Binding Properties of Large Antiviral Polyamides (PA1 and PA25) and Natural Product Derivatives as Inhibitors of Serine Hydrolases

Polyamides are a class of DNA minor groove binders that were developed from the natural product Distamycin A. PA25 (20-ring PA) showed better activity (3-fold) in the elimination of HPV16 episomes than PA1 (14-ring PA). Binding studies of PA1 and PA25 were performed in the long control region of HPV16 (7348-122 bp). PA1 showed similar binding affinity to perfect match and single mismatch binding sites. PA1 bound to double, triple, and quadruple mismatch sites with lower affinity. PA25 bound with similar binding affinity to perfect through triple mismatch binding sites. PA25 bound quadruple mismatch sites and nonspecifically. Therefore, it was concluded that PA25 is better at accommodating mismatches in its binding sites. The serine hydrolase family has a catalytic triad that consists of Serine, Histidine, and Glutamic/Aspartic Acid. Acetylcholinesterase (AChE) belongs to the serine hydrolase family. AChE hydrolyzes acetylcholine to stop signal transmission between neurons and thus is a drug target for Alzheimer’s disease. The previously extracted natural product cyclophostin showed a low nM inhibitory effect against AChE; its phosphonate derivative irreversibly modified the AChE active site. The cyclophostin phosphate or phosphonate, bicyclic or monocyclic derivatives showed low μM potency against human AChE. Fluorination of the monocyclic phosphonate cyclophostin showed no inhibitory effect against AChE up to 100 μM. Hormone sensitive lipase (HSL) is also a serine hydrolase. It hydrolyzes diacylglycerol to monoacylglycerol and is a drug target for type II diabetes. The previously extracted natural product cyclipostin, showed low nM potency against HSL. Cyclipostin has a similar structure to cyclophostin; the only difference is that cyclipostin has a long alkyl chain off the phosphate moiety. SAR studies on the cyclipostin derivatives showed that absence of the long alkyl chain and the phosphate to phosphonate substitution in the bicyclic framework decreased the inhibitory effect against HSL while lactone ring opening did not affect inhibition. SAR studies in the monocyclic phosphonate framework showed that compounds with the alkyl chain on the phosphate moiety have a better inhibitory effect than compounds with the alkyl chain on the 5th carbon in the seven-membered ring

Financial dollarization in Russia: causes and consequences

We review some aspects of financial dollarization in Russia, applying the main relevant theories to analyze the dynamics of several dollarization indicators. An econometric model of the short run dynamics of deposit and loan dollarization is estimated for the last decade. We find that ruble appreciation was the main driver of the de-dollarization that occurred then and of the later episode of renewed dollarization. We estimate the overall (and sectoral) currency mismatches of the Russian economy. The results show a gradual improvement of the net foreign currency position of the public sector, where we have seen significant accumulation of international reserves by the Bank of Russia and repayment of government debt. Evidence is also presented for the significant currency risk vulnerability of the nonbanking private sector. Several existing empirical studies are examined in order to assess the growth losses of the Russian economy following the crisis of 2008, which was linked with the financial dollarization.financial dollarization; currency mismatch; balance sheet effects; Russia

DESIGN-THINKING: PRACTICE OF CUSTOMER EXPERIENCE RESEARCH

The purpose of our research is to find new tools for analysing hidden client needs (pains), regulating the sequence of reasoning when making decisions during the creation of innovative projects. We propose an approach of a creating a map of studying the customer experience of interaction with the product in which we can use Customer Jorney Map (CJM), method of triads and model PEDPL: Pre-Experience, Experience, Post-Experience, Lost-Experience). An important segment of model PEDPL is analysis “Lost Experience” when we can study new processes out-of-plane current business, an alternative to the use of a known product, expansion of functions, the reincarnation of the user experience in another plane, taking into account unrealized characteristics and interests of consumers (cultural characteristics, preferences, hab- its, traditions, etc.). This analysis can account for all patterns of the user experience in the product. This methodology puts in evidence new approaches to structuring information, which is important for im- mersing in user experience, understanding their problems and finding new solutions. Scientific novelty consists of proposed new tools for visualizing associative thinking, constructing a sequence of steps and methods for studying consumers, isolating the problem, developing an idea. The article presents a quest for the rector and the mayor, solving the problem: how easy and inexpensive to make a comfortable life of a short-sighted person in the city and University. In the preparation of the prototype used such methods of design thinking as the map of empathy, the method of the triad, CJM, PEDPL, SAP business origami. The results of the application can be in demand when developing a new Internet service or mobile application, or, for example, to develop a brand strategy, when it is important to explore the hidden needs of the client

Corpus-based conceptualization in sociology: possibilities and limits

The problem of the quantitative interpretation of qualitative data is one of the most important in sociological research. Textual analysis has placed emphasis on deep and careful study of texts how personal strategies embodied in the concepts. However, quantitative interpretation has always been problematic. Our paper deals with the corpus-based conceptualization method, which can considered as a method of collecting and organizing data material from linguistic corpora. The corpus-based conceptualization allows us to establish a closer link with the meaning and identify the whole spectrum of meanings. It shows that some sociologists lose essential meanings in the research process because of lack of in-deep immersion in the daily life and speech of the people. We chose the concepts of "altruism" and "mercy" as examples to demonstrate the corpus-based conceptualization and its place in sociological research methodology. Data comes from the Russian National Corpus. The Russian National Corpus consists of 1802 relevant words, with 775 for altruism and 1047 for mercy. Data processing carried out by SPSS 19.0. As the result, we have discussed what difficulties the researcher can meet using this method and have offered SFL and Role and Reference grammar as a way to accurately determine the context. Our suggestions can be used in the preparation of questionnaires, guides, in an analysis of interview transcripts

Wolbachia-based biocontrol for dengue reduction using dynamic optimization approach

Aedes aegypti females mosquitoes are the principal transmitters of dengue and other arboviral infections. In recent years, it was disclosed that, when deliberately infected with Wolbachia symbiont, this mosquito species loses its vectorial competence and becomes less capable of transmitting the virus to human hosts. Thanks to this important discovery, Wolbachia-based biocontrol is now accepted as an ecologically friendly and potentially cost-effective method for prevention and control of dengue and other arboviral infections. In this paper, we propose a dengue transmission model that accounts for the presence of wild Aedes aegypti females and those deliberately infected with wMelPop Wolbachia strain, which is regarded as the best blocker of dengue and other arboviral infections. However, wMelPop strain of Wolbachia considerably reduces the individual fitness of mosquitoes, what makes rather challenging to achieve the gradual extrusion of wild mosquitoes and ensure their posterior replacement by Wolbachia-carriers. Nonetheless, this obstacle have been overcome by employing the optimal control approach for design of specific intervention programs based on daily releases of Wolbachia-carrying mosquitoes. The resulting optimal release programs ensure the population replacement and eventual local extinction of wild mosquitoes in the finite time and also entail a significant reduction in the number of expected dengue infections among human hosts under the long-term setting

Corpus-based conceptualization in sociology: possibilities and limits

The problem of the quantitative interpretation of qualitative data is one of the most important in sociological research. Textual analysis has placed emphasis on deep and careful study of texts how personal strategies embodied in the concepts. However, quantitative interpretation has always been problematic. Our paper deals with the corpus-based conceptualization method, which can considered as a method of collecting and organizing data material from linguistic corpora. The corpus-based conceptualization allows us to establish a closer link with the meaning and identify the whole spectrum of meanings. It shows that some sociologists lose essential meanings in the research process because of lack of in-deep immersion in the daily life and speech of the people. We chose the concepts of "altruism" and "mercy" as examples to demonstrate the corpus-based conceptualization and its place in sociological research methodology. Data comes from the Russian National Corpus. The Russian National Corpus consists of 1802 relevant words, with 775 for altruism and 1047 for mercy. Data processing carried out by SPSS 19.0. As the result, we have discussed what difficulties the researcher can meet using this method and have offered SFL and Role and Reference grammar as a way to accurately determine the context. Our suggestions can be used in the preparation of questionnaires, guides, in an analysis of interview transcripts

Типы конституциональных диатезов у детей с туберкулезной инфекцией

Diathesis or constitutional abnormality is a polygenically inherited tendency of an organism to diseases, objectively recognized by deviations from the normal phenotype. There are 4 types of diatheses: exudative-catarrhal, lymphatic-hypoplastic, neuro-arthritic and allergic. The aim of the work was to identify and determine the frequency of diathesis in children with different course of tuberculosis infection. 225 children aged from 1 to 14 years were examined: 108 children with active forms of tuberculosis; 54 children with residual post-tuberculosis changes; 63 children with latent tuberculosis infection. It was found that among patients with active tuberculosis, children with lymphatic-hypoplastic (17.6 ± 3.7%) and neuro-arthritic diathesis (16.7 ± 3.6%) are most common, and children with allergic diathesis (11.1 ± 3.0% of cases) are less common. Children with lymphatic-hypoplastic diathesis often develop a complicated course of tuberculosis (26.3 ± 10.1%), there is a pronounced intoxication syndrome (58.0± 11.3%). The frequency of occurrence of children with allergic diathesis is higher in patients with residual post-tuberculosis changes (29.6 ± 6.2%) and with latent tuberculosis infection (33.3 ± 6.0%) than in patients with active tuberculosis (11.1 ± 3.0%)Diateza sau anomalia constituţională este o tendinţă moştenită poligenic a unui organism către maladii, obiectiv recunoscută prin devieri de la fenotipul normal. Există 4 tipuri de diateze: exudativ-catarală, limfatic-hipoplastică, ne-uro-artritică şi alergică. Scopul lucrării a fost de a identifica şi determina frecvenţa diatezei la copiii cu curs diferit de infecţie cu tuberculoză. Au fost examinaţi 225 de copii cu vârste cuprinse între 1 şi 14 ani: 108 copii cu forme active de tuberculoză; 54 de copii cu modificări reziduale post-tuberculoză; 63 de copii cu infecţie latentă cu tuberculoză. S-a constatat că printre pacienţii cu tuberculoză activă, copiii cu diateză limfo-hipoplastică (17,6 ± 3,7%) şi neuro-artritică (16,7 ± 3,6%) sunt cei mai frecvenţi, iar copiii cu diateză alergică (11,1 ± 3,0% din cazuri) sunt mai puţini. Copiii cu diateză limfatic-hipoplastică dezvoltă adesea un curs complicat de tuberculoză (26,3 ± 10,1%), există un sindrom de intoxicaţie pronunţat (58,0 ± 11,3%). Frecvenţa apariţiei copiilor cu diateză alergică este mai mare la pacienţii cu modificări post-tuberculoase reziduale (29,6 ± 6,2%) şi cu infecţie latentă a tuberculozei (33,3 ± 6,0%) decât la pacienţii cu tuberculoză activă (11,1 ± 3,0%)Диатез или аномалия конституции — полигенно наследуемая склонность организма к заболеваниям, объективно распознаваемая по отклонениям от нормального фенотипа. Выделяют 4 типа диатезов: экссудативно-катаральный, лимфатико-гипопластический, нервно-артритический и аллергический. Целью работы было выявление и определение частоты встречаемости диатезов при различном течение туберкулезной инфекции у детей. Обследованы 225 детей в возрасте от 1 года до 14 лет: 108 детей с активными формами туберкулеза; 54 ребенка с остаточными посттуберкулезными изменениями; 63 ребенка с латентной туберкулезной инфекцией. Выявлено, что среди пациентов с активным туберкулезом наиболее часто встречаются дети с лимфатико-гипопластическим (17,6 ± 3,7%) и нервно-артритическим диатезом (16,7 ± 3,6%), реже дети с аллергическим диатезом (11,1 ±3,0% случаев). У детей с лимфатико-гипопластическим диатезом чаще развивается осложненное течение туберкулеза (26,3 ± 10,1%), наблюдается выраженный синдром интоксикации (58,0± 11,3%). Частота встречаемости детей с аллергическим диатезом выше у пациентов с остаточными посттуберкулезными изменениями (29,6 ± 6,2%) и с латентной туберкулезной инфекцией (33,3 ± 6,0%), чем у пациентов с активным туберкулезом (11,1 ± 3,0%

Leveraging Big Data Analytics for Urban Planning: A Study Using the Big Data Analytics Efficiency Test

Data from a variety of sample cities was evaluated as part of a research looking into the integration of big data analytics into urban planning. The goals were to evaluate the impact of data analytics infrastructure, data volume and processing time, urban development initiatives, and data analytics efficiency. The results showed significant differences in data analytics resources across cities, indicating different levels of investment and preparedness for data-driven decision making. It was clear that cities could handle large amounts of data efficiently thanks to their strong data processing skills. Data analytics have an impact on urban development initiatives, highlighting the revolutionary potential of data-driven urban planning. The outcomes of efficiency tests demonstrated how data analytics procedures are useful for improving urban services and for making well-informed judgments. This study offers important new insights into the mechanics of data-driven urban planning and how it can influence how cities develop in the future