567 research outputs found
Preliminary hidrological results from Sarennes glacier basin, French Alps
Located in the French Alps, Glacier de Sarennes is a small glacier which has its mass balance, measured since 1948. Now since 1992, the Snow Engineenng and Avalanche control department of Cemagref Grenoble measures water leve1 in the emissary of this glacier at the altitude of 2800 meters. The time step of these records is 10 minutes. The aim of this study is to realize the first hydrological assessment, despite having few records until now, to be able to control the new experimental discharge station, and to extract the first scientific results
Preliminary hidrological results from Sarennes glacier basin, French Alps
Located in the French Alps, Glacier de Sarennes is a small glacier which has its mass balance, measured since 1948. Now since 1992, the Snow Engineenng and Avalanche control department of Cemagref Grenoble measures water leve1 in the emissary of this glacier at the altitude of 2800 meters. The time step of these records is 10 minutes. The aim of this study is to realize the first hydrological assessment, despite having few records until now, to be able to control the new experimental discharge station, and to extract the first scientific results
Impact of DOTA Conjugation on Pharmacokinetics and Immunoreactivity of [177Lu]Lu-1C1m-Fc, an Anti TEM-1 Fusion Protein Antibody in a TEM-1 Positive Tumor Mouse Model.
1C1m-Fc, an anti-tumor endothelial marker 1 (TEM-1) scFv-Fc fusion protein antibody, was previously successfully radiolabeled with <sup>177</sup> Lu. TEM-1 specific tumor uptake was observed together with a non-saturation dependent liver uptake that could be related to the number of dodecane tetraacetic acid (DOTA) chelator per 1C1m-Fc. The objective of this study was to verify this hypothesis and to find the best DOTA per 1C1m-Fc ratio for theranostic applications. 1C1m-Fc was conjugated with six concentrations of DOTA. High-pressure liquid chromatography, mass spectrometry, immunoreactivity assessment, and biodistribution studies in mice bearing TEM-1 positive tumors were performed. A multi-compartment pharmacokinetic model was used to fit the data and a global pharmacokinetic model was developed to illustrate the effect of liver capture and immunoreactivity loss. Organ absorbed doses in mice were calculated from biodistribution results. A loss of immunoreactivity was observed with the highest DOTA per 1C1m-Fc ratio. Except for the spleen and bone, an increase of DOTA per 1C1m-Fc ratio resulted in an increase of liver uptake and absorbed dose and a decrease of uptake in tumor and other tissues. Pharmacokinetic models correlated these results. The number of DOTA per antibody played a determining role in tumor targeting. One DOTA per 1C1m-Fc gave the best pharmacokinetic behavior for a future translation of [ <sup>177</sup> Lu]Lu-1C1m-Fc in patients
A phase I study of a new polyamine biosynthesis inhibitor, SAM486A, in cancer patients with solid tumours
Because tumour cell proliferation is highly dependent upon up-regulation of de-novo polyamine synthesis, inhibition of the polyamine synthesis pathway represents a potential target for anticancer therapy. SAM486A (CGP 48664) is a new inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), more potent and specific than the first-generation SAMDC inhibitor methylglyoxal (bis) guanylhydrazone (MGBG). Preclinical testing confirmed promising antiproliferative activity. In this phase I study, SAM486A was given 4-weekly as a 120 h infusion. 39 adult cancer patients were enrolled with advanced/refractory disease not amenable to established treatments, PS †2, adequate marrow, liver, renal and cardiac function. Doses were escalated in 100% increments without toxicity in 24 pts from 3 mg mâ2cycleâ1up to 400 mg mâ2cycleâ1. At 550 and 700 mg mâ2cycleâ1reversible dose-limiting neutropenia occurred. Other toxicities included mild fatigue, nausea and vomiting. No objective remission was seen. Pharmakokinetic analysis showed a terminal half-life of approximately 2 days. AUC and Cmax were related to dose; neutropenia correlated with AUC. The recommended dose for further phase II studies on this schedule is 400 mg mâ2cycleâ1. © 2000 Cancer Research Campaig
Development of Shuttle Vectors for Transformation of Diverse Rickettsia Species
Plasmids have been identified in most species of Rickettsia examined, with some species maintaining multiple different plasmids. Three distinct plasmids were demonstrated in Rickettsia amblyommii AaR/SC by Southern analysis using plasmid specific probes. Copy numbers of pRAM18, pRAM23 and pRAM32 per chromosome in AaR/SC were estimated by real-time PCR to be 2.0, 1.9 and 1.3 respectively. Cloning and sequencing of R. amblyommii AaR/SC plasmids provided an opportunity to develop shuttle vectors for transformation of rickettsiae. A selection cassette encoding rifampin resistance and a fluorescent marker was inserted into pRAM18 yielding a 27.6 kbp recombinant plasmid, pRAM18/Rif/GFPuv. Electroporation of Rickettsia parkeri and Rickettsia bellii with pRAM18/Rif/GFPuv yielded GFPuv-expressing rickettsiae within 2 weeks. Smaller vectors, pRAM18dRG, pRAM18dRGA and pRAM32dRGA each bearing the same selection cassette, were made by moving the parA and dnaA-like genes from pRAM18 or pRAM32 into a vector backbone. R. bellii maintained the highest numbers of pRAM18dRGA (13.3 â 28.1 copies), and R. parkeri, Rickettsia monacensis and Rickettsia montanensis contained 9.9, 5.5 and 7.5 copies respectively. The same species transformed with pRAM32dRGA maintained 2.6, 2.5, 3.2 and 3.6 copies. pRM, the plasmid native to R. monacensis, was still present in shuttle vector transformed R. monacensis at a level similar to that found in wild type R. monacensis after 15 subcultures. Stable transformation of diverse rickettsiae was achieved with a shuttle vector system based on R. amblyommii plasmids pRAM18 and pRAM32, providing a new research tool that will greatly facilitate genetic and biological studies of rickettsiae
LongâDistance Natal Dispersal Is Relatively Frequent and Correlated with Environmental Factors in a Widespread Raptor
Dispersal is a critical process influencing population dynamics and responses to global change. Longâdistance dispersal (LDD) can be especially important for gene flow and adaptability, although little is known about the factors influencing LDD because studying largeâscale movements is challenging and LDD tends to be observed less frequently than shorterâdistance dispersal (SDD). We sought to understand patterns of natal dispersal at a large scale, specifically aiming to understand the relative frequency of LDD compared to SDD and correlates of dispersal distances. We used bird banding and encounter data for American kestrels (Falco sparverius) to investigate the effects of sex, migration strategy, population density, weather, year and agricultural land cover on LDD frequency, LDD distance and SDD distance in North America from 1961 to 2015. Nearly half of all natal dispersal (48.9%) was LDD (classified as \u3e30 km), and the likelihood of LDD was positively associated with the proportion of agricultural land cover around natal sites. Correlates of distance differed between LDD and SDD movements. LDD distance was positively correlated with latitude, a proxy for migration strategy, suggesting that migratory individuals disperse farther than residents. Distance of LDD in males was positively associated with maximum summer temperature. We did not find sexâbias or an effect of population density in LDD distance or frequency. Within SDD, females tended to disperse farther than males, and distance was positively correlated with density. Sampling affected all responses, likely because local studies more frequently capture SDD within study areas. Our findings that LDD occurs at a relatively high frequency and is related to different proximate factors from SDD, including a lack of sexâbias in LDD, suggest that LDD may be more common than previously reported, and LDD and SDD may be distinct processes rather than two outcomes originating from a single dispersal distribution. To our knowledge, this is the first evidence that LDD and SDD may be separate processes in an avian species, and suggests that environmental change may have different outcomes on the two processes
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