Temporal changes in the water mass distribution and transports along the 20ºW CAIBOX section (NE Atlantic)

The CAIBOX cruise was conducted from 25 July to 14 August 2009. Three consecutive transects (zonal, meridional, and transverse) formed a closed box to the west of the Strait of Gibraltar. This study aimed to analyze the thermohaline properties, volume transports, and water mass distributions (percentages) along the meridional section (30–41.5º N, 20º W). We identified the main geostrophic current (Azores Current) and its associated volume transport and interannual changes. Data from previous cruises (AZORES I, A16N, CLIVAR, OACES, and CHAOS) with similar tracks were employed to compare with the CAIBOX meridional section. All but one (CHAOS) were summer cruises. We estimated a mean transport for the Azores Current at 20º W of 9.3 ± 2.6 Sv. There appears to be an inverse relation between the position of this current and its associated transport, with relatively high (low) transports when the current is located roughly south (north) of 35º N. Regarding water masses, an increase of 14.4% was found for Mediterranean Water compared with the 1993, 1998, and 2003 cruises; however, Labrador Sea Water decreased its contribution and southward spreading between 1998 and 2009. Key words: Northeast Atlantic, Azores Current, water masses, multiparametric mixing analysis

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

Optimizing Cadences with Realistic Light Curve Filtering for Serendipitous Kilonova Discovery with Vera Rubin Observatory

Current and future optical and near-infrared wide-field surveys have the potential of finding kilonovae, the optical and infrared counterparts to neutron star mergers, independently of gravitational-wave or high-energy gamma-ray burst triggers. The ability to discover fast and faint transients such as kilonovae largely depends on the area observed, the depth of those observations, the number of re-visits per field in a given time frame, and the filters adopted by the survey; it also depends on the ability to perform rapid follow-up observations to confirm the nature of the transients. In this work, we assess kilonova detectability in existing simulations of the LSST strategy for the Vera C. Rubin Wide Fast Deep survey, with focus on comparing rolling to baseline cadences. Although currently available cadences can enable the detection of more than 300 kilonovae out to 1400 Mpc over the ten-year survey, we can expect only 3-32 kilonovae similar to GW170817 to be recognizable as fast-evolving transients. We also explore the detectability of kilonovae over the plausible parameter space, focusing on viewing angle and ejecta masses. We find that observations in redder izy bands are crucial for identification of nearby (within 300 Mpc) kilonovae that could be spectroscopically classified more easily than more distant sources. Rubin's potential for serendipitous kilonova discovery could be increased by gain of efficiency with the employment of individual 30s exposures (as opposed to 2x15s snap pairs), with the addition of red-band observations coupled with same-night observations in g- or r-bands, and possibly with further development of a new rolling-cadence strategy

SPSmart: adapting population based SNP genotype databases for fast and comprehensive web access

<p>Abstract</p> <p>Background</p> <p>In the last five years large online resources of human variability have appeared, notably HapMap, Perlegen and the CEPH foundation. These databases of genotypes with population information act as catalogues of human diversity, and are widely used as reference sources for population genetics studies. Although many useful conclusions may be extracted by querying databases individually, the lack of flexibility for combining data from within and between each database does not allow the calculation of key population variability statistics.</p> <p>Results</p> <p>We have developed a novel tool for accessing and combining large-scale genomic databases of single nucleotide polymorphisms (SNPs) in widespread use in human population genetics: SPSmart (SNPs for Population Studies). A fast pipeline creates and maintains a data mart from the most commonly accessed databases of genotypes containing population information: data is mined, summarized into the standard statistical reference indices, and stored into a relational database that currently handles as many as 4 × 10⁹genotypes and that can be easily extended to new database initiatives. We have also built a web interface to the data mart that allows the browsing of underlying data indexed by population and the combining of populations, allowing intuitive and straightforward comparison of population groups. All the information served is optimized for web display, and most of the computations are already pre-processed in the data mart to speed up the data browsing and any computational treatment requested.</p> <p>Conclusion</p> <p>In practice, SPSmart allows populations to be combined into user-defined groups, while multiple databases can be accessed and compared in a few simple steps from a single query. It performs the queries rapidly and gives straightforward graphical summaries of SNP population variability through visual inspection of allele frequencies outlined in standard pie-chart format. In addition, full numerical description of the data is output in statistical results panels that include common population genetics metrics such as heterozygosity, <it>Fst </it>and <it>In</it>.</p

The long-lived Type IIn SN 2015da: Infrared echoes and strong interaction within an extended massive shell star star star

In this paper we report the results of the first similar to four years of spectroscopic and photometric monitoring of the Type IIn supernova SN 2015da (also known as PSN J13522411+3941286, or iPTF16tu). The supernova exploded in the nearby spiral galaxy NGC 5337 in a relatively highly extinguished environment. The transient showed prominent narrow Balmer lines in emission at all times and a slow rise to maximum in all bands. In addition, early observations performed by amateur astronomers give a very well-constrained explosion epoch. The observables are consistent with continuous interaction between the supernova ejecta and a dense and extended H-rich circumstellar medium. The presence of such an extended and dense medium is difficult to reconcile with standard stellar evolution models, since the metallicity at the position of SN 2015da seems to be slightly subsolar. Interaction is likely the mechanism powering the light curve, as confirmed by the analysis of the pseudo bolometric light curve, which gives a total radiated energy greater than or similar to 10(51) erg. Modeling the light curve in the context of a supernova shock breakout through a dense circumstellar medium allowed us to infer the mass of the prexisting gas to be similar or equal to 8 M-circle dot, with an extreme mass-loss rate for the progenitor star similar or equal to 0.6 M-circle dot yr(-1), suggesting that most of the circumstellar gas was produced during multiple eruptive events. Near- and mid-infrared observations reveal a fluxexcess in these domains, similar to those observed in SN 2010jl and other interacting transients, likely due to preexisting radiatively heated dust surrounding the supernova. By modeling the infrared excess, we infer a mass greater than or similar to 0.4 x 10(-3) M-circle dot for the dustSpanish MICINN gran

Towards a concentration closure of sub-6 nm aerosol particles and sub-3 nm atmospheric clusters

Atmospheric clusters play a key role in atmospheric new particle formation and they are a sensitive indicator for atmospheric chemistry. Both the formation and loss of atmospheric clusters include a complex set of interlinked physical and chemical processes, and therefore their dynamics is highly non-linear. Here we derive a set of simple equations to estimate the atmospheric cluster concentrations in size ranges of 1.5–2 nm and 2–3 nm as well as 3–6 nm aerosol particles. We compared the estimated concentrations with measured ones both in a boreal forest site (the SMEAR II station in Hyytiälä, Finland) and in an urban site (the AHL/BUCT station in Beijing, China). We made this comparison first for 3–6 nm particles, since in this size range observations are more reliable than at smaller sizes, and then repeated it for the 2–3 nm size range. Finally, we estimated cluster concentrations in the 1.5–2 nm size range. Our main finding is that the present observations are able to detect a major fraction of existing atmospheric clusters.Atmospheric clusters play a key role in atmospheric new particle formation and they are a sensitive indicator for atmospheric chemistry. Both the formation and loss of atmospheric clusters include a complex set of interlinked physical and chemical processes, and therefore their dynamics is highly non-linear. Here we derive a set of simple equations to estimate the atmospheric cluster concentrations in size ranges of 1.5–2 nm and 2–3 nm as well as 3–6 nm aerosol particles. We compared the estimated concentrations with measured ones both in a boreal forest site (the SMEAR II station in Hyytiälä, Finland) and in an urban site (the AHL/BUCT station in Beijing, China). We made this comparison first for 3–6 nm particles, since in this size range observations are more reliable than at smaller sizes, and then repeated it for the 2–3 nm size range. Finally, we estimated cluster concentrations in the 1.5–2 nm size range. Our main finding is that the present observations are able to detect a major fraction of existing atmospheric clusters.Peer reviewe

In vitro and in vivo delivery of the secretagogue diadenosine tetraphosphate from conventional and silicone hydrogel soft contact lenses

Purpose: To evaluate the possible use of soft contact lenses (CL) to improve the secretagogue role of diadenosine tetraphosphate (Ap4A) promoting tear secretion. Methods: Two conventional hydrogel CL (Omafilcon A and Ocufilcon D) and two silicone hydrogel (SiH) CL (Comfilcon A and Balafilcon A) were used. Ap4A was loaded into the lenses by soaking in a 1 mM Ap4A solution during 12 h. In vitro experiments were performed by placing the lenses in multi-wells during 2 h containing 1 ml of ultrapure water. 100 l aliquots were taken at time zero and every minute for the first 10 min, and then every 15 min. In vivo experiments were performed in New Zealand rabbits and both the dinucleotide release from SiH and tear secretion were measured by means of Schirmer strips and high-pressure liquid chromatography (HPLC) analysis. Results: Ap4A in vitro release experiments in hydrogel CL presented a release time 50 (RT50) of 3.9 ± 0.2 min and 3.1 ± 0.1 min for the non-ionic and the ionic CL, respectively. SiH CL released also Ap4A with RT50 values of 5.1 ± 0.1 min for the non-ionic and 2.7 ± 0.1 min for the ionic CL. In vivo experiments with SiH CL showed RT50 values of 9.3 ± 0.2 min and 8.5 ± 0.2 min for the non-ionic and the ionic respectively. The non-ionic lens Ap4A release was able to induce tear secretion above baseline tear levels for almost 360 min. Conclusion: The delivery of Ap4A is slower and the effect lasts longer with non-ionic lenses than ionic lenses.(undefined

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression