Probing the MSP prenatal stage: the optical identification of the X-ray burster EXO 1745-248 in Terzan 5

We report on the optical identification of the neutron star burster EXO 1745-248 in Terzan 5. The identification was performed by exploiting HST/ACS images acquired in Director's Discretionary Time shortly after (approximately 1 month) the Swift detection of the X-ray burst. The comparison between these images and previous archival data revealed the presence of a star that currently brightened by ~3 magnitudes, consistent with expectations during an X-ray outburst. The centroid of this object well agrees with the position, in the archival images, of a star located in the Turn-Off/Sub Giant Branch region of Terzan 5. This supports the scenario that the companion should has recently filled its Roche Lobe. Such a system represents the pre-natal stage of a millisecond pulsar, an evolutionary phase during which heavy mass accretion on the compact object occurs, thus producing X-ray outbursts and re-accelerating the neutron star.Comment: ApJ Letter, in pres

The Terzan 5 puzzle: discovery of a third, metal-poor component

We report on the discovery of 3 metal-poor giant stars in Terzan 5, a complex stellar system in the the Galactic bulge, known to have two populations at [Fe/H]=-0.25 and +0.3. For these 3 stars we present new echelle spectra obtained with NIRSPEC at Keck II, which confirm their radial velocity membership and provide average [Fe/H]=-0.79 dex iron abundance and [alpha/Fe]=+0.36 dex enhancement. This new population extends the metallicity range of Terzan~5 0.5 dex more metal poor, and it has properties consistent with having formed from a gas polluted by core collapse supernovae.Comment: Accepted for publication on ApJ Lette

Cancer Immunotherapy: Harnessing the Immune System to Fight Cancer

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Cancer immunotherapy: Current and future perspectives on a therapeutic revolution

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First evidence of fully spatially mixed first and second generations in globular clusters: the case of NGC 6362

We present the first evidence of multiple populations in the Galactic globular cluster NGC 6362. We used optical and near-UV Hubble Space Telescope and ground based photometry, finding that both the sub giant and red giant branches are split in two parallel sequences in all color magnitude diagrams where the F336W filter (or U band) is used. This cluster is one of the least massive globulars (M_tot~5x10^4 M_sun) where multiple populations have been detected so far. Even more interestingly and at odds with any previous finding, we observe that the two identified populations share the same radial distribution all over the cluster extension. NGC 6362 is the first system where stars from different populations are found to be completely spatially mixed. Based on N-body and hydrodynamical simulations of multiple stellar generations, we argue that, to reproduce these findings, NGC 6362 should have lost up to the 80% of its original massComment: Accepted for publication by ApJ Letters; 6 pages, 5 figure

Engineering stability in NADPH oxidases: A common strategy for enzyme production

NADPH oxidases (NOXs) are membrane enzymes whose sole function is the generation of reactive oxygen species. Humans have seven NOX isoenzymes that feature distinct functions in immune response and cell signaling but share the same catalytic core comprising a FAD-binding dehydrogenase domain and a heme-binding transmembrane domain. We previously described a mutation that stabilizes the dehydrogenase domain of a prokaryotic homolog of human NOX5. The thermostable mutant exhibited a large 19 °C increase in the apparent melting temperature (app T m ) and a much tighter binding of the FAD cofactor, which allowed the crystallization and structure determination of the domain holo-form. Here, we analyze the transferability of this mutation onto prokaryotic and eukaryotic full-length NOX enzymes. We found that the mutation exerts a significative stabilizing effect on the full-length NOX5 from both Cylindrospermum stagnale (app T m increase of 8 °C) and Homo sapiens (app ΔT m of 2 °C). Enhanced thermal stability resulted in more homogeneous preparations of the bacterial NOX5 with less aggregation problems. Moreover, we also found that the mutation increases the overall expression of recombinant human NOX4 and NOX5 in mammalian cells. Such a 2–5-fold increase is mainly due to the lowered cell toxicity, which leads to higher biomasses. Because of the high sequence identity of the catalytic core within this family of enzymes, this strategy can be a general tool to boost the production of all NOXs

Proper motions in Terzan 5: membership of the multi-iron sub-populations and first constrain to the orbit

By exploiting two sets of high-resolution images obtained with HST ACS/WFC over a baseline of ~10 years we have measured relative proper motions of ~70,000 stars in the stellar system Terzan 5. The results confirm the membership of the three sub-populations with different iron abudances discovered in the system. The orbit of the system has been derived from a first estimate of its absolute proper motion, obtained by using bulge stars as reference. The results of the integration of this orbit within an axisymmetric Galactic model exclude any external accretion origin for this cluster. Terzan 5 is known to have chemistry similar to the Galactic bulge; our findings support a kinematic link between the cluster and the bulge, further strengthening the possibility that Terzan 5 is the fossil remnant of one of the pristine clumps that originated the bulge.Comment: 25 pages, 14 figures, accepted for publication by Ap

