258 research outputs found
Design and synthesis of prostate specific antigen-activated prodrugs
No full textThe feasibility of targeted delivery of cytotoxic agents to prostate cancer cells via selective activation of peptide-linked prodrugs by prostate-specific antigen (PSA) has been previously demonstrated. PSA is a chymotryspin-like serine protease that uniquely cleaves after Gln. Using cleavage maps for its natural substrates, semenogelins I and II, the highly specific PSA substrate glutaryl-Hyp-Ala-Ser-Chg-Gln was discovered, and subsequently coupled to various cytotoxic agents as a promoiety to synthesize prodrugs with enhanced selectivity for prostate cancer cells. In order to obtain PSA peptide substrates with improved specificity and plasma stability from the known substrate sequence glutaryl-Hyp-Ala-Ser-Chg-Gln, we systematically replaced the N-terminal segment with D-retro-inverso-peptides and incorporated 7-amino-4-methylcoumarin (7-AMC) after Gln for convenient fluorometric determination and ranking of the PSA substrate activity. Based on PSA cleavage rate and resistance to hydrolysis in plasma, GABA←mGly-Ala-Ser-Chg-Gln and glutaryl-Ser-Ala-Ser-Chg-Gln were identified as optimal promoieties and coupled to doxorubicin or phosphoramide mustard as PSA-cleavable prodrugs, using various linkers. The doxorubicin conjugates demonstrated comparable PSA cleavage rates, equal or improved cytotoxic profiles in PSA-producing tumor cells compared to the prodrug L-377,202 (glutaryl-Ser-Ala-Ser-Chg-Gln-Ser-Leu-Dox). We found that human neprilysin rapidly cleaved L-377,202 through its Ser-Leu linker and may be responsible for prodrug instability in blood and normal tissues. Thus, in addition to enhancing prodrug selectivity against non-PSA-secreting prostate cancer cell lines, stability in normal tissues was improved. Our results indicated that enhanced tumor specificity of peptide prodrugs targeted for activation by PSA in prostate cancer tumors was achievable with peptide sequence and linker modifications.Ph.D.Includes bibliographical referencesby Herve Aloysiu
Control of Land Cover during Winter using Radar Data
No full textThe paper presents the investigation of ASAR images usefulness to control arable land over winter. In order to account for environmental concerns related to agricultural activities, farmers have to respect the Good Agricultural and Environmental Conditions (GAEC) to get their subsidies. The GAEC must be defined by each country of Member States. One of the GAECs is the prohibition of ploughing parcels above a give slope over the winter period. A cost effective strategy for identifying farms not respecting this GAEC is remote sensing. Due to weather conditions in winter over Europe, there is a high risk of not acquiring a suitable optical image. Therefore it is worth assessing whether radar images can be valuable alternative to optical data for detecting ploughed parcels independently from weather conditions.
To evaluate the degree of radar data usefulness an experiment for Belgian test sites was initiated. Over Wallonia, there were available: the radar and optical images, the vector parcels from LPIS and other auxiliary data (DEM, orthophotomap, meteorological conditions). The study was divided into two separate parts which together constitute complete experiment. The first part was focused on the ploughing detection, while the second part was dedicated to bare soil recognition. Detection of ploughing on the radar images had been examined using the supervised classification methodology based on the time-series compositions. The unsupervised classification of radar images towards to distinguish bare soil and vegetation was tested.
