A multi-sensor approach for volcanic ash cloud retrieval and eruption characterization: the 23 November 2013 Etna lava fountain

Volcanic activity is observed worldwide with a variety of ground and space-based remote sensing instruments, each with advantages and drawbacks. No single system can give a comprehensive description of eruptive activity, and so, a multi-sensor approach is required. This work integrates infrared and microwave volcanic ash retrievals obtained from the geostationary Meteosat Second Generation (MSG)-Spinning Enhanced Visible and Infrared Imager (SEVIRI), the polar-orbiting Aqua-MODIS and ground-based weather radar. The expected outcomes are improvements in satellite volcanic ash cloud retrieval (altitude, mass, aerosol optical depth and effective radius), the generation of new satellite products (ash concentration and particle number density in the thermal infrared) and better characterization of volcanic eruptions (plume altitude, total ash mass erupted and particle number density from thermal infrared to microwave). This approach is the core of the multi-platform volcanic ash cloud estimation procedure being developed within the European FP7-APhoRISM project. The Mt. Etna (Sicily, Italy) volcano lava fountaining event of 23 November 2013 was considered as a test case. The results of the integration show the presence of two volcanic cloud layers at different altitudes. The improvement of the volcanic ash cloud altitude leads to a mean difference between the SEVIRI ash mass estimations, before and after the integration, of about the 30%. Moreover, the percentage of the airborne “fine” ash retrieved from the satellite is estimated to be about 1%–2% of the total ash emitted during the eruption. Finally, all of the estimated parameters (volcanic ash cloud altitude, thickness and total mass) were also validated with ground-based visible camera measurements, HYSPLIT forward trajectories, Infrared Atmospheric Sounding Interferometer (IASI) satellite data and tephra deposits

Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer

Immunotherapy; PARP inhibitors; PembrolizumabImmunoteràpia; Inhibidors de PARP; PembrolizumabInmunoterapia; Inhibidores de PARP; PembrolizumabMetastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS)

D^* production from e^+e^- to ep collisions in NLO QCD

Fragmentation functions for D mesons, based on the convolution of a perturbative part, related to the heavy quark perturbative showering, and a non-perturbative model for its hadronization into the meson, are used to describe D^* production in e^+e^- and ep collisions. The non-perturbative part is determined by fitting the e^+e^- data taken by ARGUS and OPAL at 10.6 and 91.2 GeV respectively. When fitting with a non perturbative Peterson fragmentation function and using next-to-leading evolution for the perturbative part, we find an epsilon parameter sensibly different from the one commonly used, which is instead found with a leading order fit. The use of this new value is shown to increase considerably the cross section for D^* production at HERA, suggesting a possible reconciliation between the next-to-leading order theoretical predictions and the experimental data.Comment: 20 pages, LaTeX2e, 8 Postscript figure

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

During non-rapid eye movement (NREM) sleep (stage N3), when consciousness fades, cortico-cortical interactions are impaired while neurons are still active and reactive. Why is this? We compared cortico-cortical evoked-potentials recorded during wakefulness and NREM by means of time-frequency analysis and phase-locking measures in 8 epileptic patients undergoing intra-cerebral stimulations/recordings for clinical evaluation. We observed that, while during wakefulness electrical stimulation triggers a chain of deterministic phase-locked activations in its cortical targets, during NREM the same input induces a slow wave associated with an OFF-period (suppression of power > 20 Hz), possibly reflecting a neuronal down-state. Crucially, after the OFF-period, cortical activity resumes to wakefulness-like levels, but the deterministic effects of the initial input are lost, as indicated by a sharp drop of phase-locked activity. These findings suggest that the intrinsic tendency of cortical neurons to fall into a down-state after a transient activation (i.e. bistability) prevents the emergence of stable patterns of causal interactions among cortical areas during NREM. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions in which thalamo-cortical information integration and consciousness are impaired in spite of preserved neuronal activity. (C) 2015 The Authors. Published by Elsevier Inc.Peer reviewe

J/psi Production via Fragmentation at the Tevatron

The production of \jpsi at large transverse momenta (\pt > M_\jpsi) in $p\bar p$ collisions is considered by including the mechanism of fragmentation. Both contributions of fragmentation to \jpsi and of fragmentation to $\chi$ states followed by radiative decay to \jpsi are taken into account. The latter is found to be dominant and larger than direct production. The overall theoretical estimate is shown to be nearly consistent with the experimental observation.Comment: LaTeX, 7 pages. Preprint FNT/T-94/13, LNF-94/024(P). Data taken from a reference were incorrect and have been changed. Complete postscript file available via anonymous ftp at cobra1.pv.infn.it, as pub/jpsi.ps(.Z)(.gz

Dynamical Renormalization Group Study for a Class of Non-local Interface Equations

We provide a detailed Dynamic Renormalization Group study for a class of stochastic equations that describe non-conserved interface growth mediated by non-local interactions. We consider explicitly both the morphologically stable case, and the less studied case in which pattern formation occurs, for which flat surfaces are linearly unstable to periodic perturbations. We show that the latter leads to non-trivial scaling behavior in an appropriate parameter range when combined with the Kardar-Parisi-Zhang (KPZ) non-linearity, that nevertheless does not correspond to the KPZ universality class. This novel asymptotic behavior is characterized by two scaling laws that fix the critical exponents to dimension-independent values, that agree with previous reports from numerical simulations and experimental systems. We show that the precise form of the linear stabilizing terms does not modify the hydrodynamic behavior of these equations. One of the scaling laws, usually associated with Galilean invariance, is shown to derive from a vertex cancellation that occurs (at least to one loop order) for any choice of linear terms in the equation of motion and is independent on the morphological stability of the surface, hence generalizing this well-known property of the KPZ equation. Moreover, the argument carries over to other systems like the Lai-Das Sarma-Villain equation, in which vertex cancellation is known {\em not to} imply an associated symmetry of the equation.Comment: 34 pages, 9 figures. Journal of Statistical Mechanics: Theory and Experiments (in press

Flagellin delays spontaneous human neutrophil apoptosis

Neutrophils are short-lived cells that rapidly undergo apoptosis. However, their survival can be regulated by signals from the environment. Flagellin, the primary component of the bacterial flagella, is known to induce neutrophil activation. In this study we examined the ability of flagellin to modulate neutrophil apoptosis. Neutrophils cultured for 12 and 24 h in the presence of flagellin from Salmonella thyphimurim at concentrations found in pathological situations underwent a marked prevention of apoptosis. In contrast, Helicobacter pylori flagellin did not affect neutrophil survival, suggesting that Salmonella flagellin exerts the antiapoptotic effect by interacting with TLR5. The delaying in apoptosis mediated by Salmonella flagellin was coupled to higher expression levels of the antiapoptotic protein Mcl-1 and lower levels of activated caspase-3. Analysis of the signaling pathways indicated that Salmonella flagellin induced the activation of the p38 and ERK1/2 MAPK pathways as well as the PI3K/Akt pathway. Furthermore, it also stimulated IBα degradation and the phosphorylation of the p65 subunit, suggesting that Salmonella flagellin also triggers NF-B activation. Moreover, the pharmacological inhibition of ERK1/2 pathway and NF-B activation partially prevented the antiapoptotic effects exerted by flagellin. Finally, the apoptotic delaying effect exerted by flagellin was also evidenced when neutrophils were cultured with whole heat-killed S. thyphimurim. Both a wild-type and an aflagellate mutant S. thyphimurim strain promoted neutrophil survival; however, when cultured in low bacteria/neutrophil ratios, the flagellate bacteria showed a higher capacity to inhibit neutrophil apoptosis, although both strains showed a similar ability to induce neutrophil activation. Taken together, our results indicate that flagellin delays neutrophil apoptosis by a mechanism partially dependent on the activation of ERK1/2 MAPK and NF-B. The ability of flagellin to delay neutrophil apoptosis could contribute to perpetuate the inflammation during infections with flagellated bacteria.Facultad de Ciencias Exacta

The Role of the Iron Transporter ABCB7 in Refractory Anemia with Ring Sideroblasts

Refractory Anemia with Ring Sideroblasts (RARS) is an acquired myelodysplastic syndrome (MDS) characterized by an excess iron accumulation in the mitochondria of erythroblasts. The pathogenesis of RARS and the cause of this unusual pattern of iron deposition remain unknown. We considered that the inherited X-linked sideroblastic anemia with ataxia (XLSA/A) might be informative for the acquired disorder, RARS. XLSA/A is caused by partial inactivating mutations of the ABCB7 ATP-binding cassette transporter gene, which functions to enable transport of iron from the mitochondria to the cytoplasm. Furthermore, ABCB7 gene silencing in HeLa cells causes an accumulation of iron in the mitochondria. We have studied the role of ABCB7 in RARS by DNA sequencing, methylation studies, and gene expression studies in primary CD34+ cells and in cultured erythroblasts. The DNA sequence of the ABCB7 gene is normal in patients with RARS. We have investigated ABCB7 gene expression levels in the CD34+ cells of 122 MDS cases, comprising 35 patients with refractory anemia (RA), 33 patients with RARS and 54 patients with RA with excess blasts (RAEB), and in the CD34+ cells of 16 healthy controls. We found that the expression levels of ABCB7 are significantly lower in the RARS group. RARS is thus characterized by lower levels of ABCB7 gene expression in comparison to other MDS subtypes. Moreover, we find a strong relationship between increasing percentage of bone marrow ring sideroblasts and decreasing ABCB7 gene expression levels. Erythroblast cell cultures confirm the low levels of ABCB7 gene expression levels in RARS. These data provide an important link between inherited and acquired forms of sideroblastic anemia and indicate that ABCB7 is a strong candidate gene for RARS

Pharmacological targeting of the mitochondrial calcium-dependent potassium channel KCa3.1 triggers cell death and reduces tumor growth and metastasis in vivo

Ion channels are non-conventional, druggable oncological targets. The intermediate-conductance calcium-dependent potassium channel (K(Ca)3.1) is highly expressed in the plasma membrane and in the inner mitochondrial membrane (mitoK(Ca)3.1) of various cancer cell lines. The role mitoK(Ca)3.1 plays in cancer cells is still undefined. Here we report the synthesis and characterization of two mitochondria-targeted novel derivatives of a high-affinity K(Ca)3.1 antagonist, TRAM-34, which retain the ability to block channel activity. The effects of these drugs were tested in melanoma, pancreatic ductal adenocarcinoma and breast cancer lines, as well as in vivo in two orthotopic models. We show that the mitochondria-targeted TRAM-34 derivatives induce release of mitochondrial reactive oxygen species, rapid depolarization of the mitochondrial membrane, fragmentation of the mitochondrial network. They trigger cancer cell death with an EC50 in the mu M range, depending on channel expression. In contrast, inhibition of the plasma membrane K(Ca)3.1 by membrane-impermeant Maurotoxin is without effect, indicating a specific role of mitoK(Ca)3.1 in determining cell fate. At sub-lethal concentrations, pharmacological targeting of mitoK(Ca)3.1 significantly reduced cancer cell migration by enhancing production of mitochondrial reactive oxygen species and nuclear factor-kappa B (NF-kappa B) activation, and by downregulating expression of Bcl-2 Nineteen kD-Interacting Protein (BNIP-3) and of Rho GTPase CDC-42. This signaling cascade finally leads to cytoskeletal reorganization and impaired migration. Overexpression of BNIP-3 or pharmacological modulation of NF-kappa B and CDC-42 prevented the migration-reducing effect of mitoTRAM-34. In orthotopic models of melanoma and pancreatic ductal adenocarcinoma, the tumors at sacrifice were 60% smaller in treated versus untreated animals. Metastasis of melanoma cells to lymph nodes was also drastically reduced. No signs of toxicity were observed. In summary, our results identify mitochondrial K(Ca)3.1 as an unexpected player in cancer cell migration and show that its pharmacological targeting is efficient against both tumor growth and metastatic spread in vivo

Discovery of an intermediate-luminosity red transient in M51 and its likely dust-obscured, infrared-variable progenitor

We present the discovery of an optical transient (OT) in Messier 51, designated M51 OT2019-1 (also ZTF19aadyppr, AT 2019abn, ATLAS19bzl), by the Zwicky Transient Facility (ZTF). The OT rose over 15 days to an observed luminosity of $M_r=-13$ (${\nu}L_{\nu}=9\times10^6~L_{\odot}$), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of $\approx400$ km s$^{-1}$, Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called "SN impostors" and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a $4.5~\mu$m luminosity of $M_{[4.5]}\approx-12.2$ and a $[3.6]-[4.5]$ color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of $E(B-V)\approx0.7$ mag and higher intrinsic luminosity of $M_r\approx-14.9$ (${\nu}L_{\nu}=5.3\times10^7~L_{\odot}$) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51 OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.Comment: 21 pages, 5 figures, published in ApJ