Deep Mutational Engineering of broadly-neutralizing and picomolar affinity nanobodies to accommodate SARS-CoV-1 & 2 antigenic polymorphism

We report in this study the molecular engineering of nanobodies that bind with picomolar affinity to both SARS-CoV-1 and SARS-CoV-2 Receptor Binding Domains (RBD) and are highly neutralizing. We applied Deep Mutational Engineering to VHH72, a nanobody initially specific for SARS-CoV-1 RBD with little cross-reactivity to SARS-CoV-2 antigen. We first identified all the individual VHH substitutions that increase binding to SARS-CoV-2 RBD and then screened highly focused combinatorial libraries to isolate engineered nanobodies with improved properties. The corresponding VHH-Fc molecules show high affinities for SARS-CoV-2 antigens from various emerging variants and SARS-CoV-1, block the interaction between ACE2 and RBD and neutralize the virus with high efficiency. Its rare specificity across sarbecovirus relies on its peculiar epitope outside the immunodominant regions. The engineered nanobodies share a common motif of three amino acids, which contribute to the broad specificity of recognition. These nanobodies appears as promising therapeutic candidates to fight SARS-CoV-2 infection.

HYPOTHESES TESTING ON THE VALIDITY OF EFFECTIVE COMMUNICATION AND COMMON MOTIF OF SELAYAH KERINGKAM

This paper is to deliberate the subjects of the effective communication channel in delivering common motifs in Selayah Keringkam by assessing the local and International tourists’ preference. It is to evaluate the hypotheses Testing On validity of Effective Communication and Common Motif of Selayah Keringkam Towards the communication channel. The finding of this paper is to enhance the implications on developing a significant way to disseminate Selayah Keringkam as a heritage product in Sarawak. This paper will expose a substantial relationship between the independent variables (Common Motif of Selayah Keringkam), the dependent variables (Channels of Communication) and the mediator (Supplement of Effective Communication) as a new framework to the body of knowledge. This research involved 384 respondents with 5 relevant authorities related to answering research questions. The data collected from the fieldwork were analysed using SPSS version 24. The measures used in this article are methodically deliberated using factor analysis and correlation analysis. Lastly, the results of the regression analyses testing on hypotheses and summary of hypotheses assessments are presented.

A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide

Background RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism. Results Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension. Conclusions We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.

Photoenzymatic Synthesis of 𝜶-Tertiary Amines By Engineered Flavin-Dependent ‘Ene’-Reductases

𝛼-tertiary amines are a common motif in pharmaceutically important molecules but are challenging to prepare using asymmetric catalysis. Here, we demonstrate engineered flavin-dependent ‘ene’-reductases (EREDs) can catalyze radical additions into oximes to prepare this motif. Two different EREDs were evolved into competent catalysts for this transformation with high levels of stereoselectivity. Mechanistic studies indicate that the oxime contributes to the enzyme templated CT-complex formed between the substrate and cofactor. These products can be further deri-vatized to prepare a variety of motifs, highlighting the ver-satility of ERED photoenzymatic catalysis for organic syn-thesis.

Low Back Pain Exacerbation Is Predictable Through Motif Identification in Center of Pressure Time Series Recorded During Dynamic Sitting

Background: Low back pain (LBP) is a common health problem — sitting on a chair for a prolonged time is considered a significant risk factor. Furthermore, the level of LBP may vary at different times of the day. However, the role of the time-sequence property of sitting behavior in relation to LBP has not been considered. During the dynamic sitting, small changes, such as slight or big sways, have been identified. Therefore, it is possible to identify the motif consisting of such changes, which may be associated with the incidence, exacerbation, or improvement of LBP.Method: Office chairs installed with pressure sensors were provided to a total of 22 office workers (age = 43.4 ± 8.3 years) in Japan. Pressure sensors data were collected during working days and hours (from morning to evening). The participants were asked to answer subjective levels of pain including LBP. Center of pressure (COP) was calculated from the load level, the changes in COP were analyzed by applying the Toeplitz inverse covariance-based clustering (TICC) analysis, COP changes were categorized into several states. Based on the states, common motifs were identified as a recurring sitting behavior pattern combination of different states by motif-aware state assignment (MASA). Finally, the identified motif was tested as a feature to infer the changing levels of LBP within a day. Changes in the levels of LBP from morning to evening were categorized as exacerbated, did not change, or improved based on the survey questions. Here, we present a novel approach based on social spider algorithm (SSA) and probabilistic neural network (PNN) for the prediction of LBP. The specificity and sensitivity of the LBP inference were compared among ten different models, including SSA-PNN.Result: There exists a common motif, consisting of stable sitting and slight sway. When LBP level improved toward the evening, the frequency of motif appearance was higher than when LBP was exacerbated (p < 0.05) or the level did not change. The performance of the SSA-PNN optimization was better than that of the other algorithms. Accuracy, precision, recall, and F1-score were 59.20, 72.46, 40.94, and 63.24%, respectively.Conclusion: A lower frequency of a common motif of the COP dynamic changes characterized by stable sitting and slight sway was found to be associated with the exacerbation of LBP in the evening. LBP exacerbation is predictable by AI-based analysis of COP changes during the sitting behavior of the office workers.

No, I’m not… Chaucer? The Arabic motif in Troilus and Criseyde and Pushkin’s ‘The Prophet’ [‘Prorok’]

The article discusses two works of literature: Troilus and Criseyde, a long poem written in the genre of courtly romance (1382–1386/1387) by G. Chaucer, and ‘The Prophet’ [‘Prorok’] (1826), a poem by A. Pushkin. The two works are compared due to a common motif: the opening of the chest and swapping of the heart as a sign of the person’s spiritual regeneration. In her comparative analysis of the two poems, the author attempts to identify their common source or the likelihood of direct contact — whether Pushkin had come across Chaucer’s work and borrowed the motif directly. As for the heart being replaced, it seems both poets may have been inspired by several biblical stories. Further analysis of the motif of the chest being opened suggests that the research should focus on the Arabic tradition alone and take into account the potential influence of Islamic religious texts on Pushkin as well as Chaucer. Relying on the available data about Russian and European relations with the Arabic world, the article hypothesises about the ways in which the motif in question could have reached each of the poets. The author names the Quran as the common genetic source of the two poems.

Illies, F. (2019). Just now the sky was blue. Texts on art. Translated by V. Serov. Moscow: Ad Marginem Press, Muzey sovremennogo iskusstva ‘Garazh.’ (In Russ.)

The reviewer claims that Florian Illies’ essays demonstrate a perfect balance between pure scholarship and journalism. Despite representing a miscellany of genres (book and exhibition reviews, articles summarising the author’s view of various painters and art historians), the collection proves harmonious due to a common motif of the essays. The book does not draw a strict line between history of literature and art history. Similarly, Illies does not separate art history from the context of the life around art, i. e. the authors’ correspondence, their relationships with their family and friends, fellow artists and patrons. His unconventional view of art history enables Illies to identify interesting overarching subjects which include the problem of the patron’s influence on a work of art and the category of taste. The essayist is particularly interested in ‘second-rank’ authors, who, he suggests, emerge as first-rank in various historical periods.

SYNCRETISM OF THE SACRED IN ANNA BAGRYANA’S LYRICS

The article presents an analysis of sacred syncretism as one of the leading motifs of the work of the modern Ukrainian writer Anna Bagryana. It is noted that the phenomenon of this transcendent phenomenon is interpreted by modern Ukrainian literature based on the aesthetic practices of postmodernism and traditionalism in culture.It is emphasized that Ukrainian poetry of the XXI century, having absorbed these opposite trends, uses them, on the one hand, to formalize the linguistic and communicative shell of the poem, on the other, to reflect the exclusivity of the national character, creating a type of new worldview not on differences, but on syncretism, the interpenetration of various trends, in which the whole diversity of the world is revealed.With the help of cultural, phenomenological, comparative-historical methods that study the philosophical perception of the sacred by the author, as well as using aesthetic, biographical approaches and psychoanalysis to understand the artistic world of her poems, the research has achieved its purpose: the eclectic nature of the sacred in the lyrics of Anna Bagryana is revealed.The article notes that, following the main trends of postmodernism, including the loss of the highest meaning of human life, reflection, relativism and internal confusion, the manner of presentation of the writer is also characterized by specific features: a certain theocentricity, religiosity, the desire to preserve spiritual values. In the conflict of these polarities, a synergistic transformation of the sacred matures, its so-called illogical form, characterized by the sublimity of the supernatural and at the same time its ordinariness.The results of the work are implemented tasks: the concept of the sacred in the poems of Anna Bagryana is clarified, its syncretism is revealed and the change in the aesthetics of the transcendent is reflected; the eclecticism of the feeling of the supernatural by the lyrical heroine is characterized; the protective function of the sacred in the artistic work of the poetess is analyzed. Conclusions. The sacred, which is a common motif of Anna Bagryana’s poetry, is perceived by her in the context of a scientific approach. This understanding implies a distinction between the human and otherworldly worlds. The traditional aesthetics of the sacred is based on beauty as a means of sensory-spiritual worldview, which led to the replacement of the material worldview with a value one. Postmodern stylistics reproduces the syncretism of the sacred, adding to its interpretation the illogical nature of used images, the search for new meanings, and internal expression. Recognizing the specifics of Ukrainian literature, which in modern social theory does not break with the achievements of previous eras, the writer retains the human-centered and imaginative richness of her lyrics.Key words: sacrum, eclecticism, postmodernism, tradition, symbolism. У статті подано аналіз синкретизму сакрального як одного із провідних мотивів творчості сучасної української письменниці Анни Багряної.Зазначено, що феномен цього трансцендентного явища сучасна українська література інтерпретує, виходячи з естетичних практик постмодернізму та традиціоналізму в культурі.Підкреслено, що українська поезія ХХІ ст., увібравши ці протилежні тенденції, послуговується ними, з одного боку, для оформлення мовно-комунікативної оболонки вірша, з іншого, щоб відобразити винятковість національного характеру, створюючи тип нового світовідчуття не на розбіжностях, а на синкретизмі, взаємопроникненні різних тенденцій, у якому розкри-вається вся багатоплановість світу.За допомогою культурологічного, феноменологічного, порівняльно-історичного методів, що досліджують філософське сприйняття сакрального авторкою, а також послуговуючись естетичним, біографічним підходами та психоаналізом для розуміння худож-нього світу її поезій, у розвідці досягнуто поставлену мету: розкрито еклектичну природу сакрального в ліриці Анни Багряної.У статті зауважено, що, наслідуючи основні тенденції постмодерну, серед яких втрата вищого сенсу життя людини, рефлексія, релятивізм і внутрішня розгубленість, манера викладу письменниці характеризується й специфічними рисами: певною теоцентричністю, релігійністю, прагненням зберегти духовні цінності. У конфлікті цих полярностей визріває синергетична трансформація сакрального, його т.зв. алогічна форма, що характеризується піднесеністю надприродного та водночас його буденністю.Результатами роботи є реалізовані завдання: з’ясовано поняття сакрального у віршах Анни Багряної, розкрито його синкретизм і відображено зміну естетики трансцендентного; схарактеризовано еклектику відчуття надприродного ліричною героїнею; проаналізовано захисну функцію сакрального в художній творчості поетеси.Висновки. Сакральне, яке є поширеним мотивом поезії Анни Багряної, сприймається нею в контексті наукового підходу. Таке розуміння передбачає розрізнення світу людського та потойбічного. Традиційна естетика сакрального ґрунтується на красі як засобі чуттєво-духовного світогляду, що спричинило заміну матеріального світосприйняття ціннісним. Постмодерна стилістика відтворює синкретизм сакрального, додаючи до його інтерпретації алогічність уживаних образів, пошук нових смислів, внутрішню експресію. Визнаючи специфіку української літератури, яка в сучасній соціальній теорії не пориває з надбаннями попередніх епох, письменниця зберігає антропоцентричність та образне багатство своєї лірики. Ключові слова: sacrum, еклектика, постмодерн, традиція,символізм.