This book examines how Russia, the world’s most complicated country, is governed. As it resumes its place at the centre of global affairs, the book explores Russia’s overarching strategies, and how it organizes itself (or not) in policy areas ranging from foreign policy and national security to health care, education, immigration, science, sport, agriculture, the environment and criminal justice. The book also discusses the structures and institutions on which Russia relies in order to deliver its goals in these areas of national life, as well as what’s to be done, in policy terms, to improve the country’s performance in its first post-Soviet century. Edited by Irvin Studin, the book includes contributions from a tremendous list of Russia’s leading thinkers and specialists, including Alexei Kudrin, Vladimir Mau, Alexander Auzan, Simon Kordonsky, Fyodor Lukyanov, Natalia Zubarevich and Andrey Melville.
The authors proposed and mathematically described model of a new type of the Fermi-Pasta-Ulam recurrence (the FPU auto recurrence) and hypothesized an adequate description of the heart's electrical dynamics within the observed phenomenon. The dynamics of the FPU auto recurrence making appropriate electrical dynamics of the normal functioning of the heart in the form of an electrocardiogram (ECG) was obtained by a computer model study. The model solutions in the form of the FPU auto recurrence – ECG Fourier spectrum were evaluated for resistance to external disturbances in the form of random effects, as well as periodic perturbation at a frequency close to the heart beating rate of about 1 Hz. In addition, in order to simulate the dynamics of myocardial infarction model, studied the effect of the surface area of the myocardium on the stability and shape of the auto recurrence – ECG spectrum. It has been found that the intense external disturbing periodic impacts at a frequency of about 1 Hz lead to a sharp disturbance spectrum shape FPU auto recurrence – ECG structure. In addition, the decrease in the surface of the myocardium by 50% in the model led to the destruction of structures of the auto recurrence – ECG, which corresponds to the state of atrial myocardium. Research models have revealed a hypothetical basis of coronary heart disease in the form of increasing the energy of high-frequency harmonics spectrum of the auto recurrence by reducing the energy of low-frequency harmonic spectrum of the auto recurrence, which ultimately leads to a sharp decrease in myocardial contractility. In order to test the hypothesis has been studied more than 20,000 ECGs both healthy people and patients with cardiovascular disease. As a result of these studies, it was found that the dynamics of the electrical activity of normal functioning of the heart can be interpreted by the display of the detected by authors the FPU auto recurrence, and coronary heart disease is a violation of the energy ratio between the low and high frequency harmonics of the FPU auto recurrence Fourier spectrum equal to the ECG spectrum. Thus, the hypothesis has been confirmed.
The materials of The International Scientific – Practical Conference is presented below. The Conference reflects the modern state of innovation in education, science, industry and social-economic sphere, from the standpoint of introducing new information technologies.
It is interesting for a wide range of researchers, teachers, graduate students and professionals in the field of innovation and information technologies.
Adequate assessment of individual functional motor potentials is important for developing appropriate rehabilitation strategies in ischemic stroke . Microstructural changes in corticospinal tract (CST) and corpus callosum (CC) were repeatedly correlated to post-stroke outcome [2, 3]. However, relationship between them and functional recovery remains unclear. Here we investigated relationship between integrity of CST and CC assessed with diffusion tensor imaging (DTI) and brain functional state assessed with navigated transcranial magnetic stimulation (nTMS) in chronic ischemic supratentorial stroke.
The present volume is the fourth issue of the Yearbook series entitled ‘Evolution’. The title of the present volume is ‘From Big Bang to Nanorobots’. In this way we demonstrate that all phases of evolution and Big History are covered in the articles of the present Yearbook. Several articles also present the forecasts about future development.
The main objective of our Yearbook as well as of the previous issues is the creation of a unified interdisciplinary field of research in which the scientists specializing in different disciplines could work within the framework of unified or similar paradigms, using the common terminology and searching for common rules, tendencies and regularities. At the same time for the formation of such an integrated field one should use all available opportunities: theories, laws and methods. In the present volume, a number of such approaches are used.
The volume consists of four sections: Universal Evolutionary Principles; Biosocial Evolution, Ecological Aspects, and Consciousness; Projects for the Future; In Memoriam.
This Yearbook will be useful both for those who study interdisciplinary macroproblems and for specialists working in focused directions, as well as for those who are interested in evolutionary issues of Cosmology, Biology, History, Anthropology, Economics and other areas of study. More than that, this edition will challenge and excite your vision of your own life and the new discoveries going on around us!
The book presents the most important aspects of safe digital image workflows, starting from the basic practical implications and gradually uncovering the underlying concepts and algorithms. With an easy-to-follow, down-to-earth presentation style, the text helps you to optimize your diagnostic imaging projects and connect the dots of medical informatics.
