The iterative application of a large chemical space in the drug discovery process

Aim. To demonstrate the advantages of large-scale virtual libraries generated using chemical protocols previously validated in primary steps of the drug discovery process.Results and discussion. Two validated parallel chemistry protocols reported earlier were used to create the chemical space. It was then sampled based on diversity metric, and the sample was subjected to the virtual screening on BRD4 target. Hits of virtual screening were synthesized and tested in the thermal shift assay.Experimental part. The chemical space was generated using commercially available building blocks and synthetic protocols suitable for parallel chemistry and previously reported. After narrowing it down, using MedChem filters, the resulting sub-space was clustered based on diversity metrics. Centroids of the clusters were put to the virtual screening against the BRD4 active center. 29 Hits from the docking were synthesized and subjected to the thermal shift assay with BRD4, and 2 compounds showed noticeable dTm.Conclusions. A combination of cheminformatics and molecular docking was applied to find novel potential binders for BRD4 from a large chemical space. The selected set of predicted molecules was synthesized with a 72 % success rate and tested in a thermal shift assay to reveal a 6 % hit rate. The selection can be performed iteratively to fast support of the drug discovery.

ANDROPAUSE AND ITS IMPACTS ON MEN'S HEALTH:

INTRODUCTION: Andropause or Androgenic Disorder of Male Aging (ADD) affects the male population between 60 and 70 years old, and which sometimes starts after 50 years old, as a consequence of the decline of the testosterone hormone. to the health of men who are going through their aging process. OBJECTIVE: Therefore, the present work was developed with the objective of identifying in the literature the implications of andropause in men's health. METHODOLOGY: This is an integrative literature review of a descriptive-exploratory nature, searches were carried out in November 2021, based on a bibliographic survey in the scientific databases of virtual libraries (LILACS), (ScieElo) Google Academic and (MEDLINE), under the application of the descriptors selected by (DeCS), through the Boolean operator and. RESULTS AND DISCUSSION: It was shown in the literature that andropause symptoms can be manifested differently from person to person, among the most common symptoms were irritability, decreased libido, erectile dysfunction, depression, sleep disorders and premature ejaculation. However, there are ways of hormone replacement treatment to treat the impacts that andropause can have on men's health. FINAL CONSIDERATIONS: This work achieved the proposed objective, as it showed the symptoms that andropause can cause in the male population. Therefore, there is hormone replacement as a treatment method, however there are still taboos that make it difficult for men to take care of their own. health.

Peran Media Sosial Instagram Dalam Upaya Menjaga Eksistensi Bahasa Bali

Language is one of the most important needs in social life. Balinese as a mother tongue is one of the identities and ancestral heritage that must be maintained and maintained properly. Existence can also be known by one word, namely existence. where existence is meant by the response from people around us which proves that our existence is recognized. This paper aims to describe the role of social media Instagram in an effort to maintain the existence of the use of Balinese language. The method used in this study is a qualitative method with descriptive analysis techniques. The results show that on Instagram social media accounts such as @wikibasabali, @Bahasa_bali which contains an online dictionary of three languages ​​(Bali-Indonesian-English), virtual libraries, the use of anggah ungguhing basa, the use of Balinese in daily life, as well as on the @beluluk account which presents humor or entertainment in the form of Balinese comics, in this case Instagram social media can be one of the media that plays a role in efforts to maintain the existence of the Balinese language.

"HABEMUS BASE"?REFLEXÕES SOBRE O PROCESSO DE ALFABETIZAÇÃO NA BASE NACIONAL COMUM CURRICULAR

This work has as general objective to reflect on the curricular transformations for literacy from the 1980s on. As specific objectives, it is intended to: a) discuss the degree of importance in the teaching and learning process attributed by the BNCC to literacy; b) reflect on the BNCC construction process; c) to discuss the findings made by research on the theme "literacy and BNCC" that occurred between 2015 and 2020. Characterized as a research of qualitative and bibliographic approach, studied the theme through books and articles made available in virtual libraries, scientific journals and in the Capes Database considering the research published between 2015 and 2020. We conclude that there are many problems in the BNCC proposal, such as not offering more concrete actions related to literacy, while focusing much of this function only on the teacher. Finally, we answer ed the main question of this research: "Habemos Base"? If we are going to think of a document that has the text as the main work, we can mention that we have a basic proposal. However, if we think of the student as a subject and the teacher who needs resources at his disposal, as well as a continuous quality training, we can measure that only the BNCC does not guarantee this evolution that we want, and there is a risk that, once again, it will be a proposal that does not leave the role with the expected effectiveness.

A liderança como competência essencial na formação do enfermeiro

Relatar sobre a liderança como uma competência importante para os enfermeiros. Trata-se de revisão integrativa de literatura com busca de artigos nas bases de dados SciELO, bibliotecas virtuais e websites. Foram critérios de inclusão artigos publicados na íntegra, em português e publicados a partir de 2010 a 2020. Foram utilizadas 22 referências, sendo 19 artigos científicos e três sites. Considerou-se como tópicos: Autoria; Ano de publicação; Periódico; Título do estudo; Objetivo do estudo. Os principais achados foram categorizados em: Formação acadêmica como influência no processo de liderança, características de liderança essenciais na formação do enfermeiro e a liderança do enfermeiro. A liderança é uma competência essencial para o enfermeiro. Sendo assim, é fundamental a abordagem teórico-prática na trajetória acadêmica do enfermeiro.Descritores: Enfermagem, Liderança, Líder, Acadêmicos de Enfermagem. Leadership like an essential concept in nursing graduatesAbstract: Report on leadership as an important competence for nurses. This is an integrative literature review with the search of articles in SciELO databases, virtual libraries, and websites. Inclusion criteria were articles published in full, in Portuguese, and published from 2010 to 2020. 22 references were used, 19 scientific articles, and 3 sites. The topics considered: Authorship; Year of publication; Journal; Title of the study; Objective of the study. The perspectives of the study were categorized into: Academic background as an influence in the leadership process; essential leadership characteristics in nurse training and the leadership of the nurse; and Leadership is an essential competence for the nurse. Therefore, the theoretical-practical approach is fundamental in the academic trajectory of the nurse.Descriptors: Nursing, Leadership, Leader, Nursing Academics. El liderazgo como una competencia esencial en la formación de enfermeroResumen: Informar sobre el liderazgo como una competencia importante para los enfermeros. Se trata de revisión integral de literatura con búsqueda de artículos en las bases de datos Scielo, bibliotecas virtuales y sitios web. Fueron criterios de inclusión artículos publicados íntegramente, en portugués y publicados a partir de 2010 a 2020. Fueron utilizadas 22 referencias, siendo 19 artículos científicos y três sites. Se consideró como tópicos: Autoría; Año de publicación; Periódico; Título del estudio; Objetivo del estudio. Los principales hallazgos fueron categorizados en: Formación académica como influencia en el proceso de liderazgo, características de liderazgo esenciales en la formación del enfermero y el liderazgo del enfermero. El liderazgo es una competencia esencial para el enfermero. Por lo tanto, es fundamental el enfoque teórico-práctico en la trayectoria académica del enfermero.Descriptores: Enfermería, Liderazgo, Líder, Académicos de Enfermería.

State of the Art Iterative Docking with Logistic Regression and Morgan Fingerprints

<p>There is renewed interest in docking campaigns for ligand-discovery since the advent of ultra-large scale virtual libraries. Using brute-force search, the scale of the libraries suggests highly parallelized compute should be used to avoid years-long computations. This paper reports a re-analysis of docking data from an ultra-large docking campaign at the D4 receptor and AmpC beta lactamase, and demonstrates large reductions in computation time to identify the top-ranked ligands. A search of ‘baseline’ featurizations shows that logistic regression on Morgan fingerprints with pharmacophoric atom invariants can match the reported performance on the same task using message-passing networks. With this approach, an ultra-large docking campaign could be performed in a matter of weeks using consumer-grade CPUs with <i>RDKit </i>and <i>scikit-learn</i>. All code and figures are available at <a href="https://github.com/ljmartin/dockop">https://github.com/ljmartin/dockop</a> </p><br>

State of the Art Iterative Docking with Logistic Regression and Morgan Fingerprints

<p>There is renewed interest in docking campaigns for ligand-discovery since the advent of ultra-large scale virtual libraries. Using brute-force search, the scale of the libraries suggests highly parallelized compute should be used to avoid years-long computations. This paper reports a re-analysis of docking data from an ultra-large docking campaign at the D4 receptor and AmpC beta lactamase, and demonstrates large reductions in computation time to identify the top-ranked ligands. A search of ‘baseline’ featurizations shows that logistic regression on Morgan fingerprints with pharmacophoric atom invariants can match the reported performance on the same task using message-passing networks. With this approach, an ultra-large docking campaign could be performed in a matter of weeks using consumer-grade CPUs with <i>RDKit </i>and <i>scikit-learn</i>. All code and figures are available at <a href="https://github.com/ljmartin/dockop">https://github.com/ljmartin/dockop</a> </p><br>

The role of Spanish health libraries in scientific publication

Health libraries have been established as publication support services. Despite its importance, there is currently no study about the services that these centers offer. The aim of this work is to understand the role that libraries play in institutional scientific publishing policies. The sample was taken from the National Catalogue of Hospitals, the list of libraries of the Catalogue of Periodicals in Spanish Health Sciences Libraries (c17) and the National Catalogue of Health Sciences Publications (CNCS). Subsequently, virtual health libraries have also been incorporated. From this list, a questionnaire about library staff and activities related to publication process was sent. We obtained a participation rate of 61.21%. The average number of technical personnel was 1.15 in virtual libraries and 0.81 in hospital libraries. The activities carried out have been: training activities (82.2%), counselling (90.1%), dissemination (30.7%) and evaluation (50.5%). The staff in libraries are insufficient. In many cases technicians assume an overwork of serving in both (virtual and hospital libraries). Most libraries offer training and research support services although there are differences between virtual and hospital ones. There is a relationship between the number of technicians and the publication support services.