bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovering the pharmacodynamics of conolidine and cannabidiol using a cultured neuronal network based workflow
Authors: Mendis G. D. C. , Berecki G. , Morrisroe E. , Pachernegg S. , Li M. , Varney M. , Osborne P. B. , Reid C. A. , Halgamuge S. , Petrou S. 
Published: January 2019

AbstractDetermining the mechanism of action (MOA) of novel or naturally occurring compounds mostly relies on assays tailored for individual target proteins. Here we explore an alternative approach based on pattern matching response profiles obtained using cultured neuronal networks. Conolidine and cannabidiol are plant-derivatives with known antinociceptive activity but unknown MOA. Application of conolidine/cannabidiol to cultured neuronal networks altered network firing in a highly reproducible manner and created similar impact on network properties suggesting engagement with a common biological target. We used principal component analysis (PCA) and multi-dimensional scaling (MDS) to compare network activity profiles of conolidine/cannabidiol to a series of well-studied compounds with known MOA. Network activity profiles evoked by conolidine and cannabidiol closely matched that of ω-conotoxin CVIE, a potent and selective Cav2.2 calcium channel blocker with proposed antinociceptive action suggesting that they too would block this channel. To verify this, Cav2.2 channels were heterologously expressed, recorded with whole-cell patch clamp and conolidine/cannabidiol was applied. Remarkably, conolidine and cannabidiol both inhibited Cav2.2, providing a glimpse into the MOA that could underlie their antinociceptive action. These data highlight the utility of cultured neuronal network-based workflows to efficiently identify MOA of drugs in a highly scalable assay.
Multi-step planning of eye movements in visual search
Authors: Hoppe David , Rothkopf Constantin A. 
Published: January 2019

AbstractThe capability of directing gaze to relevant parts in the environment is crucial for our survival. Computational models have proposed quantitative accounts of human gaze selection in a range of visual search tasks. Initially, models suggested that gaze is directed to the locations in a visual scene at which some criterion such as the probability of target location, the reduction of uncertainty or the maximization of reward appear to be maximal. But subsequent studies established, that in some tasks humans instead direct their gaze to locations, such that after the single next look the criterion is expected to become maximal. However, in tasks going beyond a single action, the entire action sequence may determine future rewards thereby necessitating planning beyond a single next gaze shift. While previous empirical studies have suggested that human gaze sequences are planned, quantitative evidence for whether the human visual system is capable of finding optimal eye movement sequences according to probabilistic planning is missing. Here we employ a series of computational models to investigate whether humans are capable of looking ahead more than the next single eye movement. We found clear evidence that subjects’ behavior was better explained by the model of a planning observer compared to a myopic, greedy observer, which selects only a single saccade at a time. In particular, the location of our subjects’ first fixation differed depending on the stimulus and the time available for the search, which was well predicted quantitatively by a probabilistic planning model. Overall, our results are the first evidence that the human visual system’s gaze selection agrees with optimal planning under uncertainty.
Ablation of brainstem C1 neurons improves cardiac function in volume overload heart failure
Authors: Andrade David C. , Toledo Camilo , Díaz Hugo S. , Lucero Claudia , Arce-Álvarez Alexis , Oliveira Luiz M. , Takakura Ana C. , Moreira Thiago S. , Schultz Harold D. , Marcus Noah J. , Alcayaga Julio , Del Rio Rodrigo 
Published: January 2019

Abstract
Activation of the sympathetic nervous system is a hallmark of heart failure (HF) and is positively correlated with disease progression. Catecholaminergic (C1) neurons located in the rostral ventrolateral medulla (RVLM) are known to modulate sympathetic outflow and are hyperactivated in volume overload HF. However, there is no conclusive evidence showing a contribution of RVLM-C1 neurons to the development of cardiac dysfunction in the setting of HF. Therefore, the aim of this study was to determine the role of RVLM-C1 neurons in cardiac autonomic control and deterioration of cardiac function in HF rats. A surgical arteriovenous shunt was created in adult male Sprague-Dawley rats to induce HF. RVLM-C1 neurons were selectively ablated using cell-specific immunotoxin (dopamine-β hydroxylase saporin [DβH-SAP]) and measures of cardiac autonomic tone, function, and arrhythmia incidence were evaluated. Cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction were present in HF rats and improved after DβH-SAP toxin treatment. Most importantly, the progressive decline in fractional shortening observed in HF rats was reduced by DβH-SAP toxin. Our results unveil a pivotal role played by RVLM-C1 neurons in cardiac autonomic imbalance, arrhythmogenesis and cardiac dysfunction in volume overload-induced HF.
Three‐hot‐wire acoustic particle velocity sensor with improved detection capability
Authors: Li Zhe , Chang Wenhan , Gao Chengchen , Hao Yilong 
Published: January 2019

This Letter proposes a novel 3‐hot‐wire acoustic particle velocity sensor with high sensitivity and low self‐noise for the first time. Three parallel wires, covered with platinum film, are suspended on silicon substrate by MEMS process. The middle wire works as a heater and the left and right ones work as both heaters and temperature sensors. Compared with the 1‐hot‐wire and 2‐hot‐wire counterparts, this sensor has higher sensitivity and lower self‐noise, showing its potential for sound source localisation, acoustic camera and so on. The self‐noise of the sensor is about at 1 kHz and the relative direction sensitivity is as high as 42 dB.
Effect of epitaxial layer's thickness on spectral response of 4H‐SiC p‐i‐n ultraviolet photodiodes
Authors: Hou Yansong , Sun Cunzhi , Wu Junkang , Hong Rongdun , Cai Jiafa , Chen Xiaping , Lin Dingqu , Wu Zhengyun 
Published: January 2019

4H‐SiC ultraviolet p‐i‐n photodiodes with four different epitaxial structures were fabricated. The experimental results prove that both a thin P+‐type Ohmic contact layer and a thick intrinsic layer were indispensible for a high‐performance ultraviolet p‐i‐n photodiode. A 4H‐SiC p‐i‐n photodiode with responsivity as high as 0.139 A/W at 278 nm incident wavelength was achieved. Meanwhile, within a certain wavelength range, the peak response wavelength of an ultraviolet p‐i‐n photodiode would be modulated by properly varying the thicknesses of P+‐type layer and the intrinsic layer. Moreover, the theoretical calculation was carried out to further authorise the experimental results.
Investigating the presence of two belts in the HD 15115 system
Authors: Engler N. , Boccaletti A. , Schmid H. M. , Milli J. , Augereau J.-C. , Mazoyer J. , Maire A.-L. , Henning T. , Avenhaus H. , Baudoz P. , Feldt M. , Galicher R. , Hinkley S. , Lagrange A.-M. , Mawet D. , Olofsson J. , Pantin E. , Perrot C. , Stapelfeldt K. 
Published: January 2019

Context.High-contrast instruments like SPHERE (Spectro- Polarimetric High-contrast Exoplanet REsearch) enable spatial resolution of young planetary systems and allow us to study the connection between planets and the dust contained in debris discs by the gravitational influence a planet can have on its environment.Aims.We present new observations of the edge-on debris disc around HD 15115 (F star at 48.2 pc) obtained in the near-IR. We search for observational evidence for a second inner planetesimal ring in the system.Methods.We obtained total intensity and polarimetric data in the broad bandsJandHand processed the data with differential imaging techniques achieving an angular resolution of about 40 mas. A grid of models describing the spatial distribution of the grains in the disc is generated to constrain the geometric parameters of the disc and to explore the presence of a second belt. We perform a photometric analysis of the data and compare disc brightness in two bands in scattered and in polarized light.Results.We observe an axisymmetric planetesimal belt with a radius of ~2′′, an inclination of 85.8° ± 0.7° and position angle of 278.9° ± 0.1°. The photometric analysis shows that the west side is ~2.5 times brighter in total intensity than the east side in both bands, while for polarized light in theJband this ratio is only 1.25. We also find that theJ–Hcolour of the disc appears to be red for the radial separationsr≲ 2′′ and is getting bluer for the larger separations. The maximum polarization fraction is 15–20% atr~ 2.5′′. The polarized intensity image shows some structural features inside the belt which can be interpreted as an additional inner belt.Conclusions.The apparent change of disc colour from red to blue with an increasing radial separation from the star could be explained by the decreasing average grain size with distance. The presence of an inner belt slightly inclined with respect to the main planetesimal belt is suspected from the data but the analysis and modelling presented here cannot establish a firm conclusion due to the faintness of the disc and its high inclination.
A deep X-ray view of the bare AGN Ark 120
Authors: Porquet D. , Done C. , Reeves J. N. , Grosso N. , Marinucci A. , Matt G. , Lobban A. , Nardini E. , Braito V. , Marin F. , Kubota A. , Ricci C. , Koss M. , Stern D. , Ballantyne D. , Farrah D. 
Published: January 2019

Context. The spin of supermassive black holes (SMBH) in active galactic nuclei (AGN) can be determined from spectral signature(s) of relativistic reflection such as the X-ray iron Kα line profile, but this can be rather uncertain when the line of sight intersects the so-called warm absorber and/or other wind components as these distort the continuum shape. Therefore, AGN showing no (or very weak) intrinsic absorption along the line-of-sight such as Ark 120, a so-called bare AGN, are the ideal targets for SMBH spin measurements. However, in our previous work on Ark 120, we found that its 2014 X-ray spectrum is dominated by Comptonisation, while the relativistic reflection emission only originates at tens of gravitational radii from the SMBH. As a result, we could not constrain the SMBH spin from disc reflection alone.
Aims. Our aim is to determine the SMBH spin in Ark 120 from an alternative technique based on the global energetics of the disc-corona system. Indeed, the mass accretion rate (Ṁ) through the outer disc can be measured from the optical-UV emission, while the bolometric luminosity (Lbol) can be fairly well constrained from the optical to hard X-rays spectral energy distribution, giving access to the accretion efficiency η = Lbol/(Ṁc2) which depends on the SMBH spin.
Methods. The spectral analysis uses simultaneous XMM-Newton (OM and pn) and NuSTAR observations on 2014 March 22 and 2013 February 18. We applied the OPTXCONV model (based on OPTXAGNF) to self consistently reproduce the emission from the inner corona (warm and hot thermal Comptonisation) and the outer disc (colour temperature corrected black body), taking into account both the disc inclination angle and relativistic effects. For self-consistency, we modelled the mild relativistic reflection of the incident Comptonisation components using the XILCONV convolution model.
Results. We infer a SMBH spin of 0.83+0.05−0.03, adopting the SMBH reverberation mass of 1.50 × 108 M⊙. In addition, we find that the coronal radius decreases with increasing flux (by about a factor of two), from 85+13−10Rg in 2013 to 14 ± 3 Rg in 2014.
Conclusions. This is the first time that such a constraint is obtained for a SMBH spin from this technique, thanks to the bare properties of Ark 120, its well determined SMBH reverberation mass, and the presence of a mild relativistic reflection component in 2014 which allows us to constrain the disc inclination angle. We caution that these results depend on the detailed disc-corona structure, which is not yet fully established. However, the realistic parameter values (e.g. Lbol/LEdd, disc inclination angle) found suggest that this is a promising method to determine spin in moderate-Ṁ AGN.
The puzzle of transparency and how to solve it
Authors: Barz Wolfgang 
Published: January 2019

AbstractAccording to the transparency approach, achievement of self-knowledge is a two-stage process: first, the subject arrives at the judgment ‘p’; second, the subject proceeds to the judgment ‘I believe thatp.’ The puzzle of transparency is to understand why the transition from the first to the second judgment is rationally permissible. After revisiting the debate between Byrne and Boyle on this matter, I present a novel solution according to which the transition is rationally permissible in virtue of a justifying argument that begins from a premise referring to the mental utterance that is emitted in the course of judging ‘p.’
Mindfulness, Experiential Avoidance, and Recovery From Hematopoietic Stem Cell Transplantation
Authors: Larson Anna G , Morris Keayra J , Juckett Mark B , Coe Christopher L , Broman Aimee T , Costanzo Erin S 
Published: January 2019

AbstractBackgroundMood disturbance, pain, and fatigue are prevalent and distressing concerns for patients with hematologic cancer recovering from hematopoietic stem cell transplantation (HSCT). The way in which individuals approach difficult thoughts and emotions may affect symptoms and functioning. Specifically, mindfulness has been associated with more optimal psychological and physical functioning, whereas experiential avoidance has been associated with poorer outcomes.PurposeThe primary objective was to determine whether mindfulness and experiential avoidance measured prior to HSCT were associated with recovery of psychological and physical functioning following HSCT. We also evaluated dimensions of mindfulness to determine which were most robustly associated with outcomes.MethodsParticipants completed measures of mindfulness and experiential avoidance prior to HSCT. Depression and anxiety symptoms and pain and fatigue interference with daily activities were assessed prior to HSCT and 1, 3, and 6 months post-HSCT.ResultsParticipants who reported better ability to describe their internal experiences and who were better able to act with awareness experienced less depression, anxiety, and fatigue interference following HSCT. Participants who were nonjudgmental and nonreactive toward thoughts and emotions experienced less depression and anxiety following HSCT, but these traits were not associated with pain or fatigue interference. Being a good observer of internal experiences was not associated with outcomes, nor was experiential avoidance.ConclusionsResults suggest that most facets of mindfulness may optimize psychological functioning following HSCT, and the ability to describe one’s internal experience and to focus on the present moment may have a beneficial influence on physical functioning.
Intersemiotic Translation, Cognitive Artefact, and Creativity
Authors: Queiroz João , Atã Pedro 
Published: January 2019

AbstractIntersemiotic translation (IT) can be described as a cognitive artefact designed as a predictive, generative, and metasemiotic tool that distributes artistic creativity. Cognitive artefacts have a huge variety of forms and are manipulated in many different ways and domains. As a projective augmented intelligence technique, IT works as a predictive tool, anticipating new, and surprising patterns of semiotic events and processes, keeping under control the emergence of new patterns. At the same time, it works as a generative model, providing new, unexpected, surprising data in the target-system,​​ and affording competing results​ ​which allow the system to generate candidate instances. As a metasemiotic tool, IT creates a metalevel semiotic process, a sign-action which stands for the action of a sign. It creates an ‘experimental laboratory’ for performing semiotic experiments. IT submits semiotic systems to unusual conditions and provides a scenario for observing the emergence of new and surprising semiotic behaviour as a result. We explore these ideas taking advantage of two examples of ITs to theatrical dance: (1) from one-point visual perspective to classical ballet and (2) from John Cage’s protocols of music indeterminacy to Merce Cunningham’s choreographic composition.
Added Value of Aortic Pulse Wave Velocity Index in a Predictive Diagnosis Decision Tree of Coronary Heart Disease
Authors: Vallée Alexandre , Petruescu Laura , Kretz Sandrine , Safar Michel E , Blacher Jacques 
Published: January 2019

Abstract

BACKGROUND
Coronary heart disease (CHD) is among the main causes of death in the world. Individual study of cardiovascular risk is an important way to predict CHD risk. The aim of this study was to evaluate the added role of the aortic pulse wave velocity (PWV) index in the prediction of CHD risk.

METHODS
A cross-sectional study was conducted from December 2012 to September 2017; 530 patients were included: 99 CHD, 338 non-CHD patients, and 93 nonhypertensives, nondiabetics and non-CHD subjects, whose theoretical PWV were calculated. Theoretical PWV was calculated according to age, blood pressure, gender, and heart rate. The results were expressed as an index ((measured PWV − theoretical PWV)/theoretical PWV) for each patient. The differences observed, the differential diagnostic performance, and the quantification of the added value of diagnostic performance of PWV index were tested using logistic regression, comparisons between receiver operating characteristic (ROC) curves, and decision tree nonlinear methodology.

RESULTS
PWV index (P = 0.006), carotid plaque (P = 0.005), and dyslipidemia (P = 0.04) were the independent modulators of CHD diagnosis. PWV index appears to be the highest specific classifier (81%) compared to carotid plaque (75%) and dyslipidemia (78%). For the decision tree, sensitivity, specificity, and area under the ROC curve for CHD diagnosis were 62%, 83%, and 0.87, respectively.

