Algorithm for constructing three-dimensional Barcodes to represent nD spatial objects in GIS

В статье рассмотрен алгоритм создания трехмерных Баркодов для представления nD пространственных объектов. Алгоритм основан на методах компьютерной топологии с использованием алгоритма 3D sweep hull для вычисления выпуклых оболочек и триангуляции Делоне. Результатом работы алгоритма являются 3D Баркоды пространственных объектов. Также были построены графики 3D Баркодов, которые отражают их различия во времени. Алгоритм построения 3D Баркодов позволит анализировать пространственные nD объекты в разные временные интервалы. The article describes the algorithm for creating three-dimensional Barcodes to represent nD features. The algorithm is based on computer topology methods using the 3D sweep hull algorithm for computing convex hulls and Delaunay triangulation. The result of the algorithm are 3D Barcodes of features. Were also constructed 3D Barcode graphics, which reflect their differences in time. The algorithm for constructing 3D Barcodes will allow analyzing spatial nD objects at different time intervals.Исследование выполнено при финансовой поддержке РФФИ и администрации Владимирской области в рамках научного проекта № 17-47-330387

PSMA-targeted small-molecule docetaxel conjugate: Synthesis and preclinical evaluation

Prostate cancer is one of the most commonly diagnosed men's cancers and remains one of the leading causes of cancer death. The development of approaches to the treatment of this oncological disease is an ongoing process. In this work, we have carried out the selection of ligands for the creation of conjugates based on the drug docetaxel and synthesized a series of three docetaxel conjugates. In vitro cytotoxicity of these molecules was evaluated using the MTT assay. Based on the assay results, we selected the conjugate which showed cytotoxic potential close to unmodified docetaxel. At the same time, the molar solubility of the resulting compound increased up to 20 times in comparison with the drug itself. In vivo evaluation on 22Rv1 (PSMA+) xenograft model demonstrated a good potency of the synthesized conjugate to inhibit tumor growth: the inhibition turned out to be more than 80% at a dose of 30 mg/kg. Pharmacokinetic parameters of conjugate distribution were analyzed. Also, it was found that PSMA-targeted docetaxel conjugate is less toxic than docetaxel itself, the decrease of molar acute toxicity in comparison with free docetaxel was up to 20%. Obtained conjugate PSMA-DOC is a good candidate for further expanded preclinical trials because of high antitumor activity, fewer side toxic effects and better solubility. © 2021 Elsevier Masson SA

Synthesis, Characterization, and Preclinical Evaluation of a Small-Molecule Prostate-Specific Membrane Antigen-Targeted Monomethyl Auristatin e Conjugate

Prostate cancer is the second most common type of cancer among men. Its main method of treatment is chemotherapy, which has a wide range of side effects. One of the solutions to this challenge is targeted delivery to prostate cancer cells. Here we synthesized a novel small-molecule PSMA-targeted conjugate based on the monomethyl auristatin E. Its structure and conformational properties were investigated by NMR spectroscopy. Cytotoxicity, intracellular reactive oxygen species induction, and stability under liver microsomes and P450-cytochrome species were investigated for this conjugate. The conjugate demonstrated 77-85% tumor growth inhibition levels on 22Rv1 (PSMA (+)) xenografts, compared with a 37% inhibition level on PC-3 (PSMA (-)) xenografts, in a single dose of 0.3 mg/kg and a sufficiently high therapeutic index of 21. Acute, chronic, and subchronic toxicities and pharmacokinetics have shown that the synthesized conjugate is a promising potential agent for the chemotherapy of prostate cancer. © 2021 American Chemical Society

High-energy neutrino-induced cascade from the direction of the flaring radio blazar TXS 0506+056 observed by the Baikal Gigaton Volume Detector in 2021

The existence of high-energy astrophysical neutrinos has been unambiguously demonstrated, but their sources remain elusive. IceCube reported an association of a 290-TeV neutrino with a gamma-ray flare of TXS 0506+056, an active galactic nucleus with a compact radio jet pointing to us. Later, radio blazars were shown to be associated with IceCube neutrino events with high statistical significance. These associations remained unconfirmed with the data of independent experiments. Here we report on the detection of a rare neutrino event with the estimated energy of 224 +- 75 TeV from the direction of TXS 0506+056 by the new Baikal-GVD neutrino telescope in April 2021 followed by a radio flare observed by RATAN-600. This event is the highest-energy cascade detected so far by Baikal-GVD from a direction below horizon. The result supports previous suggestions that radio blazars in general, and TXS 0506+056 in particular, are the sources of high-energy neutrinos, and opens up the cascade channel for the neutrino astronomy

High-energy neutrino-induced cascade from the direction of the flaring radio blazar TXS 0506+056 observed by the Baikal Gigaton Volume Detector in 2021

The existence of high-energy astrophysical neutrinos has been unambiguously demonstrated, but their sources remain elusive. IceCube reported an association of a 290-TeV neutrino with a gamma-ray flare of TXS 0506+056, an active galactic nucleus with a compact radio jet pointing to us. Later, radio blazars were shown to be associated with IceCube neutrino events with high statistical significance. These associations remained unconfirmed with the data of independent experiments. Here we report on the detection of a rare neutrino event with the estimated energy of 224 +- 75 TeV from the direction of TXS 0506+056 by the new Baikal-GVD neutrino telescope in April 2021 followed by a radio flare observed by RATAN-600. This event is the highest-energy cascade detected so far by Baikal-GVD from a direction below horizon. The result supports previous suggestions that radio blazars in general, and TXS 0506+056 in particular, are the sources of high-energy neutrinos, and opens up the cascade channel for the neutrino astronomy

High-energy neutrino-induced cascade from the direction of the flaring radio blazar TXS 0506+056 observed by the Baikal Gigaton Volume Detector in 2021

The existence of high-energy astrophysical neutrinos has been unambiguously demonstrated, but their sources remain elusive. IceCube reported an association of a 290-TeV neutrino with a gamma-ray flare of TXS 0506+056, an active galactic nucleus with a compact radio jet pointing to us. Later, radio blazars were shown to be associated with IceCube neutrino events with high statistical significance. These associations remained unconfirmed with the data of independent experiments. Here we report on the detection of a rare neutrino event with the estimated energy of 224 +- 75 TeV from the direction of TXS 0506+056 by the new Baikal-GVD neutrino telescope in April 2021 followed by a radio flare observed by RATAN-600. This event is the highest-energy cascade detected so far by Baikal-GVD from a direction below horizon. The result supports previous suggestions that radio blazars in general, and TXS 0506+056 in particular, are the sources of high-energy neutrinos, and opens up the cascade channel for the neutrino astronomy

Baikal-GVD Astrophysical Neutrino Candidate near the Blazar TXS~0506+056

International audienceWe report on the observation of a rare neutrino event detected by Baikal-GVD in April 2021. The event GVD210418CA is the highest-energy cascade observed by Baikal-GVD so far from the direction below the horizon. The estimated cascade energy is $224\pm75$~TeV. The evaluated signalness parameter of GVD210418CA is 97.1% using an assumption of the E$^{-2.46}$ spectrum of astrophysical neutrinos. The arrival direction of GVD210418CA is near the position of the well-known radio blazar TXS~0506+056, with the angular distance being within a 90% directional uncertainty region of the Baikal-GVD measurement. The event was followed by a radio flare observed by the RATAN-600 radio telescope, further strengthening the case for the neutrino-blazar association