Pathologic Complete Response in Urothelial Carcinoma Patients Receiving Neoadjuvant Immune Checkpoint Inhibitors: A Meta-Analysis

Background. Immune checkpoint inhibitors (ICIs) have been evaluated as neoadjuvant treatment in urothelial carcinoma (UC) patients, with these agents reporting encouraging pathologic complete response (pCR) rates. Herein, we performed a systematic review and meta-analysis aimed at evaluating the incidence of pCR in UC patients treated with neoadjuvant ICI. Moreover, we investigated the impact of PD-L1 expression in this patient population, exploring the possible role of PD-L1 status as predictive biomarker. Materials and Methods. We retrieved all the relevant trials through PubMed/Medline, Cochrane Library and EMBASE; moreover, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible trials assessed pre-operative ICI in UC patients. Results. Our meta-analysis has highlighted a pooled pCR rate of 36.6% in the overall population; interestingly, pCR was higher in PD-L1 positive compared with PD-L1 negative UCs (49.5% versus 35.1%, respectively). Conclusions. Positive signals emanating from neoadjuvant immunotherapy should encourage the scientific community to persist in the long road toward finding more effective treatments for UC patients

Detection of Building Damage Using Helmholtz Tomography

High‐rise buildings with dense permanent installations of continuously recording accelerometers offer a unique opportunity to observe temporal and spatial variations in the propagation properties of seismic waves. When precise, floor‐by‐floor measurements of frequency‐dependent travel times can be made, accurate models of material properties (e.g., stiffness or rigidity) can be determined using seismic tomographic imaging techniques. By measuring changes in the material properties, damage to the structure can be detected and localized after shaking events such as earthquakes. Here, seismic Helmholtz tomography is applied to simulated waveform data from a high‐rise building, and its feasibility is demonstrated. A 52‐story dual system building—braced‐frame core surrounded by an outrigger steel moment frame—in downtown Los Angeles is used for the computational basis. It is part of the Community Seismic Network and has a three‐component accelerometer installed on every floor. A finite‐element model of the building based on structural drawings is used for the computation of synthetic seismograms for 60 damage scenarios in which the stiffness of the building is perturbed in different locations across both adjacent and distributed floors and to varying degrees. The dynamic analysis loading function is a Gaussian pulse applied to the lowest level fixed boundary condition, producing a broadband response on all floors. After narrowband filtering the synthetic seismograms and measuring the maximum amplitude, the frequency‐dependent travel times and differential travel times are computed. The travel‐time and amplitude measurements are converted to shear‐wave velocity at each floor via the Helmholtz wave equation whose solutions can be used to track perturbations to wavefronts through densely sampled wavefields. These results provide validation of the method’s application to recorded data from real buildings to detect and locate structural damage using earthquake, explosion, or ambient seismic noise data in near‐real time

Detection of Building Damage Using Helmholtz Tomography

High‐rise buildings with dense permanent installations of continuously recording accelerometers offer a unique opportunity to observe temporal and spatial variations in the propagation properties of seismic waves. When precise, floor‐by‐floor measurements of frequency‐dependent travel times can be made, accurate models of material properties (e.g., stiffness or rigidity) can be determined using seismic tomographic imaging techniques. By measuring changes in the material properties, damage to the structure can be detected and localized after shaking events such as earthquakes. Here, seismic Helmholtz tomography is applied to simulated waveform data from a high‐rise building, and its feasibility is demonstrated. A 52‐story dual system building—braced‐frame core surrounded by an outrigger steel moment frame—in downtown Los Angeles is used for the computational basis. It is part of the Community Seismic Network and has a three‐component accelerometer installed on every floor. A finite‐element model of the building based on structural drawings is used for the computation of synthetic seismograms for 60 damage scenarios in which the stiffness of the building is perturbed in different locations across both adjacent and distributed floors and to varying degrees. The dynamic analysis loading function is a Gaussian pulse applied to the lowest level fixed boundary condition, producing a broadband response on all floors. After narrowband filtering the synthetic seismograms and measuring the maximum amplitude, the frequency‐dependent travel times and differential travel times are computed. The travel‐time and amplitude measurements are converted to shear‐wave velocity at each floor via the Helmholtz wave equation whose solutions can be used to track perturbations to wavefronts through densely sampled wavefields. These results provide validation of the method’s application to recorded data from real buildings to detect and locate structural damage using earthquake, explosion, or ambient seismic noise data in near‐real time