Search of new pharmaceuticals on the basis of darbepoetin in the treatment of ischemic stroke: review of literature

The article contains the analysis of medical and biological publications from the global database created by the National Centre for Biology Information (NCBI), an intramural biotechnological division of the US National Library of Medicine. The authors have analyzed publications of the recent ten years. Major results of study of erythropoietins and their recombinant analogues have been generalized and systematized. There has been revealed the significant potential of the preparations of this group to be studied and used. Major advantages and drawbacks of erythropoietins and their recombinant analogues have been describe

The susceptibility and excitation spectrum of (VO)2_2P2_2O7_7 in ladder and dimer chain models

We present numerical results for the magnetic susceptibility of a Heisenberg antiferromagnetic spin ladder, as a function of temperature and the spin-spin interaction strengths $J_\perp$ and $J_{||}$. These are contrasted with new bulk limit results for the dimer chain. A fit to the experimental susceptibility of the candidate spin-ladder compound vanadyl pyrophosphate, (VO)$_2$P$_2$O$_7$, gives the parameters $J_\perp = 7.82$ meV and $J_{||} = 7.76$ meV. With these values we predict a singlet-triplet energy gap of $E_{gap} = 3.9$ meV, and give a numerical estimate of the ladder triplet dispersion relation $\omega(k)$. In contrast, a fit to the dimer chain model leads to $J_1=11.11$ meV and $J_2=8.02$ meV, which predicts a gap of $E_{gap} = 4.9$ meV.Comment: 16 pages, 6 figures available upon request, RevTex 3.0, preprint ORNL-CCIP-94-04 / RAL-94-02

Inelastic Neutron Scattering from the Spin Ladder Compound (VO)2P2O7

We present results from an inelastic neutron scattering experiment on the candidate Heisenberg spin ladder vanadyl pyrophosphate, (VO)2P2O7. We find evidence for a spin-wave excitation gap of $E_{gap} = 3.7\pm 0.2$ meV, at a band minimum near $Q=0.8 A^{-1}$. This is consistent with expectations for triplet spin waves in (VO)2P2O7 in the spin-ladder model, and is to our knowledge the first confirmation in nature of a Heisenberg antiferromagnetic spin ladder.Comment: 11 pages and 2 figures (available as hard copy or postscript files from the authors, send request to [email protected] or [email protected]), TEX using jnl, reforder and eqnorder, ORNL-CCIP-94-05 / RAL-94-04

Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS

Background In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS. Methods Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≥ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≥ 2. Results Of 507 randomized patients, 496 had baseline QoL data available. The analysis cut-off was 6 cycles for trifluridine/tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS. Conclusion QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo

Future of the universe in modified gravitational theories: Approaching to the finite-time future singularity

We investigate the future evolution of the dark energy universe in modified gravities including $F(R)$ gravity, string-inspired scalar-Gauss-Bonnet and modified Gauss-Bonnet ones, and ideal fluid with the inhomogeneous equation of state (EoS). Modified Friedmann-Robertson-Walker (FRW) dynamics for all these theories may be presented in universal form by using the effective ideal fluid with an inhomogeneous EoS without specifying its explicit form. We construct several examples of the modified gravity which produces accelerating cosmologies ending at the finite-time future singularity of all four known types by applying the reconstruction program. Some scenarios to resolve the finite-time future singularity are presented. Among these scenarios, the most natural one is related with additional modification of the gravitational action in the early universe. In addition, late-time cosmology in the non-minimal Maxwell-Einstein theory is considered. We investigate the forms of the non-minimal gravitational coupling which generates the finite-time future singularities and the general conditions for this coupling in order that the finite-time future singularities cannot emerge. Furthermore, it is shown that the non-minimal gravitational coupling can remove the finite-time future singularities or make the singularity stronger (or weaker) in modified gravity.Comment: 25 pages, no figure, title changed, accepted in JCA

Analysis of the Key Directions of Low-Carbon Transformation of the Moscow Economy for the Period until 2035

