Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study.

BACKGROUND: Arsenic Trioxide (ATO) is effective in about 20% of patients with myelodysplasia (MDS); its mechanisms of action have already been evaluated in vitro, but the in vivo activity is still not fully understood. Since ATO induces apoptosis in in vitro models, we compared the expression of 93 apoptotic genes in patients’ bone marrow before and after ATO treatment. For this analysis, we selected 12 patients affected by MDS who received ATO in combination with Ascorbic Acid in the context of the Italian clinical trial NCT00803530, EudracT Number 2005-001321-28. METHODS: Real-time PCR quantitative assays for genes involved in apoptosis were performed using TaqMan® Assays in 384-Well Microfluidic Cards “TaqMan® Human Apoptosis Array”. Quantitative RT-PCR for expression of EVI1 and WT1 genes was also performed. Gene expression values (Ct) were normalized to the median expression of 3 housekeeping genes present in the card (18S, ACTB and GAPDH). RESULTS: ATO treatment induced up-regulation of some pro-apoptotic genes, such as HRK, BAK1, CASPASE-5, BAD, TNFRSF1A, and BCL2L14 and down-regulation of ICEBERG. In the majority of cases with stable disease, apoptotic gene expression profile did not change, whereas in cases with advanced MDS more frequently pro-apoptotic genes were up-regulated. Two patients achieved a major response: in the patient with refractory anemia the treatment down-regulated 69% of the pro-apoptotic genes, whereas 91% of the pro-apoptotic genes were up-regulated in the patient affected by refractory anemia with excess of blasts-1. Responsive patients showed a higher induction of BAD than those with stable disease. Finally, WT1 gene expression was down-regulated by the treatment in responsive cases. CONCLUSIONS: These results represent the basis for a possible association of ATO with other biological compounds able to modify the apoptotic pathways, such as inhibitors of the BCL2 family

The optimality of word lengths. Theoretical foundations and an empirical study

Zipf's law of abbreviation, namely the tendency of more frequent words to be shorter, has been viewed as a manifestation of compression, i.e. the minimization of the length of forms -- a universal principle of natural communication. Although the claim that languages are optimized has become trendy, attempts to measure the degree of optimization of languages have been rather scarce. Here we present two optimality scores that are dualy normalized, namely, they are normalized with respect to both the minimum and the random baseline. We analyze the theoretical and statistical pros and cons of these and other scores. Harnessing the best score, we quantify for the first time the degree of optimality of word lengths in languages. This indicates that languages are optimized to 62 or 67 percent on average (depending on the source) when word lengths are measured in characters, and to 65 percent on average when word lengths are measured in time. In general, spoken word durations are more optimized than written word lengths in characters. Our work paves the way to measure the degree of optimality of the vocalizations or gestures of other species, and to compare them against written, spoken, or signed human languages.Comment: On the one hand, the article has been reduced: analyses of the law of abbreviation and some of the methods have been moved to another article; appendix B has been reduced. On the other hand, various parts have been rewritten for clarity; new figures have been added to ease the understanding of the scores; new citations added. Many typos have been correcte

Direct and indirect evidence of compression of word lengths. Zipf's law of abbreviation revisited

Zipf's law of abbreviation, the tendency of more frequent words to be shorter, is one of the most solid candidates for a linguistic universal, in the sense that it has the potential for being exceptionless or with a number of exceptions that is vanishingly small compared to the number of languages on Earth. Since Zipf's pioneering research, this law has been viewed as a manifestation of a universal principle of communication, i.e. the minimization of word lengths, to reduce the effort of communication. Here we revisit the concordance of written language with the law of abbreviation. Crucially, we provide wider evidence that the law holds also in speech (when word length is measured in time), in particular in 46 languages from 14 linguistic families. Agreement with the law of abbreviation provides indirect evidence of compression of languages via the theoretical argument that the law of abbreviation is a prediction of optimal coding. Motivated by the need of direct evidence of compression, we derive a simple formula for a random baseline indicating that word lengths are systematically below chance, across linguistic families and writing systems, and independently of the unit of measurement (length in characters or duration in time). Our work paves the way to measure and compare the degree of optimality of word lengths in languages.Comment: In press in Glottometrics. arXiv admin note: substantial text overlap with arXiv:2208.1038

ErbB in NSCLC as a molecular target: Current evidences and future directions

A number of treatments have been developed for HER1, 2 and 3-driven non-small cell lung cancer (NSCLC), of which the most successful have been the epidermal growth factor receptor-tyrosine kinase inhibitors in HER1-mutant tumours resulting in highly improved progression-free survival. Human epidermal growth factor (HER)2 and 3-driven tumours represent the minority of NSCLC, and effective therapies in these patients still represent an unmet medical need. The encouraging results seen with anti-HER2 and anti-HER3 monoclonal antibodies need to be validated in larger studies, even if the greatest obstacle is represented by the exiguous number of patients bearing deregulated HER2/3 system and abnormalities of signal transduction pathway. Considering NSCLC tumour heterogeneity, which affects response and resistance to treatment, combined multiparametric approaches, such as liquid biopsy together with radiomics, may provide a better understanding of the tumour dynamics and clonal selection during the treatments

Numerical Study of the Optical Response of ITO-In2O3 Core-Shell Nanocrystals for Multispectral Electromagnetic Shielding

Nowadays materials to protect equipment from unwanted multispectral electromagnetic waves are needed in a broad range of applications including electronics, medical, military and aerospace. However, the shielding materials currently in use are bulky and work effectively only in a limited frequency range. Therefore, nanostructured materials are under investigation by the relevant scientific community. In this framework, the design of multispectral shielding nanomaterials must be supplemented with proper numerical models that allow dealing with non-linearities and being effective in predicting their absorption spectra. In this study, the electromagnetic response of metal-oxide nanocrystals with multispectral electromagnetic shielding capability has been investigated. A numerical framework was developed to predict energy bands and electron density profiles of a core-shell nanocrystal and to evaluate its optical response at different wavelengths. To this aim, a finite element method software is used to solve a non-linear Poisson's equation. The numerical simulations allowed to model the optical response of ITO-In2O3 core-shell nanocrystals and can be effectively applied to different nanotopologies to support an enhanced design of nanomaterials with multispectral shielding capabilities

Projeto Marca - avaliação da implantação do projeto na ETB, safra 2004/05.

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