Screening of Pleural Mesotheliomas for DNA-damage Repair Players by Digital Gene Expression Analysis Can Enhance Clinical Management of Patients Receiving Platin-Based Chemotherapy

Background: Malignant pleural mesothelioma (MPM) is a rare, predominantly asbestos-related and biologically highly aggressive tumour leading to a dismal prognosis. Multimodality therapy consisting of platinum-based chemotherapy is the treatment of choice. The reasons for the rather poor efficacy of platinum compounds remain largely unknown. Material and Methods: For this exploratory mRNA study, 24 FFPE tumour specimens were screened by digital gene expression analysis. Based on data from preliminary experiments and recent literature, a total of 366 mRNAs were investigated using a Custom CodeSet from NanoString. All statistical analyses were calculated with the R i386 statistical programming environment. Results: CDC25A and PARP1 gene expression were correlated with lymph node spread, BRCA1 and TP73 expression levels with higher IMIG stage. NTHL1 and XRCC3 expression was associated with TNM stage. CHECK1 as well as XRCC2 expression levels were correlated with tumour progression in the overall cohort of patients. CDKN2A and MLH1 gene expression influenced overall survival in this collective. In the adjuvant treated cohort only, CDKN2A, CHEK1 as well as ERCC1 were significantly associated with overall survival. Furthermore, TP73 expression was associated with progression in this subgroup. Conclusion: DNA-damage response plays a crucial role in response to platin-based chemotherapeutic regimes. In particular, CHEK1, XRCC2 and TP73 are strongly associated with tumour progression. ERCC1, MLH1, CDKN2A and most promising CHEK1 are prognostic markers for OS in MPM. TP73, CDKN2A, CHEK1 and ERCC1 seem to be also predictive markers in adjuvant treated MPMs. After a prospective validation, these markers may improve clinical and pathological practice, finally leading to a patients' benefit by an enhanced clinical management

Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors

Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors

People, pollution and pathogens – Global change impacts in mountain freshwater ecosystems

Mountain catchments provide for the livelihood of more than half of humankind, and have become a key destination for tourist and recreation activities globally. Mountain ecosystems are generally considered to be less complex and less species diverse due to the harsh environmental conditions. As such, they are also more sensitive to the various impacts of the Anthropocene. For this reason,mountain regions may serve as sentinels of change and provide ideal ecosystems for studying climate and global change impacts on biodiversity. We here review different facets of anthropogenic impacts on mountain freshwater ecosystems. We put particular focus on micropollutants and their distribution and redistribution due to hydrological extremes, their direct influence on water quality and their indirect influence on ecosystem health via changes of freshwater species and their interactions. We show that those changes may drive pathogen establishment in new environments with harmful consequences for freshwater species, but also for the human population. Based on the reviewed literature, we recommend reconstructing the recent past of anthropogenic impact through sediment analyses, to focus efforts on small, but highly productive waterbodies, and to collect data on the occurrence and variability of microorganisms, biofilms, plankton species and key species, such as amphibians due to their bioindicator value for ecosystem health and water quality. The newly gained knowledge can then be used to develop a comprehensive framework of indicators to robustly inform policy and decision making on current and future risks for ecosystem health and human well-being

Project of a photovoltaic power plant with an output of 200 kW for the energy community community

Předkládaná práce se zaměřuje na návrh fotovoltaické elektrárny. Nejprve je popsána teorie solární energie, principu fotoelektrického jevu, typů fotovoltaických článků, druhů fotovoltaických systémů a recyklace fotovoltaických panelů. Poté je zpracována současná legislativa a možnosti podpory. Dále následuje praktický návrh fotovoltaické elektrárny o instalovaném výkonu 235,79 kWp. Poslední část je věnována energetickému, ekonomickému a ekologickému zhodnocení navrhované elektrárny.ObhájenoSubmitted thesis focuses on a design of a photovoltaic power plant. First of all, solar energy is described, followed by the principle of the photoelectric effect, types of photovoltaic cells and systems and recycling of photovoltaic panels. After that the current legislation and support options are elaborated. The main part of this theses is devoted to a design of a photovoltaic power plant with an installed capacity of 235,79 kW. In the last part, energy, economic and ecological evaluation of the proposed power plant are outlined

Resistive Films Realized by Thick Film Technology

Předkládaná práce je zaměřena na tištěné odporové vrstvy tvořené tlustovrstvou technologií. Nejprve je popsán princip technologie tlustých vrstev, používané pasty a metoda nanášení těchto past pomocí sítotisku. Poté je zpracován přehled odporových past, kde jsou uvedeny jejich základní vlastnosti. Dále je uveden přehled tištěných výkonových rezistorů vyhledaných na trhu. Závěr práce shrnuje praktické měření základních elektrických vlastností tištěných rezistorů.ObhájenoSubmitted bachelor´s thesis is focused on printed resistive films created by thick film technology. First, the principle of thick film technology, used pastes and method of applying these pastes by screen printing are described in this thesis. Then there is an overview of resistence pastes, where their basic properties are listed. There is also a summary of high-power resistors on the market. The final part of thesis is focused on the practical applications and on the practical measurement of the electrical properties of printed resistors

Modelling mountain hydrology to understand the impact of abiotic environmental variables on the health of aquatic ecosystems

International audienc

Modeling abiotic controls on amphibian epidemics due to a chytrid fungus in mountain aquatic ecosystems

International audienc

Modeling abiotic controls on amphibian epidemics due to a chytrid fungus in mountain aquatic ecosystems

International audienc

<i>ACTB</i>, <i>CDKN1B</i>, <i>GAPDH</i>, <i>GRB2</i>, <i>RHOA</i> and <i>SDCBP</i> Were Identified as Reference Genes in Neuroendocrine Lung Cancer via the nCounter Technology

<div><p>Background</p><p>Neuroendocrine lung cancer (NELC) represents 25% of all lung cancer cases and large patient collectives exist as formalin-fixed, paraffin-embedded (FFPE) tissue only. FFPE is controversially discussed as source for molecular biological analyses and reference genes for NELC are poorly establishes.</p><p>Material and methods</p><p>Forty-three representative FFPE-specimens were used for mRNA expression analysis using the digital nCounter technology (NanoString). Based on recent literature, a total of 91 mRNA targets were investigated as potential tumor markers or reference genes. The geNorm, NormFinder algorithms and coefficient of correlation were used to identify the most stable reference genes. Statistical analysis was performed by using the R programming environment (version 3.1.1)</p><p>Results</p><p>RNA integrity (RIN) ranged from 1.8 to 2.6 and concentrations from 34 to 2,109 ng/μl. However, the nCounter technology gave evaluable results for all samples tested. <i>ACTB</i>, <i>CDKN1B</i>, <i>GAPDH</i>, <i>GRB2</i>, <i>RHOA</i> and <i>SDCBP</i> were identified as constantly expressed genes with high stability (M-)values according to geNorm, NormFinder and coefficients of correlation.</p><p>Conclusion</p><p>FFPE-derived mRNA is suitable for molecular biological investigations via the nCounter technology, although it is highly degraded. <i>ACTB</i>, <i>CDKN1B</i>, <i>GAPDH</i>, <i>GRB2</i>, <i>RHOA</i> and <i>SDCBP</i> are potent reference genes in neuroendocrine tumors of the lung.</p></div