52 research outputs found

    Antiproliferative activity and mode of action analysis of novel amino and amido substituted phenantrene and naphtho[2,1-b]thiophene derivatives

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    Herein we present and describe the design and synthesis of novel phenantrene derivatives substituted with either amino or amido side chains and their biological activity. Antiproliferative activities were assessed in vitro on a panel of human cancer cell lines. Tested compounds showed moderate activity against cancer cells in comparison with 5-fluorouracile. Among all tested compounds, some compounds substituted with cyano groups showed a pronounced and selective activity in the nanomolar range of inhibitory concentrations against HeLa and HepG2. The strongest selective activity against HeLa cells was observed for acrylonitriles 8 and 11 and their cyclic analogues 15 and 17 substituted with two cyano groups with a corresponding IC50 = 0.33, 0.21, 0.65 and 0.45 μM, respectively. Compounds 11 showed the most pronounced selectivity being almost non cytotoxic to normal fibroblasts. Additionally, mode of biological action analysis was performed in silico and in vitro by Western blot analysis of HIF-1-α relative expression for compounds 8 and 11

    Patterns of diabetes care in Slovenia, Croatia, Serbia, Bulgaria and Romania : An observational, non-interventional, cross-sectional study

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    BACKGROUND: National guidelines for treating type 2 diabetes in the Balkans generally follow European guidelines. The current study was undertaken to estimate the rate of glycated hemoglobin (HbA1c) measurements and level of HbA1c control in diabetic patients treated in regular clinical practice settings in the Balkans and to evaluate if providing HbA1c measurements improves adherence to treatment guidelines. METHODS: This cross-sectional study enrolled type 2 diabetic patients treated by 79 primary care physicians and 102 specialists. The participants were provided with HbA1c measuring devices to measure HbA1c during regular office visits and a physician survey evaluated HbA1c the results feedback. Relevant clinical, demographic, drug treatment and specialist referral data were extracted from patient charts. Descriptive statistics and stepwise multivariate regression analysis were used. RESULTS: Among 1853 patients included (average age 63.5 ± 10.7 years, 51% male) the average diabetes duration was 8.9 ± 7.1 years, 40% of patients had HbA1c measured every 6 months and 34% every 12 months (or less frequently). The rate of 6‑month measurement was higher among specialists (43%) vs. primary care physicians (32%, p < 0.01). The average HbA1c was 7.3 ± 1.5 and 35% of patients achieved the target HbA1c level of < 6.5%. Metformin monotherapy was prescribed to 28% of patients and metformin + sulphonylurea to 23%, 55% of patients on metformin monotherapy and 32% of patients on dual therapy metformin + sulphonylurea achieved the target HbA1c < 6.5%. Treatment remained unchanged in 91% and was stepped up in only 7.2% of patients. Physicians were not surprised (in 79% of patients) or were pleasantly surprised (in 11%) by the HbA1c results at the time of visit. Average diabetes duration and patient use of home glucometers were associated with the level of disease control. CONCLUSIONS: The rates of HbA1c measurements remain low in the Balkans, although higher among specialists. Over 60% of patients, mostly treated with traditional oral antidiabetics did not achieve disease control. Providing convenient HbA1c measurement devices was not associated with a marked change in diabetes management. Future research is needed to evaluate the impact of these treatment patterns on long-term outcomes and costs to society

