Explicit integration scheme for generalized plasticity constitutive models with automatic error control

An explicit algorithm for integrating Generalized Plasticity constitutive models is presented. This automatically divides the applied strain increment into subincrements using an estimate of the local error controlling the global integration error in the stress. The algorithm modifies the well known S. W. Sloan substepping scheme to account for Generalized Plasticity constitutive models, in which, unlike Classical Elastoplasticity, the yield surface is not explicitly defined. The integration scheme is described and results are presented for a rigid footing resting on a layer of specific Generalized Plasticity model for sands, in which a hyperelastic formulation is introduced to describe the reversible component of the soil response instead of the hypoelastic approach originally proposed. The explicit algorithm with automatic substepping and error control is shown to be reliable and efficient for these complex constitutive laws

San Pedro Martir observations of microvariability in obscured quasars

Fast brightness variations are a unique tool to probe the innermost regions of active galactic nuclei (AGN). These variations are called microvariability or intra-night variability, and this phenomenon has been monitored in samples of blazars and unobscured AGNs. Detecting optical microvariations in targets hidden by the obscuring torus is a challenging task because the region responsible for the variations is hidden from our sight. However, there have been reports of fast variations in obscured Seyfert galaxies in X-rays, which rises the question whether microvariations can also be detected in obscured AGNs in the optical regime. Because the expected variations are very small and can easily be lost within the noise, the analysis requires a statistical approach. We report the use of a one-way analysis of variance, ANOVA, with which we searched for microvariability. ANOVA was successfully employed in previous studies of unobscured AGNs. As a result, we found microvariable events during three observing blocks: in two we observed the same object (Mrk 477), and in another, J0759+5050. The results on Mrk 477 confirm previous findings. However, since Mrk 477 is quite a peculiar target with hidden broad-line regions, we cannot rule out the possibility that we have serendipitously chosen a target prone to variations.Comment: Research note, 5 pages, 2 figures, accepted for publication in Astronomy and Astrophysic

Lyman break and ultraviolet-selected galaxies at z ̃ 1-I. Stellar populations from the ALHAMBRA survey

We take advantage of the exceptional photometric coverage provided by the combination of GALEX data in the ultraviolet (UV) and the ALHAMBRA survey in the optical and near-infrared to analyse the physical properties of a sample of 1225 GALEX-selected Lyman break galaxies (LBGs) at 0.8 ≲ z ≲ 1.2 that are located in the COSMOS field. This is the largest sample of LBGs studied in this redshift range to date. According to a spectral energy distribution (SED) fitting with synthetic stellar population templates, we find that LBGs at z ̃ 1 are mostly young galaxies with a median age of 341 Myr and have intermediate dust attenuation, (Es(B - V)) ̃ 0.20. Owing to the selection criterion, LBGs at z ̃ 1 are UV-bright galaxies and have a high dust-corrected total star formation rate (SFR), with a median value of 16.9M⊙ yr-1. Their median stellar mass is log (M*/M⊙) = 9.74. We find that the dustcorrected total SFR of LBGs increases with stellar mass and that the specific SFR is lower for more massive galaxies (downsizing scenario). Only 2 per cent of the galaxies selected through the Lyman break criterion have an active galactic nucleus nature. LBGs at z ̃ 1 are located mostly over the blue cloud of the colour-magnitude diagram of galaxies at their redshift, with only the oldest and/or the dustiest deviating towards the green valley and red sequence. Morphologically, 69 per cent of LBGs are disc-like galaxies, with the fractions of interacting, compact, or irregular systems being much lower, below 12 per cent. LBGs have a median effective radius of 2.5 kpc, and larger galaxies have a higher total SFR and stellar mass. Compared with their high-redshift analogues, we find evidence that LBGs at lower redshifts are larger, redder in the UV continuum, and have a major presence of older stellar populations in their SEDs. However, we do not find significant differences in the distributions of stellar mass or dust attenuation.NASA NAS5-26555NASA Office of Space Science NNX09AF08GEuropean Southern Observatory LP175.A-0839.Junta de Andalucia TIC-114, P08-TIC03531Ministerio de Economía y Competitividad AYA2011-29517-C03- 01, AYA2010-1516

IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog, MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ (a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and miRNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins (p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity. These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epitheliaThis work was funded by project PI17/00578, from the “Instituto de Salud Carlos III” (Ministry of Science, Innovation and Universities) and co-funded by the European Regional Development Fund, and approved by the Ethics Committee of our Institution. It has been founded also by projects CB16/12/00228, PI16/00161, RD16/0011/0011, RD12/0019/0023 and SAF2017–84248-PS

Lyman break and ultraviolet-selected galaxies at z ~ 1 - II. PACS 100μm/160μm FIR detections

In this work, we report the Photodetector Array Camera and Spectrometer (PACS) 100 μm/160 μm detections of a sample of 42 GALEX-selected and far-infrared (FIR)-detected Lyman break galaxies (LBGs) at z ~ 1 located in the Cosmic Evolution Survey (COSMOS) field and analyse their ultraviolet (UV) to FIR properties. The detection of these LBGs in the FIR indicates that they have a dust content high enough so that its emission can be directly detected. According to a spectral energy distribution (SED) fitting with stellar population templates to their UV-to-near-IR observed photometry, PACS-detected LBGs tend to be bigger (Reff ~ 4.1 kpc), more massive [log (M*/M⊙) ~ 10.7], dustier [Es(B - V) ~ 0.40], redder in the UV continuum (β ~ -0.60) and UV-brighter [log (LUV/L⊙) ~ 10.1] than PACSundetected LBGs. PACS-detected LBGs at z ~ 1 are mostly disc-like galaxies and are located over the green valley and red sequence of the colour-magnitude diagram of galaxies at their redshift. By using their UV and IR emission, we find that PACS-detected LBGs tend to be less dusty and have slightly higher total star formation rates (SFRs) than other PACS-detected UV-selected galaxies within the same redshift range. As a consequence of the selection effect due to the depth of the FIR observations employed, all our PACS-detected LBGs have total IR luminosities, LIR, higher than 1011 L⊙ and thus are luminous IR galaxies. However, none of the PACS-detected LBGs are in the ultra-luminous IR galaxy (ULIRG) regime, LIR =1012 L⊙, where the FIR observations are complete. The finding of ULIRGs-LBGs at higher redshifts (z ~ 3) suggests an evolution of the FIR emission of LBGs with cosmic time. In an IRX-β diagram, PACS-detected LBGs at z~1 tend to be located around the relation for local starburst similarly to other UV-selected PACS-detected galaxies at the same redshift. Consequently, the dust-correction factors obtained with theirUVcontinuum slope allowus to determine their total SFR, unlike at higher redshifts. However, the dust attenuation derived from UV to NIR SED fitting overestimates the total SFR for most of our PACS-detected LBGs in an age-dependent way: the overestimation factor is higher in younger galaxies. This is likely due to the typical degeneracy between dust attenuation and age in the SED fitting with synthetic templates and highlights the importance of the FIR measurements in the analysis of star-forming galaxies at intermediate redshifts.Generalitat Valenciana PROMETEO-2008/132NASA Office of Space Science NNX09AF08GEuropean Southern Observatory LP175.A-0839Junta de Andalucía TIC-114, P08-TIC-03531Ministerio de Economía y Competitividad AYA2011- 29517-C03-01, AYA2010-22111-C03-02, AYA2010-1516

San Pedro Mártir observations of microvariability in obscured quasars

Fast brightness variations are a unique tool to probe the innermost regions of active galactic nuclei (AGN). These variations are called microvariability or intra-night variability, and this phenomenon has been monitored in samples of blazars and unobscured AGNs. Detecting optical microvariations in targets hidden by the obscuring torus is a challenging task because the region responsible for the variations is hidden from our sight. However, there have been reports of fast variations in obscured Seyfert galaxies in X-rays, which rises the question whether microvariations can also be detected in obscured AGNs in the optical regime. Because the expected variations are very small and can easily be lost within the noise, the analysis requires a statistical approach. We report the use of a one-way analysis of variance, ANOVA, with which we searched for microvariability. ANOVA was successfully employed in previous studies of unobscured AGNs. As a result, we found microvariable events during three observing blocks: in two we observed the same object (Mrk 477), and in another, J0759+5050. The results on Mrk 477 confirm previous findings. However, since Mrk 477 is quite a peculiar target with hidden broad-line regions, we cannot rule out the possibility that we have serendipitously chosen a target prone to variations.This research has been supported by the Spanish Ministerio de Economía y Competitividad (MINECO) under the grant AYA2014-58861-C3-1. I.O. acknowledges support from the European Research Council (ERC) in the form of Advanced Grant, COSMICISM. J.A.D. is grateful for the support from the grant UNAM-DGAPA-PAPIIT IN110013 Program and the Canary islands CIE: Tricontinental Atlantic Campus. A.E. acknowledges support by the grant AYA2012-30789. J. I. González-Serrano is grateful for the support from AYA2011-29517-C03-02.Peer Reviewe

II. The faint-end of the Hα luminosity function at z ∼ 0.40

[Aims] We take advantage of the capability of the OTELO survey to obtain the H alpha luminosity function (LF) at z similar to 0.40. Because of the deepest coverage of OTELO, we are able to determine the faint end of the LF, and thus better constrain the star formation rate and the number of galaxies at low luminosities. The AGN contribution to this LF is estimated as well. [Methods] We make use of the multiwavelength catalogue of objects in the field compiled by the OTELO survey, which is unique in terms of minimum flux and equivalent width. We also take advantage of the pseudo-spectra built for each source, which allow the identification of emission lines and the discrimination of different types of objects. [Results] The H alpha luminosity function at z similar to 0.40 is obtained, which extends the current faint end by almost 1 dex, reaching minimal luminosities of log(10) L-lim = 38.5 erg s(-1) (or similar to 0.002 M-circle dot yr(-1)). The AGN contribution to the total H alpha luminosity is estimated. We find that no AGN should be expected below a luminosity of log(10) L = 38.6 erg s(-1). From the sample of non-AGN (presumably, pure SFG) at z similar to 0.40 we estimated a star formation rate density of rho(SFR) = 0.012 +/- 0.005 M-circle dot yr(-1) Mpc(-3).This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under the grants AYA2013- 46724- P, AYA2014 58861-C3-1- P, AYA2014-58861-C3-2-P, AYA2014-58861-C3-3- P, AYA2016 -75808-R, AYA2016-75931-C2-2-P, AYA2017-88007-C3-1-P, and AYA2017 -88007-C3-2- P. Based on observations made with the Gran Telescopio Canarias installed in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias, in the island of La Palma. The authors thanks the anonymous referee for her/his feedback and suggestions

Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1–10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field

The ALHAMBRA survey: reliable morphological catalogue of 22 051 early- and late-type galaxies

Advanced Large Homogeneous Area Medium Band Redshift Astronomical (ALHAMBRA) is photometric survey designed to trace the cosmic evolution and cosmic variance. It covers a large area of ~4 deg2 in eight fields, where seven fields overlap with other surveys, allowing us to have complementary data in other wavelengths. All observations were carried out in 20 continuous, medium band (30 nm width) optical and 3 near-infrared (JHK) bands, providing the precise measurements of photometric redshifts. In addition, morphological classification of galaxies is crucial for any kind of galaxy formation and cosmic evolution studies, providing the information about star formation histories, their environment and interactions, internal perturbations, etc. We present a morphological classification of >40 000 galaxies in the ALHAMBRA survey. We associate to every galaxy a probability to be early type using the automated Bayesian code GALSVM. Despite of the spatial resolution of theALHAMBRAimages (~1 arcsec), for 22 051 galaxies, we obtained the contamination by other type of less than 10 per cent. Of those, 1640 and 10 322 galaxies are classified as early-(down to redshifts ~0.5) and late-type (down to redshifts ~1.0), respectively, with magnitudes F613W ≤ 22.0. In addition, for magnitude range 22.0 < F613W ≤ 23.0, we classified other 10 089 late-type galaxies with redshifts ≤1.3.We show that the classified objects populate the expected regions in the colour-mass and colour-magnitude planes. The presented data set is especially attractive given the homogeneous multiwavelength coverage available in the ALHAMBRA fields, and is intended to be used in a variety of scientific applications. The low-contamination catalogue (<10 per cent) is made publicly available with this paper. © 2013 The Authors Published by Oxford University Press on behalf of the Royal Astronomical Society.This research was supported by the Junta de Andalucía through projects PO8-TIC-03531 and TIC114, the Spanish Ministry of Economy and Competitiveness (MINECO) through projects AYA2006-14046, AYA2010-15169, AYA2010-22111-C03-02, AYA2011-29517-C03-01, and the Generalitat Valenciana through project GV/Prometeo 2009/064. MP acknowledges financial support from JAE-Doc program of the Spanish National Research Council (CSIC), co-funded by the European Social Fund.Peer Reviewe

Development of anti-membrane type 1-matrix metalloproteinase nanobodies as immunoPET probes for triple negative breast cancer imaging

14 p.-6 fig.1 tab.Triple-negative breast cancer (TNBC) is characterized by aggressiveness and high rates of metastasis. The identification of relevant biomarkers is crucial to improve outcomes for TNBC patients. Membrane type 1-matrix metalloproteinase (MT1-MMP) could be a good candidate because its expression has been reported to correlate with tumor malignancy, progression and metastasis. Moreover, single-domain variable regions (VHHs or Nanobodies) derived from camelid heavy-chain-only antibodies have demonstrated improvements in tissue penetration and blood clearance, important characteristics for cancer imaging. Here, we have developed a nanobody-based PET imaging strategy for TNBC detection that targets MT1-MMP. A llama-derived library was screened against the catalytic domain of MT1-MMP and a panel of specific nanobodies were identified. After a deep characterization, two nanobodies were selected to be labeled with gallium-68 (68Ga). ImmunoPET imaging with both ([68Ga]Ga-NOTA-3TPA14 and [68Ga]Ga-NOTA-3CMP75) in a TNBC mouse model showed precise tumor-targeting capacity in vivo with high signal-to-background ratios. (68Ga)Ga-NOTA-3CMP75 exhibited higher tumor uptake compared to (68Ga)Ga-NOTA-3TPA14. Furthermore, imaging data correlated perfectly with the immunohistochemistry staining results. In conclusion, we found a promising candidate for nanobody-based PET imaging to be further investigated as a diagnostic tool in TNBC.This research was supported by BBVA Foundation grants for Scientific Research Teams: “Imaging of triple-negative breast cancer with specific miniaturized antibodies by ImmunoPET (BREIMPET)” Ref.:PR[17]_BIO_IMG_0114 (2017) and “Radioinmunotheragnostics for metastatic lung cancer with pretargeted clickable Ab Fragments (TherAbnostic)” Ref.: PR[19]_BIO_IMG_0096. (2020).Peer reviewe