Geometrical Frustration: A Study of 4d Hard Spheres

The smallest maximum kissing-number Voronoi polyhedron of 3d spheres is the icosahedron and the tetrahedron is the smallest volume that can show up in Delaunay tessalation. No periodic lattice is consistent with either and hence these dense packings are geometrically frustrated. Because icosahedra can be assembled from almost perfect tetrahedra, the terms "icosahedral" and "polytetrahedral" packing are often used interchangeably, which leaves the true origin of geometric frustration unclear. Here we report a computational study of freezing of 4d hard spheres, where the densest Voronoi cluster is compatible with the symmetry of the densest crystal, while polytetrahedral order is not. We observe that, under otherwise comparable conditions, crystal nucleation in 4d is less facile than in 3d. This suggest that it is the geometrical frustration of polytetrahedral structures that inhibits crystallization.Comment: 4 pages, 3 figures; revised interpretatio

A discrete Laplace-Beltrami operator for simplicial surfaces

We define a discrete Laplace-Beltrami operator for simplicial surfaces. It depends only on the intrinsic geometry of the surface and its edge weights are positive. Our Laplace operator is similar to the well known finite-elements Laplacian (the so called ``cotan formula'') except that it is based on the intrinsic Delaunay triangulation of the simplicial surface. This leads to new definitions of discrete harmonic functions, discrete mean curvature, and discrete minimal surfaces. The definition of the discrete Laplace-Beltrami operator depends on the existence and uniqueness of Delaunay tessellations in piecewise flat surfaces. While the existence is known, we prove the uniqueness. Using Rippa's Theorem we show that, as claimed, Musin's harmonic index provides an optimality criterion for Delaunay triangulations, and this can be used to prove that the edge flipping algorithm terminates also in the setting of piecewise flat surfaces.Comment: 18 pages, 6 vector graphics figures. v2: Section 2 on Delaunay triangulations of piecewise flat surfaces revised and expanded. References added. Some minor changes, typos corrected. v3: fixed inaccuracies in discussion of flip algorithm, corrected attributions, added references, some minor revision to improve expositio

The formation of secondary arylphosphines in the reaction of organonickel sigma-complex [NiBr(Mes)(bpy)], where Mes = 2,4,6-trimethylphenyl, bpy = 2,2′-bipyridine, with phenylphosphine

© 2016 Taylor & Francis Group, LLC.The reactivity of organonickel sigma-complex [NiBr(Mes)(bpy)], where Mes = 2,4,6-trimethylphenyl, bpy = 2,2’-bipyridine towards phenylphosphine (PhPH2) has been investigated. It was found that this interaction leads to secondary mesitylphenylphosphine and dimesitylphosphine by formation of new carbon-phosphorus bond involving mesityl fragment of starting organonickel sigma-complex

Применение методов фрактальной и вычислительной геометрии для картографической генерализации линейных объектов

We present an algorithm for simplifying linear cartographic objects and results obtained with a computer program implementing this algorithm.Предлагается новый алгоритм генерализации линейных картографических объектов. Основным новшеством алгоритма является автоматическая сегментация – разбиение ломаной на участки с одинаковыми свойствами. Сегментация позволяет подобрать параметры сглаживания индивидуально для каждого участка, за счет чего существенно повышается качество результата

Study of "racemic compound-like" behavior of diastereomeric mixture of pinanyl sulfoxides by x-ray diffraction, ir spectroscopy, and DFT calculations

The oxidation of a β-hydroxysulfide in the pinane series by use of mchloroperbenzoic acid resulted in the formation of the corresponding β-hydroxysulfoxide as a mixture of two diastereomers in 4:5 ratio. According to single-crystal X-ray diffraction (XRD) results, it is established that the diastereomeric mixture of sulfoxides crystallizes in the "racemic compound-like" manner under formation of asymmetric dimers through S=O··H-O interactions. This asymmetric dimer formed from diastereomeric molecules is a structural unit in both crystal modifications, the triclinic and the monoclinic one. The behavior of the diastereomeric mixture of pinane derived sulfoxides in crystals, melts and in tetrachloromethane solutions was studied by IR spectroscopy. The density functional theory (DFT) method with 6-31G (d, p) basis set was used to calculate the optimized geometrical parameters and vibrational frequencies of different associates in solution. The calculated vibrational frequencies are compared with experimental IR spectra. Copyright © 2014 Taylor & Francis Group, LLC

Bis-phosphonium salts of pyridoxine: The relationship between structure and antibacterial activity

A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr > Et > Me. Further increasing of length and branching of alkyl chain leads to the reduction of antibacterial activity. Replacement of the phenyl substituents at the phosphorus atoms in 5,6- bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]-dioxino[4,5-c] pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl as well as chloride anions in the compound 1 with bromides (compound 14a) increased the activity against Staphylococcus aureus and Staphylococcus epidermidis up to 5 times (MICs = 1-1.25 μg/ml). But in practically all cases chemical modifications of compound 1 led to the increase of its toxicity for HEK-293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]-2,2,8- trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which demonstrated lower MIC values against S. aureus and S. epidermidis (1 μg/ml) and lower cytotoxicity on HEK-293 cells (CC50 = 200 μg/ml). Compound 10a had no significant mutagenic and genotoxic effects and was selected for further evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine were much more toxic than vancomycin. © 2013 Elsevier Ltd. All rights reserved

Unintentional high density p-type modulation doping of a GaAs/AlAs core-multi-shell nanowire

Achieving significant doping in GaAs/AlAs core/shell nanowires (NWs) is of considerable technological importance but remains a challenge due to the amphoteric behavior of the dopant atoms. Here we show that placing a narrow GaAs quantum well in the AlAs shell effectively getters residual carbon acceptors leading to an \emph{unintentional} p-type doping. Magneto-optical studies of such a GaAs/AlAs core multi-shell NW reveal quantum confined emission. Theoretical calculations of NW electronic structure confirm quantum confinement of carriers at the core/shell interface due to the presence of ionized carbon acceptors in the 1~nm GaAs layer in the shell. Micro-photoluminescence in high magnetic field shows a clear signature of avoided crossings of the $n=0$ Landau level emission line with the $n=2$ Landau level TO phonon replica. The coupling is caused by the resonant hole-phonon interaction, which points to a large 2D hole density in the structure.Comment: just published in Nano Letters (http://pubs.acs.org/doi/full/10.1021/nl500818k

Клинический случай лечения метастатического почечноклеточного рака комбинацией ниволумаба с кабозантинибом в рутинной клинической практике

According to GLOBOCAN, there were about 18 million new cases of cancer and 9.6 million deaths from malignancies worldwide in 2018. Renal cell carcinoma is a malignant tumor characterized by the loss of the VHL gene, which leads to increased angiogenesis. The potential of immuno-oncology and anti-angiogenic drugs has significantly improved outcomes for patients with metastatic renal cell carcinoma. The phase III CheckMate 9ER study compared the efficacy and safety of nivolumab plus cabozantinib versus sunitinib in the first-line treatment of patients with metastatic clear cell renal cell carcinoma. The advantages of nivolumab plus cabozantinib over sunitinib in terms of progression-free survival, overall survival, and objective response rate were generally similar across subgroups based on IMDC risk, PD-L1 expression, and the presence or absence of bone metastases. We present a case report of metastatic renal cell carcinoma. The patient has been on cabozantinib plus nivolumab therapy for 12 months, with a partial response achieved. Treatment was well tolerated; the profile of adverse events was consistent with that in the clinical study.По данным GLOBOCAN, в 2018 году зарегистрировано около 18 миллионов новых случаев рака и 9,6 миллионов смертей от злокачественных новообразований во всем мире. Почечно-клеточный рак представляет собой опухоль, характеризующуюяся потерей гена VHL, и эта потеря приводит к усилению ангиогенеза. Возможности применения иммуноонкологических и антиангиогенных препаратов значительно улучшили результаты лечения пациентов с метастатическим почечно-клеточный раком. Исследование III фазы CheckMate 9ER посвящено сравнению эффективности и безопасности комбинации ниволумаба с кабозантинибом и сунитиниба в терапии первой линии пациентов со светлоклеточным метастатическим почечно-клеточным раком. Преимущества комбинации ниволумаба и кабозантиниба в сравнении с сунитинибом в отношении отсутствия прогрессирования, общей выживаемости и частоты объективных ответов в целом были одинаковыми в подгруппах, включая группу риска по IMDC, экспрессию опухолевого PD-L1 и наличие или отсутствие метастатического поражения костной ткани. Приведено клиническое наблюдение лечения пациента с метастатическим почечно-клеточным раком. В настоящее время пациенту на протяжении 12 месяцев продолжается терапия кабозантинибом и ниволумабом, сохраняется частичный ответ. Переносимость терапии удовлетворительная, спектр нежелательных явлений соответствует таковому в клиническом исследовании

Атезолизумаб и бевацизумаб у пациентов с гепатоцеллюлярной карциномой в реальной клинической практике

   Randomized clinical trials and actual clinical practice differsignificantly. Evidence-based medicine develops new agents referring to, primarily, pharmaceutical findings, preclinical studies and, most importantly, randomized clinical trials. Hepatocellular carcinoma is the most common primary malignancy of the liver, and one of the main causes of fatal outcomes among cancer patients worldwide, including in the Asia-Pacific region, with an estimated 800,000 deaths annually. For more than 10 years, sorafenib, a tyrosine kinase inhibitor, was the only authorized treatment for advanced hepatocellular carcinoma. The next stage in the development of drug therapy for hepatocellular carcinoma involved immune checkpoint inhibitors. The combination of atezolizumab with bevacizumab in the phase III trial (IMbrave150) improved outcomes of advanced hepatocellular carcinoma, such as overall survival and progression-free survival (6.8 versus 4.3). The paper presents the trials of atezolizumab and bevacizumab combination, demonstrates comparable data on the treatment of patients with HCC in real clinical practice and data on the phase III IMbrave150. To further analyze the efficacy of the combination of atezolizumab and bevacizumab, prospective clinical trials should include heterogeneous patient groups.   Рандомизированные клинические исследования и реальная клиническая практика имеют много различий. Создание новых лекарственных средств во время доказательной медицины основано прежде всего на фармацевтических разработках, проведении доклинических исследований и, самое основное, рандомизированных клинических исследованиях. Гепатоцеллюлярная карцинома является наиболее распространенной первичной злокачественной опухолью печени и одной из ведущих причин смертности среди онкологических пациентов во всем мире с примерным количеством 800 000 смертей ежегодно. Более 10 лет тирозинкиназный ингибитор сорафениб был единственным зарегистрированным средством лечения распространенной гепатоцеллюлярной карциномы. Следующим этапом развития лекарственной терапии гепатоцеллюлярной карциномы явилась терапия ингибиторами контрольных точек иммунитета. Комбинация атезолизумаба с бевацизумабом в исследовании III фазы (IMbrave150) улучшила результаты лечения распространенной гепатоцеллюлярной карциномы, такие как общая выживаемость и выживаемость без прогрессирования (6,8 против 4,3). Приведенные в статье исследования комбинации атезолизумаба и бевацизумаба демонстрируют сопоставимые данные при лечении пациентов с ГЦК в реальной клинической практике и в исследовании III фазы IMbrave150. Проспективные клинические испытания, которые включают разнородные группы пациентов, необходимы для дальнейшего анализа эффективности комбинации атезолизумаба и бевацизумаба