The contribution motorcycles can make to sustainable transport in London

This thesis examines the contribution motorcycles can make to sustainable transport in London. Following a literature review, and some definitions of the subject matter, there is an analysis of transport data, including the historic use of motorcycles, and policy documents at a national, regional and local level informs a discussion on the utility of motorcycles within a sustainable transport strategy, and its implementation by London Boroughs. As well as examining travel patterns in London, the thesis details the characteristics of London motorcyclists and what differentiates them from riders elsewhere in the UK. The thesis considers some issues associated with the use of motorcycles that help inform policy and strategy at both the national and the local level. These include safety, emissions, noise, congestion and use of the road space. These issues are then tested through case studies of policies and strategies produced by two the City of Westminster and the London Borough of Harrow. The final section compares the characteristics of motorcycles against the requirements of a sustainable transport system and summarises the positive and negative contributions that motorcycles can make. This thesis attempts to answer the questions: Do motorcycles represent a more sustainable transport mode than the private car in Greater London Could an increase in motorcycle use, at the expense of either car or public transport use, have a significant impact on the sustainability of transport in London Would encouraging motorcycle use present a more sustainable approach to London overall, in terms of secondary environmental measures What role can land-use planning have in assisting motorcycle use The thesis concludes that motorcycles do have a role to play in helping to achieve a more sustainable transport system in London, but this is to some extent, dependent on the type and location of journey the vehicle is used for. The thesis also concludes that increasing motorcycle use would be beneficial to motorcyclists' road safety, and how motorcycling would be a beneficiary of policies intended to reduce car use

Reductive chain separation of botulinum A toxin — a prerequisite to its inhibitory action on exocytosis in chromaffin cells

Cleavage of the disulfide bond linking the heavy and the light chains of tetanus toxin is necessary for its inhibitory action on exocytotic release ofcatecholamines from permeabi1ized chromaffin cells [(1989) FEBS Lett. 242, 245-248; (1989) J. Neurochern., in press]. The related botulinum A toxin also consists of a heavy and a light chain linked by a disulfide bond. The actions ofboth neurotoxins on exocytosis were presently compared using streptolysin O-permeabilized bovine adrenal chromaffin cells. Botulinum A toxin inhibited Ca2 +-stimulated catecholamine release from these cells. Addition of dithiothreitollowered the effective doses to values below 5 nM. Under the same conditions, the effective doses of tetanus toxin were decreased by a factor of five. This indicates that the interchain S-S bond of botulinum A toxin must also be split before the neurotoxin can exert its effect on exocytosis

Student Guided Transition Assistance

In the Faculty of Science at the University of Melbourne a transition program has been in place for new students entering the Bachelor of Science since 2000. During this time the program has been modified regularly in response to staff and student feedback. However, with the introduction of a new Science degree structure combined with the changing nature of student experiences and expectations, a more extensive review of the current program is being undertaken. The aim of the review is to gather feedback from students and the student facilitators of study groups, on the program’s effectiveness in assisting students. The information collected will be used to develop new strategies to maximize the program’s effectiveness. In 2012 we have probed student expectations and provided them with an opportunity to reflect on the challenges of transition. The program has also been reviewed from the perspectives of the first year teaching staff. The data collected will guide modification of the program for 2013 with the objective of targeting the transition program more effectively to assist first year science students’ transition from school to University. Our findings will be presented in this paper

GTP and Ca2+ Modulate the Inositol 1,4,5-Trisphosphate-Dependent Ca2+ Release in Streptolysin O-Permeabilized Bovine Adrenal Chromaffin Cells

The inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release was studied using streptolysin O-permeabilized bovine adrenal chromaffin cells. The IP3-induced Ca2+ release was followed by Ca2+ reuptake into intracellular compartments. The IP3-induced Ca2+ release diminished after sequential applications of the same amount of IP3. Addition of 20 μM GTP fully restored the sensitivity to IP3. Guanosine 5'-O-(3-thio)triphosphate (GTPγS) could not replace GTP but prevented the action of GTP. The effects of GTP and GTPγS were reversible. Neither GTP nor GTPγS induced release of Ca2+ in the absence of IP3. The amount of Ca2+ whose release was induced by IP3 depended on the free Ca2+ concentration of the medium. At 0.3 μM free Ca2+, a half-maximal Ca2+ release was elicited with ∼0.1 μM IP3. At 1 μM free Ca2+, no Ca2+ release was observed with 0.1 μM IP3; at this Ca2+ concentration, higher concentrations of IP3 (0.25 μM) were required to evoke Ca2+ release. At 8 μM free Ca2+, even 0.25 μM IP3 failed to induce release of Ca2+ from the store. The IP3-induced Ca2+ release at constant low (0.2 μM) free Ca2+ concentrations correlated directly with the amount of stored Ca2+. Depending on the filling state of the intracellular compartment, 1 mol of IP3 induced release of between 5 and 30 mol of Ca2+

AUTC Physics Project: Learning outcomes and curriculum development

The Australian Universities Teaching Committee is funding a project to investigate the learning outcomes and curriculum development in physics at Australian universities. The project aims to map current practices and future directions in the broad areas of curriculum relating to service/multidisciplinary teaching and majors, employer satisfaction and industry involvement, and student satisfaction. A questionnaire has been administered with 85% return to date from the 34 physics departments or groups in Australian universities. In this paper we present the study design and initial results which include consideration of challenges faced by departments with respect to teaching and learning, departmental strengths and the development of new courses

The Synthesis, Structural Characterization, and Receptor Specificity of the {alpha}-Conotoxin Vc1.1

The {alpha}-conotoxin Vc1.1 is a small disulfide-bonded peptide currently in development as a treatment for neuropathic pain. This study describes the synthesis, determination of the disulfide connectivity, and the determination of the three-dimensional structure of Vc1.1 using NMR spectroscopy. Vc1.1 was shown to inhibit nicotine-evoked membrane currents in isolated bovine chromaffin cells in a concentration-dependent manner and preferentially targets peripheral nicotinic acetylcholine receptor (nAChR) subtypes over central subtypes. Specifically, Vc1.1 is selective for {alpha}3-containing nAChR subtypes. The three-dimensional structure of Vc1.1 comprises a small {alpha}-helix spanning residues Pro6 to Asp11 and is braced by the I-III, II-IV disulfide connectivity seen in other {alpha}-conotoxins. A comparison of the structure of Vc1.1 with other {alpha}-conotoxins, taken together with nAChR selectivity data, suggests that the conserved proline at position 6 is important for binding, whereas a number of residues in the C-terminal portion of the peptide contribute toward the selectivity. The structure reported here should open new opportunities for further development of Vc1.1 or analogues as analgesic agents

The Differential Organization of F-Actin Alters the Distribution of Organelles in Cultured When Compared to Native Chromaffin Cells

Cultured bovine chromaffin cells have been used extensively as a neuroendocrine model to study regulated secretion. In order to extend such experimental findings to the physiological situation, it is necessary to study mayor cellular structures affecting secretion in cultured cells with their counterparts present in the adrenomedullary tissue. F-actin concentrates in a peripheral ring in cultured cells, as witnessed by phalloidin?rodhamine labeling, while extends throughout the cytoplasm in native cells. This result is also confirmed when studying the localization of ?-fodrin, a F-actin-associated protein. Furthermore, as a consequence of this redistribution of F-actin, we observed that chromaffin granules and mitochondria located into two different cortical and internal populations in cultured cells, whereas they are homogeneously distributed throughout the cytoplasm in the adrenomedullary tissue. Nevertheless, secretion from isolated cells and adrenal gland pieces is remarkably similar when measured by amperometry. Finally, we generate mathematical models to consider how the distribution of organelles affects the secretory kinetics of intact and cultured cells. Our results imply that we have to consider F-actin structural changes to interpret functional data obtained in cultured neuroendocrine cells.This study was supported by grants from the Spanish Ministerio de Economía y Competitividad (BFU2011-25095 and BFU2015- 63684-P, MINECO, FEDER, UE) to LMG

CLIMB-COVID: continuous integration supporting decentralised sequencing for SARS-CoV-2 genomic surveillance.

Funder: Wellcome TrustIn response to the ongoing SARS-CoV-2 pandemic in the UK, the COVID-19 Genomics UK (COG-UK) consortium was formed to rapidly sequence SARS-CoV-2 genomes as part of a national-scale genomic surveillance strategy. The network consists of universities, academic institutes, regional sequencing centres and the four UK Public Health Agencies. We describe the development and deployment of CLIMB-COVID, an encompassing digital infrastructure to address the challenge of collecting and integrating both genomic sequencing data and sample-associated metadata produced across the COG-UK network

Synthetic α-Conotoxin Mutants as Probes for Studying Nicotinic Acetylcholine Receptors and in the Development of Novel Drug Leads

α-Conotoxins are peptide neurotoxins isolated from venomous marine cone snails that are potent and selective antagonists for different subtypes of nicotinic acetylcholine receptors (nAChRs). As such, they are valuable probes for dissecting the role that nAChRs play in nervous system function. In recent years, extensive insight into the binding mechanisms of α-conotoxins with nAChRs at the molecular level has aided in the design of synthetic analogs with improved pharmacological properties. This review examines the structure-activity relationship studies involving α-conotoxins as research tools for studying nAChRs in the central and peripheral nervous systems and their use towards the development of novel therapeutics

From Toxins Targeting Ligand Gated Ion Channels to Therapeutic Molecules

Ligand-gated ion channels (LGIC) play a central role in inter-cellular communication. This key function has two consequences: (i) these receptor channels are major targets for drug discovery because of their potential involvement in numerous human brain diseases; (ii) they are often found to be the target of plant and animal toxins. Together this makes toxin/receptor interactions important to drug discovery projects. Therefore, toxins acting on LGIC are presented and their current/potential therapeutic uses highlighted