Description and 238U, 234U, 232Th and 230Th measurements of the manganese nodule analysed from station SO79_63KG, R/V SONNE

Thorium and uranium isotopes were measured in a diagenetic manganese nodule from the Peru basin applying alpha- and thermal ionization mass spectrometry (TIMS). Alpha-counting of 62 samples was carried out with a depth resolution of 0.4 mm to gain a high-resolution Th-230(excess) profile. In addition, 17 samples were measured with TIMS to obtain precise isotope concentrations and isotope ratios. We got values of 0.06-0.59 ppb (Th-230), 0.43-1.40 ppm (Th-232), 0.09-0.49 ppb (U-234) and 1.66-8.24 ppm (U-238). The uranium activity ratio in the uppermost samples (1-6 mm) and in two further sections in the nodule at 12.5+/-1.0 mm and 27.3-33.5 mm comes close to the present ocean wa ter value of 1.144+/-0.004. In two other sections of the nodule, this ratio is significantly higher, probably reflecting incorporation of diagenetic uranium. The upper 25 mm section of the Mn nodule shows a relatively smooth exponential decrease in the Th-230(excess) concentration (TIMS). The slope of the best fit yields a growth rate of 110 mm/Ma up to 24.5 mm depth. The section from 25 to 30.3 mm depth shows constant Th-230(excess) concentrations probably due to growth rates even faster than those in the top section of the nodule. From 33 to 50 mm depth, the growth rate is approximately 60 mm/Ma. Two layers in the nodule with distinct laminations (11-15 and 28-33 mm depth) probably formed during the transition from isotopic stage 8 to 7 and in stage 5e, respectively. The Mn/Fe ratio shows higher values during interglacials 5 and 7, and lower ones during glacials 4 and 6. A comparison of our data with data from adjacent sediment cores suggests (a) a variable sb supply of hydrothermal Mn to sediments and Mn nodules of the Peru basin or (b) suboxic conditions at the water sediment interface during periods with lower Mn/Fe ratios.

Dell'argenteo imbusto al primo patrono S. Gennaro da re Carlo Secondo di Angiò decretato : con una disquisizione intorno al Libro delle spese della casa dello stesso re, dove s'indagano gli anni ai quali va assegnato se ne classificato le notizie più interessanti, e si fa accurata rassegna dei pesi e delle misure state in uso nel reame di Napoli /

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The new missioner /

Frontispiece and plates facing p. 12, 96, 134, 144, 206, 234 and 266, signed by J. Walter Taylor.

Quality assurance experience with the randomized neuropathic bone pain trial (Trans-Tasman Radiation Oncology Group, 96.05)

Background and purpose: Trans-Tasman Radiation Oncology Group 96.05 is a prospective randomized controlled trial comparing a single 8 Gy with 20 Gy in five fractions of radiotherapy (RT) for neuropathic pain due to bone metastases. This paper summarizes the quality assurance (QA) activities for the first 234 patients (accrual target 270). Materials and methods: Independent audits to assess compliance with eligibility/exclusion criteria and appropriateness of treatment of the index site were conducted after each cohort of approximately 45 consecutive patients. Reported serious adverse events (SAEs) in the form of cord/cauda equina compression or pathological fracture developing at the index site were investigated and presented in batches to the Independent Data Monitoring Committee. Finally, source data verification of the RT prescription page and treatment records was undertaken for each of the first 234 patients to assess compliance with the protocol. Results: Only one patient was found conclusively not to have genuine neuropathic pain, and there were no detected 'geographical misses' with RT fields. The overall rate of detected infringements for other eligibility criteria over five audits (225 patients) was 8% with a dramatic improvement after the first audit. There has at no stage been a statistically significant difference in SAEs by randomization arm. There was a 22% rate of RT protocol variations involving ten of the 14 contributing centres, although the rate of major dose violations (more than +/- 10% from protocol dose) was only 6% with no statistically significant difference by randomization arm (P = 0.44). Conclusions: QA auditing is an essential but time-consuming component of RT trials, including those assessing palliative endpoints. Our experience confirms that all aspects should commence soon after study activation. Crown Copyright (C) 2003 Published by Elsevier Science Ltd. All rights reserved.

A novel technique for polarisation mode dispersion measurements in optical fibres

A novel technique for determining the polarisation mode dispersion in optical fibres is described. The technique makes use of a sinusoidally frequency modulated source, and is applied to the measurement of the beat length of highly birefringent monomode fibre. The temporal delay between the two modes of the fibre is measured with a resolution of approximately ±0.6 ps.

Stand-alone groundwater desalination system using reverse osmosis combined with a cooled greenhouse for use in arid and semi-arid zones of India

In many areas of northern India, salinity renders groundwater unsuitable for drinking and even for irrigation. Though membrane treatment can be used to remove the salt, there are some drawbacks to this approach e.g. (1) depletion of the groundwater due to over-abstraction, (2) saline contamination of surface water and soil caused by concentrate disposal and (3) high electricity usage. To address these issues, a system is proposed in which a photovoltaic-powered reverse osmosis (RO) system is used to irrigate a greenhouse (GH) in a stand-alone arrangement. The concentrate from the RO is supplied to an evaporative cooling system, thus reducing the volume of the concentrate so that finally it can be evaporated in a pond to solid for safe disposal. Based on typical meteorological data for Delhi, calculations based on mass and energy balance are presented to assess the sizing and cost of the system. It is shown that solar radiation, freshwater output and evapotranspiration demand are readily matched due to the approximately linear relation among these variables. The demand for concentrate varies independently, however, thus favouring the use of a variable recovery arrangement. Though enough water may be harvested from the GH roof to provide year-round irrigation, this would require considerable storage. Some practical options for storage tanks are discussed. An alternative use of rainwater is in misting to reduce peak temperatures in the summer. An example optimised design provides internal temperatures below 30EC (monthly average daily maxima) for 8 months of the year and costs about €36,000 for the whole system with GH floor area of 1000 m2 . Further work is needed to assess technical risks relating to scale-deposition in the membrane and evaporative pads, and to develop a business model that will allow such a project to succeed in the Indian rural context.

The SECURE study:long-term safety of Ranibizumab 0.5 mg in neovascular age-related macular degeneration

Objective - To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Design - Twenty-four–month, open-label, multicenter, phase IV extension study. Participants - Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Methods - Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Main Outcome Measures - Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Results - Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. Conclusions - The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

Alpha helical trans-membrane proteins:enhanced prediction using a Bayesian approach

Membrane proteins, which constitute approximately 20% of most genomes, are poorly tractable targets for experimental structure determination, thus analysis by prediction and modelling makes an important contribution to their on-going study. Membrane proteins form two main classes: alpha helical and beta barrel trans-membrane proteins. By using a method based on Bayesian Networks, which provides a flexible and powerful framework for statistical inference, we addressed alpha-helical topology prediction. This method has accuracies of 77.4% for prokaryotic proteins and 61.4% for eukaryotic proteins. The method described here represents an important advance in the computational determination of membrane protein topology and offers a useful, and complementary, tool for the analysis of membrane proteins for a range of applications.

Permanent open water surfaces in central Siberia from ENVISAT ASAR wide swath data 2003/2004, link to shapefile

Permanent water bodies not only store dissolved CO2 but are essential for the maintenance of wetlands in their proximity. From the viewpoint of greenhouse gas (GHG) accounting wetland functions comprise sequestration of carbon under anaerobic conditions and methane release. The investigated area in central Siberia covers boreal and sub-arctic environments. Small inundated basins are abundant on the sub-arctic Taymir lowlands but also in parts of severe boreal climate where permafrost ice content is high and feature important freshwater ecosystems. Satellite radar imagery (ENVISAT ScanSAR), acquired in summer 2003 and 2004, has been used to derive open water surfaces with 150 m resolution, covering an area of approximately 3 Mkm**2. The open water surface maps were derived using a simple threshold-based classification method. The results were assessed with Russian forest inventory data, which includes detailed information about water bodies. The resulting classification has been further used to estimate the extent of tundra wetlands and to determine their importance for methane emissions. Tundra wetlands cover 7% (400,000 km**2) of the study region and methane emissions from hydromorphic soils are estimated to be 45,000 t/d for the Taymir peninsula.

Growth rates and possible age of a North Pacific manganese nodule

The rate of accumulation of a ferromanganese coating on a fragment of pillow basalt was estimated using a variety of techniques. Unsupported 230 Th activity decrease in the oxide layer, K/A dating of the basalt, fission tracks dating of the glassy layer around the basalt, thickness of the palagonitization rind, and integrated 230 Th activity give ages from approximately 3 x 10-6 years to 5 x 10-3 years. Data suggest that the ferromanganese material formed rapidly (33 mm/10-6 years) and by hydrothermal or volcanic processes.

The Evolution of the Los Negritos Porphyry Copper Deposit, Coquimbo, Chile: Geological, Geochronological, Mineralogical and Geochemical Evidence

The Los Negritos porphyry copper deposit is located ~ 4 km to the northeast of Carmen de Andacollo Mine in the Chilean Cretaceous metallogenic belt. The mineralization is hosted in andesite of the Quebrada Marquesa Formation and a series of at least four early to intramineral porphyry intrusive rock types: plagioclase quartz biotite porphyry (P1b and P1a dated at 109.60± 0.75 Ma and 107.22± 0.40 Ma); plagioclase biotite porphyry (P2: 106.30 ± 0.47 Ma); and quartz plagioclase biotite porphyry (P3: 106.19 ± 0.42 Ma). These units are cut by late‐ to post‐mineral plagioclase‐hornblende porphyritic rocks (P4b: 106.20 ± 0.69 Ma and P4a: 106.50 ± 0.68 Ma). The earliest intrusive units (P1) were affected by an initial stage of K‐feldspar‐biotite alteration, with chalcopyrite, molybdenite (date at 108.5 ± 0.5 Ma) and gold (up to 0.11 ppm), and the surrounding volcanic host rock was overprinted by chlorite‐epidote dominated (propylitic) alteration. Subsequent to the P2 and P3 intrusion, these rocks were affected by albite and then a second stage of potassic alteration. The Ti and Ba contents in hydrothermal biotite are notably lower (typically Ti = 0.100‐0.144 a.p.f.u. and Ba = 0.001‐0.005 a.p.f.u) than in magmatic ones (generally Ti = 0.186‐0.222 a.p.f.u. and Ba = 0.014‐0.023 a.p.f.u.), and constitute an excellent discriminant of the nature of biotite. These early stages of alteration were overprinted by copper‐molybdenum bearing chlorite‐sericite alteration at 106.60 ± 0.5 Ma (Re‐Os age in molybdenite) and by quartz‐sericite‐pyrite veins (phyllic), respectively in the southwest and northeast areas. The average temperature associated with these two alteration facies is estimated around 305 °C. Weak albite‐calcite alteration, spatially associated with sulfosalts and distributed along the margins of P3, overprinted the phyllic facies. The intrusive rock units at the Los Negritos and Carmen de Andacollo deposits are geochemically classified as diorite to granodiorite with a calc‐alkaline magmatic affinity, and formed in a volcanic arc setting from partial melting of a metasomatized mantle wedge. They are interpreted to be cogenetic, and related to a common long‐lived magma chamber that emplaced during a period of tectonic inversion known as the Subhercynian, Peruvian or Pacific event.

