Search results for "points"
showing 10 items of 415 documents
TORC1 controls G1–S cell cycle transition in yeast via Mpk1 and the greatwall kinase pathway
2015
The target of rapamycin complex 1 (TORC1) pathway couples nutrient, energy and hormonal signals with eukaryotic cell growth and division. In yeast, TORC1 coordinates growth with G1–S cell cycle progression, also coined as START, by favouring the expression of G1 cyclins that activate cyclin-dependent protein kinases (CDKs) and by destabilizing the CDK inhibitor Sic1. Following TORC1 downregulation by rapamycin treatment or nutrient limitation, clearance of G1 cyclins and C-terminal phosphorylation of Sic1 by unknown protein kinases are both required for Sic1 to escape ubiquitin-dependent proteolysis prompted by its flagging via the SCFCdc4 (Skp1/Cul1/F-box protein) ubiquitin ligase complex.…
Oscillatory integrals and fractal dimension
2021
Theory of singularities has been closely related with the study of oscillatory integrals. More precisely, the study of critical points is closely related to the study of asymptotic of oscillatory integrals. In our work we investigate the fractal properties of a geometrical representation of oscillatory integrals. We are motivated by a geometrical representation of Fresnel integrals by a spiral called the clothoid, and the idea to produce a classification of singularities using fractal dimension. Fresnel integrals are a well known class of oscillatory integrals. We consider oscillatory integral $$ I(\tau)=\int_{; ; \mathbb{; ; R}; ; ^n}; ; e^{; ; i\tau f(x)}; ; \phi(x) dx, $$ for large value…
Stochastic sensitivity of bull and bear states
2021
We study the price dynamics generated by a stochastic version of a Day–Huang type asset market model with heterogenous, interacting market participants. To facilitate the analysis, we introduce a methodology that allows us to assess the consequences of changes in uncertainty on the dynamics of an asset price process close to stable equilibria. In particular, we focus on noise-induced transitions between bull and bear states of the market under additive as well as parametric noise. Our results are obtained by combining the stochastic sensitivity function (SSF) approach, a mixture of analytical and numerical techniques, due to Mil’shtein and Ryashko (1995) with concepts and techniques from th…
Calibrations and isoperimetric profiles
2007
We equip many noncompact nonsimply connected surfaces with smooth Riemannian metrics whose isoperimetric profile is smooth, a highly nongeneric property. The computation of the profile is based on a calibration argument, a rearrangement argument, the Bol-Fiala curvature dependent inequality, together with new results on the profile of surfaces of revolution and some hardware know-how.
Functional impact and evolution of a novel human polymorphic inversion that disrupts a gene and creates a fusion transcript
2015
Despite many years of study into inversions, very little is known about their functional consequences, especially in humans. A common hypothesis is that the selective value of inversions stems in part from their effects on nearby genes, although evidence of this in natural populations is almost nonexistent. Here we present a global analysis of a new 415-kb polymorphic inversion that is among the longest ones found in humans and is the first with clear position effects. This inversion is located in chromosome 19 and has been generated by non-homologous end joining between blocks of transposable elements with low identity. PCR genotyping in 541 individuals from eight different human populatio…
Efficacy and safety of first-line checkpoint inhibitors-based treatments for non-oncogene-addicted non-small-cell lung cancer: a systematic review an…
2021
Background: Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis. Methods: A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs). Results: Nineteen RCTs involving 17 treatment regimens were included. For the all-co…
Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors
2022
Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlight…
OFN Capital Budgeting Under Uncertainty and Risk
2017
The aim of this chapter is to propose a new approach to incorporating uncertainty into capital budgeting. The chapter presents methods that can be used by an investor when the decision maker wants to be able to make an investment decision where there are alternative investment projects. This kind of problem is undertaken under the conditions of uncertainty and risk using Ordered Fuzzy Numbers (OFN). The starting point is the concept of Ordered Fuzzy Numbers. The chapter illustrates the implementation of the proposed approach with an example where two alternative investment projects are analyzed. The authors present the capital budgeting problem using a numerical example. The described metho…
Synthesis and biological evaluation of a D-ring-contracted analogue of lamellarin D
2017
A D-ring contracted analogue of the strongly cytotoxic marine pyrrole alkaloid lamellarin D was synthesized and investigated for its antiproliferative action towards a wild type and a multidrug resistant (MDR) cancer cell line. The compound was found to inhibit tumor cell growth at submicromolar concentrations and showed a lower relative resistance in the MDR cell line than the antitumor drug camptothecin to which lamellarin D shows cross resistance and with which lamellarin D shares the same binding site.
Cell cycle arrest and induction of apoptosis by cajanin stilbene acid from Cajanus cajan in breast cancer cells
2015
Abstract Background: The low abundant cajanin stilbene acid (CSA) from Pigeon Pea ( Cajanus cajan ) has been shown to kill estrogen receptor α positive cancer cells in vitro and in vivo . Downstream effects such as cell cycle and apoptosis-related mechanisms have not been analyzed yet. Material and methods: We analyzed the activity of CSA by means of flow cytometry (cell cycle distribution, mitochondrial membrane potential, MMP), confocal laser scanning microscopy (MMP), DNA fragmentation assay (apoptosis), Western blotting (Bax and Bcl-2 expression, caspase-3 activation) as well as mRNA microarray hybridization and Ingenuity pathway analysis. Results: CSA induced G2/M arrest and apoptosis …