Differentiation of Cancer Stem Cells by Using Synthetic Small Molecules: Toward New Therapeutic Strategies against Therapy Resistance

Despite the existing arsenal of anti-cancer drugs, 10 million people die each year worldwide due to cancers; this highlights the need to discover new therapies based on innovative modes of action against these pathologies. Current chemotherapies are based on the use of cytotoxic agents, targeted drugs, monoclonal antibodies or immunotherapies that are able to reduce or stop the proliferation of cancer cells. However, tumor eradication is often hampered by the presence of resistant cells called cancer stem-like cells or cancer stem cells (CSCs). Several strategies have been proposed to specifically target CSCs such as the use of CSC-specific antibodies, small molecules able to target CSC signaling pathways or drugs able to induce CSC differentiation rendering them sensitive to classical chemotherapy. These latter compounds are the focus of the present review, which aims to report recent advances in anticancer-differentiation strategies. This therapeutic approach was shown to be particularly promising for eradicating tumors in which CSCs are the main reason for therapeutic failure. This general view of the chemistry and mechanism of action of compounds inducing the differentiation of CSCs could be particularly useful for a broad range of researchers working in the field of anticancer therapies as the combination of compounds that induce differentiation with classical chemotherapy could represent a successful approach for future therapeutic applications.     

The AFLATOX® Project: Approaching the Development of New Generation,Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox^® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem.     

Niobium Containing Micro-, Meso- and Macroporous Silica Materials as Catalysts for the Epoxidation of Olefins with Hydrogen Peroxide

Niobia–silica mesoporous materials (xerogel, aerogel and MCM type) have been synthesized by sol–gel techniques using different co-solvents as templates. All materials are active catalysts in the epoxidation of cyclohexene with hydrogen peroxide, but only meso–macroporous aerogels give a stable and recyclable catalyst.     

Selective catalytic transformations of methanol to C2-C3 hydrocarbons over the new zeolite type LZ 132

The small pore zeolite HLZ 132 exhibits, in comparison with other zeolites, an increased selectivity for the transformation of methanol to ethylene in the reaction temperature range 350–500 °C: the weight ratio of C₂H₄ to C₃H₆ in the products ranges between 1 and 4 at WHSV=2 h^–1. Besides the effect of the reactant shape selectivity this fact may be interpreted by the participation of the asymmetrical methoxy groups in the surface as well as by proton-donor centres of lower acidity which do not catalyze the oligomerization of ethylene but which do the more basic molecule of propylene, thereby generating polyene-type coke.     

Fine coal desulphurization by leaching with bromine containing hydrobromic acid

Sulphur extraction from coal by leaching with bromine-containing aqueous hydrobromic acid has been investigated in the temperature range from ambient to 120 °C. This procedure was found to be selective for the removal of high levels of sulphate and pyritic sulphur within a few minutes of leaching, while no significant reduction of the organic sulphur could be observed. Leaching led to an appreciable reduction of the ash yield and the up-take of substantial quantities of bromine. The bromine can be removed as hydrogen bromide by thermal treatment under nitrogen, without significant loss of volatile matter; for reduction of the bromine level to below 0.1 wt%, treatment for at least 1 h at ≈ 500 °C was needed.     

Straightforward modeling of dynamic I–V characteristics for microwave FETs

This work presents a straightforward approach aimed at modeling the dynamic I–V characteristics of microwave active solid‐state devices. The drain‐source current generator represents the most significant source of nonlinearity in a transistor and, therefore, its correct modeling is fundamental to predict accurately the current and voltage waveforms under large‐signal operation. The proposed approach relies on using a small set of low‐frequency time‐domain waveform measurements combined with numerical optimization‐based estimation of the nonlinear model parameters. The procedure is applied to a gallium nitride HEMT and silicon FinFET. The effectiveness of the modeling procedure in terms of prediction accuracy and generalization capability is demonstrated by validation of the extracted models under operating conditions different than the ones used for the parameters estimation. Good agreement between measurements and model simulations is achieved for both technologies and in both low‐ and high‐frequency range. © 2013 Wiley Periodicals, Inc. Int J RF and Microwave CAE 24:109–116, 2014.     

Ceramic Microtubes from Preceramic Polymers

A novel process for the production of ceramic microtubes involving the microextrusion of preceramic polymers was studied. Microtubes with a wide range of inner and outer diameters and several centimeters long were produced from two silicone resins. A coextrusion approach was also used to extend the forming capability of the technique. The addition of carbon black resulted in electrically conductive silicon oxycarbide (SiOC) ceramic microtubes. SiOC microtubes possessed a high bending strength, ranging from ∼30–1100 MPa.     

Requirement-oriented risk management for incremental software development

In incremental software development (ISD) functionalities are delivered incrementally and requirements keep on evolving across iterations. The requirements evolution involves the addition of new dependencies and conflicts among functional and non-functional requirements along with changes in priorities and dependency weights. This, in turn, demands refactoring the order of development of system components to minimize the impact of these changes. Neglecting the non-functional constraints in the software development process exposes it to risks that may accumulate across several iterations. In this research work, we propose a risk management framework for ISD processes that provides an estimate of risk exposure for the project when functional features are frozen while ignoring the associations with non-functional requirements. Our framework proposes suitable risk reduction strategies that work in tandem with the risk assessment module. We also provide a tool interface for our risk management framework.