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      • KCI등재
      • KCI등재

        Reclassification of Five BRCA1/2 Variants with Unknown Significance Using Complex Functional Study

        Anikó Bozsik,János Papp,Vince Kornél Grolmusz,Attila Patócs,Edit Oláh,Henriett Butz 대한암학회 2022 Cancer Research and Treatment Vol.54 No.4

        Purpose While BRCA1/2 genes are commonly investigated, variants of unknown significance (VUS) and variants with potential splice effect are still being detected and they represent a substantial challenge in genetic counseling and therapy. Materials and Methods Out of genetically tested 3,568 hereditary breast and ovarian cancer probands five, functionally not investigated variants with potential splice-modifying effect were subjected to functional characterization. Transcript-level analysis on peripheral blood-derived RNA of the carriers was performed to test aberrant splicing. The completeness of the aberrant splicing event was also studied, existence and extent of nonsense-mediated decay was even addressed. Clinical and phenotype data, pedigree and co-segregation analyses were also done. Locus-specific loss of heterozygosity (LOH) in tumor tissues was additionally tested. Results In case of the BRCA1:c.4484+4dupA and the BRCA1:c.5407-10G>A variants functional results allowed us to reclassify them from VUS into likely pathogenic category. BRCA1:c.4358-31A>C, by producing incomplete aberrant splicing, was highlighted as strong VUS, but in lack of other supporting evidence, re-categorization was not possible. The likely pathogenic assertion of previously not reported BRCA2:c.8487G>T was reinforced based on its spliceogenic property and tumor LOH, while BRCA2:c.793G>A failed to present aberrant splicing in spite of suggestive predictions, which altered its original VUS evaluation into likely benign class. Conclusion We presented molecular and clinical evidence for reclassification of four out of five BRCA1/2 variants. Both up- and down-classification harbour important clinical significance. Patients carrying re-classified pathogenic variants in the future will not be dropped out from medical surveillance, preventive measures, treatment and predictive family screening in relatives at risk.

      • Organizational-Economic Mechanism of Attracting Investment Resources in the Innovative Development of Regions in Teams of Sustainable Development

        Krasnonosova, Olena,Perepeliukova, Olena,Papp, Vasyl,Doronina, Maya,Romaniuk, Mykhailo International Journal of Computer ScienceNetwork S 2022 International journal of computer science and netw Vol.22 No.2

        The article considers the features of the organizational-economic mechanism of attracting investment resources in the innovative development of regions in terms of sustainable development. Factors influencing the investment activity of regions in terms of sustainable development, including: institutional structure, intellectual capital, level of innovation infrastructure, business development, financial and credit component, level of human resources development, information environment, production development, environmental component. Factors influencing the attraction of investment resources in the regions are identified. The dynamics of changes in the volume of capital investments and foreign direct investment in Ukraine is analyzed. The regional features of the distribution of capital investments in the conditions of sustainable development are revealed. The essence of the main principles on the basis of which the organizational - economic mechanism of attraction of investment resources in innovative development of regions in the conditions of sustainable development should be formed is analyzed. A set of measures to regulate the investment processes of the regions has been identified. The mechanism of attraction of investment resources in innovative development of regions in the conditions of sustainable development is outlined. The results of activity of separate Agencies of regional development for 2020 in the direction of investment and innovation activity and increase of level of investment attractiveness of regions are analyzed. Important prerequisites for the effective implementation of the organizational-economic mechanism for attracting investment resources in the innovative development of regions in terms of sustainable development are identified. The main directions of directing the efforts of the organizational-economic mechanism to ensure the attraction of investment resources in the innovative development of regions in the context of increasing the level of investment activity in the regional aspect are substantiated.

