The hypoxic transcription factor KlMga2 mediates the response to oxidative stress and influences longevity in the yeast Kluyveromyces lactis

Hypoxia is defined as the decline of oxygen availability, depending on environmental supply and cellular consumption rate. The decrease in O2 results in reduction of available energy in facultative aerobes. The response and/or adaptation to hypoxia and other changing environmental conditions can influence the properties and functions of membranes by modifying lipid composition. In the yeast Kluyveromyces lactis, the KlMga2 gene is a hypoxic regulatory factor for lipid biosynthesis-fatty acids and sterols-and is also involved in glucose signaling, glucose catabolism and is generally important for cellular fitness. In this work we show that, in addition to the above defects, the absence of the KlMGA2 gene caused increased resistance to oxidative stress and extended lifespan of the yeast, associated with increased expression levels of catalase and SOD genes. We propose that KlMga2 might also act as a mediator of the oxidative stress response/adaptation, thus revealing connections among hypoxia, glucose signaling, fatty acid biosynthesis and ROS metabolism in K. lactis

Operational Angular Track Reconstruction in Space Surveillance Radars through an Adaptive Beamforming Approach

In the last few years, many space surveillance initiatives have started to consider the problem represented by resident space object overpopulation. In particular, the European Space Surveillance and Tracking (EUSST) consortium is in charge of providing services like collision avoidance, fragmentation analysis, and re-entry, which rely on measurements obtained through ground-based sensors. BIRALES is an Italian survey radar belonging to the EUSST framework and is capable of providing measurements including Doppler shift, slant range, and angular profile. In recent years, the Music Approach for Track Estimate and Refinement (MATER) algorithm has been developed to retrieve angular tracks through an adaptive beamforming technique, guaranteeing the generation of more accurate and robust measurements with respect to the previous static beamforming approach. This work presents the design of a new data processing chain to be used by BIRALES to compute the angular track. The signal acquired by the BIRALES receiver array is down-converted and the receiver bandwidth is split into multiple channels, in order to maximize the signal-to-noise ratio of the measurements. Then, the signal passes through a detection block, where an isolation procedure creates, for each epoch, signal correlation matrices (CMs) related to the channels involved in the detection and then processes them to isolate the data stream related to a single detected source. Consequently, for each epoch and for each detected source, just the CM featuring the largest signal contribution is kept, allowing deriving the Doppler shift measurement from the channel illumination sequence. The MATER algorithm is applied to each CM stream, first estimating the signal directions of arrival, then grouping them in the observation time window, and eventually returning the target angular track. Ambiguous estimates may be present due to the configuration of the receiver array, which cause spatial aliasing phenomena. This problem can be addressed by either exploiting transit prediction (in the case of cataloged objects), or by applying tailored criteria (for uncatalogued objects). The performance of the new architecture was assessed in real operational scenarios, demonstrating the enhancement represented by the implementation of the channelization strategy, as well as the angular measurement accuracy returned by MATER, in both nominal and off-nominal scenarios

Mechanisms of immune escape and resistance to checkpoint inhibitor therapies in mismatch repair deficient metastatic colorectal cancers

SIMPLE SUMMARY: A subset of colorectal cancers (CRCs) is characterized by a mismatch repair deficiency that is frequently associated with microsatellite instability (MSI). The compromised DNA repair machinery leads to the accumulation of tumor neoantigens affecting the sensitivity of MSI metastatic CRC to immune checkpoint inhibitors (CPIs), both upfront and in later lines of treatment. However, up to 30% of MSI CRCs exhibit primary resistance to frontline immune based therapy, and an additional subset develops acquired resistance. Here, we first discuss the clinical and molecular features of MSI CRCs and then we review how the loss of antigenicity, immunogenicity, and a hostile tumor microenvironment could influence primary and acquired resistance to CPIs. Finally, we describe strategies to improve the outcome of MSI CRC patients upon CPI treatment. ABSTRACT: Immune checkpoint inhibitors (CPIs) represent an effective therapeutic strategy for several different types of solid tumors and are remarkably effective in mismatch repair deficient (MMRd) tumors, including colorectal cancer (CRC). The prevalent view is that the elevated and dynamic neoantigen burden associated with the mutator phenotype of MMRd fosters enhanced immune surveillance of these cancers. In addition, recent findings suggest that MMRd tumors have increased cytosolic DNA, which triggers the cGAS STING pathway, leading to interferon-mediated immune response. Unfortunately, approximately 30% of MMRd CRC exhibit primary resistance to CPIs, while a substantial fraction of tumors acquires resistance after an initial benefit. Profiling of clinical samples and preclinical studies suggests that alterations in the Wnt and the JAK-STAT signaling pathways are associated with refractoriness to CPIs. Intriguingly, mutations in the antigen presentation machinery, such as loss of MHC or Beta-2 microglobulin (B2M), are implicated in initial immune evasion but do not impair response to CPIs. In this review, we outline how understanding the mechanistic basis of immune evasion and CPI resistance in MMRd CRC provides the rationale for innovative strategies to increase the subset of patients benefiting from CPIs

The Northern Cross fast radio burst project–I: overview and pilot observations at 408 MHz

Fast radio bursts (FRBs) remain one of the most enigmatic astrophysical sources. Observations have significantly progressed over the last few years, due to the capabilities of new radio telescopes and the refurbishment of existing ones. Here, we describe the upgrade of the Northern Cross radio telescope, operating in the 400–416 MHz frequency band, with the ultimate goal of turning the array into a dedicated instrument to survey the sky for FRBs

Project of a multibeam UHF receiver to improve survey capabilities

The Institute of Radioastronomy (IRA-Bologna) of the National Institute for Astrophysics of Italy (INAF – Rome) joined the European group for the Square Kilometer Array Design Study (SKA-DS) in the frame of the FP6 program. One of the goals of the Design Study was the construction and test of a state of the art very small SKA prototype. A segment (1/8) of the N/S arm of the large Northern Cross array (408 MHz+/−8 MHz) was exploited to obtain a prototype array, made up by 8 cylindrical concentrators (23.5 mt×7.5 mt) equipped with 4 receivers each. In this way a 32 receivers array with a total collecting area of about 1400 m2 was obtained. Signals are directly carried from the receivers, located on the focal lines, down to the back end, located in the processing room, via a very cost effective analog optical links. Here a fast back end, presently based on Field Programmable Gate Array (FPGA) Berkeley-Roach boards, takes care of running the required complex algorithms to perform (non-adaptive) multi-beamforming with a 2D FFT. The main advantage of such an already working array is to produce 21 independent 31’×104’ beams located inside a 38 deg2 Field Of View (FoV). Our plan is to search for funds to refit the remaining 56 cylinders of the N/S arm, to dramatically increase both the sensitivity and number of beams (pixels) placed in the same FoV. In this way, it could be possible to perform a deep SETI survey in the UHF band by an about 11.200 m2 antenna (equivalent to a 119 m dish), a 37.6 deg2 FOV and 189 independent beams. The system could be further expanded by installing more receivers on each N/S focal line, increasing the FOV and the number of pixels with the same sensitivity. Assuming that adequate funds could be found for refitting the giant E/W arm as well, an equivalent 180 m dish could be obtained to perform a very deep SETI sky survey with a 120 deg2 FOV at high sensitivity. This would allow a very fast and deep sky survey in the UHF band

The Northern Cross Fast Radio Burst project -- III. The FRB-magnetar connection in a sample of nearby galaxies

Fast radio bursts (FRBs) are millisecond radio transients observed at cosmological distances. The nature of their progenitors is still a matter of debate, although magnetars are invoked by most models. The proposed FRB-magnetar connection was strengthened by the discovery of an FRB-like event from the Galactic magnetar SGR J1935+2154. In this work, we aim to investigate how prevalent magnetars such as SGR J1935+2154 are within FRB progenitors. We carried out an FRB search in a sample of seven nearby (< 12 Mpc) galaxies with the Northern Cross radio telescope for a total of 692 h. We detected one 1.8 ms burst in the direction of M101 with a fluence of $58 \pm 5$ Jy ms. Its dispersion measure of 303 pc cm$^{-3}$ places it most-likely beyond M101. Considering that no significant detection comes indisputably from the selected galaxies, we place a 38 yr$^{-1}$ upper limit on the total burst rate (i.e. including the whole sample) at the 95\% confidence level. This upper limit constrains the event rate per magnetar $\lambda_{\rm mag} < 0.42$ magnetar$^{-1}$ yr$^{-1}$ or, if combined with literature observations of a similar sample of nearby galaxies, it yields a joint constraint of $\lambda_{\rm mag} < 0.25$ magnetar$^{-1}$ yr$^{-1}$. We also provide the first constraints on the expected rate of FRBs hypothetically originating from ultraluminous X-ray (ULX) sources, since some of the galaxies observed during our observational campaign host confirmed ULXs. We obtain $< 13$ yr$^{-1}$ per ULX for the total sample of galaxies observed. Our results indicate that bursts with energies $E>10^{34}$ erg from magnetars like SGR J1935+2154 appear more rarely compared to previous observations and further disfavour them as unique progenitors for the cosmological FRB population, leaving more space open to the contribution from a population of more exotic magnetars, not born via core-collapsed supernovae.Comment: 9 pages, 4 figures, published in A&

Procedura di montaggio del sistema di movimentazione e controllo del ramo N/S per il sistema BIRALES

Lo scopo di questo documento è quello di descrivere la procedura dell’installazione del nuovo sistema di movimentazione delle antenne cilindrico paraboliche del ramo Nord/Sud del radiotelescopio “Croce del Nord”, studiato per venire incontro alle esigenze del programma “Space Surveillance and Tracking”, oltre a programmi scientifici quale la ricerca degli FRB. Oltre alla procedura di installazione, è indicata la lista del materiale necessario alla replicazione e i disegni costruttivi, e viene inoltre descritta la procedura di manutenzione

Upgrading the Sardinia Radio Telescope to a bistatic tracking radar for space debris

In order to prevent the harmful impacts for spacecrafts deriving from the presence of space debris, many surveillance and monitoring programs of the space environment have been started in recent years. The Sardinia Radio Telescope is a new comer in such a scenario, but it has already showed its potential. However, since the actual receiving chain is not optimized for the reception of the echoes scattered from the debris, some modifications has been planned to upgrade the telescope and made it suitable for these types of observations

Monitoring the final orbital decay and the re-entry of Tiangong-1 with the Italian SST ground sensor network

The uncontrolled re-entry of spacecraft and upper stages is quite common, occurring nearly every week. Among them, intact objects having a mass greater than five metric tons re-enter, on average, 1–2 times per year. Therefore, the re-entry of the first Chinese Space Station, Tiangong-1, was far from unusual, but attracted anyway a great worldwide attention and some concerns. For these reasons, the Italian component of the European SST (Space Surveillance and Tracking) consortium took this opportunity for carrying out a national exercise. According to Chinese official sources, the ground control of Tiangong-1 was lost in March 2016, precluding the planned de-orbiting in the South Pacific Ocean Unpopulated Area (SPOUA). Tiangong-1 consisted of a cylindrical section, 10:5 m in length and 3:4 m in (maximum) diameter, with two rectangular solar panels of 3 m × 7 m. The mass was estimated to be around 7500 kg. The Italian network of sensors activated for the campaign included mono-static and bi-static radars, optical telescopes, a laser ranging station and a network of all-sky cameras, originally deployed for the observation of fireballs and bolides. In addition to providing complementary information, concerning the orbit, the attitude and the photometry of Tiangong-1, this quite heterogeneous collection of national assets provided also the occasion for testing, in an operational environment, the Italian sensor tasking preparedness and the data acquisition, exchange and processing capabilities within the European SST consortium. In this respect, it is important to remember that in 2014 the European Commission, well aware of the topic criticality, took the commitment to implement a European network of sensors for surveillance and tracking of objects in Earth's orbit by starting a dedicated SST support framework program. Italy, France, Germany, Spain and UK joined it and constituted, together with SatCent, the front desk for SST services, the EUSST Consortium. In this paper, a description of the Tiangong-1 monitoring activities and of the main observations results obtained by the Italian sensor network are reported. Attention is also devoted to the coordination aspects of several Italian entities (military, civil and research organizations) that worked together. Finally, a description of the re-entry prediction and alert procedure for the national civil protection authorities is presented