The paper presents also the assessment of the results displayed in the analysis section. Although the confusion between ploughed and sown parcels occurred, the identification of ploughing based on ASAR images analysis is possible with high probability. The detection of bare soil as risky area is feasible on radar data with quite high accuracy as well.JRC.G.3 - Agricultur
Performances of moment resisting frames with slender steel and composite sections in low and moderate seismic areas
No full textSpecific investigations have been carried out regarding typical beam profiles commonly used for steel and composite frames. In a first stage, experimental tests on class-3 and class-4 built up steel profiles and composite beam-to-column nodes were performed. The measurement results were evaluated with regard to the development of the hysteretic behavior with particular emphasis on the cyclic degradation. These test results have been used as reference for the calibration and validation of numerical models aiming at extending the scope of the experimental outcomes through appropriate parametric variations regarding the behavior of nodal connections as well as towards the global analysis and behavior of structures made of class 3 and 4 profiles. Based on the outcomes of these investigations, practical design recommendations are finally derived for moment resisting frames located in low and moderate seismicity regions.This research has been carried out with the support of the Research Fund for Coal and Steel (RFCS) of the European Commission under the grant agreement RFSR-CT-2013-00022.Degee, H (corresponding author), Hasselt Univ, Hasselt, Belgium
Correction to: Potassium Fertilizer Value of Raw and Hydrothermally Treated Igneous Rocks
No full textInternational audienceThe name of author Aaron Mbissik was presented incorrectly (as “Aaron Herve”) in this article as originally published
The discovery of SycO reveals a new function for type three secretion effector chaperones
No full textThe Type Three Secretion (T3S) system is a device used by many Gram-negative pathogens that allows bacteria to deliver effector proteins straight into the eukaryotic cell cytosol. These effectors interfere with various signaling pathways to subvert the host cell functions. The secretion machinery of the T3S system consist of a basal body spanning the bacterial inner and outer membrane followed by a stiff hollow needle outside the bacterium. The fully assembled secretion apparatus constitute a continuous hollow conduit that connects the bacteria to the eukaryotic target cell. After cell contact, virulence proteins -called effectors- are injected directly into the cytosol of the host cell via the T3S apparatus. Several effectors of the T3S system require the assistance of specific cytosolic chaperones to be efficiently exported. There are three classes of T3S chaperones. Effector proteins are assisted by Class I chaperones. Although Class I chaperones are well characterized, their main function is still a matter of controversy. In this thesis, we demonstrate that orf155 encodes a specific chaperone for the effector YopO that we called SycO. We showed that SycO enhances YopO secretion in vitro and is required for translocation of YopO into infected cells. By pulldown assay we demonstrated that residues 20 to 77 of YopO are required and sufficient for SycO binding. Using crosslinking experiments and size exclusion chromatography analysis, we determined the stoichiometry of purified SycO and YopO-SycO complexes. SycO alone forms dimers in solution and the YopO-SycO complex has a 1:2 stoichiometry. These results suggested that SycO is a typical chaperone of the Class I. YopO is a serine/theronine kinase that interacts with Rho and Rac and disrupts the cytoskeleton of the target cells. YopO has been shown to localize at the cell plasma-membrane. By transfection of YopO-EGFP hybrid proteins into HEK293T cells, we demonstrated that the chaperone-binding domain (CBD) coincides with the membrane localization domain of YopO. Nevertheless, the CBD was not needed for the kinase activity of YopO. By ultracentrifugation, we also showed that the CBD causes YopO aggregation in the bacteria, when SycO does not cover it. Further, we show that the CBD of YopE and YopT also caused aggregation in the bacteria in the absence of SycE and SycT respectively. YopE, YopT and T3S effectors in other systems also act at the membrane of the eukaryotic host cell. We propose a new hypothesis concerning the role of T3S chaperones. The sub-cellular localization domain of effectors is aggregation-prone and creates the need for a chaperone inside bacteria. We propose that masking such aggregation-prone localization domains may be a general function for type III effector chaperones
Assessment of Parcel Area Measurement based on VHR SAR Images
No full textIn the frame of the Common Agriculture Policy, Member States have to measure parcels claimed for subsidies with a recommended precision. This is usually done using Very High Resolution (VHR) optical images with ground sampling distance of around 1m or better. However acquisition of such imagery may fail due to cloud cover. It is therefore worth examining the potential of almost weather independent VHR radar data for replacing VHR optical imagery: during this study, the identification of agricultural parcels and the assessment of the measurement accuracy on VHR SAR images were tested.
Airborne VHR X band SAR data were provided over 4 agricultural test sites in France. Three of these sites were covered with 1m monopolarized (“B&W”) data from 2002-2004 whereas the remaining one was covered with 2m multipolarized (“colour”) data from 2002. Orthophotos (1m B&W and 50 cm colour ADS 40) acquired over 2001-2004 were used as reference. All parcels falling on the frame of the VHR SAR images were digitized on the orthophotos and examined on the VHR SAR data.
