Bioreductive Alkylating Agents As Probes For Tissue Hypoxia

The research discussed in the following thesis falls under the general categories of organic chemistry and radiochemistry and the application of these disciplines to the development of imaging agents and labelling techniques for the branch of Nuclear Medicine involving single photon emitting radionuclides. The thesis is made up of three sections; one dealing with the synthesis, labelling and biological testing of a series of radioiodinated 2-nitrobenzyl alcohol derivatives as potential probes for tissue hypoxia; a second chapter dealing with the synthesis, labelling and biological testing of 1-(4- ({dollar}\sp{lcub}123{rcub}{dollar}I) -iodophenyl-2,6,7-trioxabicyclo- (2.2.2) octane as a potential imaging agent for the GABA{dollar}\sb{lcub}\rm A{rcub}{dollar} receptor and a third chapter which deals with a novel radiolabelling procedure based on an organotin polymer.;The radioiodinated 2-nitrobenzyl alcohol derivatives were tested in the EMT-6 tumour model in Balb/c mice to determine whether specific uptake was occurring in the tumours. The first compound in the series, O-(N-methyl carbamoyl),3-iodo-6-nitrobenzyl alcohol did not show specific tumour uptake and appeared to be metabolically deiodinated in vivo. The second compound tested, O-(N-methyl carbamoyl),4-iodo-6-nitrobenzyl alcohol did not show specific tumour uptake but showed a decrease in metabolic deiodination. A third compound, O-(N-methyl carbamoyl), 4-iodo-2,6-dinitrobenzyl alcohol, did appear to exhibit specific uptake in the tumour. Unfortunately, high levels of blood activity preclude the use of this compound as an hypoxia imaging agent.;1-(4- ({dollar}\sp{lcub}123{rcub}{dollar}I) -iodophenyl-2,6,7-trioxabicyclo- (2.2.2) octane was synthesized, labelled and was then tested in male CD1 mice for specific uptake in the brain. The compound underwent rapid metabolic elimination via the kidneys resulting in a short plasma half-life. The compound was found to be unacceptably lipophilic. The lipophilicity of the molecule coupled with its rapid metabolic elimination rendered it unsuitable as a receptor imaging agent.;A new polymer with aryltrialkyltin functions coupled to a polystyrene backbone was prepared. The specific aryl group used was N-isopropyl amphetamine. The new polymer was successfully employed in the synthesis of N-isopropyl-p- ({dollar}\sp{lcub}131{rcub}{dollar}I) iodoamphetamine. The method should have general applicability and may eliminate the need for chromatographic purification of some iodine radiopharmaceuticals

Methanotrophy potential versus methane supply by pore water diffusion in peatlands

Journal ArticlePublished by Copernicus Publications on behalf of the European Geosciences UnionAuthor(s) 2009.Low affinity methanotrophic bacteria consume a significant quantity of methane in wetland soils in the vicinity of plant roots and at the oxic-anoxic interface. Estimates of the efficiency of methanotrophy in peat soils vary widely in part because of differences in approaches employed to quantify methane cycling. High resolution profiles of dissolved methane abundance measured during the summer of 2003 were used to quantity rates of upward methane flux in four peatlands situated in Wales, UK. Aerobic incubations of peat from a minerotrophic and an ombrotrophic mire were used to determine depth distributions of kinetic parameters associated with methane oxidation. The capacity for methanotrophy in a 3 cm thick zone immediately beneath the depth of nil methane abundance in pore water was significantly greater than the rate of upward diffusion of methane in all four peatlands. Rates of methane diffusion in pore water at the minerotrophic peatlands were small (<10%) compared to surface emissions during June to August. The proportions were notably greater in the ombrotrophic bogs because of their typically low methane emission rates. Methanotrophy appears to consume entirely methane transported by pore water diffusion in the four peatlands with the exception of 4 of the 33 gas profiles sampled. Flux rates to the atmosphere regardless are high because of gas transport through vascular plants, in particular, at the minerotrophic sites. Cumulative rainfall amount 3-days prior to sampling correlated well with the distance between the water table level and the depth of 0 μmol l-1 methane, indicating that precipitation events can impact methane distributions in pore water. Further work is needed to characterise the kinetics of methane oxidation spatially and temporally in different wetland types in order to determine generalized relationships for methanotrophy in peatlands that can be incorporated into process-based models of methane cycling in peat soils.Natural Environment Research Council (NERC)Royal Societ

