Efficient bio-production of citramalate using an engineered Escherichia coli strain

Citramalic acid is a central intermediate in a combined biocatalytic and chemocatalytic route to produce bio-based methylmethacrylate, the monomer used to manufacture Perspex and other high performance materials. We developed an engineered E. coli strain and a fed-batch bioprocess to produce citramalate at concentrations in excess of 80 g l-1 in only 65 h. This exceptional efficiency was achieved by designing the production strain and the fermentation system to operate synergistically. Thus, a single gene encoding a mesophilic variant of citramalate synthase from Methanococcus jannaschii, CimA3.7, was expressed in E. coli to convert acetyl-CoA and pyruvate to citramalate, and the ldhA and pflB genes were deleted. By using a bioprocess with a continuous, growth-limiting feed of glucose, these simple interventions diverted substrate flux directly from central metabolism towards formation of citramalate, without problematic accumulation of acetate. Furthermore, the nutritional requirements of the production strain could be satisfied through the use of a mineral salts medium supplemented only with glucose (172 g l-1 in total) and 1.4 g l-1 yeast extract. Using this system, citramalate accumulated to 82±1.5 g l-1, with a productivity of 1.85 g l-1 h-1 and a conversion efficiency of 0.48 gcitramalate g-1 glucose. The new bioprocess forms a practical first step for integrated bio- and chemocatalytic production of methylmethacrylate

Developing an open data portal for the ESA climate change initiative

We introduce the rationale for, and architecture of, the European Space Agency Climate Change Initiative (CCI) Open Data Portal (http://cci.esa.int/data/). The Open Data Portal hosts a set of richly diverse datasets – 13 “Essential Climate Variables” – from the CCI programme in a consistent and harmonised form and to provides a single point of access for the (>100 TB) data for broad dissemination to an international user community. These data have been produced by a range of different institutions and vary across both scientific and spatio-temporal characteristics. This heterogeneity of the data together with the range of services to be supported presented significant technical challenges. An iterative development methodology was key to tackling these challenges: the system developed exploits a workflow which takes data that conforms to the CCI data specification, ingests it into a managed archive and uses both manual and automatically generated metadata to support data discovery, browse, and delivery services. It utilises both Earth System Grid Federation (ESGF) data nodes and the Open Geospatial Consortium Catalogue Service for the Web (OGC-CSW) interface, serving data into both the ESGF and the Global Earth Observation System of Systems (GEOSS). A key part of the system is a new vocabulary server, populated with CCI specific terms and relationships which integrates OGC-CSW and ESGF search services together, developed as part of a dialogue between domain scientists and linked data specialists. These services have enabled the development of a unified user interface for graphical search and visualisation – the CCI Open Data Portal Web Presence

Functional Redundancy of Class I Phosphoinositide 3-Kinase (PI3K) Isoforms in Signaling Growth Factor-Mediated Human Neutrophil Survival

We have investigated the contribution of individual phosphoinositide 3-kinase (PI3K) Class I isoforms to the regulation of neutrophil survival using (i) a panel of commercially available small molecule isoform-selective PI3K Class I inhibitors, (ii) novel inhibitors, which target single or multiple Class I isoforms (PI3Kα, PI3Kβ, PI3Kδ, and PI3Kγ), and (iii) transgenic mice lacking functional PI3K isoforms (p110δKOγKO or p110γKO). Our data suggest that there is considerable functional redundancy amongst Class I PI3Ks (both Class IA and Class IB) with regard to GM-CSF-mediated suppression of neutrophil apoptosis. Hence pharmacological inhibition of any 3 or more PI3K isoforms was required to block the GM-CSF survival response in human neutrophils, with inhibition of individual or any two isoforms having little or no effect. Likewise, isolated blood neutrophils derived from double knockout PI3K p110δKOγKO mice underwent normal time-dependent constitutive apoptosis and displayed identical GM-CSF mediated survival to wild type cells, but were sensitized to pharmacological inhibition of the remaining PI3K isoforms. Surprisingly, the pro-survival neutrophil phenotype observed in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) was resilient to inactivation of the PI3K pathway

Enhanced Blood Pressure Acquisition

Blood pressure is considered a primary vital sign that is regularly monitored in a healthcare setting. Current blood pressure measurement equipment lacks reproducible measurements which leads to questionable accuracy. Therefore, there is a need for an accurate and reproducible blood pressure measurement device that can take remote measurements. This project will be designed in The University of Akron\u27s biomedical engineering capstone course. The goal of this senior design project is to design and fabricate a blood pressure measuring device that meets the customer requirements and engineering requirements identified by the team

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Advantages of the no-scalpel vasectomy technique

The no-scalpel vasectomy (NSV) technique should be used instead of the standard incisional method. (Strength of Recommendation: A, based on systematic reviews, mixed-quality randomized controlled trials [RCTs], cohort studies, and case-control series.) The NSV technique is associated with fewer complications, produces less perioperative and postoperative pain, results in quicker recovery, takes less time to perform, and is as effective as standard incisional vasectomy