Summary It is now clearly established that proteolytic enzymes, including plasminogen activator (uPA), play an important role in breaking down the extracellular matrix, which is considered to be a step in metastasis formation. Plasminogen activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2, have been identified, the latter being more specific for uPA. In attempts to determine their prognostic value, it is essential to investigate the relative importance of these parameters and their interactions. We used an immunoenzymatic method to assay uPA, PAI-I and PAI-2 antigens in cytosols prepared from 314 primary breast tumours. The patients were followed up for a minimum of 6 years and all relevant clinical and laboratory findings were recorded. Univariate analysis confirmed the poor outcome of patients whose tumours contained large amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with shorter disease-free survival in the overall population (P= 0.02), post-menopausal women (P= 0.02) and women without lymph node involvement (P = 0.02). Multivariate analysis in the 'main effects' Cox model identified node involvement, macroscopic tumour size and PAI-2 as significant variables. The 'interactive' model, taking into account interactions between uPA and its two inhibitors, identified a first subgroup with a very poor prognosis associating either high levels of PAI-I with low levels of PAI-2 in the overall population and the women with no node involvement or high levels of uPA with low levels of PAI-2 in the group of menopausal women. We conclude that PAI-I provides the same prognostic information as uPA, and does not appear to play a role as an inhibitor. In contrast, PAI-2 increases the prognostic value of uPA, particularly in post-menopausal women, and PAI-1 in patients with no node involvement.

NAFLD conveys a nearly fourfold increase of DILI risk in obese middle-aged patients. NAFLD, characterized by mitochondrial dysfunction, could predispose to drug-induced hepatotoxicity that probably shares the same pathophysiological mechanism.

Oleuropein (OL) and hydroxytyrosol (HT), the main olive oil polyphenols, possess anti-proliferative effects in vitro. Fatty acid synthase, a key anabolic enzyme of biosynthesis of fatty acids, plays an important role in colon carcinoma development. Our aim was to investigate whether gene expression of FAS, as well as its enzymatic activity, is regulated by HT and OL in two human colon cancer cell lines, as HT-29 and SW620. In addition, we investigated the effects of these polyphenols on growth and apoptosis in these cells. FAS gene expression and activity in treated HT-29 and SW620 cells were evaluated by realtime PCR and radiochemical assay, respectively. Cell growth and apoptosis, after polyphenols treatment, were measured by MTT test and flow cytometry, respectively. The inhibition of proliferation, detected after HT treatment, was mediated by an inhibition of FAS expression and its enzymatic activity in SW620 cells, while the anti-proliferative effect in HT-29 cells seems to be independent from FAS. OL exerted an anti-proliferative effect only on SW620 cells with a mechanism which excluded FAS.Olive oil polyphenols used were able to induce apoptosis in both cell lines studied. The increase of apoptosis in these cells was accompanied by the block of cell cycle in the S phase. This study demonstrates that HT and OL may induce anti-proliferative and pro-apoptotic effects only in certain human colorectal cancer cell types. These effects are FAS mediated only in SW620 cells after treatment with HT.

The large implementation of electrochemical energy storage devices requires the development of new chemistries tailored for specific uses. Sodium‐ion batteries (SIBs) can cover different application fields, however the state‐of‐the‐art negative material, hard carbon, suffers from poor cyclability and rate capability. MXenes are a vast class of 2D‐materials of the general formula Mn+1XnTx (M = transition metal, X = C or N, and T = M‐terminating group) with peculiar structural features able to reversible intercalate chemical species, such as alkaline cations. The MXene compound Ti3C2Tx is one of the most investigated, thanks to the easy preparation route by etching of the pristine compound Ti3AlC2. In this work, the effect of the etching conditions and of the postsynthesis thermal treatments on the chemical, morphological, and structural properties of Ti3C2Tx are investigated, and in turn the correlation between its features and the functional properties as negative materials in SIBs are studied. The Ti3C2Tx obtained in high hydrofluoric concentration and after a 300 °C thermal treatment shows 110 mAh g−1 at 30 mA g−1 with an average potential of 1.33 V versus Na+/Na, 100% and good rate capability, since it is still able to deliver 73 mAh g−1 at 1500 mA g−1.

Automatic Road Sign Recognition Systems are aimed at detection and recognition of one or more road signs from real-world color images. In this research, road signs are detected and extracted from real world scenes on the basis of their color and shape features. A dynamic region growing technique is adopted to enhance color segmentation results obtained in the HSV color space. The technique is based on a dynamic threshold that reduces the effect of hue instability in real scenes due to external brightness variation. Classification is then performed on extracted candidate regions using Multi-Layer Perceptron neural networks. The obtained results show good detection and recognition rates of the entire system with real outdoor scenes, using several light conditions. Finally, the implementation of the neural layer on the Georgia Institute of Technology SIMD Pixel Processor is outlined.

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The most common MXene composition Ti 3 C 2 T x (T = F, O) shows outstanding stability as anode for sodium ion batteries (100% of capacity retention after 530 cycles with charge efficiency >99.7%). However, the reversibility of the intercalation/deintercalation process is strongly affected by the synthesis parameters determining, in turn, significant differences in the material structure. This study proposes a new approach to identify the crystal features influencing the performances, using a structural model built with a multitechnique approach that allows exploring the short-range order of the lamella. The model is then used to determine the long-range order by inserting defective elements into the structure. With this strategy it is possible to fit the MXene diffraction patterns, obtain the structural parameters including the stoichiometric composition of the terminations (neutron data), and quantify the structural disorder which can be used to discriminate the phases with the best electrochemical properties.

Infection occurs frequently in the organ transplant recipients during the post-transplant period because of immunosuppression. Therefore, prophylactic antimicrobial agents are often used. The azole antifungals, widely prescribed prophylactically, are known to have many drug-drug interactions. This report presents a case of drug-drug interaction between voriconazole and tacrolimus in a kidney transplant recipient. Voriconazole treatment led to a dramatic increase in tacrolimus concentration that required its discontinuation in spite of the manufacturer's guidelines that recommend a reduction of tacrolimus dosage by one-third. The present drug-drug interaction can be attributed to a strong inhibitory effect on cytochrome P450-3A4 activity by voriconazole. When voriconazole and tacrolimus are coadministered, close monitoring of tacrolimus blood levels is recommended as the rule-of-thumb reduction of tacrolimus dose by one-third may not be satisfactory.