results
Nine patients underwent breast reconstruction with thirteen Sc-GAP makeover flaps, of which nine flaps were innervated. Indications were the abdomen not being available as a donor site (n = 4) or the flank region was preferred as a donor site by the patient (n = 5). The total operative time was 430 min on average (range 311–683). Mean flap weight was 638 g (range 370–1004) and the mean ischemia time was 53 ± 9.96 min. Coupler size used was 2.0–2.5 mm. All flaps survived.

Conclusion
The Sc-GAP makeover flap overcomes the disadvantages of the conventional gluteal flaps, especially by eliminating the need for position changes during the reconstruction procedure. It is a reliable flap that provides sufficient volume and good esthetic outcomes.
Level of evidence: Level IV, therapeutic study.
68Ga-PSMA Cerenkov luminescence imaging in primary prostate cancer: first-in-man series
Authors: olde Heuvel Judith , de Wit-van der Veen Berlinda J. , van der Poel Henk G. , Bekers Elise M. , Grootendorst Maarten R. , Vyas Kunal N. , Slump Cornelis H. , Stokkel Marcel P. M. 
Published: April 2020

Abstract
Purpose
Currently, approximately 11–38% of prostate cancer (PCa) patients undergoing radical prostatectomy have a positive surgical margin (PSM) on histopathology. Cerenkov luminescence imaging (CLI) using 68Ga-prostate-specific membrane antigen (68Ga-PSMA) is a novel technique for intraoperative margin assessment. The aim of this first-in-man study was to investigate the feasibility of intraoperative 68Ga-PSMA CLI. In this study, feasibility was defined as the ability to distinguish between a positive and negative surgical margin, imaging within 45 min and low radiation exposure to staff.

Methods
Six patients were included in this ongoing study. Following perioperative i.v. injection of ~ 100 MBq 68Ga-PSMA, the prostate was excised and immediately imaged ex vivo. Different acquisition protocols were tested, and hotspots on CLI images from the intact prostate were marked for comparison with histopathology.

Results
By using an acquisition protocol with 150 s exposure time, 8 × 8 binning and a 550 nm shortpass filter, PSMs and negative surgical margins (NSMs) were visually correctly identified on CLI in 3 of the 5 patients. Two patients had a hotspot on CLI from cancer < 0.1 mm from the excision margin.

Conclusion
Overall, the study showed that 68Ga-PSMA CLI is a feasible and low-risk technique for intraoperative margin assessment in PCa. The remaining patients in this ongoing study will be used to assess the diagnostic accuracy of the technique.
Trial registration: NL8256 registered at www.trialregister.nl on 04/11/20109.