Принятие федеральной Стратегии социально-экономического развития Российской Федерации с низким уровнем выбросов парниковых газов до 2050 года определяет необходимость учета климатического аспекта в стратегическом планировании, в том числе на уровне отдельных регионов и городов. Цель статьи заключается в анализе ключевых и наиболее эффективных направлений низкоуглеродной трансформации экономики города Москвы. Исследование опирается на методы математического моделирования и сценарного прогнозирования, модельный инструментарий разработан для оценки прямых эмиссий парниковых газов, обусловленных потреблением топливноэнергетических ресурсов. Москва является регионом-лидером в части снижения эмиссий парниковых газов: за 2012-2019 гг. они сократились на 9 % благодаря модернизации сектора энергоснабжения, приоритезации когенерации, развитию городского транспорта. На период до 2035 г. реалистичной и достижимой является цель снижения эмиссий еще на 7-11 %. Для этого необходимо активизировать меры по следующим ключевым направлениям: энергоэффективные капитальные ремонты и новое строительство (включая программу реновации), автоматизация центральных тепловых пунктов и узлов управления системами теплоснабжения в сфере зданий и ЖКХ, полная электрификация общественного транспорта, стимулирование топливной эффективности и использования электромобилей (личных, а также в сфере такси, каршеринга, доставки, коммерческих перевозок) в сфере транспорта. В сфере энергетики следует отказаться от форсированного наращивания собственной электрогенерации: альтернативой должны стать поддержание существующих эффективных генерирующих мощностей и закупка недостающих объемов на профицитном оптовом рынке электроэнергии. Для обеспечения условий низкоуглеродной трансформации Москвы целесообразно внедрить критерий влияния принимаемых мер на объем эмиссий при планировании всех городских программ, схем развития и инвестиционных проектов. Результаты и выводы статьи могут быть полезны при разработке документов стратегического планирования города Москвы.The adoption of the Strategy for the socio-economic development of the Russian Federation with low greenhouse gas emissions until 2050 requires considering the climate aspect of strategic planning, including at the regional and city levels. The article analyses key areas of low-carbon transformation of the Moscow economy. The study is based on the methods of mathematical modelling and scenario forecasting, utilised to estimate direct greenhouse gas emissions from energy and fuel consumption. Moscow is the leading region in terms of reducing greenhouse gas emissions, as they decreased by 9 % in 20122019 due to the modernisation of the energy sector, use of cogeneration, and development of urban transport. For the period until 2035, a realistic and achievable goal is to reduce emissions by another 7-11 %. To this end, it is necessary to strengthen measures in the following areas: energy-efficient capital repairs and construction (including the renovation programme); automation of central heating systems and heat supply units of buildings and housing and communal services; full electrification of public transport; promotion of fuel efficiency and the use of electric vehicles (personal and commercial transport, taxi, carsharing, delivery). In the energy sector, we recommend to maintain the existing generating capacities and purchase the rest on the surplus energy market rather than forcibly increase power generation. To ensure low-carbon transformation of Moscow, the criterion of the impact of adopted measures on emissions should be introduced and considered when planning city programmes, development schemes and investment projects. The research findings may be used to create strategic planning documents for Moscow.Авторы выражают признательность С. Р. Милякину, А. А. Галингеру, Н. Д. Курдюковой (ИНП РАН), А. О. Миронович, С. Н. Щукину (ЦНП) за значимый вклад в результаты исследования.The authors would like to express their gratitude to S. R. Milyakin, A. A. Galinger, N. D. Kurdyukova (Institute of Economic Forecasting of RAS,), A. O. Mironovich and S. N. Shchukin (Tax Policy Center) for their valuable contributions to the study

Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: Results of a randomized phase III trial

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Genome-wide sequence analyses of ethnic populations across Russia

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation. Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country

Expression of NES-hTERT in Cancer Cells Delays Cell Cycle Progression and Increases Sensitivity to Genotoxic Stress

Telomerase is a reverse transcriptase associated with cellular immortality through telomere maintenance. This enzyme is activated in 90% of human cancers, and inhibitors of telomerase are currently in clinical trials to counteract tumor growth. Many aspects of telomerase biology have been investigated for therapy, particularly inhibition of the enzyme, but little was done regarding its subcellular shuttling. We have recently shown that mutations in the nuclear export signal of hTERT, the catalytic component of telomerase, led to a mutant (NES-hTERT) that failed to immortalize cells despite nuclear localization and catalytic activity. Expression of NES-hTERT in primary fibroblast resulted in telomere-based premature senescence and mitochondrial dysfunction. Here we show that expression of NES-hTERT in LNCaP, SQ20B and HeLa cells rapidly and significantly decreases their proliferation rate and ability to form colonies in soft agar while not interfering with endogenous telomerase activity. The cancer cells showed increased DNA damage at telomeric and extra-telomeric sites, and became sensitive to ionizing radiation and hydrogen peroxide exposures. Our data show that expression of NES-hTERT efficiently counteracts cancer cell growth in vitro in at least two different ways, and suggest manipulation with the NES of hTERT or its subcellular shuttling as a new strategy for cancer treatment