      • SCIESCOPUSKCI등재

        Purification and Properties of Extracellular Lipases with Transesterification Activity and 1,3-Regioselectivity from Rhizomucor miehei and Rhizopus oryzae

        ( Miklos Tako ),( Alexandra Kotogan ),( Tamas Papp ),( Shine Kadaikunnan ),( Naiyf S. Alharbi ),( Csaba Vagvolgyi ) 한국미생물 · 생명공학회 2017 Journal of microbiology and biotechnology Vol.27 No.2

        Rhizomucor miehei NRRL 5282 and Rhizopus oryzae NRRL 1526 can produce lipases with high synthetic activities in wheat bran-based solid-state culture. In this study, the purification and biochemical characterization of the lipolytic activities of these lipases are presented. SDSPAGE indicated a molecular mass of about 55 and 35 kDa for the purified R. miehei and Rh. oryzae enzymes, respectively. p-Nitrophenyl palmitate (pNPP) hydrolysis was maximal at 40°C and pH 7.0 for the R. miehei lipase, and at 30°C and pH 5.2 for the Rh. oryzae enzyme. The enzymes showed almost equal affinity to pNPP, but the V<sub>max</sub> of the Rh. oryzae lipase was about 1.13 times higher than that determined for R. miehei using the same substrate. For both enzymes, a dramatic loss of activity was observed in the presence of 5 mM Hg<sup>2+</sup>, Zn<sup>2+</sup>, or Mn<sup>2+</sup>, 10 mM N-bromosuccinimide or sodium dodecyl sulfate, and 5-10% (v/v) of hexanol or butanol. At the same time, they proved to be extraordinarily stable in the presence of nhexane, cyclohexane, n-heptane, and isooctane. Moreover, isopentanol up to 10% (v/v) and propionic acid in 1 mM concentrations increased the pNPP hydrolyzing activity of R. miehei lipase. Both enzymes had 1,3-regioselectivity, and efficiently hydrolyzed p-nitrophenyl (pNP) esters with C8-C16 acids, exhibiting maximum activity towards pNP-caprylate (R. miehei) and pNP-dodecanoate (Rh. oryzae). The purified lipases are promising candidates for various biotechnological applications.

      • Hydrotropic solubilization of poorly water-soluble drugs

        Kim, Ji Young,Kim, Sungwon,Papp, Michelle,Park, Kinam,Pinal, Rodolfo Wiley Subscription Services, Inc., A Wiley Company 2010 journal of pharmaceutical sciences Vol.99 No.9

        <P>The solubilizing ability of two aromatic hydrotropes, N,N-diethylnicotinamide (DENA) and N,N-dimethylbenzamide (DMBA), was investigated using a set of 13 poorly soluble, structurally diverse drugs. The number of aromatic rings in the solute molecule has a very strong effect on the solubility enhancement produced by either hydrotrope. However, although solubility enhancements in the order of 1000- to 10,000-fold were obtained with each of the hydrotropic agents, important differences were found between the two. DMBA is more hydrophobic and undergoes more extensive self-association than DENA, as determined by vapor osmometry. As a result, DMBA is generally a more powerful solubilizer of hydrophobic drugs. DENA, on the other hand, is more polar and its self-association is essentially limited to dimer formation. However, despite being less hydrophobic, DENA is an extremely powerful solubilizer of paclitaxel, a highly hydrophobic compound. Such a result is attributed to the higher hydrogen bonding ability of DENA over DMBA and the very high hydrogen bonding ability of paclitaxel. These observations in turn illustrate the strong interplay between specific and hydrophobic interactions on the observed solubilization by hydrotropic agents. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3953–3965, 2010</P>

      • KCI등재

        Hemorheological parameters in coronary artery disease detected by multi-slice CT

        Andras Toth,Sandor Szukits,Edit Varady,Barbara Sandor,Miklos Rabai,Judit Papp,Istvan Juricskay,Gabor Kesmarky,Kalman Toth,Balazs Sumegi,Istvan Battyani 한국유변학회 2014 Korea-Australia rheology journal Vol.26 No.2

