Search results for "D02"
showing 10 items of 11 documents
Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells
2016
We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide\ud hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor\ud (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast\ud cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically\ud synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-\ud 5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on\ud cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation,\ud an…
Splittings of Toric Ideals
2019
Let $I \subseteq R = \mathbb{K}[x_1,\ldots,x_n]$ be a toric ideal, i.e., a binomial prime ideal. We investigate when the ideal $I$ can be "split" into the sum of two smaller toric ideals. For a general toric ideal $I$, we give a sufficient condition for this splitting in terms of the integer matrix that defines $I$. When $I = I_G$ is the toric ideal of a finite simple graph $G$, we give additional splittings of $I_G$ related to subgraphs of $G$. When there exists a splitting $I = I_1+I_2$ of the toric ideal, we show that in some cases we can describe the (multi-)graded Betti numbers of $I$ in terms of the (multi-)graded Betti numbers of $I_1$ and $I_2$.
The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells
2015
The histone deacetylase inhibitor N-1-(ferrocenyl)-N-8-hydroxyoctanediamide (JAHA) down-regulates extracellular-signal-regulated kinase (ERK) and its activated form in triple-negative MDA-MB231 breast cancer cells after 18 h and up to 30 h of treatment, and to a lesser extent AKT and phospho-AKT after 30 h and up to 48 h of treatment. Also, DNA methyltransferase 1 (DNMT1), 3b and, to a lesser extent, 3a, downstream ERK targets, were down-regulated already at 18 h with an increase up to 48 h of exposure. Methylation-sensitive restriction arbitrarily-primed (MeSAP) polymerase chain reaction (PCR) analysis confirmed the ability of JAHA to induce genome-wide DNA hypomethylation at 48 h of expos…
Regularity and h-polynomials of toric ideals of graphs
2020
For all integers 4 ≤ r ≤ d 4 \leq r \leq d , we show that there exists a finite simple graph G = G r , d G= G_{r,d} with toric ideal I G ⊂ R I_G \subset R such that R / I G R/I_G has (Castelnuovo–Mumford) regularity r r and h h -polynomial of degree d d . To achieve this goal, we identify a family of graphs such that the graded Betti numbers of the associated toric ideal agree with its initial ideal, and, furthermore, that this initial ideal has linear quotients. As a corollary, we can recover a result of Hibi, Higashitani, Kimura, and O’Keefe that compares the depth and dimension of toric ideals of graphs.
Symmetric locally free resolutions and rationality problems
2022
We show that the birationality class of a quadric surface bundle over $\mathbb{P}^2$ is determined by its associated cokernel sheaves. As an application, we discuss stable-rationality of very general quadric bundles over $\mathbb{P}^2$ with discriminant curves of fixed degree. In particular, we construct explicit models of these bundles for some discriminant data. Among others, we obtain various birational models of a nodal Gushel-Mukai fourfold, as well as of a cubic fourfold containing a plane. Finally, we prove stable irrationality of several types of quadric surface bundles.
Targeting Cavity-Creating p53 Cancer Mutations with Small-Molecule Stabilizers: the Y220X Paradigm
2020
We have previously shown that the thermolabile, cavity-creating p53 cancer mutant Y220C can be reactivated by small-molecule stabilizers. In our ongoing efforts to unearth druggable variants of the p53 mutome, we have now analyzed the effects of other cancer-associated mutations at codon 220 on the structure, stability, and dynamics of the p53 DNA-binding domain (DBD). We found that the oncogenic Y220H, Y220N, and Y220S mutations are also highly destabilizing, suggesting that they are largely unfolded under physiological conditions. A high-resolution crystal structure of the Y220S mutant DBD revealed a mutation-induced surface crevice similar to that of Y220C, whereas the corresponding pock…
Truncated modules and linear presentations of vector bundles
2018
We give a new method to construct linear spaces of matrices of constant rank, based on truncated graded cohomology modules of certain vector bundles as well as on the existence of graded Artinian modules with pure resolutions. Our method allows one to produce several new examples, and provides an alternative point of view on the existing ones.
Torsion of a finite base locus
2018
We interpret geometrically the torsion of the symmetric algebra of the ideal sheaf of a zero-dimensional scheme Z defined by $n+1$ equations in an $n$-dimensional variety. This leads us to generalise a formula of A.Dimca and S.Papadima in positive characteristic for a rational transformation with finite base locus. Among other applications, we construct an explicit example of a homaloidal curve of degree $5$ in characteristic $3$, answering negatively a question of A.V.D\'oria, S.H.Hassanzadeh and A.Simis.
Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Neg…
2015
BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding
Conflict, Evolution, Hegemony, and the Power of the State
2013
In a model of evolution driven by conflict between societies more powerful states have an advantage. When the influence of outsiders is small we show that this results in a tendency to hegemony. In a simple example in which institutions differ in their “exclusiveness” we find that these hegemonies will be inefficiently “extractive” in the sense of having inefficiently high taxes, high compensation for state officials, and low welfare.