CONCLUSIONS
PWV index yielded added value to CHD by assessment of combined classifiers with clinical determinants and decision tree construction and significantly increased the specificity of the differential diagnostic performances of the common risk factors of CHD in daily clinical practice.
High SNP diversity in the non-toxic indigenous Jatropha curcas germplasm widens the potential of this upcoming major biofuel crop species
Authors: Vandepitte K , Valdés-Rodríquez O A , Sánchez-Sánchez O , De Kort H , Martinez-Herrera J , García-Pérez E , De Meyer T , Pérez-Vázquez A , Muys B , Honnay O 
Published: January 2019

AbstractBackground and AimsJatropha curcas (jatropha) is an oil crop cultivated in (sub)tropical regions around the world, and holds great promise as a renewable energy source. However, efforts to fully commercialize jatropha are currently hampered by the lack of genetic diversity in the extant breeding germplasm, and by the toxicity of its seeds meaning that its seed cake cannot be used as a protein source in animal feed, among other constraints. In Mexico, the species’ native range, there are jatropha plants whose seeds are used to prepare traditional meals. This non-toxic jatropha ‘type’ is considered to harbour low genetic variation due to a presumed domestication bottleneck and therefore to be of limited breeding value; yet, very little is known regarding its origin and genetic diversity.MethodsUsing genotyping-by-sequencing (GBS), we extensively genotyped both indigenous toxic and non-toxic jatropha collected along roads and home gardens throughout southern Mexico.Key ResultsSingle nucleotide polymorphism diversity in non-toxic jatropha is relatively high, particularly in northern Veracruz state, the probable origin of this germplasm. Genetic differences between toxic and non-toxic indigenous genotypes are overall quite small. A a genome-wide association study supported a genomic region (on LG 8, scaffold NW_012130064), probably involved in the suppression of seed toxicity.ConclusionsConservation actions are urgently needed to preserve this non-toxic indigenous, relatively wild germplasm, having potential as a fuel feedstock, animal feed and food source among other uses. More generally, this work demonstrates the value of conservation genomic research on the indigenous gene pool of economically important plant species.
Effects of macrophage depletion on characteristics of cervix remodeling and pregnancy in CD11b-dtr mice
Authors: Yellon S M , Greaves E , Heuerman A C , Dobyns A E , Norman J E 
Published: January 2019

Abstract
To test the hypothesis that macrophages are essential for remodeling the cervix in preparation for birth, pregnant homozygous CD11b-dtr mice were injected with diphtheria toxin (DT) on days 14 and 16 postbreeding. On day 15 postbreeding, macrophages (F4/80+) were depleted in cervix and kidney, but not in liver, ovary, or other non-reproductive tissues in DT—compared to saline—treated dtr mice or wild-type controls given DT or saline. Within 24 h of DT-treatment, the density of cell nuclei and macrophages declined in cervix stroma in dtr mice versus controls, but birefringence of collagen, as an indication of extracellular cross-linked structure, remained unchanged. Only in the cervix of DT-treated dtr mice was an apoptotic morphology evident in macrophages. DT-treatment did not alter the sparse presence or morphology of neutrophils. By day 18 postbreeding, macrophages repopulated the cervix in DT-treated dtr mice so that the numbers were comparable to that in controls. However, at term, evidence of fetal mortality without cervix ripening occurred in most dtr mice given DT—a possible consequence of treatment effects on placental function. These findings suggest that CD11b+ F4/80+ macrophages are important to sustain pregnancy and are required for processes that remodel the cervix in preparation for parturition.
Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach
Authors: Liu Chang , Hu Xu , Li Yawen , Lu Wenjie , Li Wenlin , Cao Nan , Zhu Saiyong , Cheng Jinke , Ding Sheng , Zhang Mingliang 
Published: January 2019

AbstractTransplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity. By modulating the culture signaling recapitulating the principle of OPC development, these intermediate cells could be reprogrammed towards OPC fate. The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology, gene expression, and the ability of self-renewal. Upon differentiation, ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro, validating their OPC identity molecularly and functionally. Therefore, our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy.