Varieties with too many rational points

We investigate Fano varieties defined over a number field that contain subvarieties whose number of rational points of bounded height is comparable to the total number on the variety.Comment: 23 page

Failures of weak approximation in families

Given a family of varieties $X\to \mathbb{P}^n$ over a number field $k$, we determine conditions under which there is a Brauer-Manin obstruction to weak approximation for $100\%$ of the fibres which are everywhere locally soluble.Comment: 44 pages; there is a new application to integral points (Theorem 1.4) and Cor 1.5 recovers a well-known result concerning the Hasse principl

Expression and role of the human anti-apoptotic bfl-1 gene in Hodgkin's Lymphoma

Hodgkin's Lymphoma (HL) is identified histologically by the presence of mononuclear Hodgkin (H) cells and multinucleated Reed-Stemberg (RS) cells surrounded by a background of lymphocytes, plasma cells, eosinophils, histocytes and stromal cells in the affected lymph nodes. HL affects on average 2.5 per 100,000 of population and between 30 and 50 % of HL cases are Epstein-Barr virus associated (EBV positive HL). An important feature of HL is the constitutive activation of the NF-kB anscription factor, which has proliferative and anti-apoptotic roles in HIRS cells. Bfl-1 is an anti-apoptotic protein of the Bcl-2 family, whose preferential expression in hematopoietic and endothelial cells is controlled by inflammatory stimuli. This thesis presents the novel finding that bfl-1 is highly expressed in H/RS cells from primary tumour tissue from HL patients and cultured H/RS cells irrespective of their EBV status and that the short splice variant of bfl-I, designated bfl-IS is not expressed in these cell types or in type I Burkitt Lymphoma (BL), type I11 BL or lymphoblastoid cell lines. This thesis presents the novel discovery that bfl-I is a key NF-KB target gene in WRS cells and death by apoptosis caused by inhibition of NF-KB is coincident with a loss of bfl-1 expression. It is shown in this study for the first time that ectopic expression of Bfl-1 protected WRS cells from apoptosis induced by NF-KB inhibition. The downregulation of bjZ-1 in a HL-derived cell line by RNA interference is reported in this study and shown to potentiate the effects of cytotoxic agents by decreasing the cellular apoptotic threshold. The novel finding that NF-KB regulates the bfl-1 promoter, with a key role in this cell context for a novel NF-KB binding site in the upstream regulatory regon of this gene is reported here. This study reports the mechanisms by which bjl-I expression is regulated in WRS cells and serves to establish the contribution of bjZ-1 to the pathogenesis of HL. Also as part of this thesis, as a means to generate an antibody to Bfl-I, a novel vector (pGSLink) was designed and constructed to permit high-level expression of a protein linked at the C- or N-terminal to a His-tag by a flexible, poorly immunogenic linker peptide of 21 amino acids; (Gly4Ser)4Gly (published in Analytical Biochemistry; Loughran et al., 2006). The bfl-1 coding fragment was successfully cloned into this novel vector to produce the fusion constructs from which His-Linker-Bfl-1 fusion proteins were s~rccessfullyo verexpressed and purified using Zmmobilised metal affinity chrornatwgraphy. Sufficient protein was purified and used for the prepantion of polyclonal antisera to Bf1-1. ln summary, Ihe findings presented in this thesis are relevant to our understanding of the role d 6fI-l as a crucial pro-survival NF-KB target in HRS cells and the potential of Bfl-I as a rational thcrapeuric target in HL is highlighted

Single versus multiple banking: lessons from initial public offerings

A vast research in banking addresses the question of the costs and benefits of multiple bank relationships versus a single bank relationship. Although no clear-cutting conclusion is reached, several contributions suggest that multiple bank relationships might lead to a suboptimal level of monitoring, compared to a single bank relationship, as a result of free riding and coordination problems. We take a novel approach to tackle this research question, by looking at the role, if any, played by the number of lending relationships in initial public offerings (IPOs). We look at the short-term performances of IPOs as measured by underpricing and find that firms that go public with multiple bank relationships exhibit more underpricing than those that go public with a single bank relationship. This finding is independent of the number of bank relationships and/or whether any of the lending banks also acts as underwriter in the offering. We interpret our results as suggesting that the market attributes a weaker certification role to multiple bank relationships because of their less effective monitoring of IPO firms

Direct observation of magnetization dynamics generated by nano-contact spin-torque vortex oscillators

Time-resolved scanning Kerr microscopy has been used to directly image the magnetization dynamics of nano-contact (NC) spin-torque vortex oscillators (STVOs) when phase-locked to an injected microwave (RF) current. The Kerr images reveal free layer magnetization dynamics that extend outside the NC footprint, where they cannot be detected electrically, but which are crucial to phase-lock STVOs that share common magnetic layers. For a single NC, dynamics were observed not only when the STVO frequency was fully locked to that of the RF current, but also for a partially locked state characterized by periodic changes in the core trajectory at the RF frequency. For a pair of NCs, images reveal the spatial character of dynamics that electrical measurements show to have enhanced amplitude and reduced linewidth. Insight gained from these images may improve understanding of the conditions required for mutual phase-locking of multiple STVOs, and hence enhanced microwave power emission.Comment: 10 pages, 3 figure

Overreaction to growth opportunities: an explanation of the asset growth anomaly

The negative relation between asset growth and subsequent stock returns is known as the asset growth anomaly. We propose that overreaction to growth opportunities is the source of the asset growth anomaly. This suggests that growth firms as opposed to mature firms, and firms with longer series of asset growth should experience a stronger asset growth anomaly. Our evidence supports these predictions

Epidemiology of the extent of recreational noise exposure and hearing protection use: cross-sectional survey in a nationally representative UK adult population sample

From Springer Nature via Jisc Publications RouterHistory: received 2019-12-05, accepted 2020-09-23, registration 2020-09-24, online 2020-10-09, pub-electronic 2020-10-09, collection 2020-12Publication status: PublishedFunder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Abstract: Background: Hearing loss is prevalent and disabling, yet little is known about the extent of recreational noise exposure and hearing protection use. The aim of the present research was to estimate the extent of recreational noise exposure and hearing protection use in a sample representative of the UK adult population. Methods: We conducted a cross-sectional survey of 10,401 UK adults who were representative of the population. Results: More than 7000 people (n = 7590, 73.0%) reported exposure to recreational noise excluding headphone and earphone use in the last 12 months. Just 158 people (2.1%) reported wearing hearing protection for every noisy recreational activity. Age (younger people) and beliefs of a behavioral (as opposed to genetic) cause of hearing loss were predictive of both higher recreational noise exposure and greater hearing protection use. Men were more exposed to recreational noise but women were less likely to use hearing protection. Conclusions: For the first time, the present research quantifies the recreational noise exposure and low levels of hearing protection use in a representative sample of the UK population. The biggest public health gains are likely to be achieved through interventions targeted at younger people and in explaining behavioral (as opposed to genetic) causes of hearing loss

The price of rapid exit in venture capital-backed IPOs

This paper proposes an explanation for two empirical puzzles surrounding initial public offerings (IPOs). Firstly, it is well documented that IPO underpricing increases during “hot issue” periods. Secondly, venture capital (VC) backed IPOs are less underpriced than non-venture capital backed IPOs during normal periods of activity, but the reverse is true during hot issue periods: VC backed IPOs are more underpriced than non-VC backed ones. This paper shows that when IPOs are driven by the initial investor’s desire to exit from an existing investment in order to finance a new venture, both the value of the new venture and the value of the existing firm to be sold in the IPO drive the investor’s choice of price and fraction of shares sold in the IPO. When this is the case, the availability of attractive new ventures increases equilibrium underpricing, which is what we observe during hot issue periods. Moreover, I show that underpricing is affected by the severity of the moral hazard problem between an investor and the firm’s manager. In the presence of a moral hazard problem the degree of equilibrium underpricing is more sensitive to changes in the value of the new venture. This can explain why venture capitalists, who often finance firms with more severe moral hazard problems, underprice IPOs less in normal periods, but underprice more strongly during hot issue periods. Further empirical implications relating the fraction of shares sold and the degree of underpricing are presented

Identifying Targets for Interventions to Increase Uptake and Use of Hearing Protection in Noisy Recreational Settings

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-26, pub-electronic 2021-07-29Publication status: PublishedFunder: Manchester Biomedical Research Centre; Grant(s): UnknownInterventions to increase hearing protection behaviours within noisy recreational settings are limited by the lack of an underpinning evidence base. The aim of the present study was to identify targets for interventions in a population exposed to recreational noise, including those who had used hearing protection (ever-performers) versus those who had not (never-performers). A cross-sectional survey was administered to 185 UK adults who had been involved in noisy recreational activities. Participants had an average age of 36.79 years; the majority were women (68.1%), from a white ethnic background (87.6%), and with non-manual occupations (75.7%). Using Chi-square, MANOVA and ANOVA, we looked for differences in sociodemographic variables and variables from the capabilities, opportunities and motivations model of behaviour change (COM-B) between ever- and never-performers. Ever-performers were more likely to be younger (p 0.050), men (p 0.050), and in a manual occupation (p 0.050) compared to never-performers. Although the two groups felt capable and reported similar opportunities to use hearing protection, never-performers lacked automatic motivation (p 0.001) and reflective motivation (p 0.001) compared to ever-performers. For the first time, the present study identifies potential groups at whom hearing protection interventions might be targeted and what those interventions may contain. Further work is required to develop interventions targeted at older people, women and those in non-manual occupations. Lack of motivation is a key concern, and further work that uses specific theoretical frameworks, such as the PRIME (Plans, Responses, Impulses, Motives, and Evaluations) theory of motivation, may shed light on the kinds of interventions that are needed to boost hearing protection use effectively