Development of Vortex Bioreactor Technology for Decentralised Water Treatment

The vortex bioreactor (VBR) is a simple decentralised water treatment system (DeWaTS) that sits at the interface between swirl flow, biotechnology and chemical engineering. The device utilises swirl flow and suspended activated beads to achieve downstream water processing and has been tested for applications including centrifugal-driven separation, pathogen neutralisation and metal absorption. The VBR was optimised for the treatment of faecally contaminated effluents in the developing world, and the design features related to the key challenges faced by the wastewater industry are highlighted here. The VBR has two aspects that can be modified to generate different reactor conditions: the impeller, where the swirl flow is modified through alterations of rotation speed, and impeller geometry and the suspended activated beads, which facilitate mixing and alter the reactor surface area. Data from testing for some of the different applications mentioned above are presented here, and future planned developments for the technology are discussed

Temperature and velocity measurements of a rising thermal plume

Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 16 (2015): 579–599, doi:10.1002/2014GC005576.The three-dimensional velocity and temperature fields surrounding an isolated thermal plume in a fluid with temperature-dependent viscosity are measured using Particle-Image Velocimetry and thermochromatic liquid crystals, respectively. The experimental conditions are relevant to a plume rising through the mantle. It is shown that while the velocity and the isotherm surrounding the plume can be used to visualize the plume, they do not reveal the finer details of its structure. However, by computing the Finite-Time Lyapunov Exponent fields from the velocity measurements, the material lines of the flow can be found, which clearly identify the shape of the plume head and characterize the behavior of the flow along the plume stem. It is shown that the vast majority of the material in the plume head has undergone significant stretching and originates from a wide region very low in the fluid domain, which is proposed as a contributing factor to the small-scale isotopic variability observed in ocean-island basalt regions. Lastly, the Finite-Time Lyapunov Exponent fields are used to calculate the steady state rise velocity of the thermal plume, which is found to scale linearly with the Rayleigh number, in contrast to some previous work. The possible cause and the significance of these conflicting results are discussed, and it is suggested that the scaling relationship may be affected by the temperature-dependence of the fluid viscosity in the current work.This work was funded by the National Science Foundation (grant EAR-055199) and the MAPS Dean's Office at UCL.2015-09-0

Constraining the source of mantle plumes

© The Author(s), 2016. This is the author's version of the work and is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth and Planetary Science Letters 453 (2016): 55-63, doi:10.1016/j.epsl.2015.12.008.In order to link the geochemical signature of hot spot basalts to Earth’s deep interior, it is first necessary to understand how plumes sample different regions of the mantle. Here, we investigate the relative amounts of deep and shallow mantle material that are entrained by an ascending plume and constrain its source region. The plumes are generated in a viscous syrup using an isolated heater for a range of Rayleigh numbers. The velocity fields are measured using stereoscopic Particle-Image Velocimetry, and the concept of the ‘vortex ring bubble’ is used to provide an objective definition of the plume geometry. Using this plume geometry, the plume composition can be analysed in terms of the proportion of material that has been entrained from different depths. We show that the plume composition can be well described using a simple empirical relationship, which depends only on a single parameter, the sampling coefficient, Sc. High-Sc plumes are composed of material which originated from very deep in the fluid domain, while low-Sc plumes contain material entrained from a range of depths. The analysis is also used to show that the geometry of the plume can be described using a similarity solution, in agreement with previous studies. Finally, numerical simulations are used to vary both the Rayleigh number and viscosity contrast independently. The simulations allow us to predict the value of the sampling coefficient for mantle plumes; we find that as a plume reaches the lithosphere, 90% of its composition has been derived from the lowermost 260−750 km in the mantle, and negligible amounts are derived from the shallow half of the lower mantle. This result implies that isotope geochemistry cannot provide direct information about this un-sampled region, and that the various known geochemical reservoirs must lie in the deepest few hundred kilometres of the mantle.This work was funded by the National Science Foundation (grant EAR-055199), the MAPS Dean’s Office at UCL and the CIDER workshop (EAR-1135452).2016-12-2

Experimental determination of translational starts using peptide mass mapping and tandem mass spectrometry within the proteome of Mycobacterium tuberculosis

Identification of protein translation start sites is largely a bioinformatics exercise, with relatively few confirmed by N-terminal sequencing. Translation start site determination is critical for defining both the protein sequence and the upstream DNA which may contain regulatory motifs. It is demonstrated here that translation start sites can be determined during routine protein identification, using MALDI-MS and MS/MS data to select the correct N-terminal sequence from a list of alternatives generated in silico. Applying the method to 13 proteins from Mycobacterium tuberculosis, 11 predicted translational start sites were confirmed, and two reassigned. The authors suggest that these data (be they confirmation or reassignments) are important for the annotation of both this genome and those of organisms with related genes. It was also shown that N-acetylation, reported to be rare in prokaryotes, was present in three of the 13 proteins (23 %), suggesting that in the mycobacteria this modification may be common, and an important regulator of protein function, although more proteins need to be analysed. This method can be performed with little or no additional experimental work during proteomics investigations

The coupled effects of mantle mixing and a water-dependent viscosity on the surface ocean

Water content plays a vital role in determining mantle rheology and thus mantle convection and plate tectonics. Most parameterised convection models predict that Earth initially underwent a period of rapid degassing and heating, followed by a slow and sustained period of regassing and cooling. However, these models assume water is instantaneously mixed and homogeneously distributed into the mantle. This is a limitation because the mixing time for water entering and leaving the mantle is a function of the Rayleigh number which varies dramatically with water content, temperature, and through time. Here we present an adapted parametrised model (Crowley et al., 2011) to include the coupled effects of the time scale of mixing with a water-dependent viscosity. We consider two mixing types: first, where the mixing time is constant throughout the model and second, where mixing time varies as a response to an evolving Rayleigh number. We find that, facilitated by the effects of water content in the melt region at mid-ocean ridges, a constant mixing time can induce long periods of degassing. The inclusion of a variable mixing time dependent on the Rayleigh number acts to limit the period of degassing and also results in more water being stored in the mantle and less at the surface than in both the constant and instantaneous mixing cases. Mixing time cannot be more than ∼2 billion years as large mixing times trap water in the mantle, leaving a dry surface. Even small changes in the surface ocean induced by mixing times on the order of 0.1 Gyrs can cause changes in the global-mean sea level on the order of 10's of metres. These changes in sea level could easily uncover topographic highs in the bathymetry, potentially aiding sub-aerial erosion a process thought to be important in early Earth evolution. Even in this relatively simple model, the inclusion of a mixing time between water entering and leaving the mantle creates a more dynamic water cycle

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology