Tumor Cell Death After Electrotransfer of Plasmid DNA is Associated With Cytosolic DNA Sensor Upregulation

Cytosolic DNA sensors are a subgroup of pattern recognition receptors (PRRs) and are activated by the abnormal presence of the DNA in the cytosol. Their activation leads to the upregulation of pro-inflammatory cytokines and chemokines and can also induce cell death. The presence of cytosolic DNA sensors and inflammatory cytokines in TS/A murine mammary adenocarcinoma and WEHI 164 fibrosarcoma cells was demonstrated using real time reverse transcription polymerase chain reaction (RT-PCR), western blotting and enzyme-linked immunosorbent assay (ELISA). After electrotransfer of plasmid DNA (pDNA) using two pulse protocols, the upregulation of DNA-depended activator of interferon regulatory factor or Z-DNA binding protein 1 (DAI/ZBP1), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60) and interferon-inducible protein 204 (p204) mRNAs was observed in both tumor cell lines, but their expression was pulse protocol dependent. A decrease in cell survival was also observed; it was cell type, DNA concentration and pulse protocol dependent. Furthermore, the different protocols of electrotransfer led to different cell death outcomes, necrosis and apoptosis, as indicated by an annexin V and 7AAD assays. The obtained data provide new insights on the presence of cytosolic DNA sensors in tumor cells and the activation of different types of cells death after electrotransfer of pDNA. These observations have important implications on the planning of gene therapy or DNA vaccination protocols

Long Gamma-Ray Bursts and Their Host Galaxies at High Redshift

Motivated by the recent observational and theoretical evidence that long Gamma-Ray Bursts (GRBs) are likely associated with low metallicity, rapidly rotating massive stars, we examine the cosmological star formation rate (SFR) below a critical metallicity Z_crit Z_sun/10 - Z_sun/5, to estimate the event rate of high-redshift long GRB progenitors. To this purpose, we exploit a galaxy formation scenario already successfully tested on a wealth of observational data on (proto)spheroids, Lyman break galaxies, Lyman alpha emitters, submm galaxies, quasars, and local early-type galaxies. We find that the predicted rate of long GRBs amounts to about 300 events/yr/sr, of which about 30 per cent occur at z>~6. Correspondingly, the GRB number counts well agree with the bright SWIFT data, without the need for an intrinsic luminosity evolution. Moreover, the above framework enables us to predict properties of the GRB host galaxies. Most GRBs are associated with low mass galaxy halos M_H<~10^11 M_sun, and effectively trace the formation of small galaxies in such halos. The hosts are young, with age smaller than 5*10^7 yr, gas rich, but poorly extincted (A_V<~0.1) because of their chemical immaturity; this also implies high specific SFR and quite extreme alpha-enhancement. Only the minority of hosts residing in large halos with M_H>~10^12 M_sun have larger extinction (A_V~0.7-1), SFRs exceeding 100 M_sun/yr and can be detected at submm wavelengths. Most of the hosts have UV magnitudes in the range -20 <~M_1350<~ -16, and Lyman alpha luminosity in the range 2*10^40 <~L_Lya<~2*10^42 erg/s. GRB hosts are thus tracing the faint end of the luminosity function of Lyman break galaxies and Lyman alpha emitters.Comment: 11 pages, 8 figures, uses mn2e.cls. Minor changes. In press on MNRA

A Strong Lexical Matching Method for the Machine Comprehension Test

Machine comprehension of text is theoverarching goal of a great deal of re-search in natural language processing. TheMachine Comprehension Test (Richard-son et al., 2013) was recently proposed toassess methods on an open-domain, exten-sible, and easy-to-evaluate task consistingof two datasets. In this paper we developa lexical matching method that takes intoaccount multiple context windows, ques-tion types and coreference resolution. Weshow that the proposed method outper-forms the baseline of Richardson et al.(2013), and despite its relative simplicity,is comparable to recent work using ma-chine learning. We hope that our approachwill inform future work on this task. Fur-thermore, we argue that MC500 is harderthan MC160 due to the way question an-swer pairs were created

Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

Gamma Ray Bursts as standard candles to constrain the cosmological parameters

Gamma Ray Bursts (GRBs) are among the most powerful sources in the Universe: they emit up to 10^54 erg in the hard X-ray band in few tens of seconds. The cosmological origin of GRBs has been confirmed by several spectroscopic measurements of their redshifts, distributed in the range 0.1-6.3. These two properties make GRBs very appealing to investigate the far Universe. The energetics implied by the observed fluences and redshifts span at least four orders of magnitudes. Therefore, at first sight, GRBs are all but standard candles. But there are correlations among some observed quantities which allow us to know the total energy or the peak luminosity emitted by a specific burst with a great accuracy. Through these correlations, GRBs become "known" candles to constrain the cosmological parameters. One of these correlation is between the rest frame peak spectral energy E_peak and the total energy emitted in gamma--rays E_gamma, properly corrected for the collimation factor. Another correlation, discovered very recently, relates the total GRB luminosity L_iso, its peak spectral energy E_peak and a characteristic timescale T_0.45, related to the variability of the prompt emission. It is based only on prompt emission properties, it is completely phenomenological, model independent and assumption--free. The constraints found through these correlations on the Omega_M and Omega_Lambda parameters are consistent with the concordance model. The present limited sample of bursts and the lack of low redshift events, necessary to calibrate these correlations, makes the cosmological constraints obtained with GRBs still large compared to those obtained with other cosmological probes (e.g. SNIa or CMB). However, the newly born field of GRB--cosmology is very promising for the future.Comment: 39 pages, 23 figures, 2 tables. Accepted for publication in the New Journal of Physics focus issue, "Focus on Gamma--Ray bursts in the Swift Era" (Eds. D. H. Hartmann, C. D. Dermer, J. Greiner

Edge Detection by Adaptive Splitting II. The Three-Dimensional Case

In Llanas and Lantarón, J. Sci. Comput. 46, 485–518 (2011) we proposed an algorithm (EDAS-d) to approximate the jump discontinuity set of functions defined on subsets of ℝ d . This procedure is based on adaptive splitting of the domain of the function guided by the value of an average integral. The above study was limited to the 1D and 2D versions of the algorithm. In this paper we address the three-dimensional problem. We prove an integral inequality (in the case d=3) which constitutes the basis of EDAS-3. We have performed detailed computational experiments demonstrating effective edge detection in 3D function models with different interface topologies. EDAS-1 and EDAS-2 appealing properties are extensible to the 3D cas