Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

7-Nitroindazole (7-NI) inhibits neuronal nitric oxide synthase in vivo and reduces l-DOPA-induced dyskinesias in a rat model of parkinsonism. The aim of the present study was to determine if the anti-dyskinetic effect of 7-NI was subject to tolerance after repeated treatment and if this drug could interfere with the priming effect of l-DOPA. Adult male Wistar rats (200-250 g) with unilateral depletion of dopamine in the substantia nigra compacta were treated with l-DOPA (30 mg/kg) for 34 days. On the 1st day, 6 rats received ip saline and 6 received ip 7-NI (30 mg/kg) before l-DOPA. From the 2nd to the 26th day, all rats received l-DOPA daily and, from the 27th to the 34th day, they also received 7-NI before l-DOPA. Animals were evaluated before the drug and 1 h after l-DOPA using an abnormal involuntary movement scale and a stepping test. All rats had a similar initial motor deficit. 7-NI decreased abnormal involuntary movement induced by l-DOPA and the effect was maintained during the experiment before 7-NI, median (interquartile interval), day 26: 16.75 (15.88-17.00); day 28: 0.00 (0.00-9.63); day 29: 13.75 (2.25-15.50); day 30: 0.5 (0.00-6.25); day 31: 4.00 (0.00-7.13), and day 34: 0.5 (0.00-14.63), Friedman followed by Wilcoxon test,vs day 26, P < 0.05;. The response to l-DOPA alone was not modified by the use of 7-NI before the first administration of the drug (l-DOPA vs time interaction, F1,10 = 1.5, NS). The data suggest that tolerance to the anti-dyskinetic effects of a neuronal nitric oxide synthase inhibitor does not develop over a short-term period of repeated administration. These observations open a possible new therapeutic approach to motor complications of chronic l-DOPA therapy in patients with Parkinson&#8217;s disease

Detection of inconsistencies in geospatial data with geostatistics

Almost every researcher has come through observations that “drift” from the rest of the sample, suggesting some inconsistency. The aim of this paper is to propose a new inconsistent data detection method for continuous geospatial data based in Geostatistics, independently from the generative cause (measuring and execution errors and inherent variability data). The choice of Geostatistics is based in its ideal characteristics, as avoiding systematic errors, for example. The importance of a new inconsistent detection method proposal is in the fact that some existing methods used in geospatial data consider theoretical assumptions hardly attended. Equally, the choice of the data set is related to the importance of the LiDAR technology (Light Detection and Ranging) in the production of Digital Elevation Models (DEM). Thus, with the new methodology it was possible to detect and map discrepant data. Comparing it to a much utilized detections method, BoxPlot, the importance and functionality of the new method was verified, since the BoxPlot did not detect any data classified as discrepant. The proposed method pointed that, in average, 1,2% of the data of possible regionalized inferior outliers and, in average, 1,4% of possible regionalized superior outliers, in relation to the set of data used in the study

Alert classification for the ALeRCE broker system: The real-time stamp classifier

We present a real-time stamp classifier of astronomical events for the Automatic Learning for the Rapid Classification of Events broker, ALeRCE. The classifier is based on a convolutional neural network, trained on alerts ingested from the Zwicky Transient Facility (ZTF). Using only the science, reference, and difference images of the first detection as inputs, along with the metadata of the alert as features, the classifier is able to correctly classify alerts from active galactic nuclei, supernovae (SNe), variable stars, asteroids, and bogus classes, with high accuracy (~94%) in a balanced test set. In order to find and analyze SN candidates selected by our classifier from the ZTF alert stream, we designed and deployed a visualization tool called SN Hunter, where relevant information about each possible SN is displayed for the experts to choose among candidates to report to the Transient Name Server database. From 2019 June 26 to 2021 February 28, we have reported 6846 SN candidates to date (11.8 candidates per day on average), of which 971 have been confirmed spectroscopically. Our ability to report objects using only a single detection means that 70% of the reported SNe occurred within one day after the first detection. ALeRCE has only reported candidates not otherwise detected or selected by other groups, therefore adding new early transients to the bulk of objects available for early follow-up. Our work represents an important milestone toward rapid alert classifications with the next generation of large etendue telescopes, such as the Vera C. Rubin Observatory.The authors acknowledge support from the National Agency of Research and Development’s Millennium Science Initiative through grant IC12009, awarded to the Millennium Institute of Astrophysics (RC, ER, CV, FF, PE, GP, FEB, IR, PSS, GC, SE, Ja, EC, DR, DRM, MC) and from the National Agency for Research and Development (ANID) grants: BASAL Center of Mathematical Modelling AFB-170001 (CV, FF, IR, ECN, CS, ECI) and Centro de Astrofísica y Tecnologías Afines AFB170002 (FEB, PSS, MC); FONDECYT Regular #1171678 (PE), #1200710 (FF), #1190818(FEB), #1200495 (FEB), #1171273 (MC), #1201793(GP); FONDECYT Postdoctorado #3200250 (PSS); FONDECYT Iniciación #11191130 (CV); Magíster Nacional 2019 #22190947 (ER). This work was funded in part by project CORFO 10CEII-9157 Inria Chile (PS). The authors acknowledge financial support from the Spanish Ministry of Science, Innovation, and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019- 027683 (LG)

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair