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In this study, constant angle ruled surfaces with a pointwise 1-type Gauss map, which is very useful in the classification of surfaces, are investigated in terms of the Frenet elements of the base curves of the ruled surfaces in Euclidean 3-space. In order to form a basis for our work, firstly, basic concepts related to the Gauss map of an oriented surface are given. Later, a classification is satisfied by determining the necessary conditions to be the first kind, the second kind, and the harmonic of the pointwise 1-type of the Gauss map for these surfaces. Finally, some examples of these surfaces are provided, and their graphical illustrations are displayed. [ABSTRACT FROM AUTHOR]

In this paper, we introduce a membership function used to form the fuzzy Mandelbric set and investigate the structural effects of additive and multiplicative dynamic noises on it. The newly defined membership function of this fuzzy set and its perturbations is a generalization of the indicator function for the classical Mandelbric set. We present an algorithm for detecting each complex number's fuzzy membership degree. Through the use of the membership degrees of each complex number and experimental mathematics based on the visualizations of a variety of versions by utilizing computer-aided design, we gain a deep foresight for the structure characteristics of the additive and multiplicative perturbed fuzzy Mandelbric sets. Our novel approach allows us to identify the symmetry states of the Mandelbric set and its perturbations by the membership degrees of complex numbers, unlike the existing methods described in the literature. [ABSTRACT FROM AUTHOR]

We are starting to understand the fundamental biological processes which underlie the DNA physical properties. Of particular importance is the field of epigenetics, which literally means 'outside conventional genetics', now used to describe the study of stable alterations in gene expression potential that arise during development and cell proliferation. Epigenetic changes are modifications of DNA, which occur without any alteration in the DNA sequence. Modern directions in the field of epigenetic research aimed to decipher the epigenetic signals that give stem cells their unique ability to self-renew and differentiate into different types. Stem cell-based regenerative medicine holds great promise for repair of diseased tissue. If epigenetic process are reversible, than there is the ability to cure cancer through stem cell therapy.

In this paper, we use the finite state automata to count the number of restricted permutations and the number of restricted variations. For each type of restricted permutations, we construct a finite state automaton able to recognize and enumerate them. We, also, discuss how it encompasses the other known methods for enumerating permutations with restricted position, and in one case, we establish connections with some other combinatorial structures, such as subsets and compositions.

The Primary Liver Carcinoma (PLC) is one of the most common malignant diseases in the world. In Central Serbia during the period from 2000 to 2006 the average incidence was 16.9/100 000 that complies to the European epidemiology. The main risk factors for PLC are considered to be cirrhosis of liver and viral chronic Hepatitis B and C. The goal of this research was to analyze epidemiological data of these diseases and to state the correlation between PLC, liver cirrhosis and Hepatitis B and C in Serbia. During the research period of 6 years the correlations between PLC and the corresponding risk factors were negative. For this reason it was necessary to examine other risk factors. The high incidence of PLC in Nišavski, Toplički and Šumadijski region correlate with emerging blooms of Cyanobacteria in water reservoirs supplying these areas with drinking water. Since we examined only 7 years span and have no completed cyanotoxin analysis, it is necessary to complete more research in this field. The identification of cyanotoxins as risk factors that contribute to the development of liver cancer will help in the prevention of this disease.

Having in mind that exposure to low levels of microcystin in drinking water represents the health risk for people, microcystins can be observed as potent xenobiotics. The consequences of exposure to natural products of the blue-green algae, the microcystins, are numerous. Among other things, there is a possibility of development of malignant disease of colon and liver. The occurrence of the tumor is, on one side, enabled by the active transportation of microcystin for achievement of high concentration intracellularly and, on the other side, by high affinity of microcystins for serine/threonine phosphatase PP1 and PP2A after which follows their inactivation. The system, which is responsible for the active transportation of microcystin, is a family of polypeptides for transportation of organic anions (OATP). Isoforms of these carriers are distributed in one tissue, like OATP1B1 and OATP1B3, which are specific for liver or many tissues, OATP1A2 carrier, present in the liver, kidney, brain and the small intestine. The consequences of high concentration of microcystin intracellularly, binding and the inhibitions of protein phosphatase, are numerous. For the occurrence of a tumor, the changes in the nucleus are important, which are related to the gene expression changes, changes in the system for damaged DNA repair and the changes in mitosis. Mediators of these changes have their role in protein activity regulation, signal transmission in the cell, damaged DNA repair, performance of the cell cycle, apoptosis, tumor suppression, cell proliferation and differentiation. Phosphatase inhibition is observed as the strategy of development of a new group of anticancer agents. As phosphatase inhibitors, microcystins and analogs are applied, possibly having the potential to express the difference in toxicity mechanism and detoxification mechanism between the healthy and the tumor cell of liver. High expression of OATP1B1 and OATP1B3 microcystin transporters in hepatocellular carcinoma would confirm selective impact of phosphatase inhibitors to the tumor cell.

Cyanobacteria are responsible for poisoning numerous cases of livestock and other animals, but sometimes they induce serious problems in humans. Mass occurrence and blooms of cyanobacteria were studied in rivers, canals, lakes, and accu­mulations that had been examined in Serbia during period 1980-2002. Because of massive blooming of cyanobacteria, when they produce cyanotoxins, which could be responsible for poisoning, and damage of organs, studies are steered to better understanding cyanotoxins effects on human health. The investigation on microcystins, as one of many cyanotoxins, is increas­ing due to the related ecological and public health risks. There is evidence that microcystins have a tumor promoting activity and microcystin-LRcould be tumor initiator and possibly cancerogenic to humans. Epidemiological studies have suggested that there is connection between primary liver cancer (PLC) and microcystins, as one of risk factor for high incidence rate of PLC in Serbia.

MicroRNAs are a class of short, single-stranded, noncoding RNA molecules that negatively regulate the expression target mRNA at posttranslational level. microRNAs as key regulatory molecules play important biological function and might act as tumor suppressor oncogenes in cancer and lymphomas. microRNAs cause the expression of important cancer related genes and might prove useful in the diagnostics, prognosis, and treatment of some lymphomas This review focuses on the role of microRNAs in normal lymphocyte differentiation and in development of non-Hodgkin's lymphomas.

Nikola Tesla was an ingenious and briliant scintifist which contributed to the science and technology prosperity of the world. Nikola Tesla discovered high frequency oscillator 1891 year, and afterwards, single electrode X-ray tube without target electrode, electron (“particles charged with electricity”), Bremsstrahlung or “breaking radiation” or “very special radiation” (X-radiation) in 1892 year, biological hazards of X-rays, and more about 700 inventions, and 112 patents. Tesla's research work in the field of X-rays was stopped in 1895 because burned in his laboratory. When W. C. Röntgen 1895, recognition X-rays, Tesla restored his work on this field and sent Röntgen a telegram with congratilations and Röntgen shows obtained with X-ray tubes which operated with high frequency currents. Tesla discovered many secret of nature.

Nowadays, in genomocentric era accelerated research of the human genome coupled with advances is enabling the comprehensive molecular profiling of human tissue. Particularly, DNA microarrays are powerful tools for obtaining global view of human non-Hodgkin lymphomas gene expression. Complex information from lymphomas "expression profiling" studies can, in turn, be used to create molecular markers that have diagnostic or prognostic implications. The gene "expression profiling" is not of routine clinical oncology practice, but is used in genomic classification of clinically relevant subgroups of non-Hodgkin lymphoma. The genomics biomarkers have been incorporated into current prognostic models which are based on IPI, R-IPI, and FLIPI. Molecular or pharmacogenomic profiling can be used as new therapeutic targets for patients who are refractory to current therapy. We discus the utility of DNA microarray-based lymphoma profiling in clinical oncology research, and identify future of research in lymphoma evolving fields.

Genomics is a comprehensive study of the whole genome, genetic products, and their interactions. Human genome project has identified around 25,000-30,000 genes, and prevailing presence in tumor pathogenesis, high number of mutations, epigenetic changes, and other gene disorders have been identified. Microarrays technology is used for the analysis of these changes. Postgenome age has begun, and the initial results ensure the improvement of molecular tumor diagnostics and the making of a new taxonomic tumor classification, as well as the improvement, optimization and individualization of anti-tumor therapy. First genomic classifications have been made of leukemias non-Hodgkin lymphoma, and many solid tumors. For example, 4 molecular types of breast carcinoma, three types of diffuse B cell lymphoma, two types of chromophobic renal carcinoma have been identified. Also, gene structures for favorable and unfavorable outcome in leukemia, breast cancer, prostate bronchi, and other tumors have been identified. It is absolutely possible to diagnose the primary outcome of tumors with which standard tumor position may not be proved using standard diagnostic tools. Pharmacogenomic profiles have ensured better definition of interindividual differences during therapy using antineoplastic drugs and the decrease of their toxicity, as well as individual treatment approach and patient selection with which favorable clinical outcome is expected. Pharmacogenomics has impacted the accelerated development of target drugs, which have showed to be useful in practice. New genomic markers mtDNA, meDNA, and miRNA have been identified, which, with great certainty, help the detection and diagnostics of carcinoma. In the future, functional genomics in clinical oncology provides to gain knowledge about tumor pathogenesis; it will improve diagnostics and prognosis, and open up new therapeutic options.

BACKGROUND: The study evaluates publication and distribution of biomedical and oncology articles in medical journals in Serbia from 1995 to 2000 and their correlation with socioeconomic variables. METHODS: Retrospective bibliometric research was done in the following medical journals: Srpski Arhiv, Vojnosanitetski Pregled, Medicinski Pregled, and Archive of Oncology. RESULTS: Quantitative analysis showed that 2,468 biomedical articles were published in Serbia. Out of these 855 (30.64%) were oncology papers, which accounts for 3.6% of oncology article production in the countries of European Union. The number of oncology articles in relation to the number of inhabitants was 0.00024%, and 0.10% in relation to GDP. The analysis of key words showed that breast cancer was the leading field of research. Adryamicin was the most frequently drug used in clinical trials and apoptosis was the most investigated topic of experimental research. Standardization of key words according to MeSH was highly recommended. CONCLUSION: Bibliometric analysis shows that the production of scientific oncology literature in Serbia has been very low in comparison with the same production in small and large countries of European Union. The assessment and the quality of the oncology and biomedical publications have an effect on the definition of the position and development of the strategy for scientific production in the country. Systematization of the national database for biomedical publications will help the assessment of the quality of scientific research in oncology and medicine in general.

A large part of Central Serbia experiences continual shortage of sufficient ground water resources. For that reason, more than 20 reservoirs serve as drinking water suppliers. Significant and persistent cyanobacterial “blooms” have been recognized in nine of them. Samples for cyanotoxin analyses were taken during and after “blooms” in Celije Reservoir and from Krusevac town-supplied tap water from that reservoir two days later. Concentration of microcystin-LR was 650 μ gL-1 in the reservoir, while the tap water contained 2.5 μ gL-1. In the two investigated periods, the high primary liver cancer (PLC) mortality of 11.6 from 1980-1990 and extremely high PLC incidence of 34.7 from 2000-2002 were observed in the regions affected by heavy cyanobacterial “blooms.” In contrast, PLC mortality and incidence rates were substantially lower in the regions not affected by cyanobacterial blooms: in 1980-1990 the rate of PLC mortality amounted to 2.7 in Kosovo, 7.6 in Vojvodina, and 8.3 in the non-affected regions of Central Serbia; while in 2000-2002 PLC incidence amounted to 4.1 in Kosovo, 5.2 in Vojvodina, and 13.6 in the non- or less-affected regions of Central Serbia. Keeping in mind that the most affected PLC regions in Central Serbia (Toplicki, Niski, and Sumadijski regions) have the water supply systems based on six reservoirs found regularly in bloom during summer months and that some of the regions are also connected with two boundary “blooming” reservoirs, representing a total of eight of nine blooming reservoirs, it is easy to presume that the PLC incidence could be related to drinking water quality. The uneven geographic distribution of liver cancer in Serbia is conspicuous and hot spots could be related to drinking water supply. It is very clear that the high-risk regions for PLC occurrence correspond with drinking water reservoirs continually found with cyanobacterial blooms, and the low risk regions correspond with water supplies not affected by cyanobacteria. [ABSTRACT FROM AUTHOR]

Having in mind that exposure to low levels of microcystin in drinking water represents the health risk for people, microcystins can be observed as potent xenobiotics. The consequences of exposure to natural products of the blue-green algae, the microcystins, are numerous. Among other things, there is a possibility of development of malignant disease of colon and liver. The occurrence of the tumor is, on one side, enabled by the active transportation of microcystin for achievement of high concentration intracellularly and, on the other side, by high affinity of microcystins for serine/threonine phosphatase PP1 and PP2A after which follows their inactivation. The system, which is responsible for the active transportation of microcystin, is a family of polypeptides for transportation of organic anions (OATP). Isoforms of these carriers are distributed in one tissue, like OATP1B1 and OATP1B3, which are specific for liver or many tissues, OATP1A2 carrier, present in the liver, kidney, brain and the small intestine. The consequences of high concentration of microcystin intracellularly, binding and the inhibitions of protein phosphatase, are numerous. For the occurrence of a tumor, the changes in the nucleus are important, which are related to the gene expression changes, changes in the system for damaged DNA repair and the changes in mitosis. Mediators of these changes have their role in protein activity regulation, signal transmission in the cell, damaged DNA repair, performance of the cell cycle, apoptosis, tumor suppression, cell proliferation and differentiation. Phosphatase inhibition is observed as the strategy of development of a new group of anticancer agents. As phosphatase inhibitors, microcystins and analogs are applied, possibly having the potential to express the difference in toxicity mechanism and detoxification mechanism between the healthy and the tumor cell of liver. High expression of OATP1B1 and OATP1B3 microcystin transporters in hepatocellular carcinoma would confirm selective impact of phosphatase inhibitors to the tumor cell. [ABSTRACT FROM AUTHOR]

Paper presents the effects of the newly synthesized fullerol C60(OH)22 on the growth of tumor cells in vitro and its modulating activity on doxorubicin (DOX)-induced cytotoxicity in human breast cancer cell lines. Cell growth inhibition was evaluated by tetrazolium colorimetric WST1 assay. Electron spin resonance (ESR) “trapping” method was used to investigate OH-radical scavenger activity of fullerol during Fenton''s reaction. At a range of nanomolar concentrations fullerol induced cell growth inhibition, which was cell line, dose and time dependent. Fullerol also strongly suppressed DOX-induced cytotoxicity at all concentrations regardless the time of fullerol addition. Proanthocyanidins added as single agent to MCF-7 cell culture for 48 h induced low growth inhibition but in combination with DOX strongly decreased DOX cytotoxicity. Fullerol was found to be a potent hydroxyl radical scavenger: the relative intensity of ESR signals of DMPO-hydroxyl radical (DMPO-OH) spin adduct decreased by 88% in the presence of 0.5 μg/ml of fullerol. The obtained results suggest that antiproliferative effect of the fullerol and its protective effect on DOX-induced cytotoxicity might be mediated through hydroxyl-radical scavenger activity of C60(OH)22. [Copyright &y& Elsevier]

Abstract: Background: The role of circulating TGF-β1 in prognosis of breast cancer (BC) was investigated with an intention to define TGF-β1-dependent high risk and low risk subsets of patients. Methods: Fifty three BC patients of all clinical stages and 37 healthy donors (HD) were analyzed for plasma TGF-β1 by the TβRII receptor-based Quantikine TGF-β1 ELISA kit. Results: The plasma TGF-β1 level of Stage I/II disease (median: 0.94 ng/ml; n =10)) remained close to HD (median: 1.30 ng/ml; n =37; p >0.1). In contrast, Stage III/IV disease (median: 2.34 ng/ml; n =43) exhibited highly significant TGF-β1 elevation (p <0.001) relative to HD. Further analysis revealed that TGF-β1 increase was predominantly attributed to Stage IV, metastatic disease patients (Q3=4.23 ng/ml) rather than to the group Stage III/IV (Q3=3.58 ng/ml). Using the plasma TGF-β1 concentration of 3.00 ng/ml as the cut-off value, two subgroups of patients were formed. Overall 2-year survival of the first subgroup, having elevated plasma TGF-β1 (>3.00 ng/ml; n =10), was 10%. This was significantly decreased (p <0.05) compared to 52% survival observed for the second subgroup of patients with plasma TGFβ1 values close to HD (<3.00 ng/ml, n =19). Conclusion: We have performed a pilot study to determine the relationship between overall survival and TGF-β1 concentration in the blood of metastatic breast cancer patients. The survival was significantly reduced in the patients with elevated plasma TGF-β1 levels compared to that of the patients with plasma TGF-β1 levels close to normal. We propose that plasma TGF-β1 concentration may be a new tumour marker attributed to the presence of metastatic BC cells that may be used in selection of metastatic BC patients with poor prognosis. [Copyright &y& Elsevier]

Cyanotoxins are secondary metabolites produced by cyanobacteria. They pose a threat to human health and the environment. This review summarises the existing data on human exposure to cyanotoxins through drinking water, recreational activities (e.g., swimming, canoeing or bathing), the aquatic food web, terrestrial plants, food supplements, and haemodialysis. Furthermore, it discusses the tolerable daily intake and guideline values for cyanotoxins (especially microcystins) as well as the need to implement risk management measures via national and international legislation.

Objective: To use cytoplasmic tissue extract as a new specimen source to quantify transforming growth factor beta 1 (TGFbeta1) protein in metastatic axillary lymph node tissue (ALNT) of breast cancer (BC) patients and to confirm the feasibility of this approach in a prospective pilot study on a subgroup of patients with invasive BC., Study Design: The 6 selected malignant and autologous nonmalignant pairs of ALNT were fractionated, under special preanalytical, nonaggressive/nondenaturing conditions, to obtain respective cytoplasmic extracts for TGFbeta1 detection by the Quantikine (R&D Systems Inc., Minneapolis, Minnesota, U.S.A.) enzyme-linked immunosorbent assay kit., Results: The data indicated a highly significant (r = 0.973054) positive linear correlation between the TGFbeta1 concentration and total protein concentration in cytoplasmic extract of metastatic ALNT. The subsequent patients' pilot study, performed strictly before any clinicopathologic factors were accessible, revealed significantly (p < 0.01) elevated TGFbeta1 in malignant ALNT (median value: 1.05 ng/mg protein, range: 0.67-3.6 ng/mg protein, n = 6) vs. autologous nonmalignant ALNT controls (median value: 0.48 ng/mg protein, range: 0.29-0.90 ng/mg protein, n = 6). This elevation was correlated with the number of metastatic axillary lymph nodes with respect to the total and was consistent with an increase in size of tumor deposits in axillary lymph nodes., Conclusion: Our data provide for the first time suggestive evidence that the TGFbeta1 level in cytoplasmic extracts of metastatic ALNTs may be a promising biomarker of invasiveness for BC patients. Confirmatory, large-scale studies are needed to evaluate possible implications of this putative biomarker in BC diagnosis and treatment.