Search results for "g factor"

Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.

2021

The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…

The SWI/SNF subunits BRG1 affects alternative splicing by changing RNA binding factor interactions with RNA

2019

AbstractBRG1 and BRM are ATPase core subunits of the human SWI/SNF chromatin remodelling complexes. The function of the SWI/SNF complexes in transcriptional initiation has been well studied, while a function in alternative splicing has only been studied for a few cases for BRM-containing SWI/SNF complexes. Here, we have expressed BRG1 in C33A cells, a BRG1 and BRM-deficient cell line, and we have analysed the effects on the transcriptome by RNA sequencing. We have shown that BRG1 expression affects the splicing of a subset of genes. For some, BRG1 expression favours exon inclusion and for others, exon skipping. Some of the changes in alternative splicing induced by BRG1 expression do not re…

Correcting the effect of stellar spots on ARIEL transmission spectra – II. The limb-darkening effect

2021

This paper is part of an effort to correct the transmission spectra of a transiting planet orbiting an active star. In Paper I (Cracchiolo et al. 2020) we have demonstrated a methodology to minimize the potential bias induced by unocculted star spots on the transmission spectrum, assuming a spot model parameterized by filling factor and temperature. In this work we introduce the limb darkening effect, therefore the position of the spot in the stellar disk and the impact parameter of the transiting planet now play a key role. The method is tested on simulations of planetary transits of three representative kinds of planetary systems, at ARIEL resolution. We find that a realistic treatment of…

Coupled variable selection for regression modeling of complex treatment patterns in a clinical cancer registry.

2013

For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivat…

Building up adjusted indicators of students' evaluation of university courses using generalized item response models

2012

This article advances a proposal for building up adjusted composite indicators of the quality of university courses from students’ assessments. The flexible framework of Generalized Item Response Models is adopted here for controlling the sources of heterogeneity in the data structure that make evaluations across courses not directly comparable. Specifically, it allows us to: jointly model students’ ratings to the set of items which define the quality of university courses; explicitly consider the dimensionality of the items composing the evaluation form; evaluate and remove the effect of potential confounding factors which may affect students’ evaluation; model the intra-cluster variabilit…

Stochastic Differential Equations

2020

Stochastic differential equations describe the time evolution of certain continuous n-dimensional Markov processes. In contrast with classical differential equations, in addition to the derivative of the function, there is a term that describes the random fluctuations that are coded as an Ito integral with respect to a Brownian motion. Depending on how seriously we take the concrete Brownian motion as the driving force of the noise, we speak of strong and weak solutions. In the first section, we develop the theory of strong solutions under Lipschitz conditions for the coefficients. In the second section, we develop the so-called (local) martingale problem as a method of establishing weak so…

On ordinary differential equations with interface conditions

1968

Interferon-alpha (IFN-alpha) inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF) expression at the post-transcriptional level in murin…

1995

Recently it has been shown that IFN-alpha inhibits expression of GM-CSF in adherent cells of human long-term bone marrow cultures (LTBMC) stimulated with interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) or endotoxin. The murine bone marrow stromal cell line +/+(-1).LDA11 was used to further define regulatory mechanisms of IFN-alpha inhibition on GM-CSF expression. This cell line originated from a murine Dexter type culture and exhibits a preadipocytic phenotype. As in human LTBMC, we could demonstrate a inhibitory effect of IFN-alpha co-incubation on GM-CSF activity in serum-free supernatants of +/+(-1).LDA11 stromal cell cultures stimulated with IL-1 or TNF-alpha or the combi…

Topotecan triggers apoptosis in p53-deficient cells by forcing degradation of XIAP and survivin thereby activating caspase-3-mediated Bid cleavage.

2009

The topoisomerase I inhibitor topotecan (TPT) is used in the therapy of different tumors including high-grade gliomas. We previously showed that TPT-induced apoptosis depends on p53 with p53 wild-type (wt) cells being more resistant because of p53-controlled degradation of topoisomerase I. Here, we show that p53-deficient (p53(-/-)) fibroblasts undergo excessive mitochondrial apoptosis featuring H2AX phosphorylation, Bcl-x(L) decline, cytochrome c release, caspase-9/-3/-2 activation, and cleavage of Bid. In wt and apaf-1(-/-) cells, caspase-2 did not become activated and Bid was not cleaved. In addition, p53(-/-) cells cotreated with TPT and caspase-3 inhibitor showed neither caspase-2 acti…

Contribution to the Sustainability Challenges of the Food-Delivery Sector: Finding from the Deliveroo Italy Case Study

2020

The food delivery sector is assuming increasing importance in the distribution of food products and meals as it is becoming an ordinary component of consumption habits. However, the growth of the sector has inevitably affected the demand for freight transport, especially in urban areas. The aim of this study was to investigate the main enabling factors affecting the adoption of sustainable strategies, among which the electro-mobility, in the food delivery sector and what obstacles to dissemination can be seen. Deliveroo s.r.l. was chosen as case study. Results show that Deliveroo undoubtedly represents a good example of sustainable logistics and the dissemination of good practices among the…