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Diagnostic and prognostic markers in canine inflammatory and neoplastic head and neck conditions
Ana Rejec, 2015, doktorska disertacija

Opis: Several different types of conditions with inflammatory and neoplastic background affect the anatomical localities of the head and neck in a dog. It is a well-recognized fact that these conditions affect the quality of life, as they are associated with various degree of regional dysfunction, have systemic effects and can be direct or indirect cause of death. Unfortunately, many dogs with both inflammatory and neoplastic head and neck conditions are presented at an advanced stage of the disease which can have significant impact on treatment strategies. The identification of biomarkers is advisable to enhance effective staging, grading and prognostication, which will in turn more accurately direct recommendations for therapy. These biomarkers can theoretically help to distinguish between inflammatory and neoplastic conditions, justify the management of patients more accurately and potentially predict the prognosis and the survival of patients. It was our interest to investigate the diagnostic and prognostic value of complete blood count parameters and indices in dogs with head and neck conditions of inflammatory and neoplastic origin, regulatory T cells in dogs with periodontal disease, immunohistochemical (Ki-67 and VEGFR-2) and histopathological biomarkers in dogs with inflammatory and neoplastic head and neck conditions and to evaluate the effectiveness of an accelerated radiotherapy protocol for the treatment of advanced canine HNSCC. We have proved that the parameters investigated might serve as important supportive diagnostic and/or prognostic biomarkers which might help to improve the treatment strategies of both inflammatory and neoplastic head and neck conditions in dogs and that the accelerated chemoradiotherapy protocol represents an effective alternative treatment option for dogs with advanced HNSCC.
Najdeno v: ključnih besedah
Povzetek najdenega: ...of inflammatory and neoplastic origin, regulatory T Beseda">Beseda">Beseda">cells in dogs with periodontal disease, immunohistochemical (Ki-67...
Ključne besede: biomarkers, dogs, periodontal disease, regulatory T cells, head and neck tumours, complete blood count, radiotherapy, vascular endothelial growth factor receptor 2
Objavljeno: 26.11.2015; Ogledov: 1188; Prenosov: 18
.pdf Polno besedilo (59,54 MB)

Deposition and possible influence of a self-cleaning thin TiO[sub]2 [over] (SiO [sub] 2) film on a photovoltaic module efficiency
Anja Soklič, Marko Kete, Urška Lavrenčič Štangar, Minoo Tasbihi, 2014, objavljeni znanstveni prispevek na konferenci

Najdeno v: ključnih besedah
Povzetek najdenega: Beseda">Beseda">Beseda">cells, fotokataliza, self-cleaning surface, ...
Ključne besede: solar cells, fotokataliza, self-cleaning surface
Objavljeno: 16.06.2016; Ogledov: 598; Prenosov: 0
URL Polno besedilo (0,00 KB)

Bilirubin is an Endogenous Antioxidant in Human Vascular Endothelial Cells
Lovro Žiberna, Mitja Martelanc, Mladen Franko, Sabina Passamonti, 2016, izvirni znanstveni članek

Opis: Bilirubin is a standard serum biomarker of liver function. Inexplicably, it is inversely correlated with cardiovascular disease risk. Given the role of endothelial dysfunction in originating cardiovascular diseases, direct analysis of bilirubin in the vascular endothelium would shed light on these relationships. Hence, we used high-performance liquid chromatography coupled with thermal lens spectrometric detection and diode array detection for the determination of endogenous cellular IXα-bilirubin. To confirm the isomer IXα-bilirubin, we used ultra-performance liquid chromatography coupled with a high-resolution mass spectrometer using an electrospray ionization source, as well as tandem mass spectrometric detection. We measured bilirubin in both arterial and venous rat endothelium (0.9–1.5 pmol mg−1 protein). In the human endothelial Ea.hy926 cell line, we demonstrated that intracellular bilirubin (3–5 pmol mg−1 protein) could be modulated by either extracellular bilirubin uptake, or by up-regulation of heme oxygenase-1, a cellular enzyme related to endogenous bilirubin synthesis. Moreover, we determined intracellular antioxidant activity by bilirubin, with EC50 = 11.4 ± 0.2 nM, in the range of reported values of free serum bilirubin (8.5–13.1 nM). Biliverdin showed similar antioxidant properties as bilirubin. We infer from these observations that intra-endothelial bilirubin oscillates, and may thus be a dynamic factor of the endothelial function.
Najdeno v: ključnih besedah
Ključne besede: Antioxidants, bilirubin, endothelial cells
Objavljeno: 07.07.2016; Ogledov: 879; Prenosov: 35
.pdf Polno besedilo (585,86 KB)

Atomically resolved dealloying of structurally ordered Pt nanoalloy as an oxygen reduction reaction electrocatalyst
Andraž Pavlišič, Primož Jovanovič, Vid Simon Šelih, Martin Šala, Marjan Bele, Goran Dražić, Iztok Arčon, Samo B. Hočevar, Anton Kokalj, Nejc Hodnik, Miran Gaberšček, izvirni znanstveni članek

Opis: The positive effect of intermetallic ordering of platinum alloy nanoparticles on oxygen reduction reaction (ORR) activity has been well established. What is still missing is an understanding of selective leaching of the less noble metal from the ordered structure and its correlation to longterm ORR performance. Using a combination of kinetic Monte Carlo simulations and advanced characterization techniques, we provide unprecedented insight into dealloying of intermetallic PtCu3 nanoparticles a well-known binary alloy. Comparison of ordered and disordered samples with identical initial compositions and particle size distributions reveals an unexpected correlation: whereas the copper dealloying rates in the ordered and disordered counterparts are almost the same, in the ordered structure Pt atoms are surrounded by 15−30% more Cu atoms throughout all the stages of acid leaching. This more convenient Pt−Cu coordination explains the statistically significant increase of 23−37% in ORR activity of the ordered structure at all stages of alloy degradation.
Najdeno v: ključnih besedah
Povzetek najdenega: ...ORR activity, fuel Beseda">Beseda">Beseda">cells, platinum alloy, nanoparticle stability, intermetallic ordering, kinetic...
Ključne besede: ORR activity, fuel cells, platinum alloy, nanoparticle stability, intermetallic ordering, kinetic Monte Carlo, dealloying, in situ ICP-MS
Objavljeno: 27.09.2016; Ogledov: 633; Prenosov: 0
.pdf Polno besedilo (3,27 MB)

Öznur Özlem Ibrahimoğlu, 2016, doktorska disertacija

Opis: A polymorphic variant of the phosphatase PTPN22 has recently emerged as a major risk factor for the development of multiple autoimmune diseases. The mechanism how this variant increases the susceptibility for autoimmune diseases is still unclear. A recent study by our lab showed that PTPN22 is markedly overexpressed in chronic lymphocytic leukemia (CLL), which is a common lymphoid malignancy characterized by the clonal outgrowth of autoreactive B lymphocytes. This study also showed that PTPN22 functions primarily as a negative regulator of B cell receptor (BCR) signaling, but can also positively affect the activity of certain downstream signaling pathways. To understand the role of PTPN22 in the pathogenesis of CLL, we investigated PTPN22 expression in leukemias that develop in the Eµ-TCL1 transgenic mouse model. We observed that PTPN22 is highly overexpressed in these leukemias. We also evaluated expression of PTPN22 in normal murine B cell subsets corresponding to different stages of B cell development and differentiation. We detected high PTPN22 expression in B1 B cells, which are the normal counterparts of CLL B cells, and lower levels in marginal zone B cells, whereas PTPN22 was not expressed or was expressed at extremely low levels in most of the other investigated B cell subsets.We generated knockout mice with targeted disruption of PTPN22. We showed that PTPN22 is not expressed by any B cell subset in PTPN22-/- mice, including B1 B cells. To investigate the impact of PTPN22 deficiency on B1 and marginal zone B cell development and function, we performed immunophenotyping analysis of bone marrow, spleen and peritoneal cavity B cells from a large series of PTPN22-/- and age-matched wild type mice. A small but appreciable reduction in the percentage of marginal zone B cells and an increase in the percentage of B1 B cells in older PTPN22-/- mice was observed. These changes were consistent with the increased levels of natural antibodies typically produced by B1 B cells and lower levels of antibodies typically produced by marginal zone B cells in PTPN22 deficient mice. Altogether, these data suggest that PTPN22 deficiency results in reduced marginal zone and increased B1 B cell immune responses. Importantly, this phenotype is remarkably similar to the phenotype of SHP1-/- mice, although considerably milder. Since SHP1 is the main negative regulator of proximal BCR signaling in B cells, these findings suggest that one important function of PTPN22 could be to provide additional fine-tuning of the intensity of the BCR signal in B1 and marginal zone B cells. In support of this possibility, a modest but consistent increase in anti-IgM-induced calcium mobilization was observed in B1 B cells from PTPN22-deficient compared to wild type mice.To see how PTPN22 deficiency will affect leukemia development and behavior, we crossed PTPN22 knockout mice with E-TCL1 transgenic mice. PTPN22 deficiency accelerated the expansion of the malignant B cells in this model and resulted in earlier leukemia development in comparison to wild type E-TCL1 transgenic mice. These data are consistent with other recent studies from our group showing that a greater capacity to activate downstream signaling pathways upon engagement of the BCR with external ligand is associated with more rapid disease progression in both human CLL and the E-TCL1 model. In conclusion, we show that PTPN22 is equally overexpressed in normal and leukemic B1 B cells derived from E-TCL1 transgenic mice, suggesting that PTPN22 overexpression is not due to the transforming event, at least in the case of murine CLL. The greater BCR signaling capacity of B1 B cells and the accelerated leukemia development in PTPN22-deficient mice further argues for an important role of BCR signals in determining the aggressiveness of CLL.
Najdeno v: ključnih besedah
Povzetek najdenega: ...detected high PTPN22 expression in Beseda">Beseda">Beseda">B1 Beseda">B Beseda">Beseda">Beseda">cells, which are the normal counterparts of CLL...
Ključne besede: PTPN22, BCR signalling, B1 B cells, marginal zone B cells, chronic lymphocytic leukemia (CLL), autoimmunity.
Objavljeno: 31.01.2017; Ogledov: 300; Prenosov: 30
.pdf Polno besedilo (2,95 MB)

Fabrication and characterization of ZnO and GaN devices for electronic and photonic applications
Fei Tong, 2014, doktorska disertacija

Opis: The research work presented in this book is based on two direct and wide band gap semiconductors: ZnO and GaN. On the first part of the book, the synthesis of ZnO nanorod array via the low temperature solution growth method was discussed. Due to the high surface-to-volume ratio of ZnO nanorod, to alleviate the some of the drawbacks such as carrier mobility and thickness dilemma of organic solar cells, ZnO nanorod array were integrated into organic solar cells. Power conversion efficiency (η) of 1.8% is achieved in our ZnO nanorods integrated bulk heterojunction organic solar cells on flexible In2O3-PET substrates. On the second part of the book, the fabrication and characterization of Aluminum gallium nitride/gallium nitride high electron mobility transistors (AlGaN/GaN HEMTs) were discussed. Device testing and characterization under both room temperature and high temperature up to 300 °C were performed. The results show that the device can operate even at 300 °C with minimal degradation.
Najdeno v: ključnih besedah
Povzetek najdenega: ...mobility and thickness dilemma of organic solar Beseda">Beseda">Beseda">cells, ZnO nanorod array were integrated into organic...
Ključne besede: ZnO nanorod array, organic-inorganic solar cells, AlGaN/GaN HEMTs.
Objavljeno: 25.01.2017; Ogledov: 337; Prenosov: 0
.pdf Polno besedilo (8,57 MB)

Ex Vivo Molecular Rejuvenation Improves the Therapeutic Activity of Senescent Human Cardiac Stem Cells in a Mouse Model of Myocardial Infarction
Elisa Avolio, Giuseppe Gianfranceschi, Angela Caragnano, Emmanouil Athanasakis, Rajesh Katare, Daniela Cesselli, Marco Meloni, Anita Palma, Arianna Barchiesi, Carlo Vascotto, Barbara Toffoletto, Elisa Mazzega, Nicoletta Finato, Giuseppe Aresu, Ugolino Livi, Costanza Emanueli, Giacinto Scoles, Carlo Alberto Beltrami, Paolo Madeddu, Antonio Paolo Beltrami, 2014, izvirni znanstveni članek

Opis: Cardiac stem cells (CSC) from explanted decompensated hearts (E-CSC) are, with respect to those obtained from healthy donors (D-CSC), senescent and functionally impaired. We aimed to identify alterations in signaling pathways that are associated with CSC senescence. Additionally, we inves- tigated if pharmacological modulation of altered pathways can reduce CSC senescence in vitro and enhance their reparative ability in vivo. Measurement of secreted factors showed that E-CSC release larger amounts of proinflammatory cytokine IL1b compared with D-CSC. Using blocking antibodies, we verified that IL1b hampers the paracrine protective action of E-CSC on cardiomyo- cyte viability. IL1b acts intracranially inducing IKKb signaling, a mechanism that via nuclear factor-jB upregulates the expression of IL1b itself. Moreover, E-CSC show reduced levels of AMP protein kinase (AMPK) activating phosphorylation. This latter event, together with enhanced IKKb signaling, increases TORC1 activity, thereby impairing the autophagic flux and inhibiting the phos- phorylation of Akt and cAMP response element-binding protein. The combined use of rapamycin and resveratrol enhanced AMPK, thereby restoring downstream signaling and reducing IL1b secretion. These molecular corrections reduced E-CSC senescence, re-establishing their protective activity on cardiomyocytes. Moreover ex vivo treatment with rapamycin and resveratrol improved E-CSC capacity to induce cardiac repair upon injection in the mouse infarcted heart, leading to reduced cardiomyocyte senescence and apoptosis and increased abundance of endog- enous c-Kit1 CSC in the peri-infarct area. Molecular rejuvenation of patient-derived CSC by short pharmacologic conditioning boosts their in vivo reparative abilities. This approach might prove useful for refinement of CSC-based therapies.
Najdeno v: ključnih besedah
Ključne besede: Stem cells, Myocardial infarction, Cellular senescence, Heart failure
Objavljeno: 21.03.2017; Ogledov: 251; Prenosov: 0
.pdf Polno besedilo (1,48 MB)

Analysis of mechanosensing in human cardiac stem cells
Elisa Mazzega, Eliana Pomarè, Angela Caragnano, Sebastian Martewicz, Nicola Elvassore, Antonio Paolo Beltrami, Ugo Livi, 2015, objavljeni povzetek znanstvenega prispevka na konferenci

Opis: Objectives: We have shown that age and pathology impair the biological properties of stem cells isolated from human hearts (CSC) and functional assays showed differences between CSC isolated from normal (DCSC) and end-stage failing (ECSC) hearts. As alterations of mechanical properties of the myocardium, such as stiffening and increased wall stress, are crucial features of cardiac remodeling, this work addresses the biological effects exerted on CSC by mechanical stimuli. Materials and methods: DCSC and ECSC were cultured under defined conditions to mimic specific features of the pathologic condition: increased mechanical loading (up to 15%, cyclic at 1 Hz), differential substrate stiffness (ranging from 1 to 231 kPa), differential cell densities. After 24, 48 and 72 h, cells were fixed and stained for analysis of proliferation and subcellular localization of YAP or lysed for RT-PCR analysis.Results: Cyclic stretch was significantly associated with both increased proliferation of DCSC (n = 6, p<0.0001) and ECSC (n = 4, p = 0.003), and with a significant reduction of nuclear localized YAP (nYAP) as a function of time (p<0.05). However, while significant correlation between cell density and decreased nYAP (p = 0.003, r2 = 0.37) characterized ECSC, this was not evident for unstretched DCSC, suggesting a less stringent regulation of contact inhibition in DCSC. These data were further confirmed by seeding cells at differential density. As opposed to what previously shown for epithelial cell lines, DCSC did not reduce nYAP positivity as a function of cell density, when grown in serum containing medium, suggesting that soluble factors present in the serum could maintain the nuclear localization of YAP, independently from the cell density. In line, serum significantly increased the nYAP expressing cells in DCSC, while a significant positive correlation between cell density and nYAP positivity can be demonstrated in DCSC cultured in serum free medium. RT-PCR for YAP-regulated targets confirmed immuno- fluorescence data. Furthermore, independently from the pathologic status, cyclic stretch was significantly associated with a persistent YAP signaling at high cell density. Besides, tension and assembly of cytoskeletal network, induced by increasing substrate stiffness, correlates with nYAP (p<0.05) and YAP transcriptional activation (p<0.05). Conclusions: D- and ECSC differ in their mechanosensing properties. However, in the first cell type, nYAP localization is dictated by the combined action of paracrine factors and cytoskeletal tension, thus reducing the contact inhibition effect. This finding is in line with a more primitive phenotype of SC isolated from normal hearts.
Najdeno v: ključnih besedah
Ključne besede: Stem cells, human cardiac stem cells, mechanosensing, mechanotransduction, heart failure, YAP
Objavljeno: 21.03.2017; Ogledov: 231; Prenosov: 0
.pdf Polno besedilo (65,67 KB)

Cardiac stem cell aging and heart failure
Daniela Cesselli, Aneta Aleksova, Elisa Mazzega, Angela Caragnano, Antonio Paolo Beltrami, 2017, pregledni znanstveni članek

Opis: A side effect of the medical improvements of the last centuries is the progressive aging of the world population, which is estimated to reach the impressive number of 2 billion people with more than 65 years by 2050. As a consequence, age-related diseases, such as heart failure, will affect more and more patients in the next years. To understand the biological bases of these diseases will be a crucial task in order to find better treatments, and possibly slow age-related morbidity and mortality. Cardiac stem cells have been at the center of a heated debate and their potential involvement in cardiac homeostasis has been questioned. In this review, we summarize evidence obtained by independent groups, on different animal models and humans, that strongly support the important role played by immature, cardiac resident cells in the cardioprotection against heart failure.
Najdeno v: ključnih besedah
Povzetek najdenega: ...possibly slow age-related morbidity and mortality. Cardiac stem Beseda">Beseda">Beseda">cells have been at the center of a...
Ključne besede: Aging, Heart failure, Cardiomyocyte turnover, Stem cells, Cell senescence, cKit, Sca1, PDGFRα, Cardiospheres
Objavljeno: 28.03.2017; Ogledov: 269; Prenosov: 0
.pdf Polno besedilo (1,43 MB)

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