Evaluating the uncertainty in the performance of small scale renewables

The successful delivery of low-carbon housing (both new and retrofitted) is a key aspect of the UK s commitment to an 80% reduction in carbon emissions by 2050. In this context, the inclusion of small-scale building-integrated renewable energy technologies is an important component of low carbon design strategies, and is subject to numerous regulation and incentive schemes (including the Renewable Heat Incentive (RHI)) set up by government to encourage uptake and set minimum performance benchmarks. Unfortunately there are numerous examples of in-use energy and carbon performance shortfalls for new and retrofitted buildings this is termed the performance gap . Technical and human factors associated with building subsystem performance, which are often not considered in design tools used to predict performance, are the root cause of performance uncertainty. The research presented in this doctoral thesis aims to develop and apply a novel probabilistic method of evaluating the performance uncertainty of solar thermal systems installed in the UK. Analysis of measured data from a group of low carbon retrofitted dwellings revealed that the majority of buildings failed to meet the designed-for carbon emissions target with an average percentage difference of 60%. An in-depth case study technical evaluation of one of these dwellings showed significant dysfunction associated with the combined ASHP/solar thermal heating system, resulting in a performance gap of 94%, illustrating that the performance gap can be regarded as a whole-system problem, comprising a number of subsystem causal factors. Using a detailed dataset obtained from the UK s largest field trial of domestic solar thermal systems, a cross-cutting evaluation of predicted vs. measured performance similarly revealed a discrepancy with a mean percentage difference in predicted and measured annual yield of -24%. Having defined the nature and extent of underperformance for solar thermal technology in the UK, causal factors influencing performance were mapped and the associated uncertainty quantified using a novel knowledge-based Bayesian network (BN). In addition, the BN approach along with Monte Carlo sampling was applied to the well-established BREDEM model in order to quantify performance uncertainty of solar thermal systems by producing distributions of annual yield. As such, the modified BN-based BREDEM model represents a significant improvement in the prediction of performance of small-scale renewable energy technologies. Finally, financial analysis applied to the probabilistic predictions of annual yield revealed that the current UK RHI scheme is unlikely to result in positive returns on investment for solar thermal systems unless the duration of the payments is extended or electricity is the primary source of heating

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms. METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA. RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential. CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients

Clinical disorders affecting mesopic vision

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized

Regulation of trophoblast beta1-integrin expression by contact with endothelial cells

BACKGROUND: In human and non-human primates, migratory trophoblasts penetrate the uterine epithelium, invade uterine matrix, and enter the uterine vasculature. Invasive trophoblasts show increased expression of β1 integrin. Since trophoblast migration within the uterine vasculature involves trophoblast attachment to endothelial cells lining the vessel walls, this raises the possibility that cell-cell contact and/or factors released by endothelial cells could regulate trophoblast integrin expression. To test this, we used an in vitro system consisting of early gestation macaque trophoblasts co-cultured on top of uterine microvascular endothelial cells. RESULTS: When cultured alone, trophoblasts expressed low levels of β1 integrin as determined by quantitative immunofluorescence microscopy. When trophoblasts were cultured on top of endothelial cells for 24 h, the expression of trophoblast β1 integrin was significantly increased as determined by image analysis. β1 Integrin expression was not increased when trophoblasts were cultured with endothelial cell-conditioned medium, suggesting that upregulation requires direct contact between trophoblasts and endothelial cells. To identify endothelial cell surface molecules responsible for induction of trophoblast integrin expression, trophoblasts were cultured in dishes coated with recombinant platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), or αVβ3 integrin. Trophoblast β1 integrin expression (assessed by immunofluorescence microscopy and Western blotting) was increased when PECAM-1 or αVβ3 integrin, but not ICAM-1, was used as substrate. CONCLUSIONS: Direct contact between trophoblasts and endothelial cells increases the expression of trophoblast β1 integrin

Paraneoplastic Vitelliform Retinopathy Secondary to Metastatic Melanoma.

Paraneoplastic vitelliform retinopathy secondary to metastatic melanom

Identification of a signalling molecule involved in bacterial intergeneric communication

The development of complex multispecies communities such as biofilms is controlled by interbacterial communication systems. We have previously reported an intergeneric communication between two oral bacteria, Streptococcus cristatus and Porphyromonas gingivalis, that results in inhibition of fimA expression. Here, we demonstrate that a surface protein, arginine deiminase (ArcA), of S. cristatus serves as a signal that initiates intergeneric communication. An ArcA-deficient mutant of S. cristatus is unable to communicate with P. gingivalis. Furthermore, arginase activity is not essential for the communication, and ArcA retains the ability to repress expression of fimA in the presence of arginine deiminase inhibitors. These results present a novel mechanism by which intergeneric communication in dental biofilms is accomplished

Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas

Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo