PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines

PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR)

The pre-outburst flare of the A 0535+26 August/September 2005 outburst

We study the spectral and temporal behavior of the High Mass X-ray Binary A 0535+26 during a `pre-outburst flare' which took place ~5 d before the peak of a normal (type I) outburst in August/September 2005. We compare the studied behavior with that observed during the outburst. We analyse RXTE observations that monitored A 0535+26 during the outburst. We complete spectral and timing analyses of the data. We study the evolution of the pulse period, present energy-dependent pulse profiles both at the initial pre-outburst flare and close to outburst maximum, and measure how the cyclotron resonance-scattering feature (hereafter CRSF) evolves. We present three main results: a constant period P=103.3960(5)s is measured until periastron passage, followed by a spin-up with a decreasing period derivative of Pdot=(-1.69+/-0.04)x10^(-8)s/s at MJD 53618, and P remains constant again at the end of the main outburst. The spin-up provides evidence for the existence of an accretion disk during the normal outburst. We measure a CRSF energy of Ecyc~50kev during the pre-outburst flare, and Ecyc~46kev during the main outburst. The pulse shape, which varies significantly during both pre-outburst flare and main outburst, evolves strongly with photon energy.Comment: 4 pages, 4 figures, accepted for publication in A&A Letters. To be published in parallel to Postnov et al. 200

Evaluation of virucidal activity of fabrics using feline coronavirus

Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) is an enveloped RNA virus responsible for the 2019 coronavirus disease (COVID-19) that represents a global health threat, causing an ongoing pandemic in many countries and territories. WHO recommendations emphasize the importance of all personal protective equipment (PPE) that can interrupt COVID-19 transmission. The textile industry and scientists are developing hygienic fabrics by the addition of or treatment with various antimicrobial and antiviral compounds. Methods for determining the antiviral activity of fabrics are reported in the International Standards Organization (ISO) 18184 (2019) guidelines. Three different fabric samples treated with silver derivate, copper derivative and a not treated cotton fabric used as control were examined and put in contact with a suspension of feline coronavirus (FCoV). After 2 h of incubation a significant decrease of viral titer, as high as 3.25 log10 Tissue Culture Infectious Dose (TCID)50/50 μl, in feline cells was observed in treated fabrics, with respect to not treated fabrics. In this study, we optimized laboratory methods to evaluate the virucidal activity of silver- and copper treated cotton- based fabrics against coronavirus, using FCoV suitable as a surrogate of SARS-CoV-2 but safe for laboratory technicians

Proton-counting radiography for proton therapy: a proof of principle using CMOS APS technology

Despite the early recognition of the potential of proton imaging to assist proton therapy (Cormack 1963 J. Appl. Phys. 34 2722), the modality is still removed from clinical practice, with various approaches in development. For proton-counting radiography applications such as computed tomography (CT), the water-equivalent-path-length that each proton has travelled through an imaged object must be inferred. Typically, scintillator-based technology has been used in various energy/range telescope designs. Here we propose a very different alternative of using radiation-hard CMOS active pixel sensor technology. The ability of such a sensor to resolve the passage of individual protons in a therapy beam has not been previously shown. Here, such capability is demonstrated using a 36 MeV cyclotron beam (University of Birmingham Cyclotron, Birmingham, UK) and a 200 MeV clinical radiotherapy beam (iThemba LABS, Cape Town, SA). The feasibility of tracking individual protons through multiple CMOS layers is also demonstrated using a two-layer stack of sensors. The chief advantages of this solution are the spatial discrimination of events intrinsic to pixelated sensors, combined with the potential provision of information on both the range and residual energy of a proton. The challenges in developing a practical system are discussed

