The glaciation of Serra de Queixa-Invernadoiro and Serra do Gerês-Xurés, NW Iberia. A critical review and a cosmogenic nuclide (10Be and 21 Ne) chronology.

[Abstract]The Serras of Queixa-Invernadoiro and Gerês-Xurés in the NW of the Iberian Peninsula are two small mountain massifs located at low altitude that were glaciated in the Pleistocene. The prevailing granitic lithology was a problem for mapping glacial forms (in many cases interpreted as banal granite forms) and for the identification of the tills (misunderstood as remains of regolith). A combination of geomorphological techniques (genetic mapping of granite forms and deposits), the micromorphological study of till thin sections and the morphoscopy of quartz grains at the SEM enabled to establish a model of the geomorphological evolution complemented with the chronology by cosmogenic nuclides (21Ne and 10Be) of both glacial systems. The obtained results represent the glacial evolution of the area from circa 250 ka B.P

Post-depositional processes of elemental enrichment inside dark nodular masses of an ancient aeolian dune from A Coruña, Northwest Spain

This paper focuses on a residual ancient aeolian climbing dune from Punta Penaboa (A Coruña, Northwest Spain) showing evidence of post-depositional weathering, particularly the presence of dark brown nodular masses. The partitioning of trace elements between nodular masses and host sand during post-depositional weathering of the dune is investigated in this work, with the main objective of studying the elemental enrichment patterns in the dark masses. Data of the concentrations of chemical elements were obtained by instrumental neutron activation analysis (INAA) and complemented by mineralogical and microchemical studies, using X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) / energy dispersive X-ray spectrometry (EDS). The dune was dated by optically stimulated luminescence (OSL) , yielding an age of 300ka B.P.. The dark nodular masses preserved the dune sand structure, without defined concentric layers, suggesting an early stage of formation. They consist mainly of quartz grains cemented by clay materials enriched in the majority of the elements studied, especially in Mn, Co, Ba, Sb, Ce, Tb, Th, As, Zr and Hf. The post-depositional transformations of the dune were most likely influenced by migration of chemical compounds from the surrounding slope deposits and granitic rocks, as well as microbial activity that promoted metals concentration in the solutions percolating through the pore network of the dune. Seasonal changes in the redox potential were required to produce the accumulation of Mn and other trace elements in the dune pore network and to promote the fractionation between Ce4+ and trivalent rare earth elements that was observed in the geochemical patterns

A deletion at Adamts9-magi1 Locus is associated with psoriatic arthritis risk

Objective: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. Methods: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ2 test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). Results: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). Conclusions: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk

Proportionate flow shop games

htmlabstractIn a proportionate flow shop problem several jobs have to be processed through a fixed sequence of machines and the processing time of each job is equal on all machines. By identifying jobs with agents, whose costs linearly depend on the completion time of their jobs, and assuming an initial processing order on the jobs, we face two problems: the first one is how to obtain an optimal order that minimizes the total processing cost, the second one is how to allocate the cost savings obtained by ordering the jobs optimally. In this paper we focus on the allocation problem. PFS games are defined as cooperative games associated to proportionate flow shop problems. It is seen that PFS games have a nonempty core. Moreover, it is shown that PFS games are convex if the jobs are initially ordered in decreasing urgency. For this case an explicit game independent expression for the Shapley value is provid

Antitumor activity of lurbinectedin in second-line small cell lung cancer patients who are candidates for re-challenge with the first-line treatment

Introduction: The National Comprehensive Cancer Network guidelines recommend re-challenge with the first-line treatment for relapsed small cell lung cancer (SCLC) with chemotherapy-free interval (CTFI)=180 days. A phase II study (NCT02454972) showed remarkable antitumor activity in SCLC patients treated with lurbinectedin 3.2 mg/m2 1 -h intravenous infusion every 3 weeks as second-line therapy. We report results for the pre-planned subset of patients with CTFI = 180 days. Material and Methods: Twenty patients aged =18 years with pathologically proven SCLC diagnosis, pretreated with only one prior platinum-containing line, no CNS metastases, and with CTFI = 180 days were evaluated. The primary efficacy endpoint was the overall response rate (ORR) assessed by the Investigators according to RECIST v1.1. Results: ORR was 60.0 % (95 %CI, 36.1-86.9), with a median duration of response of 5.5 months (95 %CI, 2.9-11.2) and disease control rate of 95.0 % (95 %CI, 75.1-99.9). Median progression-free survival was 4.6 months (95 %CI, 2.6-7.3). With a censoring of 55.0 %, the median overall survival was 16.2 months (95 %CI, 9.6-upper level not reached). Of note, 60.9 % and 27.1 % of patients were alive at 1 and 2 years, respectively. The most common grade 3/4 adverse events and laboratory abnormalities were hematological disorders (neutropenia, 55.0 %; anemia; 10.0 % thrombocytopenia, 10.0 %), fatigue (10.0 %) and increased liver function tests (GGT, 10 %; ALT and AP, 5.0 % each). No febrile neutropenia was reported. Conclusion: Lurbinectedin is an effective treatment for platinum-sensitive relapsed SCLC, especially in patients with CTFI = 180 days, with acceptable safety and tolerability. These encouraging results suggest that lurbinectedin can be another valuable therapeutic option rather than platinum re-challenge

The granite and glacial landscapes of the Peneda-Gerês National Park

Granite and glacial landforms are presented as the main geomorphological landscape features of the Peneda-Gerês National Park. The park was established in 1971 and it is the only national park and most important protected area in Portugal. The aesthetic attractiveness is supported mainly by the distinct granite landscape of the Gerês and Peneda Mountains, where the post-orogenic Variscan Gerês gran- ite facies occurs. The rugged relief is poorly covered by vegetation, differentiating it from the surrounding moun- tainous areas and the most distinctive landforms are bornhardts, locally named as “medas”. Typical glacial landforms, such as U-shaped valleys, cirques and moraines, express the sheltered character of a low-altitude glaciation, which is of great significance in the context of the Pleistocene glaciation in Southern Europe.This work is co-funded by the European Union through the European Regional Development Fund, based on COMPETE 2020 (Programa Operacional da Competitividade e Inter nacionalização), project ICT (UID/GEO/04683/2013) with reference POCI-01-0145- FEDER-007690 and Portuguese national funds pro vided by Fundação para a Ciência e Tecnologi

Stratification and therapeutic potential of PML in metastatic breast cancer.

Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.The work of A.C. is supported by the Ramón y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek), Health (2012111086) and Education (PI2012-03), Marie Curie (277043), Movember Foundation (GAP1), ISCIII (PI10/01484, PI13/00031), FERO (VIII Fellowship) and ERC (336343). N.M.-M. and P.A. are supported by the Spanish Association Against Cancer (AECC), AECC JP Vizcaya and Guipuzcoa, respectively. J.U. and F.S. are Juan de la Cierva Researchers (MINECO). L.A., A.A.-A. and L.V.-J. are supported by the Basque Government of education. M.L.-M.C. acknowledges SAF2014-54658-R and Asociación Española contra el Cancer. R.B. acknowledges Spanish MINECO (BFU2014-52282-P, Consolider BFU2014-57703-REDC), the Departments of Education and Industry of the Basque Government (PI2012/42) and the Bizkaia County. M.S., V.S. and J.B. acknowledge Banco Bilbao Vizcaya Argentaria (BBVA) Foundation (Tumour Biomarker Research Program). M.S. and J.B. are supported by NIH grant P30 CA008748. M.dM.V. is supported by the Institute of Health Carlos III (PI11/02251, PI14/01328) and Basque Government, Health Department (2014111145). A.M. is supported by ISCIII (CP10/00539, PI13/02277) and Marie Curie CIG 2012/712404. V.S. is supported by the SCIII (PI13/01714, CP14/00228), the FERO Foundation and the Catalan Agency AGAUR (2014 SGR 1331). R.R.G. research support is provided by the Spanish Ministry of Science and Innovation grant SAF2013-46196, BBVA Foundation, the Generalitat de Catalunya (2014 SGR 535), Institució Catalana de Recerca i Estudis Avançats, the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds (SAF2013-46196).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1259