In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1).

Vitamin D receptor (VDR) is a substrate for modification with small ubiquitin-like modifier (SUMO). To further assess the role of reversible SUMOylation within the vitamin D hormonal response, we evaluated the effects of sentrin/SUMO-specific proteases (SENPs) that can function to remove small ubiquitin-like modifier (SUMO) from target proteins upon the activities of VDR and related receptors. We report that SENP1 and SENP2 strikingly potentiate ligand-mediated transactivation of VDR and also its heterodimeric partner, retinoid X receptor (RXRα) with depletion of cellular SENP1 significantly diminishing the hormonal responsiveness of the endogenous vitamin D target gene CYP24A1. We find that SENP-directed modulation of VDR activity is cell line-dependent, achieving potent modulatory effects in Caco-2 and HEK-293 cells, while in MCF-7 cells the vitamin D signal is unaffected by any tested SENP. In support of their function as novel modulators of the vitamin D hormonal pathway we demonstrate that both SENP1 and SENP2 can interact with VDR and reverse its modification with SUMO2. In a preliminary analysis we identify lysine 91, a residue known to be critical for formation and DNA binding of the VDR-RXR heterodimer, as a minor SUMO acceptor site within VDR. In combination, our results support a repressor function for SUMOylation of VDR and reveal SENPs as a novel class of VDR/RXR co-regulatory protein that significantly modulate the vitamin D response and which could also have important impact upon the functionality of both RXR-containing homo and heterodimers.

This article assesses the combined influence of information integration and automated data analytics on project performance. To this end, retrospective data on 78 completed projects, with a total installed value of $8 billion, was collected. The data collection effort characterized, for each project, the level of internal and external information integration. Information integration was assessed as the seamlessly interoperable sharing of data produced from a work function with other functions/stakeholders so that no manual data transfer was required. Also, the level of automated data analytics, understood as the full automation of the data analysis function after input data are entered, was also characterized on a project basis. Then, non-parametric statistical techniques were used to assess the impact of such functions on cost and schedule performance. The statistical analysis was also stratified by project type, e.g. greenfield and brownfield, additions, and modifications or shutdowns. Overall, projects with a sophisticated degree of information integration and automated data analytics can control their projects with more reliable information and in a proactive manner so that informed decisions can be timely made on behalf of the project and the organization.

Construction waste management has become extremely important due to stricter disposal and landfill regulations, and a lesser number of available landfills. There are extensive works done on waste treatment and management of the construction industry. Concepts like deconstruction, recyclability, and Design for Disassembly (DfD) are examples of better construction waste management methods. Although some authors and organizations have published rich guides addressing the DfD's principles, there are only a few buildings already developed in this area. This study aims to find the challenges in the current practice of deconstruction activities and the gaps between its theory and implementation. Furthermore, it aims to provide insights about how DfD can create opportunities to turn these concepts into strategies that can be largely adopted by the construction industry stakeholders in the near future.