Two sets of around 40 parcels each were selected on the two types of VHR SAR images (2m “colour” and 1m “B&W”). Each parcel was measured randomly 3 times by 3 operators on both the SAR imagery and the orthophoto. The errors on the parcel area were translated into buffer widths around the parcel perimeter. After the elimination of outlier measurements, the buffer variations were analyzed and a tolerance interval around the buffer estimated. The results indicate that (1) about 30% of the parcels were not visible on the X-band SAR data; (2) the estimated tolerance intervals of the buffer values were of 4.14 m and 4.81 m on 2 m colour composition and 1 m black-and-white SAR data respectively, which is larger than requested by the EU Regulation.JRC.G.3 - Agricultur
GNSS Utilization in the Framework of the EU Common Agricultural Policy
No full textThe UE Member States are obliged by Article 30(1) of Commission Regulation (EC) No 796/2004 to provide proof of quality of the tools and method used in the annual control process of the area based subsidies. The measurement methods and modes with GNSS are the choice of each Member State and the GNSS devices are more or less often used for different goals: On The Spot controls, for follow up inspection of rejected claims, etc. For all purposes the GNSS devices have to be certified or validated for area measurement following the protocol based on the ISO 5725 norm.JRC.H.4 - Monitoring Agricultural Resource
Assessment of the 2019 main cropping season in the Democratic People’s Republic of Korea
No full textThis report provides an early assessment of the 2019 main crop season by analysing the meteorological (Temperature and Rainfall) and vegetation conditions until end-September 2019. Overall, the start of the season was delayed and poor due to long dry spells until June that negatively affected the establishment of early crops planted in spring as well as main season rainfed crops (Annex 1). Despite some rain improvements in June in the north of the rice bowl area, persistent dry spells in July and August negatively affected crop conditions in southwestern regions (i.e. Hwanghae Bukto, Hwanghae Namdo and Pyongyang-si). Heavy rain in September brought by Typhoon Lingling reduced water deficits and resulted in improvement of vegetation conditions but did not significantly improve crop prospects due to their late occurrence during the growing season.
According to the weather and Earth Observation data analysed, irregular rainfall distribution coupled with irrigation water shortages, negatively affected the 2019 crop production, placing the country in a critical food security situation, if we also consider the poor harvest of 2018. Nonetheless, a more detailed analysis based on field observation would be necessary to confirm this diagnosis.JRC.D.5 - Food Securit
Assessment of cropland area on sloping land in DPRK
No full textFollowing the famines of the mid 1990s, the government of the Democratic People’s Republic of Korea (DPRK) authorized cultivation on sloping land before deciding, in the years 2000, to limit this practice on slopes above 15 degrees in order to reduce erosion. There are still many cultivated fields on slopes and their total estimated area ranges from 300,000 ha to more than 2 million ha. This study aims at assessing cropland areas on slopes above 10 and 15 degrees by using high to very high resolution remote sensing satellite imagery. For this purpose, a grid of points was superimposed over the DPRK territory and stratified according to slope, as derived from two DEMs, the 30 m ASTER GDEM V2 and the 3 arc second (~90 m) SRTM Dem V4. A sample of about 2100 points was drawn using an optimal allocation sampling plan, based on a preliminary assessment of the variance of the estimated cropland percentage per class of slope. These 2100 points were interpreted into cropland, no cropland and doubt using mostly Google Earth imagery acquired after 2004. For slopes above 10 degrees, the area cropped was estimated to be around 1,000,000 ha (5.6% CV) and 742,000 ha (8.1% CV) according to the ASTER and SRTM DEM respectively. Above 15 degrees, the estimated cropland area ranges from 360,000 ha (9.7% CV) with SRTM to 540,000 ha (6.6.% CV) with ASTER. To decide between these two estimations, a validation of the two DEMs should be carried out on a region with similar relief. Alternatively, a higher accuracy DEM such as the one to be derived from the TanDEM-X mission in 2014 should provide more accurate estimates of the cropland area on sloping land.JRC.H.4 - Monitoring Agricultural Resource
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