EFFECT OF INTEGRIN α5 ON CANCER CELL MOTILITY IN 2D AND 3D MATRICES

The main cause of cancer related deaths is results from metastasis of cancer, or the spread of cancer to secondary sites. In order to metastasize, cancer cell migration is necessary. Numerous studies in cancer biology have examined mechanisms of cancer cell migration possible target molecules to prevent metastasis of cancer cells. During the early stages of metastasis, cancer cells penetrate through the basement membrane and invade into the extracellular matrix (ECM). During cell migration, integrins which are transmembrane receptors bind to extracellular matrix (ECM) molecules which mediate cell attachment and the formation of focal adhesions. Among many integrins, integrin α5β1 is often overexpressed in many cancer cells. We utilized 2D and 3D assays with an APRW model analysis to investigate the effect of downregulation of integrin α5 on cell motility using the metastatic breast cancer cell line, MDA-MB-231. We decreased integrin α5 expression using shRNA. Cells were plated on top of fibronectin, fibrinogen and collagen 2D substrates. Then, they were also embedded in a 3D collagen matrix and 3D collagen matrices with fibronectin. 2D and 3D cell movements were analyzed using an APRW model, saying cell movements are highly anisotropic. Furthermore, we performed focal adhesion staining on 2D cells to test correlation with cell migration Comparing 2D and 3D cell motility, we were able to observe integrin α5 had a remarkable effect on cell motility for 3D but showed less of an effect for 2D. We tested the correlation between 2D motility and focal adhesion and concluded that focal adhesion is not a predictor for 2D migration. With an increasing amount of fibronectin in 3D collagen matrices, the cell migration has decreased possibly due to the gel structure alteration. By investigating different parameters for cell motilities, such as diffusivity and persistence time, we were able to test effect of downregulation of integrin α5 on cell motility in 3D. Finally, the APRW model provided better characterization of cell movement than measuring cell velocities from cell trajectories data. Downregulation of integrin α5 does not alter cell speed but decreases diffusivity and persistence of metastatic cancer cells

TiDAL: Learning Training Dynamics for Active Learning

Active learning (AL) aims to select the most useful data samples from an unlabeled data pool and annotate them to expand the labeled dataset under a limited budget. Especially, uncertainty-based methods choose the most uncertain samples, which are known to be effective in improving model performance. However, AL literature often overlooks training dynamics (TD), defined as the ever-changing model behavior during optimization via stochastic gradient descent, even though other areas of literature have empirically shown that TD provides important clues for measuring the sample uncertainty. In this paper, we propose a novel AL method, Training Dynamics for Active Learning (TiDAL), which leverages the TD to quantify uncertainties of unlabeled data. Since tracking the TD of all the large-scale unlabeled data is impractical, TiDAL utilizes an additional prediction module that learns the TD of labeled data. To further justify the design of TiDAL, we provide theoretical and empirical evidence to argue the usefulness of leveraging TD for AL. Experimental results show that our TiDAL achieves better or comparable performance on both balanced and imbalanced benchmark datasets compared to state-of-the-art AL methods, which estimate data uncertainty using only static information after model training.Comment: ICCV 2023 Camera-Read

Scaling laws for the photo-ionisation cross section of two-electron atoms

The cross sections for single-electron photo-ionisation in two-electron atoms show fluctuations which decrease in amplitude when approaching the double-ionisation threshold. Based on semiclassical closed orbit theory, we show that the algebraic decay of the fluctuations can be characterised in terms of a threshold law $\sigma \propto |E|^{\mu}$ as $E \to 0_-$ with exponent $\mu$ obtained as a combination of stability exponents of the triple-collision singularity. It differs from Wannier's exponent dominating double ionisation processes. The details of the fluctuations are linked to a set of infinitely unstable classical orbits starting and ending in the non-regularisable triple collision. The findings are compared with quantum calculations for a model system, namely collinear helium.Comment: 4 pages, 1 figur

Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells.

Alzheimer's disease (AD) is often characterized by the impairment of mitochondrial function caused by excessive mitochondrial fragmentation. Thrombospondin-1 (TSP-1), which is primarily secreted from astrocytes in the central nervous system (CNS), has been suggested to play a role in synaptogenesis, spine morphology, and synaptic density of neurons. In this study, we investigate the protective role of TSP-1 in the recovery of mitochondrial morphology and function in amyloid β (Aβ)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits Aβ-induced mitochondrial fission by maintaining phosphorylated-Drp1 (p-Drp1) levels, which results in reduced Drp1 translocation to the mitochondria. By using gabapentin, a drug that antagonizes the interaction between TSP-1 and its neuronal receptor α2δ1, we observe that α2δ1 acts as one of the target receptors for TSP-1, and blocks the reduction of the p-Drp1 to Drp1 ratio, in the presence of Aβ. Taken together, TSP-1 appears to contribute to maintaining the balance in mitochondrial dynamics and mitochondrial functions, which is crucial for neuronal cell viability. These data suggest that TSP-1 may be a potential therapeutic target for AD

Total photoionization cross section of planar helium: scaling laws and collision orbits

The total photoionization cross section of planar helium has been calculated up to the single ionization threshold I22 of triple P states. The cross section shows chaotic fluctuations as the energy E approaches the double ionization threshold E=0. By analyzing the fluctuating part of the cross section, we show that its amplitude decreases as ∣E∣ mu for E-> 0- as predicted in Byunet al(2007 Phys. Rev. Lett., 98, 113001). The Fourier transform of the fluctuating part reveals peaks at the classical actions of closed triple collision orbits. Furthermore, the relative height of the peaks is consistent with the semiclassical predictions. Our findings underline that the fluctuating part of the photoionization cross section can be described by classical triple collision orbits in the semiclassical limit. These orbits all lie in the collinear eZe subspace, demonstrating that the fluctuations are dominated by the dynamics of this low dimensional phase space