ENGAGING CONSUMERS IN SUSTAINABLE BEHAVIORS USING BLOCKCHAIN APPLICATIONS

Tracking and goal setting are popular approaches in the personal health and fitness industry. In this paper we use a similar approach to assist users in their journey for a more sustainable lifestyle, starting with food. We employ Action Design Research (ADR) methodology to develop an application and subsequently propose design principles for developing blockchain-based applications for assisting users on their path to eating environmentally friendly food. The path to a sustainable lifestyle can be hard as individuals often do not realize their personal impact towards achieving a net zero carbon future. To address this shortcoming, this study conducts an ADR experiment to create affordances for users to learn, create impact and realize that they are not alone in this journey thus motivating users to a sustainable lifestyle. The design principles that emerged from the project are design for categories and labels, design for measuring collective impact, and design for rewards and redemption

On-site earthquake early warning: a partially non-ergodic perspective from the site effects point of view

We introduce in the on-site earthquake early warning (EEW) a partially non-ergodic perspective from the site effects point of view. We consider the on-site EEW approach where the peak ground velocity (PGV) for S waves is predicted from an early estimate, over the P waves, of either the peak-displacement (PD) or cumulative squared velocity (IV2). The empirical PD-PGV and IV2-PGV relationships are developed by applying a mixed-effect regression where the site-specific modifications of ground shaking are treated as random effects. We considered a large data set composed of almost 31 000 selected recordings in central Italy, a region struck by four earthquakes with magnitude between 6 and 6.5 since the 2009 L’Aquila earthquake. We split the data set into three subsets used for calibrating and validating the on-site EEW models, and for exemplifying their application to stations installed after the calibration phase. We show that the partially non-ergodic models improve the accuracy of the PGV predictions with respect to ergodic models derived for other regions of the world. Moreover, considering PD and accounting for site effects, we reduce the (apparent) aleatory variability of the logarithm of PGV from 0.31 to 0.36, typical values for ergodic on-site EEW models, to about 0.25. Interestingly, a lower variability of 0.15 is obtained by considering IV2 as proxy, which suggests further consideration of this parameter for the design of on-site EEW systems. Since being site-specific is an inherent characteristic of on-site EEW applications, the improved accuracy and precision of the PGV predicted for a target protection translate in a better customization of the alert protocols for automatic actions

DITHIOCARBAMATE SUBSTITUTED PHENOTHIAZINE DERIVATIVES: IN SILICO EXPERIMENTS, SYNTHESIS, AND BIOLOGICAL EVALUATION

Objective: The present study was designed to study the anticancer activity of a series of novel analogs of phenothiazine with dithiocarbamate as a side chain. Methods: A novel series of derivatives containing dithiocarbamate as a side chain at the tenth position of phenothiazine nucleus were synthesized, characterized by spectral analysis, and evaluated for their antimitotic and antioxidant activity using germinated Bengal gram seeds and 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, respectively. A quantitative estimate of drug-likeness was also performed, which calculated the molecular properties and screened the molecules based on drug-likeness rules. Further, molecular docking study was performed for finding the binding affinity with tubulin protein to rationalize their anticancer activity. Results: The results revealed that the antioxidant activity of compounds 3e, 3g, 3i, 3j and standard Ascorbic acid were 10 mmol, 14 mmol, 16 mmol, 16 mmol and 35 mmol, respectively. Further compounds 3e, 3g, 3h and 3i have shown promising antimitotic activity. Compound 3i (-9 K. Cal/mol) showed the highest binding energies towards tubulin protein when compared to standard drug colchicine (-8.6 K. Cal/mol). Among all, compound 3i showed promising antimitotic and antioxidant activity, which correlated with insilico docking studies. Conclusion: Dithiocarbamate substituted phenothiazine derivatives proved to be encouraging leads as tubulin inhibitors

Assessing coastal vulnerability at the village level using a robust framework, the example of Canacona in South Goa, India

Nigam, R., Luis, A. J., Gagnon, A. S., Vaz, E., Damásio, B., & Kotha, M. (2024). Assessing coastal vulnerability at the village level using a robust framework, the example of Canacona in South Goa, India. ISCIENCE, Article 109129. https://doi.org/10.1016/j.isci.2024.109129 --- The first author Mr. Ritwik Nigam, a Ph.D student acknowledges the financial support provided by the University Grant Commission (UGC), Govt. of India, New Delhi, to conduct this research. The authors also thank all the administrative authorities of their respective institutions for their support during field surveys. Bruno Damásio acknowledges the financial support provided by Fundac̨ão para a Ciência e a Tecnologia, Portugal (FCT) under the project UIDB/04152/2020 Centro de Investigação em Gestão de Informação (MagIC).Climate change poses a significant threat to coastal regions worldwide. This study presents and applies a modified CVI to assess coastal vulnerability at the village level, focusing on Canacona, a taluka in South Goa, India. It adapts the existing CVI methodology by incorporating additional variables to represent the various dimensions of vulnerability better, resulting in 21 variables split into a Physical Vulnerability Index (PVI) and a Social Vulnerability Index (SoVI). The results show spatial variability in coastal vulnerability across the studied villages, with Agonda and Nagercem-Chaudi found to be highly vulnerable and Loliem to be the least vulnerable. A hydrological modeling approach is also used to compare the CVI of every village with their susceptibility to inundation due to rising sea levels. The result demonstrates the influence of local factors on vulnerability, challenging previous taluka-level assessments given the typical scale upon which adaptation typically takes place.publishersversionpublishe

Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains

Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of aromatic and leucine residues embedded in regions of high acidity. This predictor identifies known activation domains and accurately predicts previously unidentified ones. Our results support a flexible acidic exposure model of activation domains in which the acidic residues solubilize hydrophobic motifs so that they can interact with coactivators. A record of this paper\u27s transparent peer review process is included in the supplemental information

Hsp90 and PKM2 Drive the Expression of Aromatase in Li-Fraumeni Syndrome Breast Adipose Stromal Cells

Li-Fraumeni syndrome (LFS) patients harbor germ line mutations in the TP53 gene and are at increased risk of hormone receptor-positive breast cancers. Recently, elevated levels of aromatase, the rate-limiting enzyme for estrogen biosynthesis, were found in the breast tissue of LFS patients. Although p53 down-regulates aromatase expression, the underlying mechanisms are incompletely understood. In the present study, we found that LFS stromal cells expressed higher levels of Hsp90 ATPase activity and aromatase compared with wild-type stromal cells. Inhibition of Hsp90 ATPase suppressed aromatase expression. Silencing Aha1 (activator of Hsp90 ATPase 1), a co-chaperone of Hsp90 required for its ATPase activity, led to both inhibition of Hsp90 ATPase activity and reduced aromatase expression. In comparison with wild-type stromal cells, increased levels of the Hsp90 client proteins, HIF-1α, and PKM2 were found in LFS stromal cells. A complex comprised of HIF-1α and PKM2 was recruited to the aromatase promoter II in LFS stromal cells. Silencing either HIF-1α or PKM2 suppressed aromatase expression in LFS stromal cells. CP-31398, a p53 rescue compound, suppressed levels of Aha1, Hsp90 ATPase activity, levels of PKM2 and HIF-1α, and aromatase expression in LFS stromal cells. Consistent with these in vitro findings, levels of Hsp90 ATPase activity, Aha1, HIF-1α, PKM2, and aromatase were increased in the mammary glands of p53 null versus wild-type mice. PKM2 and HIF-1α were shown to co-localize in the nucleus of stromal cells of LFS breast tissue. Taken together, our results show that the Aha1-Hsp90-PKM2/HIF-1α axis mediates the induction of aromatase in LFS

DNA Binding and Photocleavage Studies of Cobalt(III) Ethylenediamine Pyridine Complexes: [Co(en)2(py)2]3+ and [Co(en)2(mepy)2]3+

Two novel cobalt(III) pyridine complexes (1) [Co(en)2(py)2]3+ and (2) [Co(en)2(mepy)2]3+ (en=ethylenediamine, py=pyridine, and mepy=methylpyridine) have been synthesized and characterized. The interaction of these complexes with calf thymus DNA was investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photocleavage. Results suggest that the two complexes bind to DNA via groove mode and complex 2 binds more strongly to CT DNA than complex 1. Moreover, these Co(III) complexes have been found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm, cytotoxicity results of complexes are also showing anticancer activity

The Coxsackievirus and Adenovirus Receptor Has a Short Half-Life in Epithelial Cells

The coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell adhesion, cell signaling, and viral infection. The 8-exon encoded isoform (CAREx8) resides at the apical surface of polarized epithelia, where it is accessible as a receptor for adenovirus entering the airway lumen. Given its pivotal role in viral infection, it is a target for antiviral strategies. To understand the regulation of CAREx8 and determine the feasibility of receptor down regulation, the half-life of total and apical localized CAREx8 was determined and correlated with adenovirus transduction. Total and apical CAREx8 has a relatively short half-life of approximately 2 h. The half-life of apical CAREx8 correlates well with adenovirus transduction. These results suggest that antiviral strategies that aim to degrade the primary receptor for apical adenovirus infection will be effective within a relatively short time frame after application

High yielding synthesis of N-ethyl dehydroamino acids

Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain N-ethyl-α, β-dehydroamino acid derivatives. The application of this N-alkylation procedure to several methyl esters of β, β-dibromo and β--bromo, β-substituted dehydroamino acids protected with standard amine protecting groups was subsequently reported. The corresponding N-ethyl, β-bromo dehydroamino acid derivatives were obtained in fair to high yields and some were used as substrates in Suzuki cross coupling reactions to give N-ethyl, β, β-disubstituted dehydroalanine derivatives. Herein, we further explore N-ethylation of β-halo dehydroamino acid derivatives using triethyloxonium tetrafluoroborate as alkylating agent but substituting N,N-diisopropylethylamine for potassium tert-butoxide as auxiliary base. In these conditions, for all β-halo dehydroamino acid derivatives, reactions were complete and the N-ethylated derivative could be isolated in high yield. This method was also applied for N-ethylation of non-halogenated dehydroamino acids. Again, with all compounds the reactions were complete and the N-ethyl dehydroamino acid derivatives could be isolated in high yields. Some of these N-ethyl dehydroamino acid methyl ester derivatives were converted in high yields to their corresponding acids and coupled to an amino acid methyl ester to give N-ethyl dehydrodipeptide derivatives in good yields. Thus, this method constitutes a general procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.Foundation for Science and Technology (FCT)-Portugal and Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMR spectrometer Bruker Avance II+ 400 is part of the National NMR Network and was purchased in the framework of the National Program for Scientific Re-equipment; contract REDE/1517/RMN/2005, with funds from POCI 2010, FEDER and FCT