69 research outputs found
Targeting histone demethylases: A new avenue for the fight against cancer
No full textIn addition to genetic disorders, epigenetic alterations have been shown to be involved in cancer, through misregulation of histone modifications. Miswriting, misreading, and mis-erasing of histone acetylation as well as methylation marks can be actually associated with oncogenesis and tumor proliferation. Historically, methylation of Arg and Lys residues has been considered a stable, irreversible process due to the slow turnover of methyl groups in chromatin. The discovery in recent years of a large number of histone Lys demethylases (KDMs, belonging to either the amino oxidase or the JmjC family) totally changed this point of view and suggested a new role for dynamic histone methylation in biological processes. Since overexpression, alteration, or mutation of a number of KDMs has been found in many types of cancers, such enzymes could represent diagnostic tools as well as epigenetic targets to modulate for obtaining novel therapeutic weapons against cancer. The first little steps in this direction are described here. © The Author(s) 2011
Enhanced Multichannel Histogram Equalization for Speech Recognition in noisy acoustic conditions
No full textFeature statistics normalization in the cepstral domain is one of the most performing approaches for robust automatic Speech Recognition (ASR) in noisy acoustic scenarios. According to this approach, feature coefficients are normalized by using suitable linear or nonlinear transformations in order to match the noisy speech statistics to the clean speech one. Histogram Equalization (HEQ) is an effective algorithm belonging to this category. Recently some of the authors have proposed an interesting extension to the HEQ original algorithm, in order to suitably deal with the multichannel audio information coming from multi-microphone sensory activity in far-field acoustic scenarios. In this paper the feature normalization capabilities of the multichannel HEQ technique are further enhanced by introducing the kernel estimation technique and employing the multi-condition training for ASR system parametrization. Computer simulations based on the Aurora 2 database have shown that a significant recognition improvement with respect to the single-channel counterpart and other multi-channel techniques can be achieved confirming the effectiveness of the idea
Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans
No full textAmong fungal pathogens such as Candida albicans, acquired drug resistance has not been associated with plasmids or other transferable elements, but it is thought to involve primarily mutations and genetic or epigenetic phenomena. This prompted us to test some histone deacetylase inhibitors (HDACi) from our library, in combination with fluconazole, against C. albicans strains in vitro. Among the tested compounds, the two chloro-containing uracil-hydroxamates 1c and 1d showed a strong reduction of the MIC values on Candida strains that show the trailing growth effect. In this assay, 1c,d were more potent than SAHA, a well-known HDAC inhibitor, in reducing the Candida growth. More interestingly, 1c,d as well as SAHA were able to inhibit the fluconazole-induced resistance induction in Candida cultures. (c) 2006 Elsevier Ltd. All rights reserved
Preparation of 7-nitro-2,1,3-benzoxadiazole derivatives for antitumor therapy
No full textThe invention relates to benzoxazole derivs. of formula I [R is (un)substituted alkyl, Ph, or phenylalkyl] for use in antitumor therapy owing to their potent inhibitory activity with respect to glutathione S-transferase (GST). Thus, I (R = CH2C6H4CO2Et-p) was prepd. by reaction of Et 4-(bromoethyl)benzoate with potassium Et xanthogenate, followed by treatment with EtONa in EtOH and 4-chloro-7-nitro-2,1,3-benzoxadiazole. The product showed IC50 = 1.19 and 0.007 vs. enzymes GSTP1-1 and GSTM2-2, resp. [on SciFinder(R)
Derivati del 7-nitro-2,1,3-benzossidiazolo per terapia antitumorale
No full textIl presente brevetto protegge una famiglia di molecole derivate dal 7-nitro-2,1,3-benzossidiazolo ed ottenute per sintesi chimica, utilizzabili per il loro effetto tossico su tumori che sovraesprimono l’enzima glutatione S-trasferasi di classe Pi
Preparation of 7-nitro-2,1,3-benzoxadiazole derivatives for antitumor therapy
No full textThe invention relates to benzoxazole derivs. of formula I [R is (un)substituted alkyl, Ph, or phenylalkyl] for use in antitumor therapy owing to their potent inhibitory activity with respect to glutathione S-transferase (GST). Thus, I (R = CH2C6H4CO2Et-p) was prepd. by reaction of Et 4-(bromoethyl)benzoate with potassium Et xanthogenate, followed by treatment with EtONa in EtOH and 4-chloro-7-nitro-2,1,3-benzoxadiazole. The product showed IC50 = 1.19 and 0.007 vs. enzymes GSTP1-1 and GSTM2-2, resp. [on SciFinder(R)
Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans
No full textCandida albicans is able to establish mucosal and invasive diseases by means of different virulence factors that are frequently regulated by epigenetic mechanisms, including the acetylation-deacetylation of histones and of other regulatory proteins. The focus of our work was on understanding the possible effects of several histone deacetylase inhibitors (HDACi) on the expression of phenotypes that are associated with virulence and pathogenicity in C. albicans, such as adhesion to epithelial cells and the yeast to hypha transition. Some of the HDACi used for experiments caused a 90% reduction in the adherence of C. albicans to human cultured pneumocytes and significantly inhibited serum-induced germination. Inhibition of germination was correlated with a significant reduction in transcription of EFG1. Inhibition appeared less evident when an HDA1-deficient strain was tested. These results suggest that selective and specific HDACi could prove to be a valid approach for selected at-risk patients in the combined treatment of infections caused by C. albicans. © 2007 Federation of European Microbiological Societies
Non-cancer uses of histone deacetylase inhibitors: effects on infectious diseases and β-hemoglobinopathies
No full textAfter the approval of suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) for the treatment of cutaneous T cell lymphoma (CTCL), a number of HDAC inhibitors (HDACi) are currently in Phase II or III clinical trials (alone or in combination) for the treatment of a great number of tumors. In addition to these cancer uses, HDACi can be successfully used in non-cancer diseases. In this review we focused on the uses of HDACi in some infectious diseases and beta-hemoglobinopaties. In C. albicans cultures, HDACi increased the frequency of cell switching (a relevant virulence trait) in the white-to-opaque transition, reduced the azole trailing effect through reduction in azole-dependent upregulation of CDR and ERG genes, and inhibited the fluconazole-dependent resistance induction. Moreover, they inhibited germination in several strains, and caused 90% reduction in the adherence of C. albicans to human cultured pneumocytes. In HIV-1-infected cells, the treatment with HDACi reactivates the HIV-1 expression in latent cellular reservoirs. Thus, the use of HDACi as adjuvant to highly active antiretroviral therapy (HAART) can represent a new potential therapeutic strategy to eradicate the viral infection. A number of HDACi have been reported as active against P. falciparum infection. Two recent papers show some 2-aminosuberic acid-based compounds as well as a series of phenylthiazolyl suberoyl hydroxamates as very potent and selective antimalarial agents. Among the many agents capable to perform post-natal reactivation of fetal hemoglobin production, HDACi for their capacity to de-repress gamma-globin gene expression in adult red cell, are presently considered promising molecules for personalized therapy of beta-hemoglobinopathies
Experimental and numerical characterization of innovative cardboard based panels: Thermal and acoustic performance analysis and life cycle assessment
No full textEfficient thermal insulating materials can significantly reduce energy consumption for both heating and cooling of buildings. When selecting an insulation material, however, it is important to consider other important aspects, such as acoustic performance, environmental impacts, effects on human health and costs of production. That is the reason why key research developments are recently achieved in the field of sustainable, highly efficient materials. Within this context, this paper deals with the thermal and acoustic performance and the environmental impact analysis of two kinds of corrugated multi-layer cardboard panels, usually applied in the packaging industry. Thermal analyses were conducted in order to measure the thermal conductivity by means of both an experimental campaign and numerical methods. The acoustic absorption coefficient and the transmission loss were experimentally determined by means of an impedance tube. Finally a Life Cycle Assessment of the considered panels was implemented and compared to the performance of other commonly used insulation materials. The main results of the study show that the cardboard-made panels usually applied for low-cost packaging present promising performance in terms of both acoustic and thermal insulation potential, i.e. of the same order of magnitude than high-performance commercialized products. The environmental impact evaluation also reveals an interesting behavior of the corrugated cardboard panels, which can by any means be considered as a promising recycled insulation material
La forma infranta. La ‘Lezione di Guerra’ di Wilhelm Windelband
No full textThe author offers a critical review of the last, unfinished writings of Wilhelm Windelband on the philosophy
of history. The text, known as the ‘lecture of war,’ is written in the dramatic situation of 1915, just before
the death of the master of the Baden School. The author interprets the ‘lecture’ in relation to the crisis into
which the project of neo-Kantian philosophy of culture was thrown by the World War. Windelband tried to
safeguard his own philosophical perspective and to make a positive contribution to the cultural struggle into
which the Great War had driven all German intellectuals
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