Water in acid boralites: Hydration effects on framework B sites

Properties and behavior of protonated boron-containing zeolites at different hydration degree have been investigated by means of periodic DFT approaches. Geometry optimization and room-temperature Car-Parrinello molecular dynamics results, in line with experimental findings, indicate that the BO3-bound silanolic acid site typical of dry boralites should convert to a solvated H3O+ hydrogen bonded to tetrahedral BO4 at moderate water content. By increasing the water loading, the tetrahedral structure of the B site is stabilized and the physicochemical properties of the water molecules solvating the acid proton gradually approach the liquid-phase ones. A relevant role of structural and vibrational properties of the zeolite framework in the water-induced trigonal-to-tetrahedral transition at the B site is highlighted by simulation results

Characterisation of flow dynamics within and around an isolated forest, through measurements and numerical simulations

The case study of ‘Bosco Fontana’, a densely-vegetated forest located in the north of Italy, is analysed both experimentally and numerically to characterise the internal ventilation of a finite forest with a vertically non-homogeneous canopy. Measurements allow for the evaluation of the turbulent exchange across the forest canopy. The case study is then reproduced numerically via a two-dimensional RANS simulation, successfully validated against experimental data. The analysis of the internal ventilation leads to the identification of seven regions of motion along the predominate-wind direction, for whose definition a new in-canopy stability parameter was introduced. In the vertical direction, the non-homogeneity of the canopy leads to the separation of the canopy layer into an upper foliage layer and a lower bush layer, characterised respectively by an increasing streamwise velocity and turbulence intensity, and a weak backflow. The conclusions report an improved description of the dynamic layer and regions of motion presented in the literature

Dissecting Immunotherapy Strategies for Small Cell Lung Cancer: Antibodies, Ionizing Radiation and CAR-T

Small cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for about 14% of all lung cancers. Platinum-based chemotherapy has been the only available treatment for a long time, until the introduction of immune checkpoint inhibitors (ICIs) recently changed first-line standard of care and shed light on the pivotal role of the immune system. Despite improved survival in a subset of patients, a lot of them still do not benefit from first-line chemo-immunotherapy, and several studies are investigating whether different combination strategies (with both systemic and local treatments, such as radiotherapy) may improve patient outcomes. Moreover, research of biomarkers that may be used to predict patients’ outcomes is ongoing. In addition to ICIs, immunotherapy offers other different strategies, including naked monoclonal antibodies targeting tumor associated antigens, conjugated antibody, bispecific antibodies and cellular therapies. In this review, we summarize the main evidence available about the use of immunotherapy in SCLC, the rationale behind combination strategies and the studies that are currently ongoing in this setting, in order to give the reader a clear and complete view of this rapidly expanding topic

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

Context. 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. Aims: In this work we aim to investigate how prevalent magnetars such as SGR J1935+2154 are within FRB progenitors. Methods: To this end, 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. Results: We detected one 1.8 ms burst in the direction of M 101 with a fluence of 58 ± 5 Jy ms. Its dispersion measure of 303 pc cm−3 places it most likely beyond M 101. 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 to λmag < 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 λmag < 0.25 magnetar−1 yr−1. We also provide the first constraints on the expected rate of FRBs hypothetically originating from ultra-luminous 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. Conclusions: Our results indicate that bursts with energies E > 1034 erg from magnetars such as SGR J1935+2154 appear more rarely compared to previous observations and further disfavour them as unique progenitors for the cosmological FRB population. This provides support to the idea that there is a greater contribution from a population of more exotic magnetars not born via core-collapsed supernovae

Urinary secretion and extracellular aggregation of mutant uromodulin isoforms

Uromodulin is exclusively expressed in the thick ascending limb and is the most abundant protein secreted in urine where it is found in high-molecular-weight polymers. Its biological functions are still elusive, but it is thought to play a protective role against urinary tract infection, calcium oxalate crystal formation, and regulation of water and salt balance in the thick ascending limb. Mutations in uromodulin are responsible for autosomal-dominant kidney diseases characterized by defective urine concentrating ability, hyperuricemia, gout, tubulointerstitial fibrosis, renal cysts, and chronic kidney disease. Previous in vitro studies found retention in the endoplasmic reticulum as a common feature of all uromodulin mutant isoforms. Both in vitro and in vivo we found that mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein. Notably, mutant uromodulin excretion was detected in patients carrying uromodulin mutations. Thus, our results suggest that mutant uromodulin exerts a gain-of-function effect that can be exerted by both intra- and extracellular forms of the protein

The Northern Cross Fast Radio Burst project - II. Monitoring of repeating FRB 20180916B, 20181030A, 20200120E and 20201124A

In this work we report the results of a nineteen-month Fast Radio Burst observational campaign carried out with the North-South arm of the Medicina Northern Cross radio telescope at 408~MHz in which we monitored four repeating sources: FRB20180916B, FRB20181030A, FRB20200120E and FRB20201124A. We present the current state of the instrument and the detection and characterisation of three bursts from FRB20180916B. Given our observing time, our detections are consistent with the event number we expect from the known burst rate ($2.7 \pm 1.9$ above our 10$\sigma$, 38~Jy~ms detection threshold) in the 5.2 day active window of the source, further confirming the source periodicity. We detect no bursts from the other sources. We turn this result into a 95\% confidence level lower limit on the slope of the differential fluence distribution $\alpha$ to be $\alpha > 2.1$ and $\alpha > 2.2$ for FRB20181030A and FRB20200120E respectively. Given the known rate for FRB20201124A, we expect $1.0 \pm 1.1$ bursts from our campaign, consistent with our non-detection.Comment: MNRAS Accepted, 10 pages, 6 figure

Urinary secretion and extracellular aggregation of mutant uromodulin isoforms.

Uromodulin is exclusively expressed in the thick ascending limb and is the most abundant protein secreted in urine where it is found in high-molecular-weight polymers. Its biological functions are still elusive, but it is thought to play a protective role against urinary tract infection, calcium oxalate crystal formation, and regulation of water and salt balance in the thick ascending limb. Mutations in uromodulin are responsible for autosomal-dominant kidney diseases characterized by defective urine concentrating ability, hyperuricemia, gout, tubulointerstitial fibrosis, renal cysts, and chronic kidney disease. Previous in vitro studies found retention in the endoplasmic reticulum as a common feature of all uromodulin mutant isoforms. Both in vitro and in vivo we found that mutant isoforms partially escaped retention in the endoplasmic reticulum and reached the plasma membrane where they formed large extracellular aggregates that have a dominant-negative effect on coexpressed wild-type protein. Notably, mutant uromodulin excretion was detected in patients carrying uromodulin mutations. Thus, our results suggest that mutant uromodulin exerts a gain-of-function effect that can be exerted by both intra- and extracellular forms of the protein

Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade >= 3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure

The lowest frequency Fast Radio Bursts: Sardinia Radio Telescope detection of the periodic FRB 180916 at 328 MHz

We report on the lowest-frequency detection to date of three bursts from the fast radio burst FRB 180916, observed at 328 MHz with the Sardinia Radio Telescope (SRT). The SRT observed the periodic repeater FRB 180916 for five days from 2020 February 20 to 24 during a time interval of active radio bursting, and detected the three bursts during the first hour of observations; no more bursts were detected during the remaining ~ 30 hours. Simultaneous SRT observations at 1548 MHz did not detect any bursts. Burst fluences are in the range 37 to 13 Jy ms. No relevant scattering is observed for these bursts. We also present the results of the multi-wavelength campaign we performed on FRB 180916, during the five days of the active window. Simultaneously with the SRT observations, others with different time spans were performed with the Northern Cross at 408 MHz, with XMM-Newton, NICER, INTEGRAL, AGILE, and with the TNG and two optical telescopes in Asiago, which are equipped with fast photometers. XMM-Newton obtained data simultaneously with the three bursts detected by the SRT, and determined a luminosity upper limit in the 0.3-10 keV energy range of ~$10^{45}$ erg/s for the burst emission. AGILE obtained data simultaneously with the first burst and determined a fluence upper limit in the MeV range for millisecond timescales of $10^{-8}$ erg cm$^{-2}$.Our results show that absorption from the circumburst medium does not significantly affect the emission from FRB 180916, thus limiting the possible presence of a superluminous supernova around the source, and indicate that a cutoff for the bursting mechanism, if present, must be at lower frequencies. Our multi-wavelength campaign sensitively constrains the broadband emission from FRB 180916, and provides the best limits so far for the electromagnetic response to the radio bursting of this remarkable source of fast radio bursts.Comment: ApJL, 896 L4