Fragment-based drug (or lead) discovery (FBDD or FBLD) has developed in the last two decades to become a successful key technology in the pharmaceutical industry for early stage drug discovery and ...development. The FBDD strategy consists of screening low molecular weight compounds against macromolecular targets (usually proteins) of clinical relevance. These small molecular fragments can bind at one or more sites on the target and act as starting points for the development of lead compounds. In developing the fragments attractive features that can translate into compounds with favorable physical, pharmacokinetics and toxicity (ADMET-absorption, distribution, metabolism, excretion, and toxicity) properties can be integrated. Structure-enabled fragment screening campaigns use a combination of screening by a range of biophysical techniques, such as differential scanning fluorimetry, surface plasmon resonance, and thermophoresis, followed by structural characterization of fragment binding using NMR or X-ray crystallography. Structural characterization is also used in subsequent analysis for growing fragments of selected screening hits. The latest iteration of the FBDD workflow employs a high-throughput methodology of massively parallel screening by X-ray crystallography of individually soaked fragments. In this review we will outline the FBDD strategies and explore a variety of
approaches to support the follow-up fragment-to-lead optimization of either: growing, linking, and merging. These fragment expansion strategies include hot spot analysis, druggability prediction, SAR (structure-activity relationships) by catalog methods, application of machine learning/deep learning models for virtual screening and several
design methods for proposing synthesizable new compounds. Finally, we will highlight recent case studies in fragment-based drug discovery where
methods have successfully contributed to the development of lead compounds.
Women represent over the half of university graduates in Spain. However, the percentage of women graduating with degrees in Computing and Engineering drops to 23% (European Commission. 2016. She ...figures. Brussels: Directorate-General for Research and Innovation). Women are a minority in the workplace in the IT sector, despite it being one of the most dynamic industries with a positive future outlook. Existent literature highlights that women face a variety of barriers that can impede their progress in the workplace, mainly related to work-life conflicts. However, the attempts carried out thus far to improve women's work-life balance have had little effect in this sector, where the numbers lag behind those of other sectors. The reasons behind those numbers must be understood. In this sense, this study aims to gain a deeper understanding of work/personal lives of women in IT sectors throughout the course of their lives. The results obtained from a tailor-made survey in Spain show that women working in IT are very work-oriented and committed to their careers and have fewer conflicts regarding work-life balance than was expected. It was in fact age, income and perception of gender discrimination that stood out as significant variables that may explain the difficulties encountered. In light of this, flexible work policies are not enough to increase the number of women in IT, and we suggest actions that could serve to fight stereotypes regarding gender and age in the workplace.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The increase in production and consumption of goods has generated a surplus of waste, which destination is commonly the landfilling sites. This represents a major bottleneck in the production chain ...and creates new challenges for sustainable development. Due to the environmental and economic benefits, the use of renewable and ecological fuels derived from waste has received global attention. Plasma is one of the techniques that enable achieving renewable energy from solid residues, contributing to landfill avoidance and resource reutilization in line with the circular economy principles and supporting United Nations Sustainable Development Goals 7 (affordable and clean energy), 12 (responsible consumption and production), and 13 (climate action). This article presents a review and analysis of literature related to the use of plasma gasification of solid waste as a method of waste recovery. This article portrays the efforts that have been made in this direction and the barriers to the dissemination of technology for commercial applications. The focus of this article comprises (a) extracting valuable aspects from various studies, including laboratory and field studies, (b) summarizing the work done so far, and (c) compiling studies and findings on plasma gasifiers and recent developments.
Tomando como punto de partida una experiencia de investigación en co-labor con dos interlocutores mapuche, este artículo explora aprendizajes derivados de la propuesta que nos estaban realizando: ...básicamente, embarcarnos en la producción intersubjetiva, interepistémica e interexistencial de conocimientos. Intersubjetiva, porque la meta debía pasar por transformar/completar nuestras comprensiones y personas a partir de la interacción. Interepistémica, en la medida en la que requería abrirnos a reconocer no tanto otros conocimientos sino otras formas de conocer. Interexistencial, pues nos iría exponiendo la opacidad de ciertos bordes ontológicos según los cuales la práctica del conversar puede, en su hacerse, involucrar —al menos para algunos— personas humanas vivas y seres y presencias no humanas. Sobre esta base, mapuche, apuntamos a intervenir en debates más amplios sobre ciertos mandatos y concepciones extendidas del quehacer antropológico contemporáneo.
This study aimed to evaluate the effect of gamma irradiation (GI) on the physicochemical, technological, antioxidant and microbiological characteristics of different whole sorghum flours (WSF), as ...well as to characterize the profile of chemical constituents by paper spray mass spectrometry (PS-MS). The doses applied interfered in the staining characteristics of the evaluated flours, providing the darkening of the same. For the other physicochemical, technological, and antioxidant parameters, no significant influence of the process was observed. The fingerprint obtained in both ionization modes had not been influenced by irradiation, being flavonoids, phenylpropanoids, amino acids, benzoic acid derivatives, carboxylic acids, and sugars tentatively identified. In microbiological terms, there was a reduction of molds, yeasts, and Bacillus cereus in irradiated WSF compared to control (non-irradiated). Therefore, the application of low doses of gamma irradiation represents an advantageous alternative for the conservation of WSF and maintenance of compounds bioactive identified by the PS-MS technique.
Active packaging is designed to control the development of decay- and disease-causing microorganisms and is emerging as a promising technology for extending shelf-life, maintaining food safety, ...reducing waste, and minimizing the risks for foodborne diseases. The goal of this work was to develop and characterize bioactive pullulan-based films, containing rockrose (Cistus ladanifer) essential oil. Among other abundant compounds (camphene, bornyl acetate and trans-pinocarveol), α-pinene was identified as the major compound of rockrose essential oil (39.25%). The essential oil presented stronger antibacterial activity against Gram-positive than against Gram-negative bacteria. The antioxidant results indicate the potential of the developed films to be used to package foods susceptible to oxidation and rancification, thus improving their shelf-life. Also, this study reflects the potential of rockrose essential oil, free or incorporated in pullulan, as a promising quorum sensing inhibitor, since it was able to interrupt intercellular communication, inhibiting violacein production. Electronic microscopy images showed the antibiofilm activity of the films with rockrose essential oil that were able to influence bacterial adhesion, which may be explained by the differences in the surface free energy of the films, as also determined.
Research on paper surface modification, paper properties, paper–ink interactions, and their influence on inkjet print quality are currently subjects of great interest. In this study, dynamic ...interactions between aqueous pigment black ink and modified paper and their effect on print quality are discussed. Formulations of starch and blends of starch and poly(diallyldimethylammonium) chloride or polyoxyethylene (100) stearyl ether were used on base paper. Modified papers were printed on two printers. The paper performance is discussed in terms of surface energy, dispersive and polar components, and air permeability given the ink spreading and absorption. Results showed that paper modified with a blend of starch and poly(diallyldimethylammonium) chloride improves inkjet print quality. This modified paper showed higher black print density and lower line width, raggedness, intercolor bleed, and dot gain because of the spreading–absorption balance arising from the low surface energy and polar component.
El 2 de abril de 2021 es, sin duda, una fecha clave para el funcionamiento del sector público, ya que en coherencia con la disposición final séptima de la Ley 39/2015, entra en vigor el Real Decreto ...203/2021, de 30 de marzo, por el que se aprueba el Reglamento de actuación y funcionamiento del sector público por medios electrónicos, que desarrolla tanto la Ley 39/2015, de 1 de octubre, del Procedimiento Administrativo Común de las Administraciones Públicas como la Ley 40/2015, de 1 de octubre, de Régimen Jurídico del Sector Público. El presente artículo analiza la incorporación de la vigente normativa al régimen jurídico administrativo y los principales puntos del Real Decreto 203/2021 a tener en cuenta en el procedimiento administrativo. Sin duda, traerá consigo un cambio definitivo del modelo administrativo de los próximos años.
2021eko apirilaren 2a, zalantzarik gabe, funtsezko data da sektore publikoaren funtzionamendurako;izan ere, 39/2015 Legearen azken xedapenaren zazpigarrenarekin bat etorriz, martxoaren 30eko 203/2021 Errege Dekretua indarrean sartu zen; horren bidez onartu zen Sektore publikoa bitarteko elektronikoen bidez jarduteko eta funtzionatzeko Erregelamendua, bai Herri Administrazioen Administrazio Prozedura Erkidearen urriaren 1eko 39/2015 Legea, bai Sektore Publikoaren Araubide Juridikoaren urriaren 1eko 40/2015 Legea garatzen dituena.
Artikulu honek aztertzen du indarreko araudia administrazio-araubide juridikoan nola txertatu den eta zein diren administrazio-prozeduran kontuan hartu beharreko 203/2021 Errege Dekretuaren puntu nagusiak. Zalantzarik gabe, datozen urteetako administrazio ereduaren behin betiko aldaketa ekarriko du horrek.
April 2, 2021 is unquestionably a key date in the functioning of the public sector since, in accordance with the seventh final provision of Law 39/2015, it marks the entry into force of Royal Decree 203/2021, of 30 March 2021, approving the Regulation on action and operation in the public sector by electronic means, which develops on both Law 39/2015, of 1 October 2015, on the Common Administrative Procedure of Public Administrations, and Law 40/2015, of 1 October 2015, on the Legal Regime of the Public Sector. This article analyzes the incorporation of the current regulations into the administrative legal regime, and the main points of Royal Decree 203/2021 to be taken into account in administrative procedure. This will unquestionably bring about a definitive change in the administrative model in the coming years.
Environmental evaluation of the waste treatment processes for the area of Greater Porto (Portugal) is presented for the year 2015. The raw data for the energy recovery plant (ERP) provided by the ...waste management entity were modelled into nine environmental impact categories, resorting to a life cycle assessment dedicated software (GaBi) for the treatment of 1 tonne of residues. Also, a sensitivity analysis was conducted for five scenarios in order to verify the assessment quality. Results were compared to two European average situations (typical incineration plant and sanitary landfill with no waste pre-treatment), which showed that these facilities perform better or at the same level as the average European situation, mostly due to the high efficiency observed at the ERP and to the electricity production in the incineration process. A detailed analysis concluded that these helped to mitigate the environmental impacts caused by some of the processes involved in the waste-to-energy technology (landfill showing the harder impacts), by saving material resources as well as avoiding emissions to fresh water and air. The overall performance of the energy recovery plant was relevant, 1 tonne of waste saving up to 1.3 million kg of resources and materials. Regarding the environmental indicators, enhanced results were achieved especially for the global warming potential (−171 kgCO2-eq.), eutrophication potential (−39 × 10−3 kgPO4-eq.) and terrestrial ecotoxicity potential (−59 × 10−3 kgDCB-eq.) categories. This work was the first to characterize this Portuguese incineration plant according to the used methodology, supporting the necessary follow-up required by legal frameworks proposed by European Union (EU), once this facility serves a wide populational zone and therefore is representative of the current waste management tendency in the country. LCA (life cycle assessment) was confirmed as a suitable and reliable approach to evaluate the environmental impacts of the waste management scenarios, acting as a functional tool that helps decision-makers to proceed accordingly.
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