Sharing Ideas and Practice In Higher Education

Sharing Ideas and Practice in Higher Education There is a substantial literature on teaching and learning in Higher Education. The majority of this literature is student facing, focusing on the student learning experience. There is also a strand in the literature which examines teaching and learning from the tutor perspective, looking at the experience of teaching in Higher Education. In both student and tutor facing approaches, the aim is to facilitate and enhance teaching and learning and tutor facing approaches emphasise in particular the contribution of staff communication and reflection in improving teaching and learning. Tutor facing approaches include Scholarship in Teaching and Learning, Communities of Practice and Disciplinary Commons. This paper discusses the experience of a School of Computing Commons (School Commons) developed in the School of Computing in a UK university. The School Commons was inspired by the Disciplinary Commons approach but also draws on the Scholarship for Teaching and Learning and Communities of Practice approaches. Elements from these three approaches were used to develop a model which brought together teaching staff from the different disciplines in the School of Computing, creating a forum in which to share practice and expertise. The main focus of the School Commons was on process, providing space for reflection and facilitating communication and the exchange of ideas. However, the School Commons also facilitated a bottom up approach to staff development, allowing staff to feed ideas and expectations into the university framework. The paper describes the motivation for the development of the School Commons, the process of establishing the School Commons and the way in which it was structured. The operation of the School Commons is reviewed and the effectiveness and value of this type of approach in terms of contribution to teaching and learning is critically evaluated. The outcomes from the project are discussed and the paper makes a number of suggestions for building on the achievements of the School Commons and future development

Efficient energy transport in an organic semiconductor mediated by transient exciton delocalization.

Efficient energy transport is desirable in organic semiconductor (OSC) devices. However, photogenerated excitons in OSC films mostly occupy highly localized states, limiting exciton diffusion coefficients to below ~10-2 cm2/s and diffusion lengths below ~50 nm. We use ultrafast optical microscopy and nonadiabatic molecular dynamics simulations to study well-ordered poly(3-hexylthiophene) nanofiber films prepared using living crystallization-driven self-assembly, and reveal a highly efficient energy transport regime: transient exciton delocalization, where energy exchange with vibrational modes allows excitons to temporarily re-access spatially extended states under equilibrium conditions. We show that this enables exciton diffusion constants up to 1.1 ± 0.1 cm2/s and diffusion lengths of 300 ± 50 nm. Our results reveal the dynamic interplay between localized and delocalized exciton configurations at equilibrium conditions, calling for a re-evaluation of exciton dynamics and suggesting design rules to engineer efficient energy transport in OSC device architectures not based on restrictive bulk heterojunctions

Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation

Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation

Ecological and Physiological Studies of Gymnodinium catenatum in the Mexican Pacific: A Review

This review presents a detailed analysis of the state of knowledge of studies done in Mexico related to the dinoflagellate Gymnodinium catenatum, a paralytic toxin producer. This species was first reported in the Gulf of California in 1939; since then most studies in Mexico have focused on local blooms and seasonal variations. G. catenatum is most abundant during March and April, usually associated with water temperatures between 18 and 25 ºC and an increase in nutrients. In vitro studies of G. catenatum strains from different bays along the Pacific coast of Mexico show that this species can grow in wide ranges of salinities, temperatures, and N:P ratios. Latitudinal differences are observed in the toxicity and toxin profile, but the presence of dcSTX, dcGTX2-3, C1, and C2 are usual components. A common characteristic of the toxin profile found in shellfish, when G. catenatum is present in the coastal environment, is the detection of dcGTX2-3, dcSTX, C1, and C2. Few bioassay studies have reported effects in mollusks and lethal effects in mice, and shrimp; however no adverse effects have been observed in the copepod Acartia clausi. Interestingly, genetic sequencing of D1-D2 LSU rDNA revealed that it differs only in one base pair, compared with strains from other regions

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Isolation, characterisation and differentiation of canine adult stem cells

Cardiac and orthopaedic diseases are significant causes of morbidity and mortality in dogs and are therefore critical areas for veterinary research. More information regarding the pathophysiology of these diseases, and the development of novel therapeutics are sorely required and adult stem cells (ASCs) are a promising source of cells for both investigation of these diseases in vitro and also potentially therapeutics in the longer term. ASCs are a readily available source of multipotent cells which bypass the ethical issues surrounding embryonic stem (ES) cells. ASCs have been described in several tissues of the body, and typically differentiate along specific cellular routes related to original source location. This thesis investigates whether ASCs can be isolated and cultured from the dog from two specific locations; cardiac, producing cardiac stem cells (CSCs); and the bone marrow, producing mesenchymal stem cells (MSCs). These cell sources will be extensively characterised at their baseline for morphology, culture behaviour and gene marker expression. Following characterisation each cell source will be subjected to differentiation techniques to examine canine ASC multipotent differentiation potential. CSCs were isolated from cultured atrial cardiac explant tissue taken from dogs post-mortem, with owners’ consent. These cells were able to survive successive passages in serum free media and formed large spherical cell clusters, termed ‘cardiospheres’. CSCs were capable of clonal expansion under controlled culture conditions, demonstrating their ability for self-renewal. Characterisation of these cells demonstrated the expression of CSC markers; c-Kit, GATA 4 and Flk-1 and no expression of cardiac lineage markers including cardiac troponin T and I, Nkx2.5, the cardiac ryanodine receptor and the β1-adrenergic receptor. Primary canine MSCs were isolated from bone marrow aspirates using ficoll separation and cultured on tissue culture plastic. Canine MSCs closely resembled MSCs described from other species, such as the human and mouse, and were found to express CD44 and STRO-1 and were negative for CD34 and CD45. CSCs and MSCs were exposed to published cardiac directed differentiation protocols and differentiation then analysed using cellular morphology and gene expression. Canine CSCs appeared to differentiate partially along cardiac lineages with upregulation of cardiac troponin T and Nkx2.5, and down regulation of c-Kit and endothelial lineage markers. Canine MSCs demonstrated some morphological changes during cardiac differentiation, and demonstrated up-regulation of Nkx2.5 and Flk-1 but no significant alteration in other markers examined. This suggested that cardiac directed differentiation was not as successful with canine MSCs compared to CSCs and conflicting with published data using rodent MSC models. Murine MSCs were used as a positive control cell line for cardiac directed differentiation, based upon published literature. Critically there were key marker expression differences between baseline murine and canine MSCs, including the expression of cardiac markers such as cardiac troponin T and I, and the Ryanodine receptor. Furthermore, expression analysis of cardiac genes changed with time in culture and passage number and no significant alteration was seen when cells were subjected to the cardiac differentiation protocol; thereby bringing into question the data regarding successful cardiac differentiation using murine MSCs. Canine MSCs were further differentiated toward a chondrocyte lineage to investigate the use of MSCs for orthopaedic research. Canine MSCs were successfully differentiated toward articular type cartilage, with demonstration of extracellular matrix secretions, an upregulation of collagen type II with downregulation of collagen type I and the development of SOX9 expression in differentiated cells. This thesis builds the groundwork for future ASC research in the dog. Successful isolation and culture of two ASC sources from the dog is demonstrated. Cardiac and cartilage directed differentiation was successful using primary sourced cells, but differentiation was found to be limited to highly specific routes for each stem cell source. The results presented here highlight the importance of analysing baseline stem cells extensively prior to differentiation and in particular, before making comparisons between cell populations isolated from different locations and species.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Geoacoustic Inversion of Tow-Ship Noise via Near-Field–Matched-Field Processing

Abstract—This paper discusses geoacoustic inversion from tow-ship noise data acquired via a horizontal towed array. Through simulations and experimental results, it is shown that even very quiet ships radiate sufficient noise power to enable self-noise inversion of basic geoacoustic parameters such as effective bottom velocity. The experimental results presented are particularly encouraging in view of the high level of interference shown to be tolerated from nearby shipping. Index Terms—Geoacoustic inversion, self-noise, tow ship. I