Dynamic stabilization of non-spherical bodies against unlimited collapse

We solve equations, describing in a simplified way the newtonian dynamics of a selfgravitating nonrotating spheroidal body after loss of stability. We find that contraction to a singularity happens only in a pure spherical collapse, and deviations from the spherical symmetry stop the contraction by the stabilising action of nonlinear nonspherical oscillations. A real collapse happens after damping of the oscillations due to energy losses, shock wave formation or viscosity. Detailed analysis of the nonlinear oscillations is performed using a Poincar\'{e} map construction. Regions of regular and chaotic oscillations are localized on this map.Comment: MNRAS, accepted, 7 pages, 9 figure

Mechanisms of the Vertical Secular Heating of a Stellar Disk

We investigate the nonlinear growth stages of bending instability in stellar disks with exponential radial density profiles.We found that the unstable modes are global (the wavelengths are larger than the disk scale lengths) and that the instability saturation level is much higher than that following from a linear criterion. The instability saturation time scales are of the order of one billion years or more. For this reason, the bending instability can play an important role in the secular heating of a stellar disk in the $z$ direction. In an extensive series of numerical $N$-body simulations with a high spatial resolution, we were able to scan in detail the space of key parameters (the initial disk thickness $z_0$, the Toomre parameter $Q$, and the ratio of dark halo mass to disk mass $M_{\rm h} / M_{\rm d}$). We revealed three distinct mechanisms of disk heating in the $z$ direction: bending instability of the entire disk, bending instability of the bar, and heating on vertical inhomogeneities in the distribution of stellar matter.Comment: 22 pages including 8 figures. To be published in Astronomy Letters (v.29, 2003

Rotational superradiant scattering in a vortex flow

When an incident wave scatters off of an obstacle, it is partially reflected and partially transmitted. In theory, if the obstacle is rotating, waves can be amplified in the process, extracting energy from the scatterer. Here we describe in detail the first laboratory detection of this phenomenon, known as superradiance 1, 2, 3, 4. We observed that waves propagating on the surface of water can be amplified after being scattered by a draining vortex. The maximum amplification measured was 14% ± 8%, obtained for 3.70 Hz waves, in a 6.25-cm-deep fluid, consistent with the superradiant scattering caused by rapid rotation. We expect our experimental findings to be relevant to black-hole physics, since shallow water waves scattering on a draining fluid constitute an analogue of a black hole 5, 6, 7, 8, 9, 10, as well as to hydrodynamics, due to the close relation to over-reflection instabilities 11, 12, 13

TIMP-1 Induces an EMT-Like Phenotypic Conversion in MDCK Cells Independent of Its MMP-Inhibitory Domain

Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) regulate epithelial-mesenchymal transition (EMT) critical for the development of epithelial organs as well as cancer cell invasion. TIMP-1 is frequently overexpressed in several types of human cancers and serves as a prognostic marker. The present study investigates the roles of TIMP-1 on the EMT process and formation of the lumen-like structure in a 3D Matrigel culture of MDCK cells. We show that TIMP-1 overexpression effectively prevents cell polarization and acinar-like structure formation. TIMP-1 induces expression of the developmental EMT transcription factors such as SLUG, TWIST, ZEB1 and ZEB2, leading to downregulation of epithelial marker and upregulation of mesenchymal markers. Importantly, TIMP-1′s ability to induce the EMT-like process is independent of its MMP-inhibitory domain. To our surprise, TIMP-1 induces migratory and invasive properties in MDCK cells. Here, we present a novel finding that TIMP-1 signaling upregulates MT1-MMP and MMP-2 expression, and potentiates MT1-MMP activation of pro-MMP-2, contributing to tumor cell invasion. In spite of the fact that TIMP-1, as opposed to TIMP-2, does not interact with and inhibit MT1-MMP, TIMP-1 may act as a key regulator of MT1-MMP/MMP-2 axis. Collectively, our findings suggest a model in which TIMP-1 functions as a signaling molecule and also as an endogenous inhibitor of MMPs. This concept represents a paradigm shift in the current view of TIMP-1/MT1-MMP interactions and functions during cancer development/progression

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

DATA AND KNOWLEDGE PARALLEL PROCESSING BY MEANS OF N-TUPLE ALGEBRA

ABSTRACT N-tuple algebra is a mathematical system to formalize n-ary relations. This algebra provides for modelling both data (graphs, n-ary relations) and knowledge (semantic networks, reasoning models, formulas of propositional and predicate calculi, production systems, ontologies, etc.) by the same structures. These structures look like matrices and can be easily processed by parallel algorithms