The Urokinase Receptor: A Multifunctional Receptor in Cancer Cell Biology. Therapeutic Implications

Proteolysis is a key event in several biological processes; proteolysis must be tightly controlled because its improper activation leads to dramatic consequences. Deregulation of proteolytic activity characterizes many pathological conditions, including cancer. The plasminogen activation (PA) system plays a key role in cancer; it includes the serine-protease urokinase-type plasminogen activator (uPA). uPA binds to a specific cellular receptor (uPAR), which concentrates proteolytic activity at the cell surface, thus supporting cell migration. However, a large body of evidence clearly showed uPAR involvement in the biology of cancer cell independently of the proteolytic activity of its ligand. In this review we will first describe this multifunctional molecule and then we will discuss how uPAR can sustain most of cancer hallmarks, which represent the biological capabilities acquired during the multistep cancer development. Finally, we will illustrate the main data available in the literature on uPAR as a cancer biomarker and a molecular target in anti-cancer therapy.     

Starch Characterisation of Araucaria angustifolia and Araucaria araucana Seeds

Araucaria angustifolia and Araucaria araucana are conifers that cover different areas of South America. Their seeds have been consumed from prehistoric times until today in Brazil, Argentina and Chile. In this work, the starch of Araucaria angustifolia and Araucaria araucana seeds were analysed by light and environmental scanning electron microscopy, X‐ray diffraction, and differential scanning calorimetry. The starch granules of A. angustifolia and A. araucana were round or slightly oval, with a central hilum. Both starches gave X‐ray diffraction patterns compatible with the A‐type, with strong peaks at 15°, 17°, and 23°. The gelatinisation temperature of A. angustifolia starch (68.5°C) was higher than that of A. araucana (66.6°C), probably due to the higher amylose content of the former (22.4 % and 17.3 %, respectively). The thermograms of A. araucana starch presented a minor peak at about 71°C, which was attributed to the fact that the starch granules population of A. araucana was heterogeneous, with large and small granules, whereas A. angustifolia starch contained mainly large granules.     

Investigating the use of Support Vector Regression for web effort estimation

Support Vector Regression (SVR) is a new generation of Machine Learning algorithms, suitable for predictive data modeling problems. The objective of this paper is twofold: first, to investigate the effectiveness of SVR for Web effort estimation using a cross-company dataset; second, to compare different SVR configurations looking at the one that presents the best performance. In particular, we took into account three variables’ preprocessing strategies (no-preprocessing, normalization, and logarithmic), in combination with two different dependent variables (effort and inverse effort). As a result, SVR was applied using six different data configurations. Moreover, to understand the suitability of kernel functions to handle non-linear problems, SVR was applied without a kernel, and in combination with the Radial Basis Function (RBF) and the Polynomial kernels, thus obtaining 18 different SVR configurations. To identify, for each configuration, which were the best values for each of the parameters we defined a procedure based on a leave-one-out cross-validation approach. The dataset employed was the Tukutuku database, which has been adopted in many previous Web effort estimation studies. Three different training and test set splits were used, including respectively 130 and 65 projects. The SVR-based predictions were also benchmarked against predictions obtained using Manual StepWise Regression and Case-Based Reasoning. Our results showed that the configuration corresponding to the logarithmic features’ preprocessing, in combination with the RBF kernel provided the best results for all three data splits. In addition, SVR provided significantly superior prediction accuracy than all the considered benchmarking techniques.     

Adding Molecules to Food,Pros and Cons: A Review on Synthetic and Natural Food Additives

The pressing issue to feed the increasing world population has created a demand to enhance food production, which has to be cheaper, but at the same time must meet high quality standards. Taste, appearance, texture, and microbiological safety are required to be preserved within a foodstuff for the longest period of time. Although considerable improvements have been achieved in terms of food additives, some are still enveloped in controversy. The lack of uniformity in worldwide laws regarding additives, along with conflicting results of many studies help foster this controversy. In this report, the most important preservatives, nutritional additives, coloring, flavoring, texturizing, and miscellaneous agents are analyzed in terms of safety and toxicity. Natural additives and extracts, which are gaining interest due to changes in consumer habits are also evaluated in terms of their benefits to health and combined effects. Technologies, like edible coatings and films, which have helped overcome some drawbacks of additives, but still pose some disadvantages, are briefly addressed. Future trends like nanoencapsulation and the development of “smart” additives and packages, specific vaccines for intolerance to additives, use of fungi to produce additives, and DNA recombinant technologies are summarized.     

Future Perspectives in Detecting EGFR and ALK Gene Alterations in Liquid Biopsies of Patients with NSCLC

Non-small-cell lung cancer (NSCLC) is a major cause of death worldwide. Alterations in such genes as EGFR and ALK are considered important biomarkers in NSCLC due to the existence of targeted therapies with specific tyrosine kinase inhibitors (TKIs). However, specific resistance-related mutations can occur during TKI treatment, which often result in therapy inefficacy. Liquid biopsies arise as a reliable tool for the early detection of these types of alterations, allowing a non-invasive follow-up of the patients. Furthermore, they can be essential for cancer screening, initial diagnosis and to check surgery success. Despite the great advantages of liquid biopsies in NSCLC and the high input that next-generation sequencing (NGS) approaches can provide in this field, its use in oncology is still limited. With improvement of assay sensitivity and the establishment of clinical guidelines for liquid biopsy analysis, it is expected that they will be used in routine procedures. This review focuses on the usefulness of liquid biopsies of NSCLC patients as a means to detect alterations in EGFR and ALK genes and in disease management, highlighting the impact of NGS methods.     

Hydrogen production through catalytic low-temperature bio-ethanol steam reforming

As a provider of our energy requirements, hydrogen seems to be one of most promising fuels, in particular when used to feed PEM fuel cells. When produced from a renewable source, it has got the potential to reduce the dependence on non-renewable fossil fuels and lower the amount of harmful emissions. Ethanol steam-reforming (ESR) reaction is an interesting option to obtain a H₂- and CH₄-rich stream with a low content of CO, combining the deep knowledge of the technology with the advantage of the biomass-derived feedstock. Thermodynamic analysis has indicated that the most interesting operating range to enhance the H₂ production and minimize CO and coke formation requires low pressure, high temperature, and high water-to-ethanol molar ratio. On the other hand, despite its endothermic nature, ESR could be carried out at low temperature, to increase overall thermal efficiency, even if at these conditions the catalyst's deactivation, due to coking and sintering phenomena, is not negligible. The main objective of this study is to investigate on the activity, stability, and durability of bimetallic Pt–Ni and Pt–Co catalysts supported on CeO₂ for low-temperature bio-ESR reaction. The catalysts have been prepared through different methods and with an optimized metal's content. They have also been characterized with various physico-chemical characterization tests, and the catalytic studies have been carried out in a lab-scale apparatus. While evaluating the effects on the catalysts' performances of preparation method, reaction temperature, space time, and water-to-ethanol molar ratio, the selected catalysts were found effective for the production of H₂ by steam reforming at low temperature. In particular, the Pt/Ni/CeO₂ catalyst shows a perfect agreement with equilibrium calculations yet at low contact times, although some carbon deposition occurs. Also the cobalt-based catalysts appear attractive. The relative rates of carbon growth versus gasification have been studied, and ascending water contents were used to study the effect of steam addition in the feed stream. An in-depth investigation of the reaction mechanism and the evaluation of the kinetic parameters will be crucial to complete the study of the proposed process.     

Candida colonization index in patients admitted to an ICU

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.