    Using self-organizing maps in the visualization and analysis of forest inventory

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    A lot of useful data on forest condition can be gathered from the Forest Inven­tory (FI). Without the help of data analysis tools, human experts cannot ma­nually interpret information in such a large data set. Conventional multivariate statistical analyses provide results that are difficult to interpret and often do not represent the information in a satisfactory way. Our goal is to identify an alternative approach that will enable fast and efficient interpretation and analysis of the FI data. Such interpretation and analysis can be performed automatically with a clustering method, but all clustering methods have some shortcomings. Therefore, our aim was also to provide information in a form suitable for fast and intuitive visualization. Kohonen’s Self Organizing Map (SOM) is an alternative approach to data visualization and analysis of large multidimensional data sets. SOM provides different possibilities and our experiments are presented with component matrices of individual stand parameters and label matrices. In forming data clusters, we experimented with hierarchi­cal and non hierarchical clustering methods. Our experiments showed that SOM provides useful information in a form suitable for data clustering and data vi­sualization. This enables an efficient analysis of large FI data sets at different analysis scales. Clustering results obtained with SOM and two clustering algorithms are in accordance with ground truth. We have also considered the efficiency of SOM component matrices by visual comparison and correlation among structural parameters and by determining contributions of individual stand parameters to clustering input data. SOM application in visualization and analysis of stand structural parameters enables gathering quickly and efficiently holistic information on the current condition of forest stands and forest ecosystem development. Therefore we recommend the application of Kohonen’s SOM for visualization and analysis of FI data

    Network Evaluation Tool to Improve Real and Perceived Bicycle Safety

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    A learning analytics approach to correlate the academic achievements of students with interaction data from an educational simulator

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    This paper presents a Learning Analytics approach for understanding the learning behavior of students while interacting with Technology Enhanced Learning tools. In this work we show that it is possible to gain insight into the learning processes of students from their interaction data. We base our study on data collected through six laboratory sessions where first-year students of Computer Engineering at the University of Genoa were using a digital electronics simulator. We exploit Process Mining methods to investigate and compare the learning processes of students. For this purpose, we measure the understandability of their process models through a complexity metric. Then we compare the various clusters of students based on their academic achievements. The results show that the measured complexity has positive correlation with the final grades of students and negative correlation with the difficulty of the laboratory sessions. Consequently, complexity of process models can be used as an indicator of variations of student learning paths

    Kaiso differentially regulates components of the Notch signaling pathway in intestinal cells

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    Abstract Background In mammalian intestines, Notch signaling plays a critical role in mediating cell fate decisions; it promotes the absorptive (or enterocyte) cell fate, while concomitantly inhibiting the secretory cell fate (i.e. goblet, Paneth and enteroendocrine cells). We recently reported that intestinal-specific Kaiso overexpressing mice (Kaiso Tg ) exhibited chronic intestinal inflammation and had increased numbers of all three secretory cell types, hinting that Kaiso might regulate Notch signaling in the gut. However, Kaiso’s precise role in Notch signaling and whether the Kaiso Tg secretory cell fate phenotype was linked to Kaiso-induced inflammation had yet to be elucidated. Methods Intestines from 3-month old Non-transgenic and Kaiso Tg mice were “Swiss” rolled and analysed for the expression of Notch1, Dll-1, Jagged-1, and secretory cell markers by immunohistochemistry and immunofluorescence. To evaluate inflammation, morphological analyses and myeloperoxidase assays were performed on intestines from 3-month old Kaiso Tg and control mice. Notch1, Dll-1 and Jagged-1 expression were also assessed in stable Kaiso-depleted colon cancer cells and isolated intestinal epithelial cells using real time PCR and western blotting. To assess Kaiso binding to the DLL1, JAG1 and NOTCH1 promoter regions, chromatin immunoprecipitation was performed on three colon cancer cell lines. Results Here we demonstrate that Kaiso promotes secretory cell hyperplasia independently of Kaiso-induced inflammation. Moreover, Kaiso regulates several components of the Notch signaling pathway in intestinal cells, namely, Dll-1, Jagged-1 and Notch1. Notably, we found that in Kaiso Tg mice intestines, Notch1 and Dll-1 expression are significantly reduced while Jagged-1 expression is increased. Chromatin immunoprecipitation experiments revealed that Kaiso associates with the DLL1 and JAG1 promoter regions in a methylation-dependent manner in colon carcinoma cell lines, suggesting that these Notch ligands are putative Kaiso target genes. Conclusion Here, we provide evidence that Kaiso’s effects on intestinal secretory cell fates precede the development of intestinal inflammation in Kaiso Tg mice. We also demonstrate that Kaiso inhibits the expression of Dll-1, which likely contributes to the secretory cell phenotype observed in our transgenic mice. In contrast, Kaiso promotes Jagged-1 expression, which may have implications in Notch-mediated colon cancer progression
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