Kui bioloog kohtab keemikut: HIV-1 inhibiitorite otsingul

Väitekirja elektrooniline versioon ei sisalda publikatsioone.HIV-1 on pandeemiline viirus ning nakatatud inimeste arv maailmas suureneb pidevalt. Vaktsiin selle vastu puudub, kuid nakatatud patsientide raviks on kliinilise kasutuse loa saanud ligi 30 erinevat ühendit. Erinevatesse klassidesse kuuluvate inhibiitorite kombineeritud kasutamine (ART) on kujunenud HIV-ga nakatunud patsientide ravimise aluseks. ART ravi kõige olulisemaks puuduseks on ravimite toksilised kõrvaltoimed ning uute resistentsete viiruse tüvede teke. Antud väitekirja põhieesmärgiks oli leida efektiivseid mittetoksilisi ühendeid, mis suruvad maha HIV-1 replikatsiooni (nii metsik-tüüpi viiruse kui ka resistentsete tüvede oma) keskendudes eelkõige pöördtranskriptaasi inhibiitoritele. Kolm gruppi keemilisi ühendeid testiti antiretroviirus-vastase toime suhtes: atsüklilised tümidiini nukleosiidi analoogid, bimorfoliinid ja nende derivaadid ning sahariidhüdrasoonid. Samuti tõestati eksperimentaalselt eelneva in silico skriiningu käigus saadud tulemusi. Käesoleva töö tulemusena töötati välja meetod HIV-1 inhibiitorite skriinimiseks ViraPower lentiviiruse ekspressioonisüsteemi (Invitrogen) põhjal. Meetod on kiire, lihtne, usaldusväärne ning on kõlblik kasutamiseks väljaspool kõrgenenud ohutustasemega laborit (BSL3). Kõige tugevam toime meie laboris uuritud ühenditest oli mitte-nukleosiidsel pöördtranskriptaasi inhibiitoril (NNRTI), mis omas tuntud ravimi Nevirapiiniga sarnast aktiivsust, kuid oli kahjuks mitteaktiivne viiruse resistentsete vormide vastu. Antud ühend leiti ratsionaalse ravimidisaini strateegiat kasutades. Antud töö tulemused võimaldasid täiustada olemasolevat in silico skriiningu meetodit, mis võimaldab tulevikus kavandada uusi ning efektiivsemaid HIV-1 inhibiitoreid.HIV-1 is a pandemic virus and the numbers of infected people are constantly increasing all over the world. There is no vaccine available, but about 30 compounds have been approved by FDA for the treatment of HIV-infected patients. ART (antiretroviral therapy) consists of a combination of at least 3 inhibitors with different mechanism of action. The main drawback of such treatment is side effects of the drugs and the appearance of new resistant forms of the virus. The aim of this work was to find non-toxic compounds which can effectively suppress HIV-1 replication (both wild-type and resistant forms of the virus). We focused our efforts mostly on the discovery of novel reverse transcriptase inhibitors. Three groups of compounds were tested for their antiretroviral activity (acyclic thymine nucleoside analogues, bimorpholines and their derivatives, and saccharide hydrazones); also we experimentally verified the results of the previous in silico screening. As a result of this work, we developed an assay for HIV-1 inhibitors′ screening. This assay is based on ViraPower Lentiviral Expression System (Invitrogen) and is simple, fast, reliable and can be used outside BSL3 facilities. The most potent compound, found by us so far, acts as a non-nucleoside reverse transcriptase inhibitor (NNRTI) and has activity comparable to the activity of a known NNRTI nevirapine, but is unfortunately inactive against the resistant forms of the virus. This compound was found using ration drug design strategy. Most importantly, the results of this work allowed us to improve the existing in silico screening method, which could result in more potent HIV-1 inhibitors in the future

Temporal nature of plasticity in the design of materials

A full spectrum of materials responses to dynamic loading and observed temporal effects of plasticity from a united viewpoint are analyzed. The relaxation model of plasticity with characteristic time idea is capable to effectively predict the instability of the stress-strain dependencies on strain rates. It is shown that empirical models cannot simultaneously simulate the appearance and disappearance of the yield drop unlike the relaxation model of plasticity presented in the paper

Dynamics of Reading Culture in the Global Information Society

The article raises the issue of reading culture dynamics in the global information society. The tendency of the development of the modern information society is the change in the axiological status of practices that previously had a marker of elitist, high-status intellectual participants (reading fiction, hearing and understanding classical art, conscious perception of modern art, etc.). Reading is connected with the definition of the status of information as a socio-cultural phenomenon and carriers of information, which are basic for modern man. Fiction acquires the importance of a marker of the relationship of the individual with the extra-utilitarian practices of modern society. Reading is still the practice of elite, despite the declared availability of knowledge in the post-industrial era. A new kind of reading culture is being born, which is presented by "texts about texts" since in the modern world, it is not the phenomenon which is important but its presentation. New network media begin to be experts which define the borders and the orientation of reading. They emphasize novelty and a broad thematic scope of literary texts, which reviews will become basic for the world view of a modern person

Проблема самопрезентации в современном литературном процессе («Нарратив об авторе» в интервью Е. Симоновой)

This article explores a particular version of the narrative of personal stories, i.e., the “narrative about the author”, which is indicative for the analysis of writers’ reflection on their role in modern Russian-language literature. The article aims to determine the specifics of the “narrative about the author”, show that it is formed in public discourse and conditioned by the existence of a narrative framework (a question-and-answer form of an interview that demonstrates public expectations from the creator). Public self-reflection captures the process of self-identification and modeling of the myth of verbal creative work in modern times. The event of the “narrative about the author” is an important change, after which they were able to define themselves as a writer (to name themselves). The author uses methods of classical and postclassical narratology, as well as personological and narrative psychology in the study of the “narrative about the author”. The study reveals that the “narrative about the author” occupies a borderline position with respect to fictionality, the narrator is non-trivial, they are both inside the event and outside it, combining personal attitude with social, cultural, and other conventions adopted about authorship. The article considers the “narrative about the author” with reference to an interview with the Ural poet E. Simonova. The empirical basis of the study is the interviews she gave from 2019 to 2022. In her interviews, Ekaterina Simonova creates an image of a “little poet”, a socio-psychological construct created under the influence of changes in the symbolic status of poetry in modern times, whose components are non-exclusivity and inclusion into everyday life. Within the narrative and within the limits of one response, one sees the formulation of a position, and in the comments given in parentheses, its ironic interpretation. As a result, the author concludes that in the interview with E. Simonova, a myth develops about the writer as an “everyday”, ordinary person who is built on a strategy of ironic sincerity, which is consistent with the artistic narrative of her poetry.В статье исследуется частный вариант нарратива личных историй — «нарратив об авторе», который показателен для анализа рефлексии писателей над их ролью в современной русскоязычной литературе. Цель анализа — определить специфику «нарратива об авторе», показать, что он формируется в публичном дискурсе и обусловлен существованием нарративной рамки (вопрос-ответной формы интервью, которая демонстрирует общественные ожидания от творца). Публичная саморефлексия фиксирует процесс самоидентификации и моделирование мифа о словесном творчестве в новейшее время. Событие «нарратива об авторе» — важное изменение, после которого он смог определить себя как писателя (наименовать себя). В исследовании «нарратива об авторе» применялись методы классической и постклассической нарратологии, а также персонологической и нарративной психологии. В ходе работы удалось выявить, что «нарратив об авторе» находится в пограничной позиции по отношению к фикциональности, нарратор нетривиален, находится одновременно внутри события и вне его, соединяя личное отношение с социальными, культурными и иными конвенциями, принятыми по поводу авторства. «Нарратив об авторе» был рассмотрен на примере интервью уральской поэтессы Е. Симоновой. Эмпирическая база исследования — интервью, данные ею с 2019 по 2022 г. Екатерина Симонова создает в интервью образ-тип «маленького поэта», это социально-психологический конструкт, созданный под влиянием изменения символического статуса поэзии в новое время, компонентами которого являются неисключительность и вписанность в повседневность. Внутри наррации в пределах одной ответной реплики мы видим формулирование позиции, а в комментариях, данных в скобках, ее ироническое обыгрывание. В результате можно сделать вывод, что в интервью Е. Симоновой складывается миф о писателе как о «повседневном», обыкновенном человеке, который построен на стратегии иронической искренности и непротиворечив художественному нарративу ее поэзии в целом

EFFECT OF COMPONENT COMPOSITION OF PIGMENT COMPLEX ON THE FORMATION OF COLOR OF RHUBARB AND GOOSEBERRY

The objective of present study is to determine the influence of component composition of pigment complex on the formation of color of rhubarb and gooseberry that defines consumer properties of these plant products. We report comparative study of rhubarb of the botanical varieties Monarch, Linney, Krupnochereshkovyy, Ogrski, and of gooseberry of the varieties Malachite, Pavlovsky green, Green urozhainyy, Green butylochnyy, zoned in the eastern regions of Ukraine. To determine the content of pigment complex substances of rhubarb and gooseberry, we used methodology by V.F. Gavrilenko and L.M. Khandobina. The method of the International Commission on Illumination (ICI) was applied for quantitative characteristic of color. Results of research into qualitative and quantitative composition of pigment complex of berries of gooseberry and rhubarb stalks revealed that the main components are the chlorophylls whose overall content for different varieties of rhubarb is (3.7…4.5)∙10-3 %, for berries of gooseberry is (3.5…4.7)∙10-3 %. The color characteristics of the examined samples of gooseberry and rhubarb are correlated with the quantitative content of pigments in the raw materials and make it possible to determine the dominant tone (λd, nm) − green, color purity − green with shades of blue, brightness – green, light green, dark green, which coincide with the visual estimation of color. We show expediency of the application of the ICI XYZ method to characterize the color, which considerably facilitates the estimation of color when assessing the quality of food products.&nbsp

Formation of Consumption Properties of Sweet Pepper (Capsicum Annuum L.) Sauce

The aim of the study is to form consumption properties of a green sweet pepper sauce with a balanced content of macro- and microelements. Due to the use of Xanthium strumarium and chitosan a new product has high organoleptic properties that attract a consumer and increase its competitiveness at the market.Sweet green pepper that relates to most valuable vegetable cultures as to food value and taste was chosen as a main component of a sauce. For giving it a necessary consistence and for decreasing a time of thermal processing, there was used chitosan. According to results of the conducted studies, it was established, that among studied types of chitosan, advantages as to forming a consistence belongs to food acid-soluble chitosan with particle sizes up to 0,5 mm in amount 0,5 %.For preserving the natural green color, pepper fruits were preliminarily processed in 1 % decoction of Xanthium strumarium at temperature 75ºС during 15 min. For increasing its food value, the recipe was added with spicy-aromatic vegetable raw materials: garlic, dill, parsley, celery.The sauce quality was formed by mathematical modeling using general criteria of optimization of organoleptic parameters. There were also determined specific criteria of optimization of the recipe composition taking into account their daily need. As a result of the conducted studies the composition of recipe components for the sauce was optimized: sweet pepper 80 %, garlic leaves – 5 %, parsley leaves,dill – 5 %, celery leaves – 5 %, salt – 1,5 %, sugar – 0,5 %, chitosan – 0,5 %.There were studied organoleptic parameters of the developed sauce, characterized by a pleasant bright-green color, homogenous paste-like consistence, pleasant taste and smell. The used stabilizing factors allowed to get the sauce with the increased content of essential factors of nutrition. They participate in the increase of protective forces of the organism, so allow to recommend them in prophylactic, child and dietary nutrition