QUALITY OF ECONOMIC SPACE: MEASUREMENT PROBLEMS AT THE MESO-LEVEL

The research of theoretical and methodological issues of assessing the quality of the economic space of Russian regions has been conducted. The concepts of economic space and its quality, institutional environment of economic space have been substantiated. In order to determine the integral indicator of the standard of living and the quality of the economic space, the method of a systematic approach has been applied, which allowed the authors to justify and identify the system-forming indicators of the quality of the ec onomic space and the features of the relationship between them. The developed method of assessing the quality of economic space at the meso-level allows you to form a rating of investment attractiveness of the subjects of the Federation and determine the integral indicator of the quality of life of the population of the regions. The results of the study can be used in the development of investment rating and typology of Russian regions, implementation of social policy and state regulation of spatial development

Avalanches in self-organized critical neural networks: A minimal model for the neural SOC universality class

The brain keeps its overall dynamics in a corridor of intermediate activity and it has been a long standing question what possible mechanism could achieve this task. Mechanisms from the field of statistical physics have long been suggesting that this homeostasis of brain activity could occur even without a central regulator, via self-organization on the level of neurons and their interactions, alone. Such physical mechanisms from the class of self-organized criticality exhibit characteristic dynamical signatures, similar to seismic activity related to earthquakes. Measurements of cortex rest activity showed first signs of dynamical signatures potentially pointing to self-organized critical dynamics in the brain. Indeed, recent more accurate measurements allowed for a detailed comparison with scaling theory of non-equilibrium critical phenomena, proving the existence of criticality in cortex dynamics. We here compare this new evaluation of cortex activity data to the predictions of the earliest physics spin model of self-organized critical neural networks. We find that the model matches with the recent experimental data and its interpretation in terms of dynamical signatures for criticality in the brain. The combination of signatures for criticality, power law distributions of avalanche sizes and durations, as well as a specific scaling relationship between anomalous exponents, defines a universality class characteristic of the particular critical phenomenon observed in the neural experiments. The spin model is a candidate for a minimal model of a self-organized critical adaptive network for the universality class of neural criticality. As a prototype model, it provides the background for models that include more biological details, yet share the same universality class characteristic of the homeostasis of activity in the brain.Comment: 17 pages, 5 figure

Antisense oligonucleotides for the arterial hypertension mechanisms study and therapy

Arterial hypertension is one of the most common chronic diseases in adults all over the world. This pathology can not only reduce patients’ life quality, but can also be accompanied by a number of complications. Despite the fact that there is a large group of antihypertensive drugs on the market, mainly representing different combinations of inhibitors of the renin-angiotensin system, adrenoreceptor blockers in combination with diuretics, there is no generally accepted “gold standard” for drugs that would not have side effects. The review discusses the main aspects of antisense oligonucleotides use in the context of arterial hypertension. It is well known that the medical implementation of antisense oligonucleotides aims to block the expression of particular genes involved in the pathology development, and a key advantage of this technique is a high selectivity of the effect. However, with the undoubted advantages of the method, there are difficulties in its application, related both to the properties of the oligonucleotides themselves (insufficient stability and poor penetration into cells), and to the variety of mechanisms of the origin of a particular pathology, arterial hypertension, in our case. The review provides a brief description of the main molecular targets for antisense treatment of hypertensive disease. The newest targets for therapy with oligonucleotides – microRNAs – are discussed. The main modifications of antisense nucleotides, designed to increase the duration of their effects and simplify the delivery of this type of drugs to the targets are discussed, in particular, combining antisense oligonucleotides with adenovirus-based expression vectors. Particular attention is given to antisense oligonucleotides in the complex with nanoparticles. The review discusses the results of the use of titanium dioxide (TiO2) containing antisense nanocomposites for the angiotensin converting enzyme in rats with stress induced arterial hypertension (ISIAH). It was shown that the use of antisense oligonucleotides continues to be a promising technique for studying the mechanisms of various forms of hypertensive disease and has a high potential for therapeutic use

Fine Structure of Avalanches in the Abelian Sandpile Model

We study the two-dimensional Abelian Sandpile Model on a square lattice of linear size L. We introduce the notion of avalanche's fine structure and compare the behavior of avalanches and waves of toppling. We show that according to the degree of complexity in the fine structure of avalanches, which is a direct consequence of the intricate superposition of the boundaries of successive waves, avalanches fall into two different categories. We propose scaling ans\"{a}tz for these avalanche types and verify them numerically. We find that while the first type of avalanches has a simple scaling behavior, the second (complex) type is characterized by an avalanche-size dependent scaling exponent. This provides a framework within which one can understand the failure of a consistent scaling behavior in this model.Comment: 10 page

