| 1. |
- Endrődi, Balázs, 1987-, et al.
(author)
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Challenges and rewards of the electrosynthesis of macroscopic aligned carbon nanotube array/conducting polymer hybrid assemblies
- 2015
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In: Journal of Polymer Science Part B. - : Wiley. - 0887-6266 .- 1099-0488. ; 53, s. 1507-1518
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Journal article (peer-reviewed)abstract
- Hybrid assemblies based on conducting polymers and carbon nanomaterials with organized nanoscale structure are excellent candidates for various application schemes ranging from thermal management to electrochemical energy conversion and storage. In the case of macroscopic samples, however, precise control of the nanoscale structure has remained a major challenge to be solved for the scientific community. In this study we demonstrate possible routes to homogeneously infiltrate poly(3-hexylthiophene), poly(3,4-ethylenedioxythiophene), and polyaniline into macroscopic arrays of vertically aligned multiwalled carbon nanotubes (MWCNTAs). Electron microscopic images and Raman spectroscopic analysis (performed along the longitudinal dimension of the hybrid samples) both confirmed that optimization of the electropolymerization circumstances allowed fine tuning of the hybrid structure towards the targeted application. In this vein, three different application avenues were tested. The remarkable anisotropy in both the electrical and thermal conductivity of the nanocomposites makes them eminently attractive candidates to be deployed in thermal management. Thermoelectric studies, aimed to understand the effect of organized nanoscale morphology on the important parameters (Seebeck coefficient, electrical-, and thermal conductivity) compared to their non-organized hybrid counterparts. Finally, extraordinary high charge storage capacity values were registered for the MWCNTA/PANI hybrids (500 F g−1 and 1–3 F cm−2).
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| 2. |
- Firsova, Alexandra, et al.
(author)
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Topographic atlas of cell states identifies regional gene expression in the adult human lung
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Other publication (other academic/artistic)abstract
- Single cell mRNA sequencing of the whole organ has become a popular technique to reveal rare types and subtypes of previously characterized cells as well as to distinguish and characterize gene expression of previously unknown cell types. Unsupervised clustering can reveal tens or even hundreds of variable genes that characterize cell types. Variation in gene expression is often observed within one cell type, and sometimes cannot be biologically explained without mapping of mRNA on tissue. In this study we aim to (i) map the majority of cell types of human lung, (ii) describe variability in their gene expression and (iii) relate this gene expression to cellular location and neighborhoods. Using three different spatial transcriptomics approaches, we mapped epithelial cell states of airways and submucosal gland, and defined cell type-unrelated gene expression variability along proximo-distal axis, including potential regulators and co-regulators of such cell states in the mesenchymal and immune cell niches. In addition, we mapped rare cell types, such as subtypes of neuroendocrine cells, ionocytes and tuft (brush) cells, revealing tracheal preference for ionocytes, and distal airways for GHRL-positive neuroendocrine cells. Finally, we used the created map as a reference for the diseased tissue from patients with stage II COPD and revealed perturbed cell states and COPD-specific imbalance of cell types, affecting immune and AT0 clusters.
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| 3. |
- Hardisty, Alex R., et al.
(author)
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BioVeL: A virtual laboratory for data analysis and modelling in biodiversity science and ecology
- 2016
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In: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 16
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Journal article (peer-reviewed)abstract
- © 2016 The Author(s).Background: Making forecasts about biodiversity and giving support to policy relies increasingly on large collections of data held electronically, and on substantial computational capability and capacity to analyse, model, simulate and predict using such data. However, the physically distributed nature of data resources and of expertise in advanced analytical tools creates many challenges for the modern scientist. Across the wider biological sciences, presenting such capabilities on the Internet (as "Web services") and using scientific workflow systems to compose them for particular tasks is a practical way to carry out robust "in silico" science. However, use of this approach in biodiversity science and ecology has thus far been quite limited. Results: BioVeL is a virtual laboratory for data analysis and modelling in biodiversