Are we ready to design oral PROTACs®?

PROTACs® are expected to strongly impact the future of drug discovery. Therefore, in this work we firstly performed a statistical study to highlight the distribution of E3 ligases and POIs collected in PROTAC-DB, the main online database focused on degraders. Moreover, since the emerging technology of protein degradation deals with large and complex chemical structures, the second part of the paper focuses on how to set up a property-based design strategy to obtain oral degraders. For this purpose, we calculated a pool of seven previously ad hoc selected 2D descriptors for the 2258 publicly available degraders in PROTAC-DB (average values: MW= 972.9 Da, nC= 49.5, NAR= 4.5, PHI= 17.3, nHDon= 4.5, nHAcc= 17.7 and TPSA= 240 Å2) and compared them to a dataset of 50 bRo5 orally approved drugs. Then, a chemical space based on nC, PHI and TPSA was built and subregions with optimal permeability and bioavailability were identified. Bioavailable degraders (ARV-110 and ARV-471) tend to be closer to the Ro5 region, using mainly semi-rigid linkers. Permeable degraders, on the other hand, are placed in an average central region of the chemical space but chameleonicity could allow them to be located closer to the two Arvinas compounds

Projectivity of Planar Zeros in Field and String Theory Amplitudes

We study the projective properties of planar zeros of tree-level scattering amplitudes in various theories. Whereas for pure scalar field theories we find that the planar zeros of the five-point amplitude do not enjoy projective invariance, coupling scalars to gauge fields gives rise to tree-level amplitudes whose planar zeros are determined by homogeneous polynomials in the stereographic coordinates labelling the direction of flight of the outgoing particles. In the case of pure gauge theories, this projective structure is generically destroyed if string corrections are taken into account. Scattering amplitudes of two scalars with graviton emission vanish exactly in the planar limit, whereas planar graviton amplitudes are zero for helicity violating configurations. These results are corrected by string effects, computed using the single-valued projection, which render the planar amplitude nonzero. Finally, we discuss how the structure of planar zeros can be derived from the soft limit behavior of the scattering amplitudes.Comment: 39 page, 5 figures. v2: typos corrected. It matches the version published in Journal of High Energy Physic

Exploring the role of immersive augmentation in hospitality

Gonzalez-Jimenez, H., & Pinto, D. C. (2024). Can AI robots foster social inclusion? Exploring the role of immersive augmentation in hospitality. International Journal of Contemporary Hospitality Management, 36(11), 3889-3905. https://doi.org/10.1108/IJCHM-09-2023-1459 --- This work was partially supported by national funds through FCT (Foundation for Science and Technology), under the project – UIDB/04152/2020 (DOI: 10.54499/UIDB/04152/2020) – Information Management Research Centre (MagIC)/NOVA IMS).Purpose Grounded on the X Reality framework and human–machine collaboration, this study aims to explore the potential of immersive augmentation through artificial intelligence (AI) service robots for promoting social inclusion in the hospitality industry. Design/methodology/approach Three experimental studies across diverse hospitality contexts examine the effects of immersive augmentation using inclusive-AI service robots compared to standard-AI robots. The studies also uncover the underlying process of perceived ethicality and the moderating role of customers’ familiarity with AI. Findings The results indicate that immersive augmentation through inclusive-AI service robots generates higher levels of supportive tipping behavior (Studies 1 and 3), superior buying intentions (Study 2) and an increased likelihood for customers to pay a premium price (Study 2). These effects are mediated by perceived ethicality (Studies 1–3). However, the impact of immersive augmentation for social inclusion is contingent upon customers’ familiarity with AI: customers with high familiarity with AI exhibit lower levels of supportive tipping behavior (Study 3). Research limitations/implications The findings emphasize the importance of perceived ethicality and customers’ familiarity with AI in determining the effectiveness of immersive augmentation for social inclusion in hospitality. Originality/value This study contributes to the literature by exploring the potential of immersive augmentation using AI service robots for social inclusion in hospitality. It offers novel insights by highlighting the importance of perceived ethicality and customers’ familiarity with AI. The findings provide valuable guidance for hospitality managers seeking to leverage AI technology to foster social inclusion.authorsversionpublishe

Born-Infeld inspired modifications of gravity

General Relativity has shown an outstanding observational success in the scales where it has been directly tested. However, modifications have been intensively explored in the regimes where it seems either incomplete or signals its own limit of validity. In particular, the breakdown of unitarity near the Planck scale strongly suggests that General Relativity needs to be modified at high energies and quantum gravity effects are expected to be important. This is related to the existence of spacetime singularities when the solutions of General Relativity are extrapolated to regimes where curvatures are large. In this sense, Born-Infeld inspired modifications of gravity have shown an extraordinary ability to regularise the gravitational dynamics, leading to non-singular cosmologies and regular black hole spacetimes in a very robust manner and without resorting to quantum gravity effects. This has boosted the interest in these theories in applications to stellar structure, compact objects, inflationary scenarios, cosmological singularities, and black hole and wormhole physics, among others. We review the motivations, various formulations, and main results achieved within these theories, including their observational viability, and provide an overview of current open problems and future research opportunities.Comment: 212 pages, Review under press at Physics Report

Intersubjetividad de la realidad empresarial del sistema financiero colombiano : el caso COLPATRIA

Dentro de los aspectos más importantes para el desarrollo organizacional se encuentra el factor humano, donde existen diferentes formas para examinar la manera en que las personas perciben el desarrollo del negocio y su entorno. La intersubjetividad como asunto de la realidad empresarial se convierte entonces en una manera de recopilar la forma en que los involucrados en diferentes niveles de una organización perciben fenómenos, siendo esto fuente fundamental para la medición de la alineación de la organización con su plataforma estratégica. Este estudio busca examinar la forma en que los empleados de la empresa Colpatria perciben el sector financiero, en el cual se desempeña la empresa.One of the most important aspects of organizational development is found within the human resources, where there are different methods to examine the way people are perceiving the business development and their surroundings. Inter-subjectivity like topic of the enterprise reality is one of the methods to gather the way in which the incumbents perceive phenomenon, being this a fundamental source for measuring the organizations alignment with its strategic platform. This study seeks to examine the way Colpatrias employees perceive the financial sector, on which the enterprise exists

LA ACCIÓN DE TUTELA COMO VÍA DE HECHO CONTRA SENTENCIAS JUDICIALES

Investigación de la acción de tutela contra sentencias judiciales.&nbsp

El impacto de la inclusión financiera en el desarrollo económico: Análisis comparativo en las Américas

La inclusión financiera se ha tornado un tema relevante para investigar, ya que la relación entre el desarrollo económico y la inclusión financiera aún mantienen ciertos puntos que necesitan concentrar en mayor medida los esfuerzos de gobiernos y empresas. Por ello, el presente estudio tiene como objetivo analizar el impacto comparativo que han tenido los diferentes componentes de la inclusión financiera en el desarrollo de las economías dentro de América. Asimismo, como objetivo específico, se busca evaluar la magnitud del impacto de los factores de la inclusión financiera en Perú en relación a otros países. Para poder encontrar esta relación entre la inclusión financiera se asignan algunas variables para estimar la relación y magnitud que tienen las variables de control macro y las variables de inclusión financiera. El resultado de esta regresión de panel de datos demuestra que el impacto y relación es diferente en países desarrollados y países no desarrollados. Sin embargo, en el caso de Perú posee una característica diferente ante sus países vecinos en el que la variable de cajeros automático por 100.000 personas no tiene una relación positiva con el desarrollo económico del país. Por tanto, en el estudio se puede concluir que existe una relación positiva entre la inclusión financiera y el desarrollo económico, pero depende cómo se realice el análisis y se observen la interrelación de las variables en cada país