A 0535+26 in the August/September 2005 outburst observed by RXTE and INTEGRAL

In this Letter we present results from INTEGRAL and RXTE observations of the spectral and timing behavior of the High Mass X-ray Binary A 0535+26 during its August/September 2005 normal (type I) outburst with an average flux F(5-100keV)~400mCrab. The search for cyclotron resonance scattering features (fundamental and harmonic) is one major focus of the paper. Our analysis is based on data from INTEGRAL and RXTE Target of Opportunity Observations performed during the outburst. The pulse period is determined. X-ray pulse profiles in different energy ranges are analyzed. The broad band INTEGRAL and RXTE pulse phase averaged X-ray spectra are studied. The evolution of the fundamental cyclotron line at different luminosities is analyzed. The pulse period P is measured to be 103.39315(5)s at MJD 53614.5137. Two absorption features are detected in the phase averaged spectra at E_1~45keV and E_2~100keV. These can be interpreted as the fundamental cyclotron resonance scattering feature and its first harmonic and therefore the magnetic field can be estimated to be B~4x10^12G.Comment: 4 pages, 5 figures, accepted for publication in A&A Letter

Peculiar outburst of A 0535+26 observed with INTEGRAL, RXTE and Suzaku

A normal outburst of the Be/X-ray binary system A0535+26 has taken place in August 2009. It is the fourth in a series of normal outbursts that have occured around the periastron passage of the source, but is unusual by starting at an earlier orbital phase and by presenting a peculiar double-peaked light curve. A first "flare" (lasting about 9 days from MJD 55043 on) reached a flux of 440 mCrab. The flux then decreased to less than 220 mCrab, and increased again reaching 440 mCrab around the periastron at MJD 55057. Target of Opportunity observations have been performed with INTEGRAL, RXTE and Suzaku. First results of these observations are presented, with special emphasis on the cyclotron lines present in the X-ray spectrum of the source, as well as in the pulse period and energy dependent pulse profiles of the source.Comment: 6 pages, Accepted for publication on PoS, Proceedings of "The Extreme sky: Sampling the Universe above 10 keV", held in Otranto (Italy) in October 200

Inhibiting DNA methylation as a strategy to enhance adipose-derived stem cells differentiation. Focus on the role of Akt/mTOR and Wnt/β-catenin pathways on adipogenesis

Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, due to their ability to repair damaged tissues and to mitigate the inflammatory/immune response. A better understanding of the underlying mechanisms regulating ASC biology might represent the chance to modulate their in vitro characteristics and differentiation potential for regenerative medicine purposes. Herein, we investigated the effects of the demethylating agent 5-azacytidine (5-aza) on proliferation, clonogenicity, migration, adipogenic differentiation and senescence of ASCs, to identify the molecular pathways involved. Through functional assays, we observed a detrimental effect of 5-aza on ASC self-renewal capacity and migration, accompanied by actin cytoskeleton reorganization, with decreased stress fibers. Conversely, 5-aza treatment enhanced ASC adipogenic differentiation, as assessed by lipid accumulation and expression of lineage-specific markers. We analyzed the involvement of the Akt/mTOR, MAPK and Wnt/beta-catenin pathways in these processes. Our results indicated impairment of Akt and ERK phosphorylation, potentially explaining the reduced cell proliferation and migration. We observed a 5-aza-mediated inhibition of the Wnt signaling pathway, this potentially explaining the pro-adipogenic effect of the drug. Finally, 5-aza treatment significantly induced ASC senescence, through upregulation of the p53/p21 axis. Our data may have important translational implications, by helping in clarifying the potential risks and advantages of using epigenetic treatment to improve ASC characteristics for cell-based clinical approaches

Three years of Fermi GBM Earth Occultation Monitoring: Observations of Hard X-ray/Soft Gamma-Ray Sources

The Gamma ray Burst Monitor (GBM) on board Fermi has been providing continuous data to the astronomical community since 2008 August 12. In this paper we present the results of the analysis of the first three years of these continuous data using the Earth occultation technique to monitor a catalog of 209 sources. From this catalog, we detect 99 sources, including 40 low-mass X-ray binary/neutron star systems, 31 high-mass X-ray binary neutron star systems, 12 black hole binaries, 12 active galaxies, 2 other sources, plus the Crab Nebula, and the Sun. Nine of these sources are detected in the 100-300 keV band, including seven black-hole binaries, the active galaxy Cen A, and the Crab. The Crab and Cyg X-1 are also detected in the 300-500 keV band. GBM provides complementary data to other sky-monitors below 100 keV and is the only all-sky monitor above 100 keV. Up-to-date light curves for all of the catalog sources can be found at http://heastro.phys.lsu.edu/gbm/.Comment: 24 pages, 12 figures, accepted for publication in ApJ