Description of an Institutional Cohort of Myeloid Neoplasms Carrying ETV6-Locus Deletions or ETV6 Rearrangements.

The gene encoding for transcription factor ETV6 presents recurrent lesions in hematologic neoplasms, most notably the ETV6-RUNX1 rearrangement in childhood B-ALL. The role of ETV6 for normal hematopoiesis is unknown, but loss of its function probably participates in oncogenic procedures. In myeloid neoplasms, ETV6-locus (12p13) deletions are rare but recurrent; ETV6 translocations are even rarer, but those reported seem to have phenotype-defining consequences. We herein describe the genetic and hematologic profile of myeloid neoplasms with ETV6 deletions (10 cases), or translocations (4 cases) diagnosed in the last 10 years in our institution. We find complex caryotype to be the most prevalent cytogenetics among patients with 12p13 deletion (8/10 patients), with most frequent coexisting anomalies being monosomy 7 or deletion 7q32 (5/10), monosomy 5 or del5q14-15 (5/10), and deletion/inversion of chromosome 20 (5/10), and most frequent point mutation being TP53 mutation (6/10 patients). Mechanisms of synergy of these lesions are unknown. We describe the entire genetic profile and hematologic phenotype of cases with extremely rare ETV6 translocations, confirming the biphenotypic T/myeloid nature of acute leukemia associated to ETV6-NCOA2 rearrangement, the association of t (1;12) (p36; p13) and of the CHIC2-ETV6 fusion with MDS/AML, and the association of the ETV6-ACSL6 rearrangement with myeloproliferative neoplasm with eosinophilia. Mutation of the intact ETV6 allele was present in two cases and seems to be subclonal to the chromosomal lesions. Decoding the mechanisms of disease related to ETV6 haploinsufficiency or rearrangements is important for the understanding of pathogenesis of myeloid neoplasms and fundamental research must be guided by observational cues

Nitrotriazole-based acetamides and propanamides with broad spectrum antitrypanosomal activity.

3-Nitro-1H-1,2,4-triazole-based acetamides bearing a biphenyl- or a phenoxyphenyl moiety have shown remarkable antichagasic activity both in vitro and in an acute murine model, as well as substantial in vitro antileishmanial activity but lacked activity against human African trypanosomiasis. We have shown now that by inserting a methylene group in the linkage to obtain the corresponding propanamides, both antichagasic and in particular anti-human African trypanosomiasis potency was increased. Therefore, IC50 values at low nM concentrations against both T. cruzi and T. b. rhodesiense, along with huge selectivity indices were obtained. Although several propanamides were active against Leishmania donovani, they were slightly less potent than their corresponding acetamides. There was a good correlation between lipophilicity (clogP value) and trypanocidal activity, for all new compounds. Type I nitroreductase, an enzyme absent from the human host, played a role in the activation of the new compounds, which may function as prodrugs. Antichagasic activity in vivo was also demonstrated with representative propanamides.This work was supported in part by internal funds of the Radiation Medicine Department at NorthShore University HealthSystem. In addition, the Drugs for Neglected Diseases initiative (DNDi) received financial support from the Bill & Melinda Gates Foundation (BMGF) to perform the in vitro screenings against parasites

A Saxon Fish Weir and undated fish trap frames near Ashlett Creek, Hampshire, UK: static structures on a dynamic foreshore

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.The remains of a wooden V-shaped fish weir and associated structures have been discovered near Ashlett Creek on the tidal mudflats of Southampton Water in Hampshire, southern Britain. Radiocarbon dating of oak roundwood stakes taken from the main weir structure date it to the middle Saxon period. Clusters of as-yet undated roundwood posts within the catchment area of the weir are interpreted as the frames for fish traps that are assumed to pre- or post-date the operational period of the weir itself. The weir is contemporary with wooden V-shaped fish weirs found elsewhere in southern and central Britain, and also Ireland, but its circular catchment ‘pound’ remains restricted, in these islands, to the Solent and Severn estuaries: it has a close parallel with another Saxon-era weir on the nearby Isle of Wight. It also shows striking structural similarities with examples in use today in Basse Normandy, on the southern shore of the English Channel. The paper discusses the function and operation of the weir, and places it in its social and historical context. Regressive cartography demonstrates that the structures have become exposed as a result of saltmarsh retreat in this area of Southampton Water since the 19th century. The radiocarbon dates returned for the posts demonstrate that this transgression of the marsh must have been preceded by a prolonged period of progradation, which covered and preserved the site; its subsequent re-exposure has negative implications for its survival.The fieldwork underpinning this research was carried out using equipment and facilities provided by the Centre for Maritime Archaeology of the University of Southampton. The authors themselves met incidental costs. Radiocarbon dating was financed from an internal University of Exeter research allowance

Illumination diagnosis for retrieval of reflections from ambient-noise seismic data in the Siilinjärvi mining site, Finland

Reflection seismic methods are becoming popular in mineral exploration, because they allow high-resolution delineation of the exploration targets, even at great depths. Seismic interferometry can be used to retrieve reflections from passive seismic data, removing the need for active seismic sources and, therefore, reducing the cost and environmental impact of exploration. The retrieval of reflections can be challenging, since passive seismic records are typically dominated by surface waves. Therefore, illumination diagnosis, a method which allows the isolation of the portions of the passive data where body-wave signals are stronger, can be a valuable step that improves the quality of the reflections retrieved from seismic interferometry and reduces the overall computational cost of the processing stage. Here, we validate the performance of the method to effectively isolate the portions of the passive data dominated by body waves and apply it on an ambient-noise seismic dataset acquired in the Siilinjärvi mining site in Finland