        Epidemiological studies have confirmed that hemorheological parameters are primary risk factors in CAD;and their alterations in CAD have been described. We aimed to investigate both macro- and microrheologicalproperties of blood in patients with CAD. The data of 121 patients (mean age: 58.8 ± 9.6 years) undergoingcoronary CT were analyzed. Blood samples were obtained right before CT examinations. Hematocrit (Hct),plasma (PV) and apparent whole blood viscosity (WBV), red blood cell (RBC) aggregation and RBC deformabilitywere measured. Patients were classified into four groups according to their coronary vessel state: Negativegroup (n = 32, mean age: 56.8 ± 11.1 years) without any coronary stenosis or atherosclerotic lesion andzero calcium-score, Non-significant group (n = 27, mean age: 59.2 ± 7.5 years) below 40% area stenosis, Single-vessel group (n = 32, mean age: 58.8 ± 8.5 years) over 40% area stenosis or history of PCI or CABG onone coronary vessel, Multi-vessel group (n = 30, mean age: 62.1 ± 8.4 years) with over 40% area stenosis orhistory of PCI or CABG on multiple coronary vessels. Hct was significantly (p < 0.05) higher in all CAD(Non-significant, Single-vessel, Multi-vessel) groups compared to the Negative group. WBV was significantly(p<0.05) higher in the Multi-vessel group compared to the Negative group. No significant (p ≥ 0.05) differenceswere observed in PV. RBC aggregation was significantly (p < 0.05) increased in the Multi-vesselgroup compared to the Negative group. RBC deformability showed a decreasing tendency with the increasingnumber of atherosclerotic vessels. Our results indicate that hemorheological variables are deteriorated inpatients with CAD established by coronary CT, which is more pronounced in severe coronary disease.

      • KCI등재

        Aspirin resistance as cardiovascular risk after kidney transplantation

        Barbara Sandor,Adam Varga,Miklos Rabai,Andras Toth,Judit Papp,Kalman Toth,Peter Szakaly 한국유변학회 2014 Korea-Australia rheology journal Vol.26 No.2

        International surveys have shown that the leading cause of death after kidney transplantation has cardiovascularorigin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA)therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurementswere performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin(100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effectivein case of low (i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirinresistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years)were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared tothe positive control group (PC) (35.9% vs. 25.6%, p < 0.002). Morbidity analysis demonstrated significantlyhigher incidence of myocardial infarction, hypertension and diabetes mellitus in the RT group (p < 0.05). Thesubgroup analysis revealed significantly higher incidence of infarction and stroke in the ASA resistant RTgroup compared to the RT patients without ASA resistance (p < 0.05). Furthermore, the incidence of myocardialinfarction and hypertension was significantly higher in the non-resistant RT group than in the groupof PC patients without ASA resistance (p < 0.05). These results may suggest that the elevated rate of aspirinresistance contributes to the high cardiovascular mortality after kidney transplantation.

      • KCI등재

        Linseed oil supplementation affects fatty acid desaturase 2, peroxisome proliferator activated receptor gamma, and insulin-like growth factor 1 gene expression in turkeys (Meleagris gallopavo)

        Szalai Klaudia,Tempfli Károly,Zsédely Eszter,Lakatos Erika,Gáspárdy András,Bali Papp Ágnes 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.4

        Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated. Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (FADS2), peroxisome proliferator activated receptor gamma (PPARγ), and insulin-like growth factor 1 (IGF1) genes was analysed by means of quantitative reverse transcription polymerase chain reaction. Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic FADS2 levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The PPARγ expression was lower (p<0.05), whereas IGF1 was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in FADS2, PPARγ, and IGF1 gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control. Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased FADS2 expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased PPARγ expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased IGF1 expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group. Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated.Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (<i>FADS2</i>), peroxisome proliferator activated receptor gamma (<i>PPARγ</i>), and insulin-like growth factor 1 (<i>IGF1</i>) genes was analysed by means of quantitative reverse transcription polymerase chain reaction.Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic <i>FADS2</i> levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The <i>PPARγ</i> expression was lower (p<0.05), whereas <i>IGF1</i> was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in <i>FADS2</i>, <i>PPARγ</i>, and <i>IGF1</i> gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control.Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased <i>FADS2</i> expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased <i>PPARγ</i> expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased <i>IGF1</i> expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group.

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