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This paper outlines why and how blockchain can digitally support and evolve the governance of collaborative project deliveries, such as integrated project deliveries (IPDs), to provide the foundation for novel and disruptive forms of organizational collaboration in the construction industry. Previous work has conceptualized IPDs as a common pool resource (CPR) scenario, where shared resources are collectively governed. Through the use of blockchain and smart contracts for trustworthy peer-to-peer transactions and execution logic, Ostrom's design principles can be digitally encoded to scale CPR scenarios. Building on the identified connections, the paper 1) synthesizes fourteen blockchain-based mechanisms to govern CPRs, 2) identifies twenty-two applications of these mechanisms to govern IPDs, and 3) introduces a conceptualization of the above relationships towards a holistic understanding of collaborative project deliveries on the crypto commons for novel collective organization of construction project delivery between both humans and machines.

Microplastics are now polluting all seas and, while studies have found numerous negative interactions between plastic pollution and marine animals, the effects on embryonic development are poorly understood. A potentially important source of developmental ecotoxicity comes from chemicals leached from plastic particles to the marine environment. Here we investigate the effects of leachates from new and beach-collected pellets on the embryonic and larval development of the sea urchin Strongylocentrotus purpuratus and demonstrate that exposure of developing embryos to these leachates elicits severe, consistent and treatment-specific developmental abnormalities including radialisation of the embryo and malformation of the skeleton, neural and immune cells. Using a multi-omics approach we define the developmental pathways disturbed upon exposure to PVC leachates and provide a mechanistic view that pinpoints cellular redox stress and energy production as drivers of phenotypic abnormalities following exposure to PVC leachates. Analysis of leachates identified high concentrations of zinc that are the likely cause of these observed defects. Our findings point to clear and specific detrimental effects of marine plastic pollution on the development of echinoderms, demonstrating that chemicals leached from plastic particles into sea water can produce strong developmental abnormalities via specific pathways, and therefore have the potential to impact on a wide range of organisms.

When collaborative project delivery models such as integrated project delivery (IPD) combine project resources, share decision-making rights, and distribute risk-and-reward among participants, the project can be conceptualized as a common-pool resource scenario. Multiple project appropriators have contractual rights to withdraw units from the shared resource system (i.e., the project budget). This theorization suggests project managers avoid the tragedy of the project by crafting effective self-governance structures in the face of pluralism. Using IPD as an example, this article suggests these project governance structures reflect Ostrom’s design principles for the successful governance of long-enduring common-pool resource scenarios., Project Management Journal, 52 (3)

The building sector has a significant potential to reduce the material resource demand needed for construction and therefore, greenhouse gas (GHG) emissions. Digitalization can help to make use of this potential and improve sustainability throughout the entire building&rsquo, s life cycle. One way to address this potential is through the integration of Life Cycle Assessment (LCA) into the building process by employing Building Information Modeling (BIM). BIM can reduce the effort needed to carry out an LCA, and therefore, facilitate the integration into the building process. A review of current industry practice and scientific literature shows that companies are lacking the incentive to apply LCA. If applied, there are two main approaches. Either the LCA is performed in a simplified way at the beginning of the building process using imprecise techniques, or it is done at the very end when all the needed information is available, but it is too late for decision-making. One reason for this is the lack of methods, workflows and tools to implement BIM-LCA integration over the whole building development. Therefore, the main objective of this study is to develop an integrated BIM-LCA method for the entire building process by relating it to an established workflow. To avoid an additional effort for practitioners, an existing structure for cost estimation in the Swiss context is used. The established method is implemented in a tool and used in a case study in Switzerland to test the approach. The results of this study show that LCA can be performed continuously in each building phase over the entire building process using existing Building Information Modeling (BIM) techniques for cost estimation. The main benefit of this approach is that it simplifies the application of LCA in the building process and therefore gives incentives for companies to apply it. Moreover, the re-work caused by the need for re-entering data and the usage of many different software tools that characterize most of the current LCA practices is minimized. Furthermore, decision-making, both at the element and building levels, is supported.

Ataxin-3 (AT3) is a deubiquitinating enzyme that triggers the inherited neurodegenerative disorder spinocerebellar ataxia type 3 when its polyglutamine (polyQ) stretch close to the C-terminus exceeds a critical length. It consists of the N-terminal globular Josephin domain (JD) and the C-terminal disordered one. Regarding its physiological role, it has ubiquitin hydrolase activity implicated in the function of the ubiquitin-proteasome system, but also plays a role in the pathway that sorts aggregated protein to aggresomes via microtubules. In the first part of this work, we further investigated its function(s) by taking advantage of Small Angle X-ray Scattering (SAXS) and Surface Plasmon Resonance (SPR). We demonstrated that an AT3 oligomer consisting of 6-7 subunits tightly binds to the tubulin hexameric oligomer at the level of three distinct tubulin-binding regions, one located in the JD, and the two others in the disordered domain, upstream and downstream of the polyQ stretch. By SPR we have also provided the first evidence of direct binding of AT3 to HDAC6, one of the components of the transport machinery that sorts protein to the aggresome. In the second part of this work, we have investigated the mechanisms of AT3 cytotoxicity triggered by expanded variants. For this purpose, we used Saccharomyces cerevisiae as a eukaryotic cellular model. We expressed a wild type (Q26), a pathogenic (Q85) and a truncated (291Δ) variant of the protein. The expanded form caused reduction in viability, accumulation of reactive oxygen species, imbalance of the antioxidant defense system and loss in cell membrane integrity. An AT3 variant truncated upstream of the polyQ also exerted a detrimental effect on cell growth and similar cytotoxicity, although to a lesser extent, which points to the involvement of also non-polyQ regions in cytotoxicity. Finally, we sought to evaluate the effects of tetracycline and epigallocatechin-3-gallate (EGCG), two well-known inhibitors of amyloid aggregation, on AT3 fibrillogenesis and cytotoxicity. We observed that tetracycline does not apparently change the aggregation mode, as supported by Fourier Transform Infrared spectroscopy and Atomic Force Microscopy data, but slightly retards further aggregation of the earliest soluble oligomers. In contrast, EGCG apparently increases the aggregation rate but also leads to the formation of off-pathway, non-amyloid, final aggregates. Despite these different effects, co-incubation of the AT3 with either compounds resulted in significantly lower cytotoxicity during AT3 aggregation.

Neuronal differentiation involves extensive modification of biochemical and morphological properties to meet novel functional requirements. Reorganization of the mitochondrial network to match the higher energy demand plays a pivotal role in this process. Mechanisms of neuronal differentiation in response to nerve growth factor (NGF) have been largely characterized in terms of signaling, however, little is known about its impact on mitochondrial remodeling and metabolic function. In this work, we show that NGF-induced differentiation requires the activation of autophagy mediated by Atg9b and Ambra1, as it is disrupted by their genetic knockdown and by autophagy blockers. NGF differentiation involves the induction of P-AMPK and P-CaMK, and is prevented by their pharmacological inhibition. These molecular events correlate with modifications of energy and redox homeostasis, as determined by ATP and NADPH changes, higher oxygen consumption (OCR) and ROS production. Our data indicate that autophagy aims to clear out exhausted mitochondria, as determined by enhanced localization of p62 and Lysotracker-red to mitochondria. In addition, we newly demonstrate that NGF differentiation is accompanied by increased mitochondrial remodeling involving higher levels of fission (P-Drp1) and fusion proteins (Opa1 and Mfn2), as well as induction of Sirt3 and the transcription factors mtTFA and PPARγ, which regulate mitochondria biogenesis and metabolism to sustain increased mitochondrial mass, potential, and bioenergetics. Overall, our data indicate a new NGF-dependent mechanism involving mitophagy and extensive mitochondrial remodeling, which plays a key role in both neurogenesis and nerve regeneration.