Fostering a community of scholars at the University of Warwick : the Wolfson Research Exchange

This paper focuses on the University of Warwick’s Wolfson Research Exchange which opened in October 2008. It describes the varied environment that the facility offers to Warwick’s research community, and explores the service model provided. The new approaches to learning space design and the students’ expectations which informed and influenced the Research Exchange’s creation (as well as its ongoing service development) are also discussed. This case study provides an overview of the Research Exchange’s developments, successes and lessons learnt which could be applicable to other institutions exploring dedicated spaces and support for their research communities

A multi-analytical investigation into glass dopant incorporation

The influence of various dopants on the properties and local structure of glass samples was explored and a quantitative determination of the structural changes in the network as the dopant concentration was varied was achieved using 27Al, 29Si, 33S MAS NMR. Findings showed that silver- and copper-doping of phosphate based glass gave rise to unexpected connectivity between the phosphate units most likely due to some phase separation creating a different composition to that intended in the majority glass. This emphasises the importance of a careful and systematic approach to sample manufacture in achieving high sample stabilities, leading to a good degree of predictability in both structure and properties. Lanthanum and yttrium ions, despite their huge difference in ionic size, showed very little difference in their effect upon the phosphate coordination in the glass samples as they remain outside the phosphate network, cross-linking between the terminal oxygen atoms. The aluminium ions however, showed evidence of behaving in both a cross-linking manner and in a network forming, tetrahedral role and it appears energetically favourable for them to avoid any Al-O-Al linkage, hence resulting in the formation of AlO4 rather than exceeding the AlO5 or AlO6 quantities that would lead to this. The sulphur NMR looks to be a very promising method for future use in understanding sulphur speciation in glasses

A multi-analytical investigation into glass dopant incorporation

The influence of various dopants on the properties and local structure of glass samples was explored and a quantitative determination of the structural changes in the network as the dopant concentration was varied was achieved using 27Al, 29Si, 33S MAS NMR. Findings showed that silver- and copper-doping of phosphate based glass gave rise to unexpected connectivity between the phosphate units most likely due to some phase separation creating a different composition to that intended in the majority glass. This emphasises the importance of a careful and systematic approach to sample manufacture in achieving high sample stabilities, leading to a good degree of predictability in both structure and properties. Lanthanum and yttrium ions, despite their huge difference in ionic size, showed very little difference in their effect upon the phosphate coordination in the glass samples as they remain outside the phosphate network, cross-linking between the terminal oxygen atoms. The aluminium ions however, showed evidence of behaving in both a cross-linking manner and in a network forming, tetrahedral role and it appears energetically favourable for them to avoid any Al-O-Al linkage, hence resulting in the formation of AlO4 rather than exceeding the AlO5 or AlO6 quantities that would lead to this. The sulphur NMR looks to be a very promising method for future use in understanding sulphur speciation in glasses.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (Great Britain) (EPSRC)GBUnited Kingdo

Non-linear enhancement of laser generated ultrasonic Rayleigh waves by cracks

Laser generated ultrasound has been widely used for detecting cracks, surface and sub-surface defects in many different materials. It provides a non-contact wideband excitation source which can be focused into different geometries. Previous workers have reported enhancement of the laser generated Rayleigh wave when a crack is illuminated by pulsed laser beam irradiation. We demonstrate that the enhancement observed is due to a combination of source truncation, the free boundary condition at the edge of the crack and interference effects. Generating a Rayleigh wave over a crack can lead to enhancement of the amplitude of the Rayleigh wave signal, a shift in the dominant frequency of the wideband Rayleigh wave and strong enhancement of the high frequency components of the Rayleigh wave

Effect of silver content on the structure and antibacterial activity of silver-doped phosphate-based glasses

Staphylococcus aureus can cause a range of diseases, such as osteomyelitis, as well as colonize implanted medical devices. In most instances the organism forms biofilms that not only are resistant to the body's defense mechanisms but also display decreased susceptibilities to antibiotics. In the present study, we have examined the effect of increasing silver contents in phosphate-based glasses to prevent the formation of S. aureus biofilms. Silver was found to be an effective bactericidal agent against S. aureus biofilms, and the rate of silver ion release (0.42 to 1.22 µg·mm–2·h–1) from phosphate-based glass was found to account for the variation in its bactericidal effect. Analysis of biofilms by confocal microscopy indicated that they consisted of an upper layer of viable bacteria together with a layer (20 µm) of nonviable cells on the glass surface. Our results showed that regardless of the silver contents in these glasses (10, 15, or 20 mol%) the silver exists in its +1 oxidation state, which is known to be a highly effective bactericidal agent compared to that of silver in other oxidation states (+2 or +3). Analysis of the glasses by 31P nuclear magnetic resonance imaging and high-energy X-ray diffraction showed that it is the structural rearrangement of the phosphate network that is responsible for the variation in silver ion release and the associated bactericidal effectiveness. Thus, an understanding of the glass structure is important in interpreting the in vitro data and also has important clinical implications for the potential use of the phosphate-based glasses in orthopedic applications to deliver silver ions to combat S. aureus biofilm infections

Dendritic cell based PSMA immunotherapy for prostate cancer using a CD40-targeted adenovirus vector

Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs) with prostate specific membrane antigen (PSMA) have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells). To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ). Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy

Re-imagining the future:repetition decreases hippocampal involvement in future simulation

Imagining or simulating future events has been shown to activate the anterior right hippocampus (RHC) more than remembering past events does. One fundamental difference between simulation and memory is that imagining future scenarios requires a more extensive constructive process than remembering past experiences does. Indeed, studies in which this constructive element is reduced or eliminated by “pre-imagining” events in a prior session do not report differential RHC activity during simulation. In this fMRI study, we examined the effects of repeatedly simulating an event on neural activity. During scanning, participants imagined 60 future events; each event was simulated three times. Activation in the RHC showed a significant linear decrease across repetitions, as did other neural regions typically associated with simulation. Importantly, such decreases in activation could not be explained by non-specific linear time-dependent effects, with no reductions in activity evident for the control task across similar time intervals. Moreover, the anterior RHC exhibited significant functional connectivity with the whole-brain network during the first, but not second and third simulations of future events. There was also evidence of a linear increase in activity across repetitions in right ventral precuneus, right posterior cingulate and left anterior prefrontal cortex, which may reflect source recognition and retrieval of internally generated contextual details. Overall, our findings demonstrate that repeatedly imagining future events has a decremental effect on activation of the hippocampus and many other regions engaged by the initial construction of the simulation, possibly reflecting the decreasing novelty of simulations across repetitions, and therefore is an important consideration in the design of future studies examining simulation

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN