Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis

Background: Early diagnosis is crucial for patients with pancreatic ductal adenocarcinoma (PDAC). The AXL receptor tyrosine kinase is proteolytically processed releasing a soluble form (sAXL) into the blood stream. Here we explore the use of sAXL as a biomarker for PDAC. Methods: AXL was analysed by immunohistochemistry in human pancreatic tissue samples. RNA expression analysis was performed using TCGA/GTEx databases. The plasma concentrations of sAXL, its ligand GAS6, and CA19-9 were studied in two independent cohorts, the HMar cohort (n = 59) and the HClinic cohort (n = 142), including healthy controls, chronic pancreatitis (CP) or PDAC patients, and in a familial PDAC cohort (n = 68). AXL expression and sAXL release were studied in PDAC cell lines and murine models. Findings: AXL is increased in PDAC and precursor lesions as compared to CP or controls. sAXL determined in plasma from two independent cohorts was significantly increased in the PDAC group as compared to healthy controls or CP patients. Patients with high levels of AXL have a lower overall survival. ROC analysis of the plasma levels of sAXL, GAS6, or CA19-9 in our cohorts revealed that sAXL outperformed CA19-9 for discriminating between CP and PDAC. Using both sAXL and CA19-9 increased the diagnostic value. These results were validated in murine models, showing increased sAXL specifically in animals developing PDAC but not those with precursor lesions or acinar tumours. Interpretation: sAXL appears as a biomarker for early detection of PDAC and PDAC–CP discrimination that could accelerate treatment and improve its dismal prognosis. Funding: This work was supported by grants PI20/00625 (PN), RTI2018-095672-B-I00 (AM and PGF), PI20/01696 (MG) and PI18/01034 (AC) from MICINN-FEDER and grant 2017/SGR/225 (PN) from Generalitat de Catalunya. © 2021 The Author(s

The Star Formation History in The Far Outer Disc of M33

The outer regions of disc galaxies are becoming increasingly recognized as key testing sites for models of disc assembly and evolution. Important issues are the epoch at which the bulk of the stars in these regions formed and how discs grow radially over time. To address these issues, we use Hubble Space Telescope Advanced Camera for Surveys imaging to study the star formation history (SFH) of two fields at 9.1 and 11.6 kpc along M33's northern major axis. These fields lie at ~ 4 and 5 V-band disc scale-lengths and straddle the break in M33's surface brightness profile. The colour-magnitude diagrams (CMDs) reach the ancient main sequence turnoff with a signal-to-noise ratio of ~ 5. From detailed modelling of the CMDs, we find that the majority of stars in both fields combined formed at z < 1. The mean age in the inner field, S1, is ~ 3 +/- 1 Gyr and the mean metallicity is [M/H] ~ -0.5 +/- 0.2 dex. The star formation history of S1 unambiguously reveals how the inside-out growth previously measured for M33's inner disc out to ~ 6 kpc extends out to the disc edge at ~ 9 kpc. In comparison, the outer field, S2, is older (mean age ~ 7 +/- 2 Gyr), more metal-poor (mean [M/H] ~ -0.8 +/- 0.3 dex), and contains ~ 30 times less stellar mass. These results provide the most compelling evidence yet that M33's age gradient reverses at large radii near the disc break and that this reversal is accompanied by a break in stellar mass surface density. We discuss several possible interpretations of this behaviour including radial stellar mixing, warping of the gaseous disc, a change in star formation efficiency, and a transition to another structural component. These results offer one of the most detailed views yet of the peripheral regions of any disc galaxy and provide a much-needed observational constraint on the last major epoch of star formation in the outer disc.Comment: 15 pages, 9 figures, accepted to MNRAS, hi-res version available at http://www.roe.ac.uk/~mkb/astroph/m33hires.pd

Revealing prevalent cancers by interrogating glycoproteins with sustainable immunoelectrochemical tools

Trabajo presentado en el 4th European Biosensor Symposium, celebrado en Aquisgrán (Alemania), del 27 al 30 de agosto de 2023Introduction. The worldwide incidence and death toll of colorectal and pancreatic cancers (CRC and PDAC) have increased considerably since 1990. For this reason, both early detection and regular follow-up are considered key factors in improving patient prognosis. In this sense, the determination of the total content of specific proteins and their aberrantly glycosylated fraction in oncologic processes could help to achieve the proposed goals. Results and Discussion. In this work, two simple but highly competitive electrochemical immunoplatforms for the determination of total and glycosylated post-translational modified haptoglobin (Hp) [1], and CA19-9 [2] (candidate biomarkers associated with colorectal and pancreatic cancer, respectively) are presented. As seen in Figure 1, these biotools are uplifted in the use of magnetic immunocaptors and another antibody or a lectin as detector elements lastly labeled with HRP, which enables subsequent amperometric detection. The presented bioplatforms exhibit attractive characteristics in terms of simplicity, affordability, and point-of-care application compared to the conventional available methodologies, highlighting low detection limits (0.07 and 0.46 ng mL¿1 for total and glycosylated Hp, respectively, and 1.5 U mL¿1 for CA19-9), and short assay times (< 2 h). The workability of these quantitative bioplatforms for the analysis of secretomes from cultured CRC cells with the distinct potential to metastasize (Hp) or serum samples from healthy and PDAC-diagnosed subjects (CA19-9) was assessed to definitely confirm full exploitation of all the above exposed enticing attributes. Conclusions. Our findings clearly revealed the unquestionable ability of these modern electrochemical immunoplatforms to discriminate between healthy and cancer-diagnosed subjects, as well as to assess disease progression, positioning these simple but effective methodologies as advanced electroanalytical tools with proven real biomedical applications, and the hope of aiding in the accurate diagnosis of prevalent and high mortality cancers

Probing quantum gravity using photons from a flare of the active galactic nucleus Markarian 501 observed by the MAGIC telescope

We analyze the timing of photons observed by the MAGIC telescope during a flare of the active galactic nucleus Mkn 501 for a possible correlation with energy, as suggested by some models of quantum gravity (QG), which predict a vacuum refractive index \simeq 1 + (E/M_{QGn})^n, n = 1,2. Parametrizing the delay between gamma-rays of different energies as \Delta t =\pm\tau_l E or \Delta t =\pm\tau_q E^2, we find \tau_l=(0.030\pm0.012) s/GeV at the 2.5-sigma level, and \tau_q=(3.71\pm2.57)x10^{-6} s/GeV^2, respectively. We use these results to establish lower limits M_{QG1} > 0.21x10^{18} GeV and M_{QG2} > 0.26x10^{11} GeV at the 95% C.L. Monte Carlo studies confirm the MAGIC sensitivity to propagation effects at these levels. Thermal plasma effects in the source are negligible, but we cannot exclude the importance of some other source effect.Comment: 12 pages, 3 figures, Phys. Lett. B, reflects published versio

Upper limit for gamma-ray emission above 140 GeV from the dwarf spheroidal galaxy Draco

The nearby dwarf spheroidal galaxy Draco with its high mass to light ratio is one of the most auspicious targets for indirect dark matter searches. Annihilation of hypothetical DM particles can result in high-energy gamma-rays, e.g. from neutralino annihilation in the supersymmetric framework. With the MAGIC telescope a search for a possible DM signal originating from Draco was performed during 2007. The analysis of the data results in a flux upper limit of 1.1x10^-11 photons cm^-2 sec^-1 for photon energies above 140 GeV, assuming a point like source. Furthermore, a comparison with predictions from supersymmetric models is given. While our results do not constrain the mSUGRA phase parameter space, a very high flux enhancement can be ruled out.Comment: Accepted for publication by Astrophysical Journa

First bounds on the high-energy emission from isolated Wolf-Rayet binary systems

High-energy gamma-ray emission is theoretically expected to arise in tight binary star systems (with high mass loss and high velocity winds), although the evidence of this relationship has proven to be elusive so far. Here we present the first bounds on this putative emission from isolated Wolf-Rayet (WR) star binaries, WR 147 and WR 146, obtained from observations with the MAGIC telescope.Comment: (Authors are the MAGIC Collaboration.) Manuscript in press at The Astrophysical Journal Letter

Unfolding of differential energy spectra in the MAGIC experiment

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses.Comment: Submitted to NIM

Implementation of the Random Forest Method for the Imaging Atmospheric Cherenkov Telescope MAGIC

The paper describes an application of the tree classification method Random Forest (RF), as used in the analysis of data from the ground-based gamma telescope MAGIC. In such telescopes, cosmic gamma-rays are observed and have to be discriminated against a dominating background of hadronic cosmic-ray particles. We describe the application of RF for this gamma/hadron separation. The RF method often shows superior performance in comparison with traditional semi-empirical techniques. Critical issues of the method and its implementation are discussed. An application of the RF method for estimation of a continuous parameter from related variables, rather than discrete classes, is also discussed.Comment: 16 pages, 8 figure

Systematic search for VHE gamma-ray emission from X-ray bright high-frequency BL Lac objects

All but three (M87, BL Lac and 3C 279) extragalactic sources detected so far at very high energy (VHE) gamma-rays belong to the class of high-frequency peaked BL Lac (HBL) objects. This suggested to us a systematic scan of candidate sources with the MAGIC telescope, based on the compilation of X-ray blazars by Donato et al. (2001). The observations took place from December 2004 to March 2006 and cover sources on the northern sky visible under small zenith distances zd < 30 degrees at culmination. The sensitivity of the search was planned for detecting X-ray bright F(1 keV) > 2 uJy) sources emitting at least the same energy flux at 200 GeV as at 1 keV. In order to avoid strong gamma-ray attenuation close to the energy threshold, the redshift of the sources was constrained to values z<0.3. Of the fourteen sources observed, 1ES 1218+304 and 1ES 2344+514 have been detected in addition to the known bright TeV blazars Mrk 421 and Mrk 501. A marginal excess of 3.5 sigma from the position of 1ES 1011+496 was observed and has been confirmed as a source of VHE gamma-rays by a second MAGIC observation triggered by a high optical state (Albert et al. 2007). For the remaining sources, we present here the 99% confidence level upper limits on the integral flux above ~200 GeV. We characterize the sample of HBLs (including all HBLs detected at VHE so far) by looking for correlations between their multi-frequency spectral indices determined from simultaneous optical, archival X-ray, and radio luminosities, finding that the VHE emitting HBLs do not seem to constitute a unique subclass. The absorption corrected gamma-ray luminosities at 200 GeV of the HBLs are generally not higher than their X-ray luminosities at 1 keV.Comment: 15 pages, 7 figures, 5 tables, submitted to ApJ (revised version