Soft tissue sarcoma: biology and therapeutic correlates

Soft tissue sarcomas (STS) comprise a heterogenenous group of greater than 50 malignancies of putative mesenchymal cell origin and as such they may arise in diverse tissue types in various anatomical locations throughout the whole body. Collectively they account for approximately 1% of all human malignancies yet have a spectrum of aggressive behaviours amongst their subtypes. They thus pose a particular challenge to manage and remain an under investigated group of cancers with no generally applicable new therapies in the past 40 years and an overall 5-year survival rate that remains stagnant at around 50%. From September 2000 to July 2006 I undertook a full time post-doctoral level research fellowship at the MD Anderson Cancer Center, Houston, Texas, USA in the department of Surgical Oncology to investigate the biology of soft tissue sarcoma and test novel anti- sarcoma adenovirus-based therapy in the preclinical nude rat model of isolated limb perfusion against human sarcoma xenografts. This work, in collaboration with colleagues as indicated herein, led to a number of publications in the scientific literature furthering our understanding of the malignant phenotype of sarcoma and reported preclinical studies with wild-type p53, in a replication deficient adenovirus vector, and oncolytic adenoviruses administered by isolated limb perfusion. Additional collaborative and pioneering preclinical studies reported the molecular imaging of sarcoma response to systemically delivered therapeutic phage RGD-4c AAVP. Doxorubicin chemotherapy is the single most active broadly applicable anti-sarcoma chemotherapeutic yet only has an approximate 30% overall response rate with additional breakthrough tumour progression and recurrence after initial chemo-responsiveness further problematic features in STS management. Doxorubicin is a substrate for the multi- drug resistance (mdr) gene product p-glycoprotein drug efflux pump and exerts its main mode of action by induction of DNA double-strand breaks during the S-phase of the cell cycle. Two papers in my thesis characterise different aspects of chemoresistance in sarcoma. The first shows that wild-type p53 suppresses Protein Kinase Calpha (PKCα) phosphorylation (and activation) of p-glycoprotein by transcriptional repression of PKCα through a Sp-1 transcription factor binding site in its -244/-234 promoter region. The second paper demonstrates that Rad51 (a central mediator of homologous recombination repair of double strand breaks) has elevated levels in sarcoma and particularly in the S- G2 phase of the cell cycle. Suppression of Rad51 with small interfering RNA in sarcoma cell culture led to doxorubicin chemosensitisation. Reintroduction of wild-type p53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression via transcriptional repression of the Rad51 promoter through increased AP-2 binding. In light of poor response rates to chemotherapy, escape from local control portends a poor prognosis for patients with sarcoma. Two papers in my thesis characterise aspects of sarcoma angiogenesis, invasion and metastasis. Human sarcoma samples were found to have high levels of matrix metalloproteinase-9 (MMP-9) with expression levels that correlated with p53 mutational status. MMP-9 is known to degrade extracellular collagen, contribute to the control of the angiogenic switch necessary in primary tumour progression and facilitate invasion and metastasis. Reconstitution of wild-type p53 function led to decreased levels of MMP-9 protein and mRNA as well as zymography-assessed MMP-9 proteolytic activity and decreased tumour cell invasiveness. Reintroduction of wild-type p53 into human sarcoma xenografts in-vivo decreased tumour growth and MMP-9 protein expression. Wild-type p53 was found to suppress mmp-9 transcription via decreased binding of NF-κB to its -607/-595 mmp-9 promoter element. Studies on the role of the VEGF165 in sarcoma found that sarcoma cells stably transfected with VEGF165 formed more aggressive xenografted tumours with increased vascularity, growth rate, metastasis, and resistance to chemotherapy. Use of the anti-VEGFR2 antibody DC101 enhanced doxorubicin sensitivity at sub-conventional dosing, inhibited tumour growth, decreased development of metastases, and reduced tumour micro-vessel density while increasing the vessel maturation index. These effects were explained primarily through effects on endothelial cells (e.c.s), rather than the tumour cells per se, where DC101 induced e.c. sensitivity to doxorubicin and suppressed e.c. production of MMPs. The p53 tumour suppressor pathway is the most frequently mutated pathway in sarcoma. Recapitulation of wild-type p53 function in sarcoma exerts a number of anti-cancer outcomes such as growth arrest, resensitisation to chemotherapy, suppression of invasion, and attenuation of angiogenesis. Using a modified nude rat-human sarcoma xenograft model for isolated limb perfusion (ILP) delivery of wild-type p53 in a replication deficient adenovirus vector I showed that functionally competent wild-type p53 could be delivered to and detected in human leiomyosarcoma xenografts confirming preclinical feasibility - although not efficacious due to low transgene expression. Viral fibre modification to express the RGD tripeptide motif led to greater viral uptake by sarcoma cells in vitro (transductional targeting) and changing the transgene promoter to a response element active in cells with active telomerase expression restricted the transgene expression to the tumour intracellular environment (transcriptional targeting). Delivery of the fibre-modified, selectively replication proficient oncolytic adenovirus Ad.hTC.GFP/ E1a.RGD by ILP demonstrated a more robust, and tumour-restricted, transgene expression with evidence of anti-sarcoma effect confirmed microscopically. Collaborative studies using the fibre modified phage RGD-4C AAVP confirmed that systemic delivery specifically, efficiently, and repeatedly targets human sarcoma xenografts, binds to αv integrins in tumours, and demonstrates a durable, though heterogeneous, transgene expression of 1-4 weeks. Incorporation of the Herpes Simplex Virus thymidine kinase (HSVtk) transgene into RGD-4C AAVP permitted CT-PET spatial and temporal molecular imaging in vivo of transgene expression and allowed quantification of tumour metabolic activity both before and after interval administration of a systemic cytotoxic with predictable and measurable response to treatment before becoming apparent clinically. These papers further the medical and scientific community’s understanding of the biology of soft tissue sarcoma and report preclinical studies with novel and promising anti- sarcoma therapeutics.

Effect of Pavement-Vehicle Interaction on Highway Fuel Consumption and Emission

Vehicle fuel consumption and emission are two important effectiveness measurements of sustainable transportation development. Pavement plays an essential role in goals of fuel economy improvement and greenhouse gas (GHG) emission reduction. The main objective of this dissertation study is to experimentally investigate the effect of pavement-vehicle interaction (PVI) on vehicle fuel consumption under highway driving conditions. The goal is to provide a better understanding on the role of pavement in the green transportation initiates. Four study phases are carried out. The first phase involves a preliminary field investigation to detect the fuel consumption differences between paired flexible-rigid pavement sections with repeat measurements. The second phase continues the field investigation by a more detailed and comprehensive experimental design and independently investigates the effect of pavement type on vehicle fuel consumption. The third study phase calibrates the HDM-IV fuel consumption model with data collected in the second field phase. The purpose is to understand how pavement deflection affects vehicle fuel consumption from a mechanistic approach. The last phase applies the calibrated HDM-IV model to Florida’s interstate network and estimates the total annual fuel consumption and CO2 emissions on different scenarios. The potential annual fuel savings and emission reductions are derived based on the estimation results. Statistical results from the two field studies both show fuel savings on rigid pavement compared to flexible pavement with the test conditions specified. The savings derived from the first phase are 2.50% for the passenger car at 112km/h, and 4.04% for 18-wheel tractor-trailer at 93km/h. The savings resulted from the second phase are 2.25% and 2.22% for passenger car at 93km/h and 112km/h, and 3.57% and 3.15% for the 6-wheel medium-duty truck at 89km/h and 105km/h. All savings are statistically significant at 95% Confidence Level (C.L.). From the calibrated HDM-IV model, one unit of pavement deflection (1mm) on flexible pavement can cause an excess fuel consumption by 0.234-0.311 L/100km for the passenger car and by 1.123-1.277 L/100km for the truck. The effect is more evident at lower highway speed than at higher highway speed. From the network level estimation, approximately 40 million gallons of fuel (combined gasoline and diesel) and 0.39 million tons of CO2 emission can be saved/reduced annually if all Florida’s interstate flexible pavement are converted to rigid pavement with the same roughness levels. Moreover, each 1-mile of flexible-rigid conversion can result in a reduction of 29 thousand gallons of fuel and 258 tons of CO2 emission yearly.

In Situ Observation of the Thermal Decomposition of Weddelite by Heating Stage Environmental Scanning Electron Microscopy

The morphological and chemical changes occurring during the thermal decomposition of weddelite, CaC2O4·2H2O, have been followed in real time in a heating stage attached to an Environmental Scanning Electron Microscope operating at a pressure of 2 Torr, with a heating rate of 10 °C/min and an equilibration time of approximately 10 min. The dehydration step around 120 °C and the loss of CO around 425 °C do not involve changes in morphology, but changes in the composition were observed. The final reaction of CaCO3 to CaO while evolving CO2 around 600 °C involved the formation of chains of very small oxide particles pseudomorphic to the original oxalate crystals. The change in chemical composition could only be observed after cooling the sample to 350 °C because of the effects of thermal radiation.

Electrochemistry of Heteroleptic Tris(phthalocyaninato) Rare Earth(III) Complexes

The electrochemical characteristics of a series of heteroleptic tris(phthalocyaninato) complexes with identical rare earths or mixed rare earths (Pc)M(OOPc)M(OOPc) [M = Eu...Lu, Y; H2Pc = unsubstituted phthalocyanine, H2(OOPc) = 3,4,12,13,21,22,30,31-octakis(octyloxy)phthalocyanine] and (Pc)Eu(OOPc)Er(OOPc) have been recorded and studied comparatively by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in CH2Cl2 containing 0.1 M tetrabutylammonium perchlorate (TBAP). Up to five quasi-reversible one-electron oxidations and four one-electron reductions have been revealed. The half-wave potentials of the first, second and fifth oxidations depend on the size of the metal center, but the fifth changes in the opposite direction to that of the first two. Moreover, the difference in redox potentials of the first oxidation and first reduction for (Pc)M(OOPc)M(OOPc), 0.85−0.98 V, also decreases linearly along with decreasing rare earth ion radius, clearly showing the rare earth ion size effect and indicating enhanced π−π interactions in the triple-deckers connected by smaller lanthanides. This order follows the red-shift seen in the lowest energy band of triple-decker compounds. The electronic differences between the lanthanides and yttrium are more apparent for triple-decker sandwich complexes than for the analogous double-deckers. By comparing triple-decker, double-decker and mononuclear [ZnII] complexes containing the OOPc ligand, the HOMO−LUMO gap has been shown to contract approximately linearly with the number of stacked phthalocyanine ligands.