bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macroscopic Chiral Recognition by Calix[4]arene‐Based Host–Guest Interactions
Authors: Quan Jiaxin , Nie Guanrong , Xue Hong , Luo Li , Zhang Ruiping , Li Haibing 
Published: August 2018

AbstractChiral recognition as an intrinsic process of life, plays a crucial role in chemical systems, and further forms various architectures in the resulted functional materials. So far, relevant studies were focused on the recognition of chiral molecules. However, weak chiral interactions transformed into macroscopic recognition, for example, for chiral drug droplets, is much more crucial due to its applicability in controlling the drugs′ selective delivery and for their enantiomer separation. In this report, chiral calix[4]arene was introduced onto a surface for the selective recognition of (S)‐naproxen droplet through host–guest interactions.
A Tautoleptic Approach to Chiral Hydrogen‐Bonded Supramolecular Tubular Polymers with Large Cavity
Authors: Neniškis Algirdas , Račkauskaitė Dovilė , Shi Qixun , Robertson Aiden J. , Marsh Andrew , Ulčinas Artūras , Valiokas Ramūnas , Brown Steven P. , Wärnmark Kenneth , Orentas Edvinas 
Published: August 2018

AbstractA new strategy towards tubular hydrogen‐bonded polymers based on the self‐assembly of isocytosine tautomers in orthogonal directions is proposed and experimentally verified, including by 1H fast magic‐angle spinning (MAS) solid‐state NMR. The molecular tubes obtained possess large internal diameter and tailor‐made outer functionalities rendering them potential candidates for a number of applications.
An Endogenous Reactive Oxygen Species (ROS)‐Activated Histone Deacetylase Inhibitor Prodrug for Cancer Chemotherapy
Authors: Bhagat Somnath D. , Singh Usha , Mishra Ram Kumar , Srivastava Aasheesh 
Published: August 2018

AbstractSuberoylanilide hydroxamic acid (SAHA, vorinostat) is a potent small‐molecule pan‐inhibitor of histone deacetylases (HDACs) approved for treatment of cutaneous T‐cell lymphoma (CTCL). However, SAHA exhibits poor selectivity for cancer cells over noncancer cells. With an aim to improving its selectivity for cancer cells, we generated a novel SAHA prodrug (SAHA‐OBP) that is activated in the presence of hydrogen peroxide, a reactive oxygen species (ROS) known to be overexpressed in cancer cells. The high endogenous ROS content in cancer cells triggers rapid removal of the 4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)benzyl carbonyl (OBP) cap to release active SAHA. The SAHA‐OBP prodrug demonstrates selective activity against multiple cancer cell lines such as HeLa, MCF‐7, MDA‐MB‐231, and B16‐F10, while remaining benign toward noncancer cells. The downstream effects of SAHA released from SAHA‐OBP in cancer cells is the induction of apoptosis. SAHA‐OBP was also found to be effective on multicellular tumor spheroids (MCTS). The SAHA prodrug designed in this study undergoes rapid ROS‐dependent activation and imparts much‐needed selectivity to SAHA for cancer cells.
Exploration of Sulfur‐Containing Analogues for Imaging Vesicular Acetylcholine Transporter in the Brain
Authors: Luo Zonghua , Liu Hui , Jin Hongjun , Gu Jiwei , Yu Yanbo , Kaneshige Kota , Perlmutter Joel S. , Parsons Stanley M. , Tu Zhude 
Published: August 2018

AbstractSixteen new sulfur‐containing compounds targeting the vesicular acetylcholine transporter (VAChT) were synthesized and assessed for in vitro binding affinities. Enantiomers (−)‐(1‐(3‐hydroxy‐1,2,3,4‐tetrahydronaphthalen‐2‐yl)piperidin‐4‐yl)(4‐(methylthio)phenyl)methanone [(−)‐8] and (−)‐(4‐((2‐fluoroethyl)thio)phenyl)(1‐(3‐hydroxy‐1,2,3,4‐tetrahydronaph‐thalen‐2‐yl)piperidin‐4‐yl)methanone [(−)‐14 a] displayed high binding affinities, with respective Ki values of 1.4 and 2.2 nm for human VAChT, moderate and high selectivity for human VAChT over σ1 (≈13‐fold) and σ2 receptors (>420‐fold). Radiosyntheses of (−)‐[11C]8 and (−)‐[18F]14 a were achieved using conventional methods. Ex vivo autoradiography and biodistribution studies in Sprague–Dawley rats indicated that both radiotracers have the capacity to penetrate the blood–brain barrier, with high initial brain uptake at 5 min and rapid washout. The striatal region had the highest accumulation for both radiotracers. Pretreating the rats with the VAChT ligand (−)‐vesamicol decreased brain uptake for both radiotracers. Pretreating the rats with the σ1 ligand YUN‐122 (N‐(4‐benzylcyclohexyl)‐2‐(2‐fluorophenyl)acetamide) also decreased brain uptake, suggesting these two radiotracers also bind to the σ1 receptor in vivo. The microPET study of (−)‐[11C]8 in the brain of a non‐human primate showed high striatal accumulation that peaked quickly and washed out rapidly. Although preliminary results indicated these two sulfur‐containing radiotracers have high binding affinities for VAChT with rapid washout kinetics from the striatum, their σ1 receptor binding properties limit their potential as radiotracers for quantifying VAChT in vivo.
RASPELD to Perform High‐End Screening in an Academic Environment toward the Development of Cancer Therapeutics
Authors: Wolle Patrik , Weisner Jörn , Keul Marina , Landel Ina , Lategahn Jonas , Rauh Daniel 
Published: August 2018

AbstractThe identification of compounds for dissecting biological functions and the development of novel drug molecules are central tasks that often require screening campaigns. However, the required architecture is cost‐ and time‐intensive. Herein we describe the devices and technologies that comprise a Robotics‐Assisted Screening Platform for Efficient Ligand Discovery (RASPELD), which we set up in an academic laboratory. RASPELD provides semi‐automated high‐end screening, and it can be maintained by graduate students. We demonstrate its successful application in biochemical and cellular screens for the identification and validation of bioactive chemical entities as candidate cancer‐relevant inhibitors. Specifically, we examined the interaction between a transcription factor, Nrf2, and its key regulator, Keap1. We also examined drug‐resistant mutants of the epidermal growth factor receptor (EGFR). Screening campaigns with more than 30 000 compounds were performed in a reasonable period of time. We identified the molecule RSL6586 as a starting point for hit optimization, which is currently ongoing.
Identification of α‐Mangostin as an Agonist of Human STING
Authors: Zhang Yibo , Sun Zhen , Pei Jianwen , Luo Qinhong , Zeng Xin , Li Qinkai , Yang Zhen , Quan Junmin 
Published: August 2018

AbstractThe xanthone derivate 5′,6′‐dimethylxanthenone‐4‐acetic acid (DMXAA, also known as ASA404 or vadimezan) is a potent agonist of murine STING (stimulator of interferon genes), but cannot activate human STING. Herein we report that α‐mangostin, which bears the xanthone skeleton, is an agonist of human STING, but activates murine STING to a lesser extent. Biochemical and cell‐based assays indicate that α‐mangostin binds to and activates human STING, leading to activation of the downstream interferon regulatory factor (IRF) pathway and production of type I interferons. Furthermore, our studies show that α‐mangostin has the potential to repolarize human monocyte‐derived M2 macrophages to the M1 phenotype. The agonist effect of α‐mangostin in the STING pathway might account for its antitumor and antiviral activities.
Genetic access to neurons in the accessory optic system reveals a role for Sema6A in midbrain circuitry mediating motion perception
Authors: Lilley Brendan N. , Sabbah Shai , Hunyara John L. , Gribble Katherine D. , Al‐Khindi Timour , Xiong Jiali , Wu Zhuhao , Berson David M. , Kolodkin Alex L. 
Published: August 2018

AbstractThe accessory optic system (AOS) detects retinal image slip and reports it to the oculomotor system for reflexive image stabilization. Here, we characterize two Cre lines that permit genetic access to AOS circuits responding to vertical motion. The first (Pcdh9‐Cre) labels only one of the four subtypes of ON direction‐selective retinal ganglion cells (ON‐DS RGCs), those preferring ventral retinal motion. Their axons diverge from the optic tract just behind the chiasm and selectively innervate the medial terminal nucleus (MTN) of the AOS. Unlike most RGC subtypes examined, they survive after optic nerve crush. The second Cre‐driver line (Pdzk1ip1‐Cre) labels postsynaptic neurons in the MTN. These project predominantly to the other major terminal nucleus of the AOS, the nucleus of the optic tract (NOT). We find that the transmembrane protein semaphorin 6A (Sema6A) is required for the formation of axonal projections from the MTN to the NOT, just as it is for the retinal innervation of the MTN. These new tools permit manipulation of specific circuits in the AOS and show that Sema6A is required for establishing AOS connections in multiple locations.
Features of the structure, development, and activity of the zebrafish noradrenergic system explored in new CRISPR transgenic lines
Authors: Farrar Matthew J. , Kolkman Kristine E. , Fetcho Joseph R. 
Published: August 2018

AbstractThe noradrenergic (NA) system of vertebrates is implicated in learning, memory, arousal, and neuroinflammatory responses, but is difficult to access experimentally. Small and optically transparent, larval zebrafish offer the prospect of exploration of NA structure and function in an intact animal. We made multiple transgenic zebrafish lines using the CRISPR/Cas9 system to insert fluorescent reporters upstream of slc6a2, the norepinephrine transporter gene. These lines faithfully express reporters in NA cell populations, including the locus coeruleus (LC), which contains only about 14 total neurons. We used the lines in combination with two‐photon microscopy to explore the structure and projections of the NA system in the context of the columnar organization of cell types in the zebrafish hindbrain. We found robust alignment of NA projections with glutamatergic neurotransmitter stripes in some hindbrain segments, suggesting orderly relations to neuronal cell types early in life. We also quantified neurite density in the rostral spinal cord in individual larvae with as much as 100% difference in the number of LC neurons, and found no correlation between neuronal number in the LC and projection density in the rostral spinal cord. Finally, using light sheet microscopy, we performed bilateral calcium imaging of the entire LC. We found that large‐amplitude calcium responses were evident in all LC neurons and showed bilateral synchrony, whereas small‐amplitude events were more likely to show interhemispheric asynchrony, supporting the potential for targeted LC neuromodulation. Our observations and new transgenic lines set the stage for a deeper understanding of the NA system.
Neuroarchitecture of the Drosophila central complex: A catalog of nodulus and asymmetrical body neurons and a revision of the protocerebral bridge catalog
Authors: Wolff Tanya , Rubin Gerald M. 
Published: August 2018

AbstractThe central complex, a set of neuropils in the center of the insect brain, plays a crucial role in spatial aspects of sensory integration and motor control. Stereotyped neurons interconnect these neuropils with one another and with accessory structures. We screened over 5,000 Drosophila melanogaster GAL4 lines for expression in two neuropils, the noduli (NO) of the central complex and the asymmetrical body (AB), and used multicolor stochastic labeling to analyze the morphology, polarity, and organization of individual cells in a subset of the GAL4 lines that showed expression in these neuropils. We identified nine NO and three AB cell types and describe them here. The morphology of the NO neurons suggests that they receive input primarily in the lateral accessory lobe and send output to each of the six paired noduli. We demonstrate that the AB is a bilateral structure which exhibits asymmetry in size between the left and right bodies. We show that the AB neurons directly connect the AB to the central complex and accessory neuropils, that they target both the left and right ABs, and that one cell type preferentially innervates the right AB. We propose that the AB be considered a central complex neuropil in Drosophila. Finally, we present highly restricted GAL4 lines for most identified protocerebral bridge, NO, and AB cell types. These lines, generated using the split‐GAL4 method, will facilitate anatomical studies, behavioral assays, and physiological experiments.
Cortical projections to the two retinotopic maps of primate pulvinar are distinct
Authors: Moore Brandon , Li Keji , Kaas Jon H. , Liao Chia‐Chi , Boal Andrew M. , Mavity‐Hudson Julia , Casagrande Vivien 
Published: August 2018

AbstractComprised of at least five distinct nuclei, the pulvinar complex of primates includes two large visually driven nuclei; one in the dorsal (lateral) pulvinar and one in the ventral (inferior) pulvinar, that contain similar retinotopic representations of the contralateral visual hemifield. Both nuclei also appear to have similar connections with areas of visual cortex. Here we determined the cortical connections of these two nuclei in galagos, members of the stepsirrhine primate radiation, to see if the nuclei differed in ways that could support differences in function. Injections of different retrograde tracers in each nucleus produced similar patterns of labeled neurons, predominately in layer 6 of V1, V2, V3, MT, regions of temporal cortex, and other visual areas. More complete labeling of neurons with a modified rabies virus identified these neurons as pyramidal cells with apical dendrites extending into superficial cortical layers. Importantly, the distributions of cortical neurons projecting to each of the two nuclei were highly overlapping, but formed separate populations. Sparse populations of double‐labeled neurons were found in both V1 and V2 but were very low in number (<0.1%). Finally, the labeled cortical neurons were predominately in layer 6, and layer 5 neurons were labeled only in extrastriate areas. Terminations of pulvinar projections to area 17 was largely in superficial cortical layers, especially layer 1.
Open‐Label, Crossover Study to Determine the Pharmacokinetics of Fluticasone Furoate and Batefenterol When Administered Alone, in Combination, or Concurrently
Authors: Ambery Claire , Young Graeme , Fuller Teresa , Georgiou Alex , Ramsay David , Puri Adeep , Daley‐Yates Peter 
Published: August 2018

AbstractThe study aim was to investigate the pharmacokinetics of single high doses and repeated therapeutic doses of fluticasone furoate (FF) and batefenterol (BAT; a bifunctional muscarinic antagonist and β2‐agonist) administered in combination (BAT/FF) or as monotherapy. In this open‐label, 6‐period, crossover study of 48 subjects, the treatment sequences were (1) single high‐dose BAT/FF 900/300 μg followed by repeated therapeutic doses of BAT/FF 300/100 μg (once daily for 7 days); (2) single high‐dose BAT 900 μg administered concurrently with FF 300 μg; (3) single high‐dose BAT 900 μg followed by repeated therapeutic‐dose BAT 300 μg; (4) single high‐dose FF 300 μg followed by repeated therapeutic‐dose FF 100 μg; (5) single high‐dose FF 300 μg (magnesium stearate); and (6) single high‐dose FF/vilanterol 300/75 μg. Plasma FF area under the plasma drug concentration‐time curve (AUC) was reduced after single high‐dose BAT/FF versus FF alone (ratio of geometric least squares means: 0.79; 90% confidence interval: 0.75‐0.83). After repeat dosing, FF AUC at the lower therapeutic dosage was similar for BAT/FF and FF (primary endpoint; AUC geometric least squares means: 1.03). Adverse events were minor, the most common being cough. These data support the feasibility of developing BAT/inhaled corticosteroid triple therapy in a single inhaler.
Heterogeneous distributed computing based on high‐level abstractions
Authors: Viñas M. , Fraguela B. B. , Andrade D. , Doallo R. 
Published: August 2018

SummaryThe rise of heterogeneous systems has given place to great challenges for users as they involve new concepts, restrictions, and frameworks. Their exploitation is further complicated in the context of distributed memory systems, which require the usage of additional different programming paradigms and tools. In this paper, we propose a novel approach to program heterogeneous clusters that is based on high‐level abstractions such as tiles and hierarchical decomposition combined with the powerful APIs that data types and embedded languages can provide in languages such as C++. Rather than building our proposal from scratch, we have implemented it as a natural integration of the existing Hierarchically Tiled Arrays (HTA) and Heterogeneous Programming Library (HPL) projects, ie, the first one being focused on distributed computing and the second one on heterogeneous processing. The result, called Heterogeneous Hierarchically Tiled Arrays (H2TA), is very intuitive and easy to use thanks to the global view of the data and the single‐threaded view of the execution that it provides at cluster level together with the transparency it provides with respect to the management of the heterogeneous devices. An evaluation comparing our proposal with MPI‐based implementations shows its large programmability advantages and the reasonable overhead incurred.
A new quality assessment for Thangka image inpainting
Authors: Hu Wenjin , Liu Zhongmin , Ye Yuqi 
Published: August 2018

SummaryThis paper presents an efficient metric for evaluation the effect of the inpainted Thangka images. In contrast to standard image quality metrics, the proposed one takes into account some constraints and characteristics related to the specific goals of inpainting techniques. The key is that we proposed a method to decompose the reference and distorted image and to compare the intensity of fuzzy edge for structure component and similarity for texture component. By comparative analyzing the experimental results with other metrics, the proposed image inpainting quality index delivers high consistency with subjective evaluation results, which will help the selecting algorithm in image restoration and could be also applied to most of inpainting image approaches.
Ionic Liquids Derived from Proline: Application as Surfactants
Authors: Fernández‐Stefanuto Verónica , Corchero Raquel , Rodríguez‐Escontrela Iria , Soto Ana , Tojo Emilia 
Published: August 2018

AbstractIonic liquids derived from prolinium esters, previously described as fully green and stable, were found to decompose in the presence of water by ester hydrolysis. To avoid this problem, a new family of these biodegradable salts incorporating an alcohol instead of the ester group is proposed. From this family, two novel ionic liquids that incorporate the prolinolium cation [HOPro] and the [DS] or [DBS] anion were selected (DS=dodecylsulfate; DBS=dodecylbenzenesulfonate). Both salts are liquid at room temperature, a property not usually found in ionic surfactants, and are also chemically and thermally stable. Moreover, they are more effective in reducing the surface tension of water than the corresponding traditional surfactants in the form of sodium salts, being useful for applications related to their aggregation capacity. They were tested for surfactant enhanced oil recovery and an optimal formulation for reservoirs at high salinity and temperature, able to produce ultra‐low interfacial tension, was found with [HOPro][DBS].
Theoretical Study on Open‐Shell Singlet Character and Second Hyperpolarizabilities in Cofacial π‐Stacked Dimers Composed of Weak Open‐Shell Antiaromatic Porphyrins
Authors: Fujiyoshi Jun‐Ya , Tonami Takayoshi , Yamane Masaki , Okada Kenji , Kishi Ryohei , Muhammad Shabbir , Al‐Sehemi Abdullah G. , Nozawa Ryo , Shinokubo Hiroshi , Nakano Masayoshi 
Published: August 2018

AbstractFrom the analysis based on the broken‐symmetry density functional theory (DFT) calculations, we in this study propose a strategy to enhance the open‐shell characters and third‐order nonlinear optical (NLO) properties of π‐stacked dimers composed of antiaromatic molecules with weak open‐shell characters. For this purpose, we here constructed cofacial π‐stacked dimer models composed of aromatic and antiaromatic NiII porphyrins in order to examine the π‐π stacking distance (R) dependence of the diradical characters (y) and static second hyperpolarizabilities (γ). The antiaromatic porphyrin dimers are found to have intermediate y around R∼3.3 Å, the result of which originates in the unique intermolecular interactions between the antiaromatic monomers. Static γ along the stacking direction of such antiaromatic porphyrin dimers with intermediate diradical characters are shown to be enhanced significantly as compared to those of the isolated monomers and the aromatic porphyrin dimers.
Pulsed Electrodeposition of Co3O4 Nanocrystals on One‐Dimensional ZnO Scaffolds for Enhanced Electrochemical Water Oxidation
Authors: Wu Hao , Li Shangyi , Lu Xinxin , Toe Cui Ying , Chung Hoi Ying , Tang Yiming , Lu Xunyu , Amal Rose , Li Laisheng , Ng Yun Hau 
Published: August 2018

AbstractPulsed electrodeposition has been introduced to deposit ultrathin flakes of Co3O4 nanocrystals on ZnO nanorods. By fixing the seeding process, the scaffolding function of ZnO nanorods was studied by varying deposition times (30 s, 60 s, and 90 s) of Co3O4 at a nucleation current of −1.0 mA cm−2. The amount of deposited Co3O4 has a strong influence on the oxygen evolution performance with ZnO scaffolds. To deliver a current density of 10.0 mA cm−2 in neutral solutions (0.5 M K2SO4), the presence of ZnO scaffold electrodes negatively shifted the overpotential by ∼200 mV. In particular, the Co3O4/ZnO hybrid nanostructured electrode (60 s) exhibits the lowest onset potential of 1.5 V (vs. reversible hydrogen electrode, RHE). Electrochemical impedance spectra and double layer capacitance showed that the enhanced oxygen evolution activities originated from the improved charge transfer capability and the increased electrochemically active interface between Co3O4 and ZnO.
[4]Cyclofluorene: Unexpected Influence of Alkyl Chain Length
Authors: Sicard Lambert , Jeannin Olivier , Rault‐Berthelot Joëlle , Quinton Cassandre , Poriel Cyril 
Published: August 2018

AbstractPresented here is the study of a new example of [4]cyclofluorene, with ethyl chains on the bridgeheads. Its molecular structure was established by solution NMR spectroscopy and single‐crystal X‐ray diffraction. Three successive oxidation processes and one reversible reduction were observed through cyclic voltammetry. The optical properties were characterized both in solution and thin film by UV/visible spectroscopy as well as stationary and time‐resolved fluorescence. It was found that this [4]cyclofluorene displays different characteristics compared with the other [4]cyclofluorenes substituted by methyl or propyl chains: a simple modification of the chain length induces a non‐negligible effect on the emission properties, which must be linked to the specific arrangement of the fluorene units. Furthermore, single‐crystal X‐ray diffraction reveals the formation of a pseudo‐tubular solid‐state arrangement of fully symmetrical ring structures, which was not observed for the other members of the [4]cyclofluorenes family. This finding could open the way to modulation of properties of cyclofluorenes through alkyl chain engineering.