In the context of global efforts to move towards universal coverage in health systems, this report reviews health financing reforms in the Republic of Moldova and looks in particular at how the population´s access to health services has been affected. In 2004, as has been widely documented elsewhere, wholesale reforms were made to the way in which government funds were used to fund health services, shifting the system overnight from a highly fragmented and inflexible one, to one in which funds for the health sector were pooled nationally, allowing improved risk-sharing as a result of greater flexibility to allocate funds in line with health needs. A new source of funding in the form of a payroll tax for health was also introduced directly leading to a growth in total levels of government health spending. A second phase of reforms starting in 2009 addressed the issue of gaps in population coverage under mandatory health insurance, with legislative measures taken to ensure that all citizens of Moldova had access to primary health care, and to ensure that the poor receive subsidized health insurance. Fiscal constraints have limited the full implementation of these reforms however. Moldova has shown that it is prepared to tackle difficult policy issues head on and has articulated clear goals for the sector. In particular, the Roadmap “Accelerating Reforms: addressing the needs of the health area through investment policies” approved on 1 March 2012, lays a clear agenda for the next phase or priority reforms focusing on principally on service delivery reorganization but also on health financing. This is the correct focus given that progress on a number of priority indicators such as equity in access to services and financial protection has been limited in recent years. This report summarizes the main impact of health financing reforms to date and agrees with the Roadmap about the major challenges for the coming decade, in particular the need to address inefficiencies in service delivery, but also to ensure that the close link between guaranteed benefits and available funding is maintained in future policy decisions.
Paired-pulse transcranial magnetic stimulation (TMS) allows investigating inhibitory and excitatory interactions in the human motor cortex noninvasively. Short-interval intracortical inhibition (SICI) and facilitation (SICF) are used to measure cortico–cortical excitability in patients with, e.g., stroke, dystonia, and Parkinson’s disease. However, the role of the induced electric field (E-field) orientation remains partly unclear. Posterior–anterior (PA)-oriented E-field elicits motor evoked potentials (MEPs) with the lowest stimulus intensities due to the recruitment of corticospinal neurons, indirectly via excitatory synaptic inputs to corticospinal axons (indirect (I-) waves). Stimulation in the lateral–medial (LM) orientation directly activates corticospinal axons, which leads to the generation of both direct (D-) and I-waves. Conditioning stimulus (CS) with an intensity between 50% and 90% of resting motor threshold (RMT) induces activation of GABAA inhibitory mechanisms observed as the SICI (inhibitory) effect on MEP amplitude. In contrast, if the CS intensity is above RMT, the SICF (excitatory) phenomenon can be present due to the superposition of D- and I-waves. Our aim was to investigate the dependence of inhibitory and facilitatory mechanisms on the orientation of the induced E-field of CS and TS. We developed a multi-locus TMS (mTMS) transducer, which allowed us to control the E-field orientation independently for CS and TS at a millisecond inter-pair interval (IPI). Eight healthy subjects (five males; mean age 29, range 21–35 years) participated in the study. mTMS was applied to the hotspot of the abductor pollicis brevis (APB) muscle in the left primary motor cortex. The stimulus intensities were based on the individual RMT of APB for PA and LM orientations. TS and single pulses were administered at 110% RMT. Twenty single pulses were applied for each TS orientation and for each of the 32 paired-pulse conditions. CS and TS stimuli were applied in every combination of the PA and LM orientations with four CS intensities (50, 70, 90, and 110% RMT) and two IPIs (1.5 and 2.7 ms) in a random order. Interaction between CS orientation, IPI, and CS intensity significantly affected TS MEP amplitudes. We observed no statistically significant difference between the responses induced by PA- and LM-oriented TS. CS at 70% RMT for SICI and at 110% RMT for SICF induced similar effects regardless of the TS orientation. We established that LM-oriented CS at 90% RMT produced a greater inhibition than stimuli at the same intensity in the PA orientation. Our results emphasize the minimal influence of the CS E-field dorientation on the test pulse. Additionally, we demonstrate the pivotal role of the stimulus intensity for any CS orientation. SICI and SICF evoked using perpendicular CS and TS directions indicate that we stimulated overlapping neuronal populations with both pulses.
Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophylic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxilic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as antibiotic heliomycin, still showed pronounced activity against tick-borne encephalitis virus (TBEV) with limited toxicity in porcine embryo kidney (PEK) cell line. 5-(Perylen-3-yl)-2-thiophenecarboxylic acid (5a) showed the highest antiviral activity with 50% effective concentration of approx. 1.6 nM.
The cooperative dynamics of cellular populations emerging from the underlying interactions determines cellular functions and thereby their identity in tissues. Global deviations from this dynamics, on the other hand, reflect pathological conditions. However, how these conditions are stabilized from dysregulation on the level of the single entities is still unclear. Here, we tackle this question using the generic Hodgkin–Huxley type of models that describe physiological bursting dynamics of pancreatic -cells and introduce channel dysfunction to mimic pathological silent dynamics. The probability for pathological behavior in -cell populations is ~100% when all cells have these defects, despite the negligible size of the silent state basin of attraction for single cells. In stark contrast, in a more realistic scenario for a mixed population, stabilization of the pathological state depends on the size of the subpopulation which acquired the defects. However, the probability to exhibit stable pathological dynamics in this case is less than 10%. These results, therefore, suggest that the physiological bursting dynamics of a population of -cells is cooperatively maintained, even under intercellular communication defects induced by dysfunctional channels of single cells.
