cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Parallel Functional Activity Profiling Reveals Valvulopathogens Are Potent 5-Hydroxytryptamine2B Receptor Agonists: Implications for Drug Safety Assessment
Creators: name: Allen, J. A.
name: Revankar, C.
name: Setola, V.
name: Robers, M.
name: Yadav, P. N.
name: Huang, X.-P.
name: Hanson, B. J.
name: Doucette, C.
name: Rogan, S. C.
name: Roth, B. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine2B (5-HT2B) receptor agonists. We have shown that activation of 5-HT2B receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscent of the fibrosis that typifies VHD. To identify current or future drugs that might induce VHD, we screened approximately 2200 U.S. Food and Drug Administration (FDA)-approved or investigational medications to identify 5-HT2B receptor agonists, using calcium-based high-throughput screening. Of these 2200 compounds, 27 were 5-HT2B receptor agonists (hits); 14 of these had previously been identified as 5-HT2B receptor agonists, including seven bona fide valvulopathogens. Six of the hits (guanfacine, quinidine, xylometazoline, oxymetazoline, fenoldopam, and ropinirole) are approved medications. Twenty-three of the hits were then “functionally profiled” (i.e., assayed in parallel for 5-HT2B receptor agonism using multiple readouts to test for functional selectivity). In these assays, the known valvulopathogens were efficacious at concentrations as low as 30 nM, whereas the other compounds were less so. Hierarchical clustering analysis of the pEC50 data revealed that ropinirole (which is not associated with valvulopathy) was clearly segregated from known valvulopathogens. Taken together, our data demonstrate that patterns of 5-HT2B receptor functional selectivity might be useful for identifying compounds likely to induce valvular heart disease.
An overview of HMI off-disk flare observations
Creators: name: Fremstad, Dennis
name: Gómez, Juan Camilo Guevara
name: Hudson, Hugh
name: Oliveros, Juan Carlos Martínez
Publisher: name: arXiv
Year: 2023
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: Instrumentation and Methods for Astrophysics (astro-ph.IM)
subject: FOS: Physical sciences

description: Context: White-light continuum observations of solar flares often have coronal counterparts, including the classical ``white-light prominence'' (WLP) phenomenon. Aims: Coronal emissions by flares, seen in white-light continuum, have only rarely been reported previously. We seek to use modern data to understand the morphology of WLP events. Methods: We have identified a set of 14 examples of WLP detected by the HMI (Heliospheric and Magnetic Imager) experiment on board SDO (the Solar Dynamics Observatory satellite), using a new on-line catalogue covering 2011-2017. These invariably accompanied white-light flares (WLF) emission from the lower atmosphere by flares near the limb, as identified by hard X-ray images from RHESSI (the Reuven Ramaty High Energy Spectroscopic Imager). HMI provides full Stokes information, and we have used the linear polarisations (Q~and~U) to distinguish Thomson scattering from cool material. Results: The event morphologies fit roughly into three categories: Ejection, Loop, and Spike, but many events show multiple phenomena. Conclusions: The coronal white-light continuum, observed by HMI analogously to the observations made by a coronagraph, detects many examples of coronal emission and dynamics. Using the Stokes linear polarisation, we estimate the masses of hot coronal plasma in 11 of the 14 events and find them to be similar to typical CME masses, but not exceeding 10$^{15}$\,g. We note that the HMI observations do not occult the bright solar disk and were not designed for coronal observations, resulting in relatively low signal-to-noise ratios. We therefore believe that future such observations with better optimisation will be even more fruitful.
description: 6 pages, 6 figures, 2 tables, Accepted for publication in A&A
Quantification of Gi-Mediated Inhibition of Adenylyl Cyclase Activity Reveals That UDP Is a Potent Agonist of the Human P2Y14 Receptor
Creators: name: Barrett, M. O.
name: Lazarowski, E. R.
name: Fricks, I. P.
name: Das, A.
name: Burianek, L. E.
name: Harden, T. K.
name: Ko, H.
name: Carter, R. L.
name: Jacobson, K. A.
name: Zhou, Y.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2009

description: The P2Y14 receptor was initially identified as a G protein-coupled receptor activated by UDP-glucose and other nucleotide sugars. We have developed several cell lines that stably express the human P2Y14 receptor, allowing facile examination of its coupling to native Gi family G proteins and their associated downstream signaling pathways (J Pharmacol Exp Ther 330:162–168, 2009). In the current study, we examined P2Y14 receptor-dependent inhibition of cyclic AMP accumulation in human embryonic kidney (HEK) 293, C6 glioma, and Chinese hamster ovary (CHO) cells stably expressing this receptor. Not only was the human P2Y14 receptor activated by UDP-glucose, but it also was activated by UDP. The apparent efficacies of UDP and UDP-glucose were similar, and the EC50 values (74, 33, and 29 nM) for UDP-dependent activation of the P2Y14 receptor in HEK293, CHO, and C6 glioma cells, respectively, were similar to the EC50 values (323, 132, and 72 nM) observed for UDP-glucose. UDP and UDP-glucose also stimulated extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in P2Y14 receptor-expressing HEK293 cells but not in wild-type HEK293 cells. A series of analogs of UDP were potent P2Y14 receptor agonists, but the naturally occurring nucleoside diphosphates, CDP, GDP, and ADP exhibited agonist potencies over 100-fold less than that observed with UDP. Two UDP analogs were identified that selectively activate the P2Y14 receptor over the UDP-activated P2Y6 receptor, and these molecules stimulated phosphorylation of ERK1/2 in differentiated human HL-60 promyeloleukemia cells, which natively express the P2Y14 receptor but had no effect in wild-type HL-60 cells, which do not express the receptor. We conclude that UDP is an important cognate agonist of the human P2Y14 receptor.
Time-symmetry breaking in turbulence
Creators: name: Jucha, Jennifer
name: Xu, Haitao
name: Pumir, Alain
name: Bodenschatz, Eberhard
Publisher: name: arXiv
Year: 2014
Subjects: subject: Fluid Dynamics (physics.flu-dyn)
subject: FOS: Physical sciences

description: In three-dimensional turbulent flows, the flux of energy from large to small scales breaks time symmetry. We show here that this irreversibility can be quantified by following the relative motion of several Lagrangian tracers. We find by analytical calculation, numerical analysis and experimental observation that the existence of the energy flux implies that, at short times, two particles separate temporally slower forwards than backwards, and the difference between forward and backward dispersion grows as $t^3$. We also find the geometric deformation of material volumes, surrogated by four points spanning an initially regular tetrahedron, to show sensitivity to the time-reversal with an effect growing linearly in $t$. We associate this with the structure of the strain rate in the flow.
description: 5 pages, 4 figures
Questioning the $H_0$ tension via the look-back time
Creators: name: Capozziello, Salvatore
name: Sarracino, Giuseppe
name: Spallicci, Alessandro D. A. M.
Publisher: name: arXiv
Year: 2023
Subjects: subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: General Relativity and Quantum Cosmology (gr-qc)
subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: The Hubble tension is investigated taking into account the cosmological look-back time. Specifically, considering a single equation, widely used in standard cosmology, it is possible to recover both values of the Hubble constant $H_0$ reported by the SH0ES and Planck collaborations: the former is obtained through cosmological ladder methods (e.g. Cepheids, Supernovae Type IA) and the latter through measurements of the Cosmic Microwave Background. Also, other values obtained in the literature are achieved with the same approach. We conclude that the Hubble tension can be removed if the look-back time is correctly referred to the redshift where the measurement is performed.
description: 8 pages, 1 figure, accepted for publication in Physics of the Dark Universe
Rockets and feathers meet Joseph: Reinvestigating the oil-gasoline asymmetry on the international markets
Creators: name: Kristoufek, Ladislav
name: Lunackova, Petra
Publisher: name: arXiv
Year: 2014
Subjects: subject: Statistical Finance (q-fin.ST)
subject: FOS: Economics and business

description: We reinvestigate the "rockets and feathers" effect between retail gasoline and crude oil prices in a new framework of fractional integration, long-term memory and borderline (non-)stationarity. The most frequently used error-correction model is examined in detail and we find that the prices return to their equilibrium value much more slowly than would be typical for the error-correction model. Such dynamics is usually referred to as "the Joseph effect". The standard procedure is shown to be troublesome and we introduce three new tests to investigate possible asymmetry in the price adjustment to equilibrium under these complicated time series characteristics. On the dataset of seven national gasoline prices, we report that apart from Belgium, there is no asymmetry found. The proposed methodology is not limited to the gasoline and crude oil case but it can be utilized for any asymmetric adjustment to equilibrium analysis.
description: 20 pages, 2 figures, 4 tables
Optical counterparts of ROSAT X-ray sources in two selected fields at low vs. high Galactic latitudes
Creators: name: Greiner, J.
name: Richter, G. A.
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: FOS: Physical sciences

description: The optical identification of large number of X-ray sources such as those from the ROSAT All-Sky Survey is challenging with conventional spectroscopic follow-up observations. We investigate two ROSAT All-Sky Survey fields of size 10 * 10 degrees each, one at galactic latitude b = 83 deg (Com), the other at b = -5 deg (Sge), in order to optically identify the majority of sources. We used optical variability, among other more standard methods, as a means of identifying a large number of ROSAT All-Sky Survey sources. All objects fainter than about 12 mag and brighter than about 17 mag, in or near the error circle of the ROSAT positions, were tested for optical variability on hundreds of archival plates of the Sonneberg field patrol. The present paper contains probable optical identifications of altogether 256 of the 370 ROSAT sources analysed. In particular, we found 126 AGN (some of them may be misclassified CVs), 17 likely clusters of galaxies, 16 eruptive double stars (mostly CVs), 43 chromospherically active stars, 65 stars brighter than about 13 mag, 7 UV Cet stars, 3 semiregular resp. slow irregular variable stars of late spectral type, 2 DA white dwarfs, 1 Am star, 1 supernova remnant and 1 planetary nebula. X-ray emission is, expectedly, tightly correlated with optical variability, and thus our new method for optically identifying X-ray sources is demonstrated to be feasible.
description: 92 pages, 521 figures, A&A (accepted)
Is Germanium (Ge, Z=32) A Neutron-Capture Element?
Creators: name: Niu, Ping
name: Liu, Weili
name: Cui, Wenyuan
name: Zhang, Bo
Publisher: name: arXiv
Year: 2014
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Historically,Ge has been considered to be a neutron-capture element. In this case, the r-process abundance of Ge is derived by subtracting the s-process abundance from the total abundance in the Solar system. However, the Ge abundance of the metal-poor star HD 108317 is lower than that of the scaled residual r-process abundance in the Solar system, about 1.2 dex. In this paper, based on a comparison of the Ge abundances of metal-poor stars and stellar yields, we find that the Ge abundances are not the result of the primary-like yields in massive stars and come mainly from the r-process. Based on the observed abundances of metal-poor stars, we derived the Ge abundances of the weak r-process and main r-process. The contributed percentage of the neutron-capture process to Ge in the Solar system is about 59 per cent, which means that the contributed percentage of the Ge residual abundance in the Solar system is about 41 per cent. We find that the Ge residual abundance is produced as secondary-like yields in massive stars. This implies that the element Ge in the Solar system is not produced solely by the neutron-capture process.
description: 12 pages, 8 figures
GeoPandas: Easy, fast and scalable geospatial analysis in Python
Creators: name: Van den Bossche, Joris
Publisher: name: Zenodo
Year: 2022

description: Abstract
 GeoPandas is an open source project to make working with geospatial vector data in Python easier. It combines the capabilities of pandas and shapely, providing geospatial operations in pandas and a high-level interface to multiple geometries to shapely. GeoPandas enables you to easily do operations in Python that would otherwise require a spatial database such as PostGIS.
 This talk will give a brief introduction to GeoPandas, highlight some of the latest developments (faster geometry operations through new vectorized functionality in Shapely 2.0, faster IO through new GDAL bindings in pyogrio and through GeoParquet, and scaling GeoPandas with Dask using the dask-geopandas subproject), and will invite for an open discussion on how the GeoPandas and Pangeo communities can more closely collaborate.
Relation of E1 pygmy and toroidal resonances
Creators: name: Nesterenko, V. O.
name: Repko, A.
name: Reinhard, P. -G.
name: Kvasil, J.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Nuclear Theory (nucl-th)
subject: FOS: Physical sciences

description: A possible relation of the low-lying E1 (pygmy resonance) and toroidal strengths is analyzed by using Skyrme-RPA results for the strength functions, transition densities and current fields in $^{208}$Pb. It is shown that the irrotational pygmy motion can appear as a local manifestation of the collective vortical toroidal dipole resonance (TDR) at the nuclear surface. The RPA results are compared to unperturbed (1ph) ones.
description: 3 pages, 5 figures, to be submitted to EPJ Web of Conferences [Proceedings of 15th International Symposium on Capture Gamma-Ray Spectroscopy and Related Topics (CGS15), Dresden, Germany, August 24-29, 2014]
Ethanol Reduces GABAA  1 Subunit Receptor Surface Expression by a Protein Kinase C -Dependent Mechanism in Cultured Cerebral Cortical Neurons
Creators: name: Lai, M. A.
name: Suryanarayanan, A.
name: Morrow, A. L.
name: Kumar, S.
name: Ren, Q.
name: Boyd, K. N.
name: Comerford, C. E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Prolonged ethanol exposure causes central nervous system hyperexcitability that involves a loss of GABAergic inhibition. We previously demonstrated that long-term ethanol exposure enhances the internalization of synaptic GABAA receptors composed of α1β2/3γ2 subunits. However, the mechanisms of ethanol-mediated internalization are unknown. This study explored the effect of ethanol on surface expression of GABAA α1 subunit-containing receptors in cultured cerebral cortical neurons and the role of protein kinase C (PKC) β, γ, and ε isoforms in their trafficking. Cultured neurons were prepared from rat pups on postnatal day 1 and maintained for 18 days. Cells were exposed to ethanol, and surface receptors were isolated by biotinylation and P2 fractionation, whereas functional analysis was conducted by whole-cell patch-clamp recording of GABA- and zolpidem-evoked responses. Ethanol exposure for 4 h decreased biotinylated surface expression of GABAA receptor α1 subunits and reduced zolpidem (100 nM) enhancement of GABA-evoked currents. The PKC activator phorbol-12,13-dibutyrate mimicked the effect of ethanol, and the selective PKC inhibitor calphostin C prevented ethanol-induced internalization of these receptors. Ethanol exposure for 4 h also increased the colocalization and coimmunoprecipitation of PKCγ with α1 subunits, whereas PKCβ/α1 association and PKCε/α1 colocalization were not altered by ethanol exposure. Selective PKCγ inhibition by transfection of selective PKCγ small interfering RNAs blocked ethanol-induced internalization of GABAA receptor α1 subunits, whereas PKCβ inhibition using pseudo-PKCβ had no effect. These findings suggest that ethanol exposure selectively alters PKCγ translocation to GABAA receptors and PKCγ regulates GABAA α1 receptor trafficking after ethanol exposure.
New mechanisms for forming multiple hotspots in radio jets
Creators: name: Horton, Maya A.
name: Krause, Martin G. H.
name: Hardcastle, Martin J.
Publisher: name: arXiv
Year: 2023
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: Astrophysics of Galaxies (astro-ph.GA)
subject: FOS: Physical sciences

description: Hotspots of radio galaxies are regions of shock-driven particle acceleration. Multiple hotspots have long been identified as potential indicators of jet movement or precession. Two frequent explanations describe a secondary hotspot as either the location of a prior jet termination point, or a deflected backflow-driven shock: the so-called Dentist's Drill and Splatter Spot models. We created high-resolution simulations of precessing jets with a range of parameters. In addition to the existing mechanisms, our results show three additional mechanisms for multiple hotspot formation: (1) the splitting of a large terminal hotspots into passive and active components; (2) jet stream splitting resulting in two active hotspots; (3) dynamic multiple hotspot complexes that form as a result of jet termination in a turbulent cocoon, linked here to rapid precession. We show that these distinct types of multiple hotspots are difficult to differentiate in synthetic radio maps, particularly hotspot complexes which can easily be mistaken for the jet itself. We discuss the implication for hypothesised binary supermassive black hole systems where jet precession is a key component of the morphology, and show a selection of potential precession candidates found using the LOFAR Two-Metre Sky Survey Data Release 2 (LoTSS DR2).
description: 14 pages, 10 figures
Optical extinction, refractive index, and multiple scattering for suspensions of interacting colloidal particles
Creators: name: Parola, Alberto
name: Piazza, Roberto
name: Degiorgio, Vittorio
Publisher: name: arXiv
Year: 2014
Subjects: subject: Soft Condensed Matter (cond-mat.soft)
subject: FOS: Physical sciences

description: We provide a general microscopic theory of the scattering cross-section and of the refractive index for a system of interacting colloidal particles, exact at second order in the molecular polarizabilities. In particular: a) we show that the structural features of the suspension are encoded into the forward scattered field by multiple scattering effects, whose contribution is essential for the so-called "optical theorem" to hold in the presence of interactions; b) we investigate the role of radiation reaction on light extinction; c) we discuss our results in the framework of effective medium theories, presenting a general result for the effective refractive index valid, whatever the structural properties of the suspension, in the limit of particles much larger than the wavelength; d) by discussing strongly-interacting suspensions, we unravel subtle anomalous dispersion effects for the suspension refractive index.
description: Submitted to Journal of Chemical Physics 37 pages, 4 figures
Investigation on the future of work: the impact of innovative strategies in a post pandemic scenario
Creators: name: Puliti, Marco
name: Di Giusto, Elena
name: Papetti, Viola
name: Montana, Federica
Publisher: name: CERN IdeaSquare Journal of Experimental Innovation
Year: 2022

description: In the following research work, an experiment of guided innovation is presented. The context is the Innovation for Change (I4C) program, in which a group of students, either PhDs or MBAs, are asked to solve a challenge provided by a stakeholder. The problem is “the future of work” in the context of a post pandemic scenario, with a focus on how to manage spaces remained empty due to remote working. The solution obtained is the consequence of a combination of brainstorming sessions, problem definition, benchmarking and interviewing stakeholders, experimental validation and prototyping. The outcome is a platform, B-Hub, which exploits empty locations to create a network of decentralised co-working spaces in which employees from every company can remotely work.
description: CERN IdeaSquare Journal of Experimental Innovation, Articles in press
Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin
Creators: name: Cerasoli, D. M.
name: Wierdl, M.
name: Fleming, C. D.
name: Potter, P. M.
name: Otto, T. C.
name: Cashman, J. R.
name: Edwards, C. C.
name: Redinbo, M. R.
name: Hemmert, A. C.
name: MacDonald, M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex with the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the PR enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the PS isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic PS isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.
О судебно-экспертном обеспечении раскрытия и расследования профессиональных преступлений, совершенных медицинскими работниками
Creators: name: Константин Евгеньевич Демин
Publisher: name: Международный журнал Актуальные проблемы медицины и биологии
Year: 2018
Subjects: автоматизация системы криминалистической регистрации; источники ультрафиолетового и инфракрасного излучения; криминалистическая техника; поисковые приборы; специальные знания; судебное исследование; судебная экспертиза; судебно-экспертное обеспечение.

description: Рассматриваются проблемы судебно-экспертного обеспечения раскрытия и расследования профессиональных преступлений, совершенных медицинскими работниками, анализируются различные формы ее реализации при оптимизации предварительного следствия. Автор, исходя из системы функционирования составляющих данного вида деятельности, определяет ее цели и задачи при расследовании указанных преступлений.
A field-induced reentrant insulator state of a gap-closed topological insulator (Bi_{1-x}Sb_x) in quantum-limit states
Creators: name: Kinoshita, Y.
name: Fujita, T.
name: Kurihara, R.
name: Miyake, A.
name: Izaki, Y.
name: Fuseya, Y.
name: Tokunaga, M.
Publisher: name: arXiv
Year: 2023
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: In the extreme quantum limit states under high magnetic fields, enhanced electronic correlation effects can stabilize anomalous quantum states. Using band-tuning with a magnetic field, we realized a spin-polarized quantum limit state in the field-induced semimetallic phase of a topological insulator Bi_{1-x}Sb_x. Further increase in the field injects more electrons and holes to this state and results in an unexpected reentrant insulator state in this topological semimetallic state. A single-particle picture cannot explain this reentrant insulator state, reminiscent of phase transitions due to many-body effects. Estimates of the binding energy and spacing of electron-hole pairs and the thermal de Broglie wavelength indicate that Bi_{1-x}Sb_x may host the excitonic insulator phase in this extreme environment.
description: 26pages, 6figures
Rotifera recorded from New Zealand, 1859-1995, with comments on zoogeography
Creators: name: Shiel, R. J
name: Green, J. D
Publisher: name: La Trobe
Year: 2023

description: Murray-Darling Freshwater Research Centre

MDFRC item.

A search of the literature on rotifers recorded from New Zealand, including its offshore and outlying islands, produced 388 valid species names and 40 subspecies or infrasubspecific variants in 66 genera recorded since 1859. New Zealand rotifer research is reviewed, and all recorded species are listed with current taxonomic status and first localities. Most of the named tars are widely distributed or cosmopolitan, with only a small proportion (<5%) apparently restricted to New Zealand or the Australasian region. It is likely that considerably more rotifers remain to be described from New Zealand and that a higher proportion will be found to be indigenous as taxonomic resolution improves.
Lyn Kinase-Dependent Regulation of miR181 and Myeloid Cell Leukemia-1 Expression: Implications for Drug Resistance in Myelogenous Leukemia
Creators: name: Zimmerman, E. I.
name: Richards, K. L.
name: Graves, L. M.
name: Dollins, C. M.
name: Nana-Sinkam, S. P.
name: Crawford, M.
name: Grant, S.
name: Hammond, S. M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Imatinib, a BCR-Abl inhibitor, is a successful front-line treatment for chronic myelogenous leukemia (CML). Despite the success of imatinib, multiple mechanisms of resistance remain a problem, including overexpression of Lyn kinase (Lyn) and Bcl-2 family antiapoptotic proteins. Profiling micro-RNA (miRNA) expression in a model of Lyn-mediated imatinib-resistant CML (MYL-R) identified approximately 30 miRNAs whose expression differed >2-fold compared with drug-sensitive MYL cells. In particular, the expression of the miR181 family (a–d) was significantly reduced (∼11- to 25-fold) in MYL-R cells. Incubation of MYL-R cells with a Lyn inhibitor (dasatinib) or nucleofection with Lyn-targeting short interfering RNA increased miR181b and miR181d expression. A similar Lyn-dependent regulation of miR181b and miR181d was observed in imatinib-resistant K562 CML cells. Sequence analysis of potential targets for miR181 regulation predicted myeloid cell leukemia-1 (Mcl-1), a Bcl-2 family member whose expression is increased in MYL-R cells and drug-resistant leukemias. Inhibition of Lyn or rescue of miR181b expression reduced Mcl-1 expression in the MYL-R cells. To further investigate the mechanism of Mcl-1 repression by miR181, a luciferase reporter construct incorporating the Mcl-1 3′-untranslated region was tested. Overexpression of miR181b reduced luciferase activity, whereas these effects were ablated by the mutation of the seed region of the miR181 target site. Finally, stimulation of Lyn expression by 1,25-dihydroxyvitamin D3 treatment in HL-60 cells, a cell model of acute myelogenous leukemia, decreased miR181b expression and increased Mcl-1 expression. In summary, our results suggest that Lyn-dependent regulation of miR181 is a novel mechanism of regulating Mcl-1 expression and cell survival.
AstroSat/UVIT Study of the open cluster NGC 2818: Membership, Blue Stragglers, Yellow Stragglers, and Planetary Nebula
Creators: name: Rani, Sharmila
name: Subramaniam, Annapurni
name: Pandey, Gajendra
name: Rao, N. K.
Publisher: name: Zenodo
Year: 2022

description: We present the first far-UV (FUV) imaging results of the intermediate-age Galactic open cluster (OC)
 NGC 2818 that has a Planetary nebula (PN) within the field. We explore whether the PN is a member
 of the cluster using images taken from the Ultra-violet Imaging Telescope (UVIT) aboard AstroSat.
 We identify the cluster members by combining the UVIT-detected sources with Gaia EDR3 data. We
 detect four bright and hot blue straggler stars (BSSs) and two yellow straggler stars (YSSs) based
 on their location in the optical and FUV-optical color-magnitude diagrams (CMDs). The theoretical
 isochrones more or less fit the observed distribution of detected stars in all the CMDs. Based on the
 parameters estimated using Spectral Energy Distribution (SED), we infer that the BSSs are either
 collisional products or might have undetectable white dwarf (WD) companions. Our photometric
 analysis of YSSs confirms their binarity, consistent with the spectroscopic results. We find the YSSs to
 be formed through a mass-transfer scenario and the hot components are likely to be A-type subdwarfs.
 A comparison of the radial velocity (RV), Gaia EDR3 proper-motion (PM) of the PN with the cluster
 members, and reddening towards the PN and the cluster does not rule out the membership of the PN.
 Using SED, the estimated stellar parameters of the PN’s central star match well with the previous
 estimations. Comparing the central star’s position with theoretical pAGB models suggest that it has
 already entered the WD cooling phase, and its mass is deduced to be ∼ 0.6Msun. The corresponding
 progenitor mass turns out to be ∼ 2.1Msun, comparable to the turn-off mass of the cluster, implying
 that the progenitor could have formed in the cluster. We suggest that the NGC 2818 might be one of
 the few known clusters to host a PN, providing a unique opportunity to test stellar evolution models.
Receptor Conformations Involved in Dopamine D2L Receptor Functional Selectivity Induced by Selected Transmembrane-5 Serine Mutations
Creators: name: Urban, J. D.
name: Bhattacharya, S.
name: Mailman, R. B.
name: Vaidehi, N.
name: Fowler, J. C.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2012

description: Although functional selectivity is now widely accepted, the molecular basis is poorly understood. We have studied how aspects of transmembrane region 5 (TM5) of the dopamine D2L receptor interacts with three rationally selected rigid ligands (dihydrexidine, dinapsoline, and dinoxyline) and the reference compounds dopamine and quinpirole. As was expected from homology modeling, mutation of three TM5 serine residues to alanine (S5.42A, S5.43A, S5.46A) had little effect on antagonist affinity. All three mutations decreased the affinity of the agonist ligands to different degrees, S5.46A being somewhat less affected. Four functions [adenylate cyclase (AC), extracellular signal-regulated kinase 1/2 phosphorylation (MAPK), arachidonic acid release (AA), and guanosine 5′-O-(3-thio)triphosphate binding (GTPγS)] were assessed. The intrinsic activity (IA) of quinpirole was unaffected by any of the mutations, whereas S5.42A and S5.46A mutations abolished the activity of dopamine and the three rigid ligands, although dihydrexidine retained IA at MAPK function only with S5.42A. Remarkably, S5.43A did not markedly affect IA for AC and MAPK for any of the ligands and eliminated AA activity for dinapsoline and dihydrexidine but not dinoxyline. These data suggest that this mutation did not disrupt the overall conformation or signaling ability of the mutant receptors but differentially affected ligand activation. Computational studies indicate that these D2 agonists stabilize multiple receptor conformations. This has led to models showing the stabilized conformations and interhelical and receptor-ligand contacts corresponding to the different activation pathways stabilized by various agonists. These data provide a basis for understanding D2L functional selectivity and rationally discovering functionally selective D2 drugs.
Confined flow of suspensions modeled by a frictional rheology
Creators: name: Lecampion, Brice
name: Garagash, Dmitry I.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Soft Condensed Matter (cond-mat.soft)
subject: FOS: Physical sciences

description: We investigate in detail the problem of confined pressure-driven laminar flow of neutrally buoyant non-Brownian suspensions using a frictional rheology based on the recent proposal of Boyer et al., 2011. The friction coefficient and solid volume fraction are taken as functions of the dimensionless viscous number I defined as the ratio between the fluid shear stress and the particle normal stress. We clarify the contributions of the contact and hydrodynamic interactions on the evolution of the friction coefficient between the dilute and dense regimes reducing the phenomenological constitutive description to three physical parameters. We also propose an extension of this constitutive law from the flowing regime to the fully jammed state. We obtain an analytical solution of the fully-developed flow in channel and pipe for the frictional suspension rheology. The result can be transposed to dry granular flow upon appropriate redefinition of the dimensionless number I. The predictions are in excellent agreement with available experimental results, when using the values of the constitutive parameters obtained independently from stress-controlled rheological measurements. In particular, the frictional rheology correctly predicts the transition from Poiseuille to plug flow and the associated particles migration with the increase of the entrance solid volume fraction. We numerically solve for the axial development of the flow from the inlet of the channel/pipe toward the fully-developed state. The available experimental data are in good agreement with our predictions. The solution of the axial development of the flow provides a quantitative estimation of the entrance length effect in pipe for suspensions. A analytical expression for development length is shown to encapsulate the numerical solution in the entire range of flow conditions from dilute to dense.
description: Submitted to J. Fluid Mech. on Dec. 24, 2013, Revised version July 10, 2014, Accepted for publication Sept. 19, 2014
Numerical and experimental investigations of a microwave interferometer for the negative ion source SPIDER
Creators: name: Agnello, R.
name: Cavazzana, R.
name: Furno, I.
name: Jacquier, R.
name: Pasqualotto, R.
name: Sartori, E.
name: Serianni, G.
Publisher: name: arXiv
Year: 2023
Subjects: subject: Plasma Physics (physics.plasm-ph)
subject: FOS: Physical sciences

description: The electron density close to the extraction grids and the co-extracted electrons represent a crucial issue when operating negative ion sources for fusion reactors. An excessive electron density in the plasma expansion region can indeed inhibit the negative ion production and introduce potentially harmful electrons in the accelerator. Among the set of plasma and beam diagnostics proposed for SPIDER upgrade, a heterodyne microwave (mw) interferometer at 100 GHz is being explored as a possibility to measure electron density in the plasma extraction region. The major issue in applying this technique in SPIDER is the poor accessibility of the probing microwave beam through the source metal walls and the long distance of 4 m at which mw modules should be located outside the vacuum vessel. Numerical investigations in a full-scale geometry showed that the power transmitted through the plasma source apertures was sufficient for the microwave module sensitivity. An experimental proof-of-principle of the setup was then performed. The microwave system was tested on an experimental full-scale test-bench mimicking SPIDER viewports accessibility constraints, including the presence of a SPIDER-like plasma. The outcome of first tests revealed that, despite the geometrical constraints, in certain conditions, the electron density measurements are possible. The main issue arises from decoupling the one-pass signal from spurious multipaths generated by mw beam reflections, requiring signal cross correlation analysis. These preliminary tests demonstrate that despite the 4 m distance between the mw modules and the presence of metal walls, plasma density measurement is possible when the 80-mm diameter ports are available. In this contribution, we discuss the numerical simulations, the preliminary experimental tests and suggest design upgrades of the interferometric setup to enhance signal transmission.
The VORTEX project: first results and perspectives
Creators: name: Absil, Olivier
name: Mawet, Dimitri
name: Delacroix, Christian
name: Forsberg, Pontus
name: Karlsson, Mikael
name: Habraken, Serge
name: Surdej, Jean
name: Absil, Pierre-Antoine
name: Carlomagno, Brunella
name: Christiaens, Valentin
name: Defrere, Denis
name: Gonzalez, Carlos Gomez
name: Huby, Elsa
name: Jolivet, Aissa
name: Milli, Julien
name: Piron, Pierre
name: Catalan, Ernesto Vargas
name: Van Droogenbroeck, Marc
Publisher: name: arXiv
Year: 2014
Subjects: subject: Instrumentation and Methods for Astrophysics (astro-ph.IM)
subject: FOS: Physical sciences

description: (abridged) Vortex coronagraphs are among the most promising solutions to perform high contrast imaging at small angular separations. They feature a very small inner working angle, a clear 360 degree discovery space, have demonstrated very high contrast capabilities, are easy to implement on high-contrast imaging instruments, and have already been extensively tested on the sky. Since 2005, we have been designing, developing and testing an implementation of the charge-2 vector vortex phase mask based on concentric subwavelength gratings, referred to as the Annular Groove Phase Mask (AGPM). Science-grade mid-infrared AGPMs were produced in 2012 for the first time, using plasma etching on synthetic diamond substrates. They have been validated on a coronagraphic test bench, showing broadband peak rejection up to 500:1 in the L band, which translates into a raw contrast of about $6\times 10^{-5}$ at $2 λ/D$. Three of them have now been installed on world-leading diffraction-limited infrared cameras (VLT/NACO, VLT/VISIR and LBT/LMIRCam). During the science verification observations with our L-band AGPM on NACO, we observed the beta Pictoris system and obtained unprecedented sensitivity limits to planetary companions down to the diffraction limit ($0.1''$). More recently, we obtained new images of the HR 8799 system at L band during the AGPM first light on LMIRCam. After reviewing these first results obtained with mid-infrared AGPMs, we will discuss the short- and mid-term goals of the on-going VORTEX project, which aims to improve the performance of our vortex phase masks for future applications on second-generation high-contrast imagers and on future extremely large telescopes (ELTs).
description: To appear in SPIE proceedings vol. 9148
A selective high-Affinity antagonist of the P2Y14 receptor inhibits udp-glucose-stimulated chemotaxis of human neutrophilss
Creators: name: Harden, T. K.
name: Barrett, M. O.
name: Ball, C. B.
name: Jayasekara, P. S.
name: Jacobson, K. A.
name: Sesma, J. I.
name: Lazarowski, E. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: The nucleotide-sugar–activated P2Y14 receptor (P2Y14-R) is highly expressed in hematopoietic cells. Although the physiologic functions of this receptor remain undefined, it has been strongly implicated recently in immune and inflammatory responses. Lack of availability of receptor-selective high-affinity antagonists has impeded progress in studies of this and most of the eight nucleotide-activated P2Y receptors. A series of molecules recently were identified by Gauthier et al. (Gauthier et al., 2011) that exhibited antagonist activity at the P2Y14-R. We synthesized one of these molecules, a 4,7-disubstituted 2-naphthoic acid derivative (PPTN), and studied its pharmacological properties in detail. The concentration-effect curve of UDP-glucose for promoting inhibition of adenylyl cyclase in C6 glioma cells stably expressing the P2Y14-R was shifted to the right in a concentration-dependent manner by PPTN. Schild analyses revealed that PPTN-mediated inhibition followed competitive kinetics, with a KB of 434 pM observed. In contrast, 1 μM PPTN exhibited no agonist or antagonist effect at the P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, or P2Y13 receptors. UDP-glucose–promoted chemotaxis of differentiated HL-60 human promyelocytic leukemia cells was blocked by PPTN with a concentration dependence consistent with the KB determined with recombinant P2Y14-R. In contrast, the chemotactic response evoked by the chemoattractant peptide fMetLeuPhe was unaffected by PPTN. UDP-glucose–promoted chemotaxis of freshly isolated human neutrophils also was blocked by PPTN. In summary, this work establishes PPTN as a highly selective high-affinity antagonist of the P2Y14-R that is useful for interrogating the action of this receptor in physiologic systems.
Electrostatic effect due to patch potentials between closely spaced surfaces
Creators: name: Ke, Jun
name: Dong, Wen-Can
name: Huang, Sheng-Hua
name: Tan, Yu-Jie
name: Tan, Wen-Hai
name: Yang, Shan-Qing
name: Shao, Cheng-Gang
name: Luo, Jie
Publisher: name: arXiv
Year: 2023
Subjects: subject: Soft Condensed Matter (cond-mat.soft)
subject: FOS: Physical sciences

description: The spatial variation and temporal variation in surface potential are important error sources in various precision experiments and deserved to be considered carefully. In the former case, the theoretical analysis shows that this effect depends on the surface potentials through their spatial autocorrelation functions. By making some modification to the quasi-local correlation model, we obtain a rigorous formula for the patch force, where the magnitude is proportional to ${\frac{1}{{{a}^{2}}}{{(\frac{a}{w})}^{β(a/w)+2}}}$ with ${a}$ the distance between two parallel plates, ${w}$ the mean patch size, and $β$ the scaling coefficient from ${-2}$ to ${-4}$. A torsion balance experiment is then conducted, and obtain a 0.4 mm effective patch size and 20 mV potential variance. In the latter case, we apply an adatom diffusion model to describe this mechanism and predicts a ${f^{-3/4}}$ frequency dependence above 0.01 ${\rm mHz}$. This prediction meets well with a typical experimental results. Finally, we apply these models to analyze the patch effect for two typical experiments. Our analysis will help to investigate the properties of surface potentials.
D1-D2 Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms
Creators: name: Rankin, M. L.
name: Doyle, T. B.
name: Free, R. B.
name: Sibley, D. R.
name: Chun, L. S.
name: Huang, X.-P.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2013

description: The D1 dopamine receptor (D1R) has been proposed to form a hetero-oligomer with the D2 dopamine receptor (D2R), which in turn results in a complex that couples to phospholipase C–mediated intracellular calcium release. We have sought to elucidate the pharmacology and mechanism of action of this putative signaling pathway. Dopamine dose-response curves assaying intracellular calcium mobilization in cells heterologously expressing the D1 and D2 subtypes, either alone or in combination, and using subtype selective ligands revealed that concurrent stimulation is required for coupling. Surprisingly, characterization of a putative D1-D2 heteromer-selective ligand, 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol (SKF83959), found no stimulation of calcium release, but it did find a broad range of cross-reactivity with other G protein–coupled receptors. In contrast, SKF83959 appeared to be an antagonist of calcium mobilization. Overexpression of Gqα with the D1 and D2 dopamine receptors enhanced the dopamine-stimulated calcium response. However, this was also observed in cells expressing Gqα with only the D1R. Inactivation of Gi or Gs with pertussis or cholera toxin, respectively, largely, but not entirely, reduced the calcium response in D1R and D2R cotransfected cells. Moreover, sequestration of Gβγ subunits through overexpression of G protein receptor kinase 2 mutants either completely or largely eliminated dopamine-stimulated calcium mobilization. Our data suggest that the mechanism of D1R/D2R–mediated calcium signaling involves more than receptor-mediated Gq protein activation, may largely involve downstream signaling pathways, and may not be completely heteromer-specific. In addition, SKF83959 may not exhibit selective activation of D1-D2 heteromers, and its significant cross-reactivity to other receptors warrants careful interpretation of its use in vivo.
Long-term modulation of solar cycles
Creators: name: Biswas, Akash
name: Karak, Bidya
name: Usoskin, Ilya
name: Weisshaar, Eckhard
Publisher: name: arXiv
Year: 2023
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Solar activity has a cyclic nature with the ~11-year Schwabe cycle dominating its variability on the interannual timescale. However, solar cycles are significantly modulated in length, shape and magnitude, from near-spotless grand minima to very active grand maxima. The ~400-year-long direct sunspot-number series is inhomogeneous in quality and too short to study robust parameters of long-term solar variability. The cosmogenic-isotope proxy extends the timescale to twelve millennia and provides crucial observational constraints of the long-term solar dynamo modulation. Here, we present a brief up-to-date overview of the long-term variability of solar activity at centennial--millennial timescales. The occurrence of grand minima and maxima is discussed as well as the existing quasi-periodicities such as centennial Gleissberg, 210-year Suess/de Vries and 2400-year Hallstatt cycles. It is shown that the solar cycles contain an important random component and have no clock-like phase locking implying a lack of long-term memory. A brief yet comprehensive review of the theoretical perspectives to explain the observed features in the framework of the dynamo models is presented, including the nonlinearity and stochastic fluctuations in the dynamo. We keep gaining knowledge of the processes driving solar variability with the new data acquainted and new models developed.
description: Accepted for Space Science Review