A System Dynamics Model of the Air Transport System

In this report, we give a complete algebraic description of a system dynamics model of the air transport system, developed to assess the impact of different policies on the adoption rate of fully electric aircraft until the year 2050. Our model consists of the interaction between three major segments, namely air travel demand, airline industry and aircraft manufacturers. This model was used in the paper “How much can electric aircraft contribute to reaching the Flightpath 2050 CO2 emissions goal? A system dynamics approach for European short haul flights” for the computational results therein

Two Antagonistic MALT1 Auto-Cleavage Mechanisms Reveal a Role for TRAF6 to Unleash MALT1 Activation.

The paracaspase MALT1 has arginine-directed proteolytic activity triggered by engagement of immune receptors. Recruitment of MALT1 into activation complexes is required for MALT1 proteolytic function. Here, co-expression of MALT1 in HEK293 cells, either with activated CARD11 and BCL10 or with TRAF6, was used to explore the mechanism of MALT1 activation at the molecular level. This work identified a prominent self-cleavage site of MALT1 isoform A (MALT1A) at R781 (R770 in MALT1B) and revealed that TRAF6 can activate MALT1 independently of the CBM. Intramolecular cleavage at R781/R770 removes a C-terminal TRAF6-binding site in both MALT1 isoforms, leaving MALT1B devoid of the two key interaction sites with TRAF6. A previously identified auto-proteolysis site of MALT1 at R149 leads to deletion of the death-domain, thereby abolishing interaction with BCL10. By using MALT1 isoforms and cleaved fragments thereof, as well as TRAF6 WT and mutant forms, this work shows that TRAF6 induces N-terminal auto-proteolytic cleavage of MALT1 at R149 and accelerates MALT1 protein turnover. The MALT1 fragment generated by N-terminal self-cleavage at R149 was labile and displayed enhanced signaling properties that required an intact K644 residue, previously shown to be a site for mono-ubiquitination of MALT1. Conversely, C-terminal self-cleavage at R781/R770 hampered the ability for self-cleavage at R149 and stabilized MALT1 by hindering interaction with TRAF6. C-terminal self-cleavage had limited impact on MALT1A but severely reduced MALT1B proteolytic and signaling functions. It also abrogated NF-κB activation by N-terminally cleaved MALT1A. Altogether, this study provides further insights into mechanisms that regulate the scaffolding and activation cycle of MALT1. It also emphasizes the reduced functional capacity of MALT1B as compared to MALT1A

Views on unlawful water abstractions along the Liebenbergsvlei River, South Africa

As a result of the growing demand for additional water supplies, officials at the National Department of Water Affairs (DWA) continually monitor consumption patterns. The unlawful abstraction of water for irrigation purposes along the Axle and Liebenbergsvlei water transfer scheme, a South African river catchment, has been identified as a potential over-consumption hotspot. An investigation into the evolution of modern farming and irrigation developments along this important water transfer scheme found that restrictions on irrigation water abstraction have primarily focused on the water security of downstream urban and industrial users who receive water at a high assurance of supply. During periods of normal rainfall the authorities paid little attention to the existing use of water from the Liebenbergsvlei water transfer scheme. Subsequent restrictions placed on local water abstraction for irrigation has achieved mixed results. This paper focuses on the perspectives of irrigation farmers who may be unlawfully using water from the transfer scheme. Their views are compared with those expressed by the authorities on this issue, and the way in which the authorities attempt to regulate water use in the region within the confines of existing legislation. The responses from the different sectors were qualitatively analysed and suggested solutions have been formulated for further discussion. The study’s major findings reveal that the contestation around water use for agricultural purposes will continue as long as the misunderstandings surrounding legal or illegal water use persist. As demand on water is escalating, it is considered important to put in place water security measures designed to safeguard the available water in light of scarcity

Low expression of the PPARγ-regulated gene thioredoxin-interacting protein accompanies human melanoma progression and promotes experimental lung metastases.

The thioredoxin system plays key roles in regulating cancer cell malignancy. Here we identify the Thioredoxin-interacting protein (TXNIP) as a gene, which expression is regulated by PPARγ in melanoma cells. We show that high TXNIP expression levels associate with benign melanocytic lesions, with tumor regression in patients on MAP kinase targeted therapy, with decreased proliferation in patients' melanoma biopsies, and with cell cycle arrest in human melanoma cell lines. In contrast, reduced TXNIP expression associates with advanced melanoma and with disease progression in patients. TXNIP depletion in human melanoma cells altered the expression of integrin beta-3 and the localization of the integrin alpha-v/beta-3 dimer at their surface. Moreover, TXNIP depletion affected human melanoma cell motility and improved their capacity to colonize mouse lungs in an in vivo assay. This study establishes TXNIP as a PPARγ-regulated gene in melanoma cells, thereby suggesting a link between these two proteins both involved in the regulation of cancer and of energy metabolism. It also reveals that the decrease in TXNIP expression, which is observed in advanced patient tumors, likely favors lung metastatic seeding of malignant cells