A microscopic description of the aging dynamics: fluctuation-dissipation relations, effective temperature and heterogeneities

We consider the dynamics of a diluted mean-field spin glass model in the aging regime. The model presents a particularly rich heterogeneous behavior. In order to catch this behavior, we perform a **spin-by-spin analysis** for a **given disorder realization**. The results compare well with the outcome of a static calculation which uses the ``survey propagation'' algorithm of Mezard, Parisi, and Zecchina [Sciencexpress 10.1126/science.1073287 (2002)]. We thus confirm the connection between statics and dynamics at the level of single degrees of freedom. Moreover, working with single-site quantities, we can introduce a new response-vs-correlation plot, which clearly shows how heterogeneous degrees of freedom undergo coherent structural rearrangements. Finally we discuss the general scenario which emerges from our work and (possibly) applies to more realistic glassy models. Interestingly enough, some features of this scenario can be understood recurring to thermometric considerations.Comment: 4 pages, 5 figures (7 eps files

Transient increases in intracellular calcium and reactive oxygen species levels in TCam-2 cells exposed to microgravity

The effects of microgravity on functions of the human body are well described, including alterations in the male and female reproductive systems. In the present study, TCam-2 cells, which are considered a good model of mitotically active male germ cells, were used to investigate intracellular signalling and cell metabolism during exposure to simulated microgravity, a condition that affects cell shape and cytoskeletal architecture. After a 24 hour exposure to simulated microgravity, TCam-2 cells showed 1) a decreased proliferation rate and a delay in cell cycle progression, 2) increased anaerobic metabolism accompanied by increased levels of intracellular Ca(2+), reactive oxygen species and superoxide anion and modifications in mitochondrial morphology. Interestingly, all these events were transient and were no longer evident after 48 hours of exposure. The presence of antioxidants prevented not only the effects described above but also the modifications in cytoskeletal architecture and the activation of the autophagy process induced by simulated microgravity. In conclusion, in the TCam-2 cell model, simulated microgravity activated the oxidative machinery, triggering transient macroscopic cell events, such as a reduction in the proliferation rate, changes in cytoskeleton-driven shape and autophagy activation

Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC). Methods. From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0. Results. Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules. Conclusions. This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients

What information could the main actors of liquid biopsy provide? A representative case of non-small cell lung cancer (NSCLC)

In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistancedriving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution

Modifications of the hydrogen bond network of liquid water in a cylindrical SiO_2 pore

We present results of molecular dynamics simulations of water confined in a silica pore. A cylindrical cavity is created inside a vitreous silica cell with geometry and size similar to the pores of real Vycor glass. The simulations are performed at different hydration levels. At all hydration levels water adsorbs strongly on the Vycor surface; a double layer structure is evident at higher hydrations. At almost full hydration the modifications of the confinement-induced site-site pair distribution functions are in qualitative agreement with neutron diffraction experiment. A decrease in the number of hydrogen bonds between water molecules is observed along the pore radius, due to the tendency of the molecules close to the substrate to form hydrogen-bonds with the hydrophilic pore surface. As a consequence we observe a substrate induced distortion of the H-bond tetrahedral network of water molecules in the regions close to the surface.Comment: Talk presented at "Physics of Liquids: Foundations, Highlights, Challenge", Murau Sept. 1998. To appear in J. Mol. Li

Trapping dust particles in the outer regions of protoplanetary disks

Aims. We attempt to explain grain growth to mm sized particles and their retention in the outer regions of protoplanetary disks, as observed at sub-mm and mm wavelengths, by investigating whether strong inhomogeneities in the gas density profiles can decelerate excessive radial drift and help the dust particles to grow. Methods. We use coagulation/fragmentation and disk-structure models, to simulate the evolution of dust in a bumpy surface density profile, which we mimic with a sinusoidal disturbance. For different values of the amplitude and length scale of the bumps, we investigate the ability of this model to produce and retain large particles on million-year timescales. In addition, we compare the pressure inhomogeneities considered in this work with the pressure profiles that come from magnetorotational instability. Using the Common Astronomy Software Applications ALMA simulator, we study whether there are observational signatures of these pressure inhomogeneities that can be seen with ALMA. Results. We present the conditions required to trap dust particles and the corresponding calculations predicting the spectral slope in the mm-wavelength range, to compare with current observations. Finally, we present simulated images using different antenna configurations of ALMA at different frequencies, to show that the ring structures will be detectable at the distances of either the Taurus Auriga or Ophiucus star-forming regions

Testing the theory of grain growth and fragmentation by millimeter observations of protoplanetary disks

Context. Observations at sub-millimeter and mm wavelengths will in the near future be able to resolve the radial dependence of the mm spectral slope in circumstellar disks with a resolution of around a few AU at the distance of the closest star-forming regions. Aims. We aim to constrain physical models of grain growth and fragmentation by a large sample of (sub-)mm observations of disks around pre-main sequence stars in the Taurus-Auriga and Ophiuchus star-forming regions. Methods. State-of-the-art coagulation/fragmentation and disk-structure codes are coupled to produce steady-state grain size distributions and to predict the spectral slopes at (sub-)mm wavelengths. Results. This work presents the first calculations predicting the mm spectral slope based on a physical model of grain growth. Our models can quite naturally reproduce the observed mm-slopes, but a simultaneous match to the observed range of flux levels can only be reached by a reduction of the dust mass by a factor of a few up to about 30 while keeping the gas mass of the disk the same. This dust reduction can either be due to radial drift at a reduced rate or during an earlier evolutionary time (otherwise the predicted fluxes would become too low) or due to efficient conversion of dust into larger, unseen bodies.Comment: Accepted for publication in A&A Letters. 5 pages, 3 figure