Activity distribution of comet 67P/Churyumov-Gerasimenko from combined measurements of non-gravitational forces and torques

Aims. Understanding the activity is vital for deciphering the structure, formation, and evolution of comets. We investigate models of cometary activity by comparing them to the dynamics of 67P/Churyumov-Gerasimenko. Methods. We matched simple thermal models of water activity to the combined Rosetta datasets by fitting to the total outgassing rate and four components of the outgassing induced non-gravitational force and torque, with a final manual adjustment of the model parameters to additionally match the other two torque components. We parametrised the thermal model in terms of a distribution of relative activity over the surface of the comet, and attempted to link this to different terrain types. We also tested a more advanced thermal model based on a pebble structure. Results. We confirm a hemispherical dichotomy and non-linear water outgassing response to insolation. The southern hemisphere of the comet and consolidated terrain show enhanced activity relative to the northern hemisphere and dust-covered, unconsolidated terrain types, especially at perihelion. We further find that the non-gravitational torque is especially sensitive to the activity distribution, and to fit the pole-axis orientation in particular, activity must be concentrated (in excess of the already high activity in the southern hemisphere and consolidated terrain) around the south pole and on the body and neck of the comet over its head. This is the case for both the simple thermal model and the pebble-based model. Overall, our results show that water activity cannot be matched by a simple model of sublimating surface ice driven by the insolation alone, regardless of the surface distribution, and that both local spatial and temporal variations are needed to fit the data. Conclusions. Fully reconciling the Rosetta outgassing, torque, and acceleration data requires a thermal model that includes both diurnal and seasonal effects and also structure with depth (dust layers or ice within pebbles). This shows that cometary activity is complex. Nonetheless, non-gravitational dynamics provides a useful tool for distinguishing between different thermophysical models and aids our understanding

TTRV30M oligomeric aggregates inhibit proliferation of renal progenitor cells but maintain their capacity to differentiate into podocytes in vitro

Publicado em: The Proceedings of the XIIIth International Symposium on Amyloidosis, May 6-10, 2012, Groningen, The NetherlandsIn Familial Amyloidotic Polyneuropathy, the amyloid deposition of mutant transthyretin TTR V30M can lead to renal complications. An unexplored mechanism is the toxicity of oligomeric TTR aggregates. A subset of renal progenitor cells (RPC) in the adult human kidney can induce regeneration of podocytes and tubular structures of the nephron, which can be critical for preventing irreversible renal failure. We assessed whether RPC are vulnerable, in vitro, to TTRV30M oligomers. RPC proliferation was reduced by 16.3±9.7% and 32.6±6.3% after 48 and 72 hours, respectively, in the presence of the oligomers. However, oligomers did not induce apoptosis or alterations in cell cycle to any significant extent, and did not influence RPC differentiation into podocytes. From this first attempt, we can say that TTRV30M oligomers inhibit RPC proliferation but do not influence their capacity to differentiate into mature podocytes, and thus should not compromise tissue regeneration.FC

Outcome following a short period of adalimumab dose escalation as rescue therapy in psoriatic patients

Background: Advances in biologic treatments have led to a new therapeutic frontier for moderate-to-severe psoriasis. Nevertheless, the efficacy of anti-TNFα decreases with time, requiring adjustments to maintain valuable Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) responses. Objectives: To evaluate the efficacy and safety of adalimumab dose escalation (40 mg, subcutaneous, once a week for 24 weeks) in psoriatic adult patients with secondary loss of response (PASI ≥50 to ≤75 or PASI≥75 and DLQI ≥5). Materials and Methods: A multicentre, observational study involving different Italian third-level referral centres for psoriasis enrolled a total of 64 adult patients with moderate-to-severe psoriasis who were treated with adalimumab and experienced a secondary loss of response. Primary end-points were PASI< 75 or PASI ≥50 to ≤ 75 with DLQI ≤ 5, and the secondary end-point was the ability to maintain a therapeutic response, resuming adalimumab every other week. Results: At Week 16 and Week 24, 29/64 (45.3%) and 35/64 (54.6%) responded based on PASI, and mean DLQI was 4.9 and 4.09, respectively. At Week 36 and Week 48, 45.3% and 28.1% patients achieved the second end-point, respectively. No adverse events were recorded except for one patient with recurrent tonsillitis. Conclusion: Adalimumab escalation could be considered in cases with loss of response before switching to alternative biologic therapy

Angiopoietin-2 and the Vascular Endothelial Growth Factor Promote Migration and Invasion in Hepatocellular Carcinoma- and Intrahepatic Cholangiocarcinoma-Derived Spheroids

Aggressive hepatocellular carcinoma (HCC) overexpressing Angiopoietin-2 (ANG-2) (a protein linked with angiogenesis, proliferation, and epithelial–mesenchymal transition (EMT)), shares 95% of up-regulated genes and a similar poor prognosis with the proliferative subgroup of intrahepatic cholangiocarcinoma (iCCA). We analyzed the pro-invasive effect of ANG-2 and its regulator vascular endothelial growth factor (VEGF) on HCC and CCA spheroids to uncover posUsible common ways of response. Four cell lines were used: Hep3B and HepG2 (HCC), HuCC-T1 (iCCA), and EGI-1 (extrahepatic CCA). We treated the spheroids with recombinant human (rh) ANG-2 and/or VEGF and then observed the changes at the baseline, after 24 h, and again after 48 h. Proangiogenic stimuli increased migration and invasion capability in HCC- and iCCA-derived spheroids and were associated with a modification in EMT phenotypic markers (a decrease in E-cadherin and an increase in N-cadherin and Vimentin), especially at the migration front. Inhibitors targeting ANG-2 (Trebananib) and the VEGF (Bevacizumab) effectively blocked the migration ability of spheroids that had been stimulated with rh-ANG-2 and rh-VEGF. Overall, our findings highlight the critical role played by ANG-2 and the VEGF in enhancing the ability of HCC- and iCCA-derived spheroids to migrate and invade, which are key processes in cancer progression

Design and Analysis of the Cis-Lunar Navigation for the ArgoMoon CubeSat Mission

In the framework of the Artemis-1 mission, 10 CubeSats will be released, including the 6U CubeSat ArgoMoon, built by the Italian company Argotec and coordinated by the Italian Space Agency. The primary goal of ArgoMoon is to capture images of the Interim Cryogenic Propulsion Stage. Then, ArgoMoon will be placed into a highly elliptical orbit around the Earth with several encounters with the Moon. In this phase, the navigation process will require a precise Orbit Determination (OD) and a Flight Path Control (FPC) to satisfy the navigation requirements. The OD will estimate the spacecraft trajectory using ground-based radiometric observables. The FPC is based on an optimal control strategy designed to reduce the dispersion with respect to the reference trajectory and minimize the total ΔV. A linear approach was used to determine the optimal targets and the number and location of the orbital maneuvers. A covariance analysis was performed to assess the expected OD performance and its robustness. The analysis results show that the reference translunar trajectory can be successfully flown and the navigation performance is strongly dependent on the uncertainties of the ArgoMoon’s Propulsion Subsystem and of the orbit injection