Developing the NACUE Student Enterprise Framework

This document sets out a review of policy and evaluation studies related to the student enterprise offer provided by universities. The review has been undertaken by the University of Lincoln as part of a broader project to develop a Student Enterprise Framework for the National Association of College and University Entrepreneurs (NACUE)

Lincolnshire economic strategy 2008-2012

An economic strategy for Lincolnshire, developed on behalf of Lincolnshire Enterprise and Lincolnshire Assembl

SME perceptions of and responses to the recession

The UK has recently experienced the worst recession since the 1930s. Despite the severity of this recent recession, there are currently few studies of its effect on small and medium-sized enterprises (SMEs). However, small business growth and entrepreneurship are recognised as essential drivers for economic recovery (Matlay, 2012; Rae, 2010). Drawing on an online bi-monthly survey of SMEs in Lincolnshire and Rutland, this paper explores owner managers’ perceptions of the UK recession. We examine the views of businesses on various aspects of the recession, and how this has affected business performance, levels of confidence, and growth ambitions. The paper explores the role of business confidence in the economy as a determinant of business growth intentions, and draws a comparison between perceptions and behaviour

PRECLINICAL TARGETING OF TREM2 FOR THE TREATMENT OF ALZHEIMER\u27S DISEASE-TYPE PATHOLOGY IN A TRANSGENIC MOUSE MODEL

Alzheimer\u27s disease (AD) is defined as a progressive neurodegenerative disorder and is characterized by a devastating mental decline. There are three pathological hallmarks of the disease necessary for its diagnosis, these are extracellular amyloid plaques comprised of the beta-amyloid (Aβ) protein, intracellular neurofibrillary tangles comprised of hyperphosphorylated tau protein, and marked neuronal loss. Active immunization against Aβ1-42 or passive immunization with monoclonal anti-Aβ antibodies has been shown to reduce amyloid deposition and improve cognition in transgenic mouse models of AD, aged beagles, and nonhuman primates. Unfortunately, due to cerebrovascular adverse events, both active and passive immunization strategies targeting Aβ have failed in clinical trials. It is, therefore, necessary to identify novel amyloid-clearing therapeutics that do not induce cerebrovascular adverse events. We hypothesized that neuroinflammatory modulation could be a potential novel target. Triggering receptor expressed on myeloid cells-2 (TREM2) is a lipid and lipoprotein binding receptor expressed exclusively in the brain by microglia. Homozygous TREM2 loss of function mutations cause early-onset progressive presenile dementia while heterozygous, function-reducing point mutations triple the risk of sporadic, late-onset AD. Heterozygous TREM2 point mutations, which reduce either ligand binding or cell surface expression, are associated with a reduction in the number of microglia surrounding amyloid plaques, microglial inability to phagocytose compact Aβ deposits and form a barrier between plaques and neurons, an increase in the number of phospho- tau-positive dystrophic neurites and increased tau in the cerebrospinal fluid. Heterozygous mutations also double the rate of brain atrophy and decrease the age of AD onset by 3-6 years. Although human genetics supports the notion that loss of TREM2 function exacerbates neurodegeneration, it is unclear whether activation of TREM2 in a disease state is beneficial. The work we present here characterizes a TREM2 agonizing antibody as a potential therapeutic for amyloid reduction. We found that its administration results in immune modulation, recruitment of microglia to the site of amyloid plaques, reduced amyloid deposition and improvement in spatial learning and novel object recognition memory in the 5xFAD model of AD. More specifically, we show that intracranial injection of TREM2 agonizing antibodies into the frontal cortex and hippocampus of 5xFAD mice leads to clearance of diffuse and compact amyloid. We also show that systemic injection of TREM2 agonizing antibodies weekly over a period of 14 weeks results in clearance of diffuse and compact amyloid as well as elevated plasma concentrations of Aβ1-40 and Aβ1-42. Furthermore, systemic administration of these antibodies led to immune modulation and enhanced cognitive performance on radial arm water maze and novel object recognition tests. Importantly, we show the TREM2 agonizing antibody does not induce the adverse cerebrovascular events known to accompany amyloid modifying therapies. Though systemic administration of both TREM2 agonizing and anti-Abantibodies does not further enhance amyloid clearance or cognitive performance, co-administration mitigates the adverse cerebrovascular events associated with anti-Aβ antibodies. Collectively, these data indicate TREM2 activators may be an effective therapeutic target for the treatment of AD

Philosophy at Cambridge

Newsletter of the Faculty of Philosophy. Articles: Rae Langton, 'From the Chair'; Michael Potter, 'The Birth of a Book'; Huw Price, 'Two Projects from 2012--a progress report; Rae Langton 'The Enlightening of Maria von Herbert, Klagenfert, 1770-1803; Philosophy and the LMU Partnership; Jessie Munton, 'Perceptual Confidence Workshop'

Structural determinants of the outer shell of β-carboxysomes in synechococcus elongatus PCC 7942: roles for CcmK2, K3-K4, CcmO, and CcmL

Cyanobacterial CO(2)-fixation is supported by a CO(2)-concentrating mechanism which improves photosynthesis by saturating the primary carboxylating enzyme, ribulose 1, 5-bisphosphate carboxylase/oxygenase (RuBisCO), with its preferred substrate CO(2). The site of CO(2)-concentration is a protein bound micro-compartment called the carboxysome which contains most, if not all, of the cellular RuBisCO. The shell of β-type carboxysomes is thought to be composed of two functional layers, with the inner layer involved in RuBisCO scaffolding and bicarbonate dehydration, and the outer layer in selective permeability to dissolved solutes. Here, four genes (ccmK2-4, ccmO), whose products were predicted to function in the outer shell layer of β-carboxysomes from Synechococcus elongatus PCC 7942, were investigated by analysis of defined genetic mutants. Deletion of the ccmK2 and ccmO genes resulted in severe high-CO(2)-requiring mutants with aberrant carboxysomes, whilst deletion of ccmK3 or ccmK4 resulted in cells with wild-type physiology and normal ultrastructure. However, a tandem deletion of ccmK3-4 resulted in cells with wild-type carboxysome structure, but physiologically deficient at low CO(2) conditions. These results revealed the minimum structural determinants of the outer shell of β-carboxysomes from this strain: CcmK2, CcmO and CcmL. An accessory set of proteins was required to refine the function of the pre-existing shell: CcmK3 and CcmK4. These data suggested a model for the facet structure of β-carboxysomes with CcmL forming the vertices, CcmK2 forming the bulk facet, and CcmO, a "zipper protein," interfacing the edges of carboxysome facets.The work was supported by an Australian National University PhD scholarship and partial funding from an Australian Research Council grant to GDP and MRB

Functions, Compositions, and Evolution of the Two Types of Carboxysomes: Polyhedral Microcompartments That Facilitate CO 2 Fixation in Cyanobacteria and Some Proteobacteria

Cyanobacteria are the globally dominant photoautotrophic lineage. Their success is dependent on a set of adaptations collectively termed the CO 2-concentrating mechanism (CCM). The purpose of the CCM is to support effective COCO2 fixation by enhancing th

Intellectual Treasure Hunting: Measuring Effects of Treasure Salvors on Spanish Colonial Shipwreck Sites

This thesis examines the impacts of treasure salvors and looters on the Pillar Dollar Wreck (site # BISC00035) in Biscayne Bay, Florida, and explores three comparative shipwrecks from the 1733 fleet, El Populo, San Josè, and San Pedro, which wrecked off the coast of Florida and were likely from a similar time period as the Pillar Dollar Wreck. The intention of this thesis is to develop a methodology for measuring the effects of cultural impacts, particularly treasure salvage and looting, on Spanish colonial shipwreck sites in the Florida Keys. There is no current basis for quantifying such effects. Further, this thesis presents the first focus on the history of the Florida Exploration and Salvage (now Recovery) Program. The information presented in this thesis is used to identify what was learned from treasure salvor endeavors on Spanish colonial shipwreck sites in the Florida Keys and examine what an academic investigation of the treasure salvor industry can reveal about what is lost or gained through commercial exploitation of Spanish colonial shipwrecks in the Florida Keys by treasure salvors. Site formation process studies provide the theoretical framework upon which this thesis is founded, creating an understanding of the processes that created and altered the four shipwreck sites. This study adds to the database of knowledge about site formation processes on Spanish colonial shipwrecks in the Florida Keys. Finally, cultural heritage management is a relevant topic that is currently at the forefront of maritime archaeology. This thesis contributes to the database of information concerning protection of sites and specifically explores management issues related to treasure salvage of Spanish colonial shipwrecks in the Florida Keys.M.A

Peripheral refractive changes associated with myopia progression

Purpose.: To evaluate the changes in peripheral refraction profiles associated with myopia progression and treatment modalities used in the Cambridge Anti-Myopia Study. Methods.: One hundred and seventy-seven myopes in the age range of 14 to 22 years were enrolled in the study. The mean spherical equivalent refractive error was −3.12 ± 1.87 diopters (D) and the refractive error of each participant was corrected with contact lenses. The participants were randomly assigned to one of four treatment groups, which included: altered spherical aberration and vision training, altered spherical aberration only, vision training only, and control. Peripheral refractive error was measured using an open field autorefractor in the central 60° of the retina in 10° steps. The refractive error was measured using cycloplegic autorefraction. Two-year refractive progression data and initial peripheral refraction measurements were available in 113 participants. Measurements of peripheral refraction and cycloplegic refraction were obtained at three visits over 2 years in 12-month intervals for 92 participants. Results.: All subjects showed a relative peripheral hyperopia, especially in the nasal retina. A limited magnitude of myopia progression of −0.34 ± 0.36 D over 2 years was found in each of the four groups on average. There were no significant differences in the rate of progression between any of the treatment groups (P > 0.05). Initial peripheral J45 astigmatic refractive error at 20° and 30° in the nasal retina was weakly correlated with progression of myopia over 2 years (r = −0.27, P = 0.004 and r = −0.20, P = 0.040, respectively; n = 113). The change in spherical equivalent peripheral refractive error at 30° nasal retina over time was also significantly correlated with progression of myopia especially at 24 months (r = −0.24, P = 0.017, n = 92). Conclusions.: Relative peripheral hyperopia is associated with myopia. Myopia progression may be weakly linked to changes in the peripheral refraction profiles in the nasal retina. However, a causative link between peripheral refractive error and myopia progression could not be established

The Cambridge Anti-myopia Study: variables associated with myopia progression

Purpose: To identify variables associated with myopia progression and to identify any interaction between accommodative function, myopia progression, age, and treatment effect in the Cambridge Anti-Myopia Study. Methods: Contact lenses were used to improve static accommodation by altering ocular spherical aberration, and vision training was performed to improve dynamic accommodation. One hundred forty-two subjects, aged 14–21 years, were recruited who had a minimum of −0.75D of myopia. Subjects were assigned to contact lens treatment only, vision training only, contact lens treatment and vision training, or control group. Spherical aberration, lag of accommodation, accommodative convergence/accommodation (AC/A) ratio, accommodative facility, ocular biometry, and refractive error were measured at regular intervals throughout the 2-year trial. Results: Ninety-five subjects completed the 24-month trial period. There was no significant difference in myopia progression between the four treatment groups at 24 months. Age, lag of accommodation, and AC/A ratio were significantly associated with myopia progression. There was a significant treatment effect at 12 months in the contact lens treatment group in younger subjects, based on a median split, aged under 16.9 years (p = 0.005). This treatment effect was not maintained over the second year of the trial. Younger subjects experienced a greater reduction in lag of accommodation with the treatment contact lens at 3 months (p = 0.03), compared to older contact lens treatment and control groups. There was no interaction between AC/A ratio and contact lens treatment effect. Conclusions: Age, lag of accommodation, and AC/A ratio were significantly associated with myopia progression. Although there was no significant treatment effect at 24 months, an interaction between age and contact lens treatment suggests younger subjects may be more amenable, at least in the short term, to alteration of the visual system using optical treatments