Structural sensitivity of chaotic dynamics in Hastings-Powell's model

The classical Hastings-Powell model is well known to exhibit chaotic dynamics in a three-species food chain. Chaotic dynamics appear through period-doubling bifurcation of stable coexistence limit cycle around an unstable interior equilibrium point. A specific choice of parameter value leads to a situation where the chaotic attractor disappears through a collision with an unstable limit cycle. As a result, the top predator goes to extinction. Here we explore the structural sensitivity of this phenomenon by replacing the Holling type II functional responses with Ivlev functional responses. Here we prove the existence of two Hopf-bifurcation thresholds and numerically detect the existence of an unstable limit cycle. The model with Ivlev functional responses does not indicate any possibility of extinction of the top predator. Further, the choice of functional responses depicts a significantly different picture of the coexistence of the three species involved with the model

Spatio-temporal Bazykin’s model with space-time nonlocality

International audienceThis work deals with a reaction-diffusion model for prey-predator interaction with Bazykin's reaction kinetics and a nonlocal interaction term in prey growth. The kernel of the integral characterizes nonlocal consumption of resources and depends on space and time. Linear stability analysis determines the conditions of the emergence of Turing patterns without and with nonlocal term, while weakly nonlinear analysis allows the derivation of amplitude equations. The bifurcation analysis and numerical simulation carried out in this work reveal the existence of stationary and dynamic patterns appearing due to the loss of stability of the coexistence homogeneous steady-state

Black Hole Spin Measurements in LMC X-1 and Cyg X-1 Are Highly Model Dependent

The black hole spin parameter, a _* , was measured to be close to its maximum value of 1 in many accreting X-ray binaries. In particular, a _* ≳ 0.9 was found in a number of studies of LMC X-1. These measurements were claimed to take into account both statistical and systematic uncertainties. We perform new measurements using a recent simultaneous observation by NICER and NuSTAR, providing a data set of high quality. We use the disk continuum method together with improved models for coronal Comptonization. With the standard relativistic disk model and optically thin Comptonization, we obtain values of a _* similar to those obtained before. We then consider modifications to the standard model. Using a color correction of 2, we find a _* ≈ 0.64–0.84. We then consider disks with dissipation in surface layers. To account for that, we assume the standard disk is covered by a warm and optically thick Comptonizing layer. Our model with the lowest χ ^2 then yields ${a}_{* }\approx {0.40}_{-0.32}^{+0.41}$ . In order to test the presence of such effects in other sources, we also study an X-ray observation of Cyg X-1 by Suzaku in the soft state. We confirm the previous findings of a _* > 0.99 using the standard model, but then we find a weakly constrained ${a}_{* }\approx {0.82}_{-0.74}^{+0.16}$ when including an optically thick Comptonizing layer. We conclude that determinations of the spin using the continuum method can be highly sensitive to the assumptions about the disk structure

Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance in glioblastoma

Glioblastoma multiforme (GBM) is an aggressive cancer without currently effective therapies. Radiation and temozolomide (radio/TMZ) resistance are major contributors to cancer recurrence and failed GBM therapy. Heat shock proteins (HSPs), through regulation of extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT), provide mechanistic pathways contributing to the development of GBM and radio/TMZ-resistant GBM. The Friend leukemia integration 1 (Fli-1) signaling network has been implicated in oncogenesis in GBM, making it an appealing target for advancing novel therapeutics. Fli-1 is linked to oncogenic transformation with up-regulation in radio/TMZ-resistant GBM, transcriptionally regulating HSPB1. This link led us to search for targeted molecules that inhibit Fli-1. Expression screening for Fli-1 inhibitors identified lumefantrine, an antimalarial drug, as a probable Fli-1 inhibitor. Docking and isothermal calorimetry titration confirmed interaction between lumefantrine and Fli-1. Lumefantrine promoted growth suppression and apoptosis in vitro in parental and radio/TMZ-resistant GBM and inhibited tumor growth without toxicity in vivo in U87MG GBM and radio/TMZ-resistant GBM orthotopic tumor models. These data reveal that lumefantrine, an FDA-approved drug, represents a potential GBM therapeutic that functions through inhibition of the Fli-1/HSPB1/EMT/ECM remodeling protein networks

Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy

Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a Synthetic Somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein Loaded Liposomes (DNL) were prepared and they were further decorated with the Synthetic and Stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. In vivo tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. In vivo pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy