The effects of water and microstructure on the performance of polymer electrolyte fuel cells

n this paper, we present a comprehensive non-isothermal, one-dimensional model of the cathode side of a Polymer Electrolyte Fuel Cell. We explicitly include the catalyst layer, gas diffusion layer and the membrane. The catalyst layer and gas diffusion layer are characterized by several measurable microstructural parameters. We model all three phases of water, with a view to capturing the effect that each has on the performance of the cell. A comparison with experiment is presented, demonstrating excellent agreement, particularly with regard to the effects of water activity in the channels and how it impacts flooding and membrane hydration. We present several results pertaining to the effects of water on the current density (or cell voltage), demonstrating the role of micro-structure, liquid water removal from the channel, water activity, membrane and gas diffusion layer thickness and channel temperature. These results provide an indication of the changes that are required to achieve optimal performance through improved water management and MEA-component design. Moreover, with its level of detail, the model we develop forms an excellent basis for a multi-dimensional model of the entire membrane electrode assembly

The feasibility of a randomised control trial to assess physiotherapy against surgery for recurrent patellar instability

Background: Patellar instability is a relatively common condition that leads to disability and restriction of activities. People with recurrent instability may be given the option of physiotherapy or surgery though this is largely driven by clinician preference rather than by a strong evidence base. We sought to determine the feasibility of conducting a definitive trial comparing physiotherapy with surgical treatment for people with recurrent patellar instability. Methods: This was a pragmatic, open-label, two-arm feasibility randomised control trial (RCT) with an embedded interview component recruiting across three NHS sites comparing surgical treatment to a package of best conservative care; 'Personalised Knee Therapy' (PKT). The primary feasibility outcome was the recruitment rate per centre (expected rate 1 to 1.5 participants recruited each month). Secondary outcomes included the rate of follow-up (over 80% expected at 12 months) and a series of participant-reported outcomes taken at 3, 6 and 12 months following randomisation, including the Norwich Patellar Instability Score (NPIS), the Kujala Patellofemoral Disorder Score (KPDS), EuroQol-5D-5L, self-reported global assessment of change, satisfaction at each time point and resources use. Results: We recruited 19 participants. Of these, 18 participants (95%) were followed-up at 12 months and 1 (5%) withdrew. One centre recruited at just over one case per month, one centre was unable to recruit, and one centre recruited at over one case per month after a change in participant screening approach. Ten participants were allocated into the PKT arm, with nine to the surgical arm. Mean Norwich Patellar Instability Score improved from 40.6 (standard deviation 22.1) to 28.2 (SD 25.4) from baseline to 12 months. Conclusion: This feasibility trial identified a number of challenges and required a series of changes to ensure adequate recruitment and follow-up. These changes helped achieve a sufficient recruitment and follow-up rate. The revised trial design is feasible to be conducted as a definitive trial to answer this important clinical question for people with chronic patellar instability. Trial registration: The trial was prospectively registered on the International Standard Randomised Controlled Trial Number registry on the 22/12/2016 (reference number: ISRCTN14950321). http://www.isrctn.com/ISRCTN1495032

Energy expenditure during flight in relation to body mass: effects of natural increases in mass and artificial load in Rose Coloured Starlings

Rose Coloured Starlings (Sturnus roseus) flew repeatedly for several hours in a wind tunnel while undergoing spontaneous variation in body mass. The treatments were as follows: flying unrestrained (U), with a control harness of 1.2% of their body mass (C), or with a harness of 7.4% of their body mass, which was either applied immediately before the flight (LS) or at least 9 days in advance (LL). Energy expenditure during flight (ef in W) was measured with the Doubly Labelled Water method. Flight costs in LS and LL were not significantly different and therefore were pooled (L). The harness itself did not affect ef, i.e. U and C flights were not different. ef was allometrically related with body mass m (in g). The slopes were not significantly different between the treatments, but ef was increased by 5.4% in L compared to C flights (log10(ef) = 0.050 + 0.47 × log10(m) for C, and log10(ef) = 0.073 + 0.47 × log10(m) for L). The difference in ef between C, LS and LL was best explained by taking the transported mass mtransp (in g) instead of m into account (log10(ef) = −0.08 + 0.54 × log10(mtransp)). Flight costs increased to a lesser extent than expected from interspecific allometric comparison or aerodynamic theory, regardless of whether the increase in mass occurred naturally or artificially. We did not observe an effect of treatment on breast muscle size and wingbeat frequency. We propose that the relatively low costs at a high mass are rather a consequence of immediate adjustments in physiology and/or flight behaviour than of long-term adaptations

The Use of High-Solids Loadings in Biomass Pretreatment – A Review

The use of high‐solids loadings (≥ 15% solids, w/w) in the unit operations of lignocellulose conversion processes potentially offers many advantages over lower‐solids loadings, including increased sugar and ethanol concentrations and decreased production and capital costs. Since the term lignocellulosic materials refers to a wide range of feedstocks (agricultural and forestry residues, distillery by‐products, and dedicated energy crops like grasses), the term “solids loading” here is defined by the amount of dry material that enters the process divided by the total mass of material and water added to the material. The goal of this study is to provide a consolidated review of studies using a high‐solids pretreatment step in the conversion process. Included in this review is a brief discussion of the limitations, such as the lack of available water to promote mass transfer, increased substrate viscosity, and increased concentration of inhibitors produced affecting pretreatment, as well as descriptions and findings of pretreatment studies performed at high solids, the latest reactor designs developed for pretreatment at bench‐ and pilot‐scales to address some of the limitations, and high‐solids pretreatment operations that have been scaled‐up and incorporated into demonstration facilities

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

A Template-Dependent Dislocation Mechanism Potentiates K65R Reverse Transcriptase Mutation Development in Subtype C Variants of HIV-1

Numerous studies have suggested that the K65R reverse transcriptase (RT) mutation develops more readily in subtype C than subtype B HIV-1. We recently showed that this discrepancy lies partly in the subtype C template coding sequence that predisposes RT to pause at the site of K65R mutagenesis. However, the mechanism underlying this observation and the elevated rates of K65R development remained unknown. Here, we report that DNA synthesis performed with subtype C templates consistently produced more K65R-containing transcripts than subtype B templates, regardless of the subtype-origin of the RT enzymes employed. These findings confirm that the mechanism involved is template-specific and RT-independent. In addition, a pattern of DNA synthesis characteristic of site-specific primer/template slippage and dislocation was only observed with the subtype C sequence. Analysis of RNA secondary structure suggested that the latter was unlikely to impact on K65R development between subtypes and that Streisinger strand slippage during DNA synthesis at the homopolymeric nucleotide stretch of the subtype C K65 region might occur, resulting in misalignment of the primer and template. Consequently, slippage would lead to a deletion of the middle adenine of codon K65 and the production of a -1 frameshift mutation, which upon dislocation and realignment of the primer and template, would lead to development of the K65R mutation. These findings provide additional mechanistic evidence for the facilitated development of the K65R mutation in subtype C HIV-1

Identification of CIITA Regulated Genetic Module Dedicated for Antigen Presentation

The class II trans-activator CIITA is a transcriptional co-activator required for the expression of Major Histocompatibility Complex (MHC) genes. Although the latter function is well established, the global target-gene specificity of CIITA had not been defined. We therefore generated a comprehensive list of its target genes by performing genome-wide scans employing four different approaches designed to identify promoters that are occupied by CIITA in two key antigen presenting cells, B cells and dendritic cells. Surprisingly, in addition to MHC genes, only nine new targets were identified and validated by extensive functional and expression analysis. Seven of these genes are known or likely to function in processes contributing to MHC-mediated antigen presentation. The remaining two are of unknown function. CIITA is thus uniquely dedicated for genes implicated in antigen presentation. The finding that CIITA regulates such a highly focused gene expression module sets it apart from all other transcription factors, for which large-scale binding-site mapping has indicated that they exert pleiotropic functions and regulate large numbers of genes

Hypoxic regulation of RIOK3 is a major mechanism for cancer cell invasion and metastasis.

Hypoxia is a common feature of locally advanced breast cancers that is associated with increased metastasis and poorer survival. Stabilisation of hypoxia-inducible factor-1α (HIF1α) in tumours causes transcriptional changes in numerous genes that function at distinct stages of the metastatic cascade. We demonstrate that expression of RIOK3 (RIght Open reading frame kinase 3) was increased during hypoxic exposure in an HIF1α-dependent manner. RIOK3 was localised to distinct cytoplasmic aggregates in normoxic cells and underwent redistribution to the leading edge of the cell in hypoxia with a corresponding change in the organisation of the actin cytoskeleton. Depletion of RIOK3 expression caused MDA-MB-231 to become elongated and this morphological change was due to a loss of protraction at the trailing edge of the cell. This phenotypic change resulted in reduced cell migration in two-dimensional cultures and inhibition of cell invasion through three-dimensional extracellular matrix. Proteomic analysis identified interactions of RIOK3 with actin and several actin-binding factors including tropomyosins (TPM3 and TPM4) and tropomodulin 3. Depletion of RIOK3 in cells resulted in fewer and less organised actin filaments. Analysis of these filaments showed reduced association of TPM3, particularly during hypoxia, suggesting that RIOK3 regulates actin filament specialisation. RIOK3 depletion reduced the dissemination of MDA-MB-231 cells in both a zebrafish model of systemic metastasis and a mouse model of pulmonary metastasis. These findings demonstrate that RIOK3 is necessary for maintaining actin cytoskeletal organisation required for migration and invasion, biological processes that are necessary for hypoxia-driven metastasis