Therapeutic modalities for central nervous system involvement by granulocytic sarcoma (chloroma) in children with acute nonlymphocytic leukemia.

Four cases of central nervous system involvement by granulocytic sarcoma (three intracranial and one paraspinal) in children with acute nonlymphocytic leukemia (FAB M1 or M2 subtype) are presented, and therapeutic modalities are discussed. All tumors were noted at initial presentation with diagnosis being made on clinical and radiological findings without biopsy. All patients had karyotypic abnormalities: three had translocation of chromosomes 8 and 21, and one had an unspecified hypodiploid clone. The three patients who developed intracranial tumors responded well to triple agent (cytosine arabinoside, hydrocortisone, and methotrexate) intrathecal chemotherapy and systemic chemotherapy, with or without local irradiation, as evidenced by rapid disappearance of the tumors. Two children are disease-free after 17 and 57 months. One patient with paraspinal tumor failed to achieve a systemic remission but had no evidence of granulocytic sarcoma at autopsy. Thus, the prognosis of CNS granulocytic sarcoma is not uniformly gloomy if treated aggressively by combined modalities. The value of surgical intervention in terms of primary management, however, is limited

Methanotrophy potential versus methane supply by pore water diffusion in peatlands

International audienceLow affinity methanotrophic bacteria consume a significant quantity of methane in wetland soils in the vicinity of plant roots and at the oxic-anoxic interface. Estimates of the efficiency of methanotrophy in peat soils vary widely in part because of differences in approaches employed to quantify methane cycling. High resolution profiles of dissolved methane abundance measured during the summer of 2003 were used to quantify rates of upward methane flux in four peatlands situated in Wales, UK. Aerobic incubations of peat from a minerotrophic and an ombrogenous mire were used to determine depth distributions of kinetic parameters associated with methane oxidation. The capacity for methanotrophy in a 3 cm thick zone immediately beneath the depth of nil methane abundance in pore water was significantly greater than the rate of upward diffusion of methane in all four peatlands. Rates of methane diffusion in pore water at the minerotrophic peatlands were small (?mol l?1 methane, indicating that precipitation events can impact methane distributions in pore water. Further work is needed to characterise the kinetics of methane oxidation spatially and temporally in different wetland types in order to determine generalized relationships for methanotrophy in peatlands that can be incorporated into process-based models of methane cycling in peat soils

Chrysanthemums for the home garden

Cover title

Human-Robot Control Strategies for the NASA/DARPA Robonaut

The Robotic Systems Technology Branch at the NASA Johnson Space Center (JSC) is currently developing robot systems to reduce the Extra-Vehicular Activity (EVA) and planetary exploration burden on astronauts. One such system, Robonaut, is capable of interfacing with external Space Station systems that currently have only human interfaces. Robonaut is human scale, anthropomorphic, and designed to approach the dexterity of a space-suited astronaut. Robonaut can perform numerous human rated tasks, including actuating tether hooks, manipulating flexible materials, soldering wires, grasping handrails to move along space station mockups, and mating connectors. More recently, developments in autonomous control and perception for Robonaut have enabled dexterous, real-time man-machine interaction. Robonaut is now capable of acting as a practical autonomous assistant to the human, providing and accepting tools by reacting to body language. A versatile, vision-based algorithm for matching range silhouettes is used for monitoring human activity as well as estimating tool pose

Surface Buildup Scenarios and Outpost Architectures for Lunar Exploration

The Constellation Program Architecture Team and the Lunar Surface Systems Project Office have developed an initial set of lunar surface buildup scenarios and associated polar outpost architectures, along with preliminary supporting element and system designs in support of NASA's Exploration Strategy. The surface scenarios are structured in such a way that outpost assembly can be suspended at any time to accommodate delivery contingencies or changes in mission emphasis. The modular nature of the architectures mitigates the impact of the loss of any one element and enhances the ability of international and commercial partners to contribute elements and systems. Additionally, the core lunar surface system technologies and outpost operations concepts are applicable to future Mars exploration. These buildup scenarios provide a point of departure for future trades and assessments of alternative architectures and surface elements

Randomized controlled trial of patient-controlled sedation for colonoscopy: Entonox vs modified patient-maintained target-controlled propofol

Aim Propofol sedation is often associated with deep sedation and decreased manoeuvrability. Patient-maintained sedation has been used in such patients with minimal side-effects. We aimed to compare novel modified patient-maintained target-controlled infusion (TCI) of propofol with patient-controlled Entonox inhalation for colonoscopy in terms of analgesic efficacy (primary outcome), depth of sedation, manoeuvrability and patient and endoscopist satisfaction (secondary outcomes). Method One hundred patients undergoing elective colonoscopy were randomized to receive either TCI propofol or Entonox. Patients in the propofol group were administered propofol initially to achieve a target concentration of 1.2 μ g/ml and then allowed to self-administer a bolus of propofol (200 μ g/kg/ml) using a patient-controlled analgesia pump with a handset. Entonox group patients inhaled the gas through a mouthpiece until caecum was reached and then as required. Sedation was initially given by an anaesthetist to achieve a score of 4 (Modified Observer's Assessment of Alertness and Sedation Scale), and colonoscopy was then started. Patients completed an anxiety score (Hospital Anxiety and Depression questionnaire), a baseline letter cancellation test and a pain score on a 100-mm visual analogue scale before and after the procedure. All patients completed a satisfaction survey at discharge and 24 h postprocedure. Results The median dose of propofol was 174 mg, and the median number of propofol boluses was four. There was no difference between the two groups in terms of pain recorded (95% confidence interval of the difference -0.809, 5.02) and patient/endoscopist satisfaction. There was no difference between the two groups in either depth of sedation or manoeuvrability. Conclusion Both Entonox and the modified TCI propofol provide equally effective sedation and pain relief, simultaneously allowing patients to be easily manoeuvred during the procedures. © 2010 The Authors. Colorectal Disease © 2010 The Association of Coloproctology of Great Britain and Ireland

Using the quality circle approach to empower disadvantaged youth in addressing cyberbullying: an exploration across five European countries

Digital communication technologies play an important role in the social development of young people, but can create vulnerabilities to cyberbullying and other negative online experiences. The Blurred Lives project aimed to tackle cyberbullying innovatively using a co-participatory approach, collaborating with 14–16-year olds living in areas of socio-economic disadvantage in five European countries. In phase one, 2,658 teenagers were surveyed on their internet use and any unpleasant online experiences. This data informed the second phase where the participating countries worked together with 237 adolescents across 10 schools with adult facilitators to create original anti-cyberbullying resources for teachers, parents/carers, peers, and social media providers using the Quality Circle approach. This methodology adopts an ethos of working together to solve a problem in small, peer-led groups. Each group was tasked with creating a resource for one of the target audience groups. The final resources comprise a rich variety of different formats including videos, comic strips, a board game, leaflets, posters, and newsletters. The pupil feedback highlights, for most but not all participants, an increased knowledge of cyberbullying and e-safety skills, as well as enhanced problem-solving skills, levels of confidence, and group work skills. Several operational challenges are also discussed, including the importance of school-level support, planning, staffing, and finding an appropriate balance between facilitator support and pupil agency