Comparing frequency and Trueness Scale Descriptors in a Likert Scale Questionnaire on Language Learning Strategies

This paper reports on the comparison of two types of scale descriptors in a questionnaire on language learning strategies.The main purpose of this study was to investigate which type of the two scale descriptors,frequency-based or trueness-based,is better for language learning strategy research. With a few weeks\u27 interval,a questionnaire on learning strategies was administered to 408 EFL learner twice with frequency-based scale descriptors and trueness-based scale descriptors alternately. First, mean differences in the responses obtained from the two different scale descriptors were examined.Second,confirmatory factor analysis was applied to see which scale descriptor of the two shows better fit to the hypothesized model. Finally,equidistance between the categories was checked. Results show that trueness-based scale descriptors elicited slightly higher mean values of responses, which resulted in a better fit to the model. The distances between the categories were almost identical for both scale descriptors.The findings of the current study partially provide supportive evidence for the claim made by Dornyei and his colleagues that trueness-based scale descriptors are preferable to frequency-based counterparts in a questionnaire on learning.But they also show that the latter descriptors are not totally “flawed” as was claimed

Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

Сравнительный анализ эхокардиографических показателей времени ускорения и соотношения времени ускорения к общему времени выброса левого желудочка с показателями катетеризации в оценке тяжести аортального стеноза у пациентов с Normal flow High Gradient

Purpose. 1. To compare the ultrasound indices of time in comparison (AT), cardiac catheterization evaluating severity (AT/ET) with the indices of direct cardiac catheterization and assess the prognostic ability in the assessment of severity of AS in patients with Normal flow High Gradient 2. To determine the threshold values for the indicators of AT and AT/ET in predicting severe AS.Materials and methods. This is prospective single center study. We evaluated results of treatment of 75 patients with mean age 72 ± 6 years that were planned for aortic valve replacement due to aortic stenosis. Inclusion criteria: isolated aortic valve stenosis with ultrasound characteristics of severe AS. Before transcatheter aortic valve implantation, all patients underwent cardiac catheterization with the measurement of parameters necessary to assess the severity of AS.Results. Linear regression analysis showed a statistically significant correlation between AT and AT/ET (p < 0.05). The ROC-analysis has showed the highest predictive ability in assessing the severity of aortic stenosis for the AT / ET index (AUC – 87%, p < 0.001), slightly lower predictive power for the AT parameter (AUC – 80%, p < 0.001). The sensitivity and specificity of the AT / ET indicator in determining severe AS was 84% and 79%, respectively. For the AT indicator, the sensitivity was 82% and the specificity was 46%. The threshold values for AT and AT / ET were 105 ms and 0.35, respectively.Conclusions. 1. AT and AT / ET have a strong correlation with catheterization data and a high predictive ability of severe aortic stenosis in patients with Normal Flow High Gradient patients. 2. Threshold values for AT and AT /ET, that predict a high probability of AS, were 105ms and 0.35ms respectively. The study showed, echocardiographic indicators AT and AT ET have a strong correlation with catheterization data and a high predictive ability of severe aortic stenosis in patients with Normal Flow High Gradient patients. Threshold values for AT and AT ET, that predict a high probability of AS, were 105 ms and 0.35 ms respectively.Цель исследования: 1. Сравнить эхокардиографические показатели времени ускорения (АТ), соотношения времени ускорения к общему времени выброса левого желудочка (AT/ET) и общего времени выброса левого желудочка (ЕТ) с данными прямой катетеризации сердца и оценить предсказательную способность тяжелого аортального стеноза (АС) у пациентов с сохраненным ударным объемом ЛЖ и высокими трансаортальными градиентами. 2. Определить пороговые значения для показателей АТ и АТ/ЕТ в диагностике тяжелого АС.Материал и методы. Проспективно собраны данные 75 пациентов, средний возраст 72 ± 6 лет, которым планировалась транскатетерная имплантация аортального клапана (АК). Критерии включения: изолированный стеноз АК с эхокардиографическими характеристиками, соответствующими тяжелому стенозу с сохраненным ударным объемом ЛЖ и высокими трансаортальными градиентами. Всем исследуемым перед транскатетерной имплантацией АК проводили катетеризацию сердца с измерением показателей, необходимых для оценки тяжести АС.Результаты. Анализ линейной регрессии продемонстрировал статистически значимую корреляционную связь между показателями АT и AT/ET, р < 0,05. Кривая ROC-анализа продемонстрировала наибольшую диагностическую способность в оценке тяжести АС для показателя AT/ET, значение площади под кривой AUC 87 (р < 0,001), несколько меньшую диагностическую способность для показателя АТ, значение под кривой АUC 0,8 (р < 0,001). Чувствительность и специфичность показателя AT/ET в определении тяжелого АС составили 84 и 79% соответственно, для показателя АТ чувствительность – 82% и специфичность – 46%. Были выявлены пороговые значения для показателя АТ и АТ/ЕТ в определении тяжелого стеноза АК – 105 и 0,35 мс соответственно.Выводы. 1. Эхокардиографические показатели АТ и АТ/ЕТ обладают сильной корреляционной связью с данными катетеризации и высокой предсказательной способностью тяжелого АС у пациентов с сохраненным ударным объемом ЛЖ и высокими трансаортальными градиентами. 2. Пороговые значения показателей АТ 105 мс и АТ/ЕТ 0,35 мс могут с высокой долей вероятности диагностировать тяжелый АС

Сравнение эхокардиографического и катетерного методов в диагностике тяжелого стеноза аортального клапана

Purpose. 1. Assess the consistency of echocardiographic measurements with catheterization data in severe aortic stenosis.Assess if inter-method consistency improves after adjusting scores for the pressure recovery factor.To identify factors affecting the consistency of echocardiography and catheterization data.Materials and methods. Prospectively, 70 patients (mean age 72 ± 6 years, 38 females) have been included. All patient underwentcardiac catheterization with single-meter echoscanning of the parameters necessary to assess the severity of aortic valve stenosis before transcatheter aortic valve implantation. Inclusion criteria were isolated aortic stenosis (EOA <1 cm2, Gmax ≥64 mm Hg, Gmean ≥40 mm Hg. Exclusion criteria were LV stroke volume index <35 ml/m2 and a reduced EF <50%, concomitant nontrivial regurgitation of the aortic and mitral valves.Result. The linear regression method showed a weak correlation between the Gmax (Doppler) and Pmean indices, r = 0.48, p = 0.001. Revealed high values of the average difference between the two methods in comparison with the Blent–Altman (SR 19 ± 17 mm Hg.) and low intraclasscorrelation values (ICC = 0.34). After adjusting the Gmax (Doppler) indices for the pressure recovery factor, the correlation between the methods r = 0.84, p ≤ 0.001, significantly improved. There was a decrease in the mean indices, the difference between the two HR methods was (3.15 ± 12 mm Hg.) with highly significant intraclasscorrelation values (ICC = 0.89). Similarly, a low correlation with high values of the average difference was observed when comparing EOA (Doppler) and EOA (catheterization) r = 0.55, p = 0.01, SR 0.21 ± 0.15 cm2, ICC = 0.53. With an improvement in the correlation between the methods after adjustment for the pressure recovery coefficient, r = 0.9, p ≤ 0.001, CP = 0.04 ± 0.08 cm2, ICC = 0.92. Comparison of Gmean (Doppler) indices with catheter Pmean has showed a high correlation between the methods, r = 0.7, p ≤ 0.001, there were relatively low indices of the average difference between the two methods of HR = 7.2 ± 22 mm Hg and a significant intraclass correlation (ICC = 0.72). The method of analysis of multiple regression revealed that the diameter of the sinotubular ridge was a significant factor affecting the correlation between echocardiography and catheterization data, OR 1.2 (CI 0.09; 2.9).ConclusionsThe maximum Doppler gradient (Gmax) and the effective orifice area (EOA) have low consistency and weak correlation with catheterization data, in contrast to the average Doppler gradient (Gmean) which have a high consistency with catheterization data.After correcting for pressure recovery factor, there is a significant improvement in the consistency between Gmax and EOA with catheterization data.The diameter of the sinotobular junction is a significant factor influencing the consistency of echocardiography and catheterization data, which must be taken into account when assessing the severity of aortic stenosis.Цель исследования. 1. Оценить согласованность измерений, проведенных методом эхокардиографии, с данными катетеризации при  тяжелом стенозе аорты.Оценить, улучшается ли согласованность между методами после коррекции показателей на коэффициент восстановления давления.Выявить факторы, влияющие на согласованность данных эхокардиографии и катетеризации.Материал и методы. Проспективно были собраны данные 70 пациентов (из них 38 женщин), средний возраст 72 ± 6 лет, которым перед транскатетерной имплантацией аортального клапана (апикальным доступом) проводили катетеризацию сердца с одномоментным эхосканированием показателей, необходимых для оценки тяжести стеноза аортального клапана.Критерии включения в исследование: изолированный стеноз аортального клапана с эхокардиографическими характеристиками, соответствующими тяжелому стенозу: эффективная площадь отверстия аортального клапана (ЕOA) <1 cм2, максимальный градиент на аортальном клапане (Gmax) ≥64 мм рт.