A Novel Immunological Assay for Hepcidin Quantification in Human Serum

Contains fulltext : 81054.pdf (publisher's version ) (Open Access)BACKGROUND: Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes a specific and non-operator demanding immunoassay for hepcidin quantification in human sera. METHODS AND FINDINGS: An ELISA assay was developed for measuring hepcidin serum concentration using a recombinant hepcidin25-His peptide and a polyclonal antibody against this peptide, which was able to identify native hepcidin. The ELISA assay had a detection range of 10-1500 microg/L and a detection limit of 5.4 microg/L. The intra- and interassay coefficients of variance ranged from 8-15% and 5-16%, respectively. Mean linearity and recovery were 101% and 107%, respectively. Mean hepcidin levels were significantly lower in 7 patients with juvenile hemochromatosis (12.8 microg/L) and 10 patients with iron deficiency anemia (15.7 microg/L) and higher in 7 patients with Hodgkin lymphoma (116.7 microg/L) compared to 32 age-matched healthy controls (42.7 microg/L). CONCLUSIONS: We describe a new simple ELISA assay for measuring hepcidin in human serum with sufficient accuracy and reproducibility

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Reconstruction de la séquence éruptive des Traps du Deccan, Inde (conséquencres climatiques et environnementales)

Dans cette thèse, nous tentons de contraindre la date, la séquence et la durée du volcanisme des traps du Deccan en Inde, et de commencer à en modéliser les conséquences climatiques. Pour cela, nous avons échantillonné 12 nouvelles coupes sur 300km (du Nord au Sud) le long de l escarpement des Western Ghats. Les résultats paléomagnétiques ont permis de reconnaître des groupes de directions statistiquement identiques dans de nombreuses coulées, soit situées en séquence dans une même coupe, soit séparées latéralement de plus de 130km. Nous proposons, sur la base des caractéristiques de la variation séculaire récente du champ géomagnétique et de la taille des intervalles de confiance à 95% des directions rémanentes, que ces groupes directionnels correspondent à des méga-coulées ou unités de refroidissement qui se sont refroidies en quelques décennies à moins d un siècle. Ces méga-coulées sont alors capables d émettre de fortes quantités de dioxyde de soufre dans l atmosphère. Nous estimons la durée totale de mise en place du volcanisme (le temps réel d éruption) à moins de 10.000 ans, la plupart du temps (de 400 à 500.000 ans) étant représentée par une dizaine de red boles épais. Les données géochronologiques ont permis d obtenir pour les Western Ghats un âge absolu (64.7+-0.6Ma; 1s) qui est statistiquement identique à celui de la limite Crétacé-Tertiaire (qui ne peut cependant pas encore être localisée avec précision dans la coupe). Pour tenter de commencer à modéliser l impact climatique d un grand trap, nous avons choisi comme brique élémentaire l éruption fissurale de 1783 au Laki en Islande (l une des plus grandes éruptions historiques basaltiques). Avec le modèle LMDZ-INCA, nous avons pu reproduire l extension (semi-globale) du nuage de brouillards exceptionnels qui fut observé cette année-là, et nous avons pu nous faire une idée des raisons de la crise de mortalité qui l a accompagné. Un seul pulse du Deccan pouvant atteindre dix fois le flux injecté par le Laki et ce pendant près de 100 fois plus longtemps, les traps du Deccan sont alors fortement susceptibles d induire une extinction en masseIn this thesis, we attempt to constrain the date, timing and duration of flood basalt volcanism in the particular case of the Deccan traps of India, and to model the climatic impact of such massive volcanism. With this goal in mind, we have sampled 12 new sections of the traps along 300km (from North to South) of the Western Ghat escarpment. Sections were selected based on previously available petrologic, geochemical and volcanological data. Using the paleomagnetic analysis we have been able to recognize groups of statistically identical directions in a number of flows, either superimposed in the same section, or laterally separated by up to 130km. We hypothesize, based on the characteristics of recent secular variation and the typical sizes of the 95% confidence intervals of the remanence directions, that these directional groups represent mega-flows or cooling units that cooled within a period of decades to at most a century. We estimate that the total amount of time represented by the flows could be less than 10,000 years, and that most of the time (400 to 500.000 years) is represented by less than 10 thick bole levels. Therefore we have established an absolute age undistinguishable from that of the Cretaceous-Tertiary boundary (although this boundary cannot yet be precisely located within the section) at 64.7+-0.6Ma. In order to start modeling the climatic impact of such flood basalt sequences, we have first used as a building block the 1783 fissure eruption at Laki in Iceland (one of the largest historical basaltic eruptions). Using the LMDZ-INCA model, we replicate the observed (semi-global) dispersal over much of northern hemisphere of the unusual haze that was observed at the time and are able to understand the spread and intensity of the mortality crisis which ensued. A single Deccan pulse could have reached 10 times the flux of Laki, and for up to 100 times longer. And there were tens of pulses suggesting the causal consequences of the climatic impact of flood basalts regarding mass extinctionsPARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Sci.Terre recherche (751052114) / SudocSudocFranceF