This study investigates whether economic freedom of a region drives firm performance. Despite the large number of papers about the relationship between economic freedom and growth, there is still little evidence on the role of economic freedom in performance of individual firms. We address this gap in the literature using hierarchical linear modelling, allowing us to investigate regional differences in company level performance. The dataset consists of information about 1096 companies combined with the Index of Economic Freedom for Russian regions during the period 2004 – 2014
Haptic illusions serve as important tools for studying neurocognitive processing of touch and can be utilized in practical contexts. We report a new spatiotemporal haptic illusion that involves mislocalization when the order of vibrotactile intensity is manipulated. We tested two types of motors mounted in a 4 × 4 array in the lower thoracic region. We created apparent movement with two successive vibrotactile stimulations of varying distance (40, 20, or 0 mm) and direction (up, down, or same) while changing the temporal order of stimulation intensity (strong-weak vs. weak-strong). Participants judged the perceived direction of movement in a 2-alternative forced-choice task. The results suggest that varying the temporal order of vibrotactile stimuli with different intensity leads to systematic localization errors: when a strong-intensity stimulus was followed by a weak-intensity stimulus, the probability that participants perceived a downward movement increased, and vice versa. The illusion is so strong that the order of the strength of stimulation determined perception even when the actual presentation movement was the opposite. We then verified this “intensity order illusion” using an open response format where observers judged the orientation of an imaginary line drawn between two sequential tactor activations. The intensity order illusion reveals a strong bias in vibrotactile perception that has strong implications for the design of haptic information systems.
BACKGROUND "Branched tail" oxyquinolines, and adaptaquin in particular, are potent HIF prolyl hydroxylase inhibitors showing promising results in in vivo hemorrhagic stroke models. The further improvement of the potency resulted in identification of a number of adaptaquin analogs. Early evaluation of toxicity and metabolism is desired right at the step of lead selection. OBJECTIVE The aim of the study is to characterize the toxicity and metabolism of adaptaquin and its new improved analogs. METHOD Liver-on-a-chip technology with differentiated HepaRG cells followed by LC-MS detection of the studied compounds and metabolites of the P450 substrate-inhibitor panel for CYP2B6, CYP2C9, CYP2C19, and CYP3A4. RESULTS The optimized adaptaquin analogs show no toxicity up to a 100-fold increased range over EC50. The drugs are metabolized by CYP3A4 and CYP2B6 as shown with the use of the cytochrome P450 substrate-inhibitor panel designed and optimized for preclinical evaluation of drugs' in vitro biotransformation on a 3D human histotypical cell model using "liver-on-a-chip" technology. Activation of CYP2B6 with the drugs tested has been observed. A scheme for adaptaquin oxidative conversion is proposed. CONCLUSION The optimized adaptaquin analogs are suitable for further preclinical trials. Activation of CYP2B6 with adaptaquin and its variants points to a potential increase in Tylenol toxicity if administered together.
Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on IGFBP6 gene, which is associated with low proliferative state and high migratory activity of basal-like breast cancer. We inhibited expression of IGFBP6 gene in a model cell line for basal-like breast carcinoma MDA-MB-231, then traced secondary and tertiary effects of this knockdown to LAMA4, a laminin encoding gene that contributes to the phenotype of triple-negative breast cancer. LAMA4-regulating miRNA miR-4274 and its host gene SORCS2 were highlighted as intermediate regulators of the expression levels of LAMA4, which correlated in a basal-like breast carcinoma sample subset of TCGA to the levels of SORCS2 negatively. Overall, our study points that the secondary and tertiary layers of regulatory interactions are certainly underappreciated. As these types of molecular event may significantly contribute to the formation of the cell phenotypes after RNA interference based knockdowns, further studies of multilayered molecular networks affected by RNAi are warranted.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver pathology. Here we propose tissue‐cooperative, homeostatic model of NAFLD. During early stages of NAFLD the intrahepatic production of miR‐122 falls, while the secretion of miRNA‐containing exosomes by adipose increases. Bloodstream carries exosome to the liver, where their miRNA cargo is released to regulate their intrahepatic targets. When the deterioration of adipose catches up with the failing hepatic parenchyma, the external supply of liver‐supporting miRNAs gradually tapers off, leading to the fibrotic decompensation of the liver and an increase in hepatic carcinogenesis. This model may explain paradoxical observations of the disease‐associated decrease in intrahepatic production of certain miRNAs with an increase in their levels in serum. Infusions of miR‐122 and, possibly, some other miRNAs may be efficient for preventing NAFLD‐associated hepatocellular carcinoma. The best candidates for exosome‐wrapped miRNA producer are adipose tissue‐derived mesenchymal stem cells (MSCs), known for their capacity to shed large amounts of exosomes into the media. Notably, MSC‐derived exosomes with no specific loading are already tested in patients with liver fibrosis. Carrier exosomes may be co‐manufactured along with their cargo. Exosome‐delivered miRNA cocktails may augment functioning of human organs suffering from a variety of chronic diseases.