HMOX1 Gene Promoter Alleles and High HO-1 Levels Are Associated with Severe Malaria in Gambian Children

Heme oxygenase 1 (HO-1) is an essential enzyme induced by heme and multiple stimuli associated with critical illness. In humans, polymorphisms in the HMOX1 gene promoter may influence the magnitude of HO-1 expression. In many diseases including murine malaria, HO-1 induction produces protective anti-inflammatory effects, but observations from patients suggest these may be limited to a narrow range of HO-1 induction, prompting us to investigate the role of HO-1 in malaria infection. In 307 Gambian children with either severe or uncomplicated P. falciparum malaria, we characterized the associations of HMOX1 promoter polymorphisms, HMOX1 mRNA inducibility, HO-1 protein levels in leucocytes (flow cytometry), and plasma (ELISA) with disease severity. The (GT)n repeat polymorphism in the HMOX1 promoter was associated with HMOX1 mRNA expression in white blood cells in vitro, and with severe disease and death, while high HO-1 levels were associated with severe disease. Neutrophils were the main HO-1-expressing cells in peripheral blood, and HMOX1 mRNA expression was upregulated by heme-moieties of lysed erythrocytes. We provide mechanistic evidence that induction of HMOX1 expression in neutrophils potentiates the respiratory burst, and propose this may be part of the causal pathway explaining the association between short (GT)n repeats and increased disease severity in malaria and other critical illnesses. Our findings suggest a genetic predisposition to higher levels of HO-1 is associated with severe illness, and enhances the neutrophil burst leading to oxidative damage of endothelial cells. These add important information to the discussion about possible therapeutic manipulation of HO-1 in critically ill patients

Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies.

CAPRISA, 2015.Abstract available in pdf

Flight 4.0: The Changing Technology Landscape of Aeronautics

This chapter draws the readers into a comprehensive discussion about the advances in Information and Communication Technologies (ICT) and their influence on the technology landscape of aeronautics. It gives a rough overview of the advances in technical systems from the industrial revolution up until Industry 4.0 and elaborates the reflection of these advancements in aeronautics from the pioneers era toward Flight 4.0. It briefly describes various recent fields of research in ICT such as Cyber-Physical Systems (CPS), Internet of Things (IoT), wireless networks, multicore architectures, Service-Oriented Architecture (SOA), cloud computing, big data, and modern software engineering methodologies as the parts of future aeronautical engineering body of knowledge. Thereafter, it describes aeronautical informatics as an establishing interdisciplinary field of study of applied informatics and aeronautics

Data Centric Workflows for Crowdsourcing

Crowdsourcing is a major paradigm to accomplish works that require human skills, by paying a small sum of money and drawing workers all across the globe. However, crowdsourcing platforms are mainly ways to solve large amounts of relatively simple and independent replicated work units.A natural extension of crowdsourcing is to enhance the definition of work, and solve more intricate problems, via orchestrations of tasks, and via higher-order, i.e. allowing workers to suggest a process to obtain data rather than a returning a plain answer. This work proposes complex workflows, a data centric workflow model for crowdsourcing. The model allows orchestration of simple tasks and concurrency. It handles data and crowdworkers and provides high-level constructs to decompose complex tasks into orchestrations of simpler subtasks. We consider termination questions: We show that existential termination (existence of at least one terminating run) is undecidable excepted for specifications with bounded recursion. On the other hand, universal termination (whether all runs of a complex workflow terminate) is decidable (and at least in co−2EXPTIME) when constraints on inputs are specified in a decidable fragment of FO. We then address correctness problems. We use FO formulas to specify dependencies between input and output data of a complex workflow. If dependencies are specified with a decidable fragment of FO, then universal correctness (whether all terminating runs satisfy dependencies) is decidable , and existential correctness (whether some terminating runs satisfy dependencies) is decidable with some restrictions