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In a highly dynamic and complex environment where risks and uncertainties are inevitable, the ability of a system to quickly recover from disturbances and maintain optimal performance is crucial for ensuring operational continuity and efficiency. In this context, resilience has become an increasingly important topic in the field of engineering and the management of productive systems. However, there is no single quantitative indicator of resilience that allows for the measurement of this characteristic in a productive system. This study proposes the use of permutation entropy of ordinal patterns in time series as an indicator of resilience in industrial equipment and systems. Based on the definition of resilience, the developed method enables precise and efficient assessment of a system's ability to withstand and recover from disturbances. The methodology includes the identification of ordinal patterns and their analysis through the calculation of a permutation entropy indicator to characterize the dynamics of industrial systems. Case studies are presented and the results are compared with other resilience models existing in the literature, aiming to demonstrate the effectiveness of the proposed approach. The results are promising and highlight a highly applicable and simple indicator for resilience in industrial systems.

We describe a protein proximity inducing therapeutic modality called Regulated Induced Proximity Targeting Chimeras or RIPTACs: heterobifunctional small molecules that elicit a stable ternary complex between a target protein (TP) selectively expressed in tumor cells and a pan-expressed protein essential for cell survival. The resulting co-operative protein-protein interaction (PPI) abrogates the function of the essential protein, thus leading to death selectively in cells expressing the TP. This approach leverages differentially expressed intracellular proteins as novel cancer targets, with the advantage of not requiring the target to be a disease driver. In this chemical biology study, we design RIPTACs that incorporate a ligand against a model TP connected via a linker to effector ligands such as JQ1 (BRD4) or BI2536 (PLK1) or CDK inhibitors such as TMX3013 or dinaciclib. RIPTACs accumulate selectively in cells expressing the HaloTag-FKBP target, form co-operative intracellular ternary complexes, and induce an anti-proliferative response in target-expressing cells., Competing Interests: Declaration of interests C.M.C. is a shareholder and consultant to Halda Therapeutics, which supports research in his laboratory., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This article aims to reconstruct the social imaginaries of Coronavirus disease 2019 (COVID-19) in Chile. We seek to understand how families interpret their experience confronting the pandemic by identifying four main aspects: (a) the COVID-19 pandemic, (b) working and learning, (c) health and (d) family life. Following Habermas' distinction between lifeworld and social systems, we consider these issues as constituting the social imaginary of lifeworld, different but related to the imaginaries of social systems. The qualitative empirical data was gathered through a sample of 38 families interviewed online between September 2020 and January 2021 in four Chilean cities: Iquique, Valparaíso, Santiago and Concepción. Other complementary sources of information are multimodal ethnography (digital diaries), press articles and state reports., (© 2022 Society for Latin American Studies.)

A novel, facile, and expeditious two-step synthesis of 3,4-unsubstituted isoquinolin-1(2 H )-ones from a Suzuki cross-coupling between 2-halobenzonitriles and commercially available vinyl boronates followed by platinum-catalyzed nitrile hydrolysis and cyclization is described.

Myotonic dystrophy type 1 originates from d(CTG·CAG) repeats that undergo aberrant expansion during normal processing because the d(CTG) repeat forms stable hairpin structures. Bidirectional transcription of d(CTG·CAG) yields two RNA transcripts that undergo repeat-associated non-ATG (RAN) translation to form homopolymeric proteins. Thus, both the r(CUG) transcript and the r(CAG) transcript are known to be toxic. We report a pairwise fragment-based, target-guided approach to screen for proximity-induced click dimers formed on the nucleic acid template. This screen uses an azide/alkyne clickable fragment library of nucleic acid-binding ligands incubated in parallel, pairwise reactions as an alternative to our previously reported one-pot screening method. MALDI-TOF mass spectroscopy was used to detect template assisted click products. Hit compounds inhibited the in vitro transcription of d(CTG·CAG) 90 bidirectionally with IC 50 values in the low micromolar range. This approach may be broadly applicable to other trinucleotide repeat diseases and in targeting other disease-associated nucleic acid sequences., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

There are few methods available for the rapid discovery of multitarget drugs. Herein, we describe the template-assisted, target-guided discovery of small molecules that recognize d(CTG) in the expanded d(CTG·CAG) sequence and its r(CUG) transcript that cause myotonic dystrophy type 1. A positive cross-selection was performed using a small library of 30 monomeric alkyne- and azide-containing ligands capable of producing >5000 possible di- and trimeric click products. The monomers were incubated with d(CTG) 16 or r(CUG) 16 under physiological conditions, and both sequences showed selectivity in the proximity-accelerated azide-alkyne [3+2] cycloaddition click reaction. The limited number of click products formed in both selections and the even smaller number of common products suggests that this method is a useful tool for the discovery of single-target and multitarget lead therapeutic agents.

Autosomal recessive congenital ichthyosis (ARCI) is a group of rare, clinically heterogeneous skin disorders that affect cornification. ARCI includes lamellar ichthyosis, congenital ichthyosiform erythroderma and harlequin ichthyosis. TGM1 mutations cause > 50% of ARCI cases in the USA. We report two siblings with ARCI. They were found to carry a novel aetiological TGM1 mutation, which leads to the synthesis of multiple abnormal transcripts. These molecules resulted from three independent mechanisms: intron retention, exon skipping and activation of expand cryptic splice sites. Taken together, our findings expand the known TGM1 mutation repertoire, and provide an insight into the molecular mechanisms leading to ARCI phenotypes. These results could be useful for genetic counselling and future potential genotype-phenotype correlations., (© 2015 British Association of Dermatologists.)

Introduction: Hirsutism is a medical entity defined as the excessive growth of body hair in women with a male distribution pattern. For evaluation it is used a visual analog scale designed by Ferriman and Gallwey in the United Kingdom in 1961, subsequently modified by Hatch. This scale consists of nine body areas, obtaining a minimum total value of 0 and a maximum of 36. It has been established a value greater than 8 points for diagnosis of hirsutism in European women, but it is recommended that the diagnosis of hirsutism should be individualized according to the study population., Objective: To determine the most appropriate cutoff point for the diagnosis of hirsutism in a Colombian population by applying the Ferriman-Gallwey Modified scale., Materials and Methods: A random scale was applied to 323 women from Santander, between the ages of 18 and 50, and without risk factors for hirsutism., Results: It was obtained a score between 0 and 9 in the Ferriman-Gallwey modified scale, and 53.5% of the women had an overall score between 0 and 1 points. The 96% of those examined evidenced a Ferriman-Gallwey score modified less or equal to 6., Conclusion: It is suggest a value less than or equal to 6 as the cutoff point for the diagnosis of hirsutism in our region.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by extreme sensitivity to actinic pigmentation changes in the skin and increased incidence of skin cancer. In some cases, patients are affected by neurological alterations. XP is caused by mutations in 8 distinct genes (XPA through XPG and XPV). The XP-V (variant) subtype of the disease results from mutations in a gene (XPV, also named POLH) which encodes for Polη, a member of the Y-DNA polymerase family. Although the presence and severity of skin and neurological dysfunctions differ between XP subtypes, there are overlapping clinical features among subtypes such that the sub-type cannot be deduced from the clinical features. In this study, in order to overcome this drawback, we undertook whole-exome sequencing in two XP sibs and their father. We identified a novel homozygous nonsense mutation (c.897T>G, p.Y299X) in POLH which causes the disease. Our results demonstrate that next generation sequencing is a powerful approach to rapid determination of XP genetic etiology.