The Role of PARP Inhibitors in the Ovarian Cancer Microenvironment: Moving Forward From Synthetic Lethality

PARP inhibitors (PARPi) have shown promising clinical results and have revolutionized the landscape of ovarian cancer management in the last few years. While the core mechanism of action of these drugs has been largely analyzed, the interaction between PARP inhibitors and the microenvironment has been scarcely researched so far. Recent data shows a variety of mechanism through which PARPi might influence the tumor microenvironment and especially the immune system response, that might even partly be the reason behind PARPi efficacy. One of many pathways that are affected is the cGAS-cGAMP-STING; the upregulation of STING (stimulator of interferon genes), produces more Interferon ϒ and pro inflammatory cytokines, thus increasing intratumoral CD4+ and CD8+ T cells. Upregulation of immune checkpoints such as PD1-PDL1 has also been observed. Another interesting mechanism of interaction between PARPi and microenvironment is the ability of PARPi to kill hypoxic cells, as these cells show an intrinsic reduction in the expression and function of the proteins involved in HR. This process has been defined “contextual synthetic lethality”. Despite ovarian cancer having always been considered a poor responder to immune therapy, data is now shedding a new light on the matter. First, OC is much more heterogenous than previously thought, therefore it is fundamental to select predictive biomarkers for target therapies. While single agent therapies have not yielded significant results on the long term, influencing the immune system and the tumor microenvironment via the concomitant use of PARPi and other target therapies might be a more successful approach

Autoscala applied at the Ionospheric Station of Warsaw

A new ionosonde VISRC2, built at the Space Research Center of Warsaw, Poland, was installed at Warsaw (52.2 N, 21.1 E) in march 2007. The main characteristics of this ionosonde are: transmitted power 10 kW, pulse duration 100 μs, sampling period 5 μs, frequency resolution 25 kHz, and capability to distinguish ordinary and extraordinary reflections. This ionosonde, able to record the sounding only as a binary file, was not equipped with a tool to perform an automatic scaling of the recorded trace. From October 2008 Autoscala (Pezzopane and Scotto, 2005, 2007, 2008; Scotto and Pezzopane, 2007) is routinely applied to the ionograms recorded by this ionosonde

Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy

Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation

Extreme value and cluster analysis of European daily temperature series

Time series of daily mean temperature obtained from the European Climate Assessment data set is analyzed with respect to their extremal properties. A time-series clustering approach which combines Bayesian methodology, extreme value theory and classification techniques is adopted for the analysis of the regional variability of temperature extremes. The daily mean temperature records are clustered on the basis of their corresponding predictive distributions for 25-, 50- and 100-year return values. The results of the cluster analysis showa clear distinction between the highest altitude stations, for which the return values are lowest, and the remaining stations. Furthermore, a clear distinction is also found between the northernmost stations in Scandinavia and the stations in central and southern Europe. This spatial structure of the return period distributions for 25-, 50- and 100-years seems to be consistent with projected changes in the variability of temperature extremes over Europe pointing to a different behavior in central Europe than in northern Europe and the Mediterranean area, possibly related to the effect of soil moisture and land-atmosphere coupling.‘Acções Integradas Luso-Espanholas’ under the grants E-83/09 and HP2008- 008

The new ionospheric station of Tucumán: first results

An Advanced Ionospheric Sounder, built at the Istituto Nazionale di Geofisica e Vulcanologia, Rome, Italy, was installed at Tucumán, Argentina, particularly interesting for its location, near the southern peak of the ionospheric equatorial anomaly. The aim of this installation is to collect a large number of continuous data useful both to study the dynamics of the equatorial ionospheric plasma and to develop reliable regional ionospheric prediction models. Moreover this ionosonde will contribute to the ionospheric database and real time knowledge of Southern Hemisphere ionospheric conditions for space weather applications. The ionosonde is completely programmable and two PCs support the data acquisition, control, storage and on-line processing. In this work the first results, in terms of ionograms and autoscaled characteristics, are presented and briefly discussed

Nanostructured tic layer is highly suitable surface for adhesion, proliferation and spreading of cells

Cell culture is usually performed in 2D polymer surfaces; however, several studies are conducted with the aim to screen functional coating molecules to find substrates more suitable for cell adhesion and proliferation. The aim of this manuscript is to compare the cell adhesion and cytoskeleton organization of different cell types on different surfaces. Human primary fibroblasts, chondrocytes and osteoblasts isolated from patients undergoing surgery were seeded on polystyrene, poly-d-lysine-coated glass and titanium carbide slides and left to grow for several days. Then their cytoskeleton was analyzed, both by staining cells with phalloidin, which highlights actin fibers, and using Atomic Force Microscopy. We also monitored the production of Fibroblast Growth Factor-2, Bone Morphogenetic Protein-2 and Osteocalcin, using ELISA, and we highlighted production of Collagen type I in fibroblasts and osteoblasts and Collagen type II in chondrocytes by immunofluorescences. Fibroblasts, chondrocytes and osteoblasts showed both an improved proliferative activity and a good adhesion ability when cultured on titanium carbide slides, compared to polystyrene and poly-d-lysine-coated glass. In conclusion, we propose titanium carbide as a suitable surface to cultivate cells such as fibroblasts, chondrocytes and osteoblasts, allowing the preservation of their differentiated state and good adhesion properties

New low power pulse compressed ionosonde at Gibilmanna Ionospheric Observatory

A digital low power pulse compressed ionosonde was developed at the Istituto Nazionale di Geofisica e Vulcanologia (INGV), Rome, Italy. The aim of this Advanced Ionospheric Sounder, AIS-INGV, is to reduce the transmitted power and, consequently, weight, size, power consumption and hardware complexity. To compensate the power reduction the most advanced HF radar techniques such as the pulse compression and a phase coherent integration are used. The ionosonde is completely programmable and a PC supports the data acquisition, control, storage and on-line processing. The first prototype was installed at Gibilmanna Ionospheric Observatory (Sicily), an interesting location in the center of Mediterranean area. The new ionosonde will contribute to ionospheric database and real time knowledge of South European ionospheric conditions for space weather applications. In this work the first results (ionograms and autoscaled characteristics) are presented and briefly discussed

Importance of a real-time monitoring of the Earth's ionosphere

The ionosphere affects the electromagnetic wave propagation and then its study is important for Earth-Earth, satellite-Earth, and satellite-satellite communication purposes. Diffractive and refractive processes due to irregular electron density structures cause signal fluctuations that can disrupt satellite-ground communications and represent a hazard for navigation systems. The study and the real-time monitoring of the ionosphere are important for Space Weather purposes. The ionospheric vertical sounding is described, together with the automatic scaling of the ionograms.UnpublishedRome2A. Fisica dell'alta atmosferaope

Implementación de una metodología toxicológica para la rápida determinación del CL50 del sulfato de cobre en peces Cebra(Danio rerio) a 24, 48, 72, 96 y 120 horas de exposición

Los bioensayos han sido el método tradicional para documentar la presencia de diversos contaminantes en el agua. Se implementó un sistema para determinar la Concentración Letal Media (CL50) del sulfato de cobre en los peces Cebra (Danio rerio). Para ello se realizaron ensayos a diferentes tiempos de exposición (24, 48, 72, 96 y 120 horas). Se determinó que la CL50 fue de 0.1875 mg/L a las 96 horas de exposición