ст., средний градиент на аортальном клапане (Gmean) ≥40 мм рт.ст.Критерии исключения: пациенты с индексируемым ударным объемом ЛЖ к площади поверхности тела <35 мл/м2, сниженной фракцией выброса <50%, пациенты с сочетанной нетривиальной регургитацией на аортальном и митральном клапанах и пациенты с сочетанным значимым стенозом митрального клапана, ускоренным кровотоком в выносящем тракте левого желудочка (выше 1,1 м/c) и постоянной  формой фибрилляции предсердий.Результаты. Метод линейной регрессии продемонстрировал слабую корреляционную связь между показателями Gmax (допплер) и Pmean, r = 0,48, р = 0,001. Отмечались высокие значения средней разницы (СР) между двумя методами при сравнении Бленда–Альтмана (СР = 19 ± 17 мм рт.ст.) и низкие значения внутриклассовой корреляции (ICC = 0,34). После корректировки показателей Gmax (допплер) на коэффициент восстановления давления значительно улучшилась корреляционная связь между методами, r = 0,84, р ≤ 0,001, отмечалось снижение показателей средней разницы между двумя методами (СР = 3,15 ± 12 мм рт.ст.) с высокодостоверными значениями внутриклассовой корреляции (ICC = 0,89).Аналогично низкая корреляционная связь с высокими значениями средней разницы наблюдалась и при сравнении ЕОА (допплер) и ЕОА (катетеризация), r = 0,55, р = 0,01, СР = 0,21 ± 0,15 см2, ICC = 0,53, с улучшением согласованности между методами после корректировки на коэффициент восстановления давления, r = 0,9, р ≤ 0,001, СР = 0,04 ± 0,08 см2, ICC = 0,92.Сравнение показателей Gmean (допплер) c катетерным Pmean продемонстрировало высокую корреляционную связь между методами, г = 0,7, р ≤ 0,001, отмечались относительно низкие показатели средней разницы между двумя методами (СР = 7,2 ± 22 мм рт.ст) и значимая внутриклассовая корреляция (ICC = 0,72).Методом анализа множественной регрессии выявлено, что диаметр синотобулярного соединения является значимым фактором, оказывающим влияние на согласованость данных эхокардиографии и катетеризации OR 1,2 (95%ДИ 0,09; 2,9).ВыводыПоказатели максимального допплеровского градиента (Gmax) и площадь эффективного отверстия (EOA) имеют низкую согласованностью и слабую корреляционную связь с данными катетеризации, в отличие от показателей среднего допплеровского градиента (Gmean), которые имеют высокую согласован ность с данными катетеризации.После коррекции на коэффициент восстановления давления значительно улучшается согласованность между показателями Gmax и EOA с данными катетеризации.Диаметр синотобулярного соединения является значимым фактором, влияющим на согласованность данных эхокардиографии и катетеризации, который необходимо учитывать при оценке тяжести стеноза аорты.

Elimination of quiescent/slow-proliferating cancer stem cells by Bcl-XL inhibition in non-small cell lung cancer

Lung cancer is the most common cause of cancer-related mortality worldwide, urging the discovery of novel molecular targets and therapeutic strategies. Stem cells have been recently isolated from non-small cell lung cancer (NSCLC), thus allowing the investigation of molecular pathways specifically active in the tumorigenic population. We have found that Bcl-XL is constantly expressed by lung cancer stem cells (LCSCs) and has a prominent role in regulating LCSC survival. Whereas chemotherapeutic agents were scarcely effective against LCSC, the small molecule Bcl-2/Bcl-XL inhibitor ABT-737, but not the selective Bcl-2 inhibitor ABT-199, induced LCSC death at nanomolar concentrations. Differently from gemcitabine, which preferentially eliminated proliferating LCSC, ABT-737 had an increased cytotoxic activity in vitro towards quiescent/slow-proliferating LCSC, which expressed high levels of Bcl-XL. In vivo, ABT-737 as a single agent was able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors. Altogether, these results indicate that quiescent/slow-proliferating LCSC strongly depend on Bcl-XL for their survival and indicate Bcl-XL inhibition as a potential therapeutic avenue in NSCLC