Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

Biodegradability Study of the Biosurfactant Contained in a Crude Extract from Corn Steep Water

Over the last few years, the global biosurfactant market has raised due to the increasing awareness among consumers, for the use of biological or bio-based products. Because of their composition, it can be speculated that these are more biocompatible and more biodegradable than their chemical homologous. However, at the moment, no studies exist in the literature about the biodegradability of biosurfactants. In this work, a biosurfactant contained in a crude extract, obtained from a corn wet-milling industry stream that ferments spontaneously in the presence of lactic acid bacteria, was subjected to a biodegradation study, without addition of external microbial biomass, under different conditions of temperature (5–45 °C), biodegradation time (15–55 days), and pH (5–7). For that, a Box–Behnken factorial design was applied, which allowed to predict the percentage of biodegradation for the biosurfactant contained in the crude extract, between the range of the independent variables selected in the study, obtaining biodegradation values between 3 and 80%. The percentage of biodegradation for the biosurfactant was calculated based on the increase in the surface tension of samples of the crude extract. Furthermore, it was also possible to predict the variation in t_1/2 for the biosurfactant (time to achieve the 50% of biodegradation) under different conditions.     

Solvent effect modelling of isocyanuric products synthesis by chemometric methods

Chemometric tools were used to generate the modelling of solvent e inverted exclamation markects on the N-alkylation of an isocyanuric acid salt. The method proceeded from a central composite design applied on the Carlson solvent classification using principal components analysis. The selectivity of the reaction was studied from the production of different substituted isocyanuric derivatives. Response graphs were obtained for each compound and used to devise a strategy for solvent selection. The prediction models were validated and used to search for the best selectivity for the reaction system. The solvent most often selected as the best for the reaction is the N,N-dimethylformamide.     

Whey Drying on Porous Carriers

Whey is an undurable product. treated very often as a waste which pollutes the natural environment. Whey which is a valuable source of protein, lactose, vitamins and mineral salts should be utilized completely. The present paper is a proposal of whey drying on porous carriers. It is proved experimentally that the proposed drying method guarantees good product quality.     

Archiving the web using page changes patterns: a case study

A pattern is a model or a template used to summarize and describe the behavior (or the trend) of data having generally some recurrent events. Patterns have received a considerable attention in recent years and were widely studied in the data mining field. Various pattern mining approaches have been proposed and used for different applications such as network monitoring, moving object tracking, financial or medical data analysis, scientific data processing, etc. In these different contexts, discovered patterns were useful to detect anomalies, to predict data behavior (or trend) or, more generally, to simplify data processing or to improve system performance. However, to the best of our knowledge, patterns have never been used in the context of Web archiving. Web archiving is the process of continuously collecting and preserving portions of the World Wide Web for future generations. In this paper, we show how patterns of page changes can be useful tools to efficiently archive Websites. We first define our pattern model that describes the importance of page changes. Then, we present the strategy used to (i) extract the temporal evolution of page changes, (ii) discover patterns, to (iii) exploit them to improve Web archives. The archive of French public TV channels France Télévisions is chosen as a case study to validate our approach. Our experimental evaluation based on real Web pages shows the utility of patterns to improve archive quality and to optimize indexing or storing.     

Bamboo reinforced concrete: a critical review

The use of small diameter whole-culm (bars) and/or split bamboo (a.k.a. splints or round strips) has often been proposed as an alternative to relatively expensive reinforcing steel in reinforced concrete. The motivation for such replacement is typically cost—bamboo is readily available in many tropical and sub-tropical locations, whereas steel reinforcement is relatively more expensive—and more recently, the drive to find more sustainable alternatives in the construction industry. This review addresses such ‘bamboo-reinforced concrete’ and assesses its structural and environmental performance as an alternative to steel reinforced concrete. A prototype three bay portal frame, that would not be uncommon in regions of the world where bamboo-reinforced concrete may be considered, is used to illustrate bamboo reinforced concrete design and as a basis for a life cycle assessment of the same. The authors conclude that, although bamboo is a material with extraordinary mechanical properties, its use in bamboo-reinforced concrete is an ill-considered concept, having significant durability, strength and stiffness issues, and does not meet the environmentally friendly credentials often attributed to it.     

Interpretations of open default theories in non-monotonic logics

It is shown that the translation of an open default into a modal formula x(L(x)LM ₁ (x)...LM _m (x)w(x)) gives rise to an embedding of open default systems into non-monotonic logics.     

Kernel orthonormalization in radial basis function neural networks

This paper deals with optimization of the computations involved in training radial basis function (RBF) neural networks. The main contribution of the reported work is the method for network weights calculation, in which the key idea is to transform the RBF kernels into an orthonormal set of functions (using the standard Gram-Schmidt orthogonalization). This significantly reduces the computing time if the RBF training scheme, which relies on adding one kernel hidden node at a time to improve network performance, is adopted. Another property of the method is that, after the RBF network weights are computed, the original network structure can be restored back. An additional strength of the method is the possibility to decompose the proposed computing task into a number of parallel subtasks so gaining further savings on computing time. Also, the proposed weight calculation technique has low storage requirements. These features make the method very attractive for hardware implementation. The paper presents a detailed derivation of the proposed network weights calculation procedure and demonstrates its validity for RBF network training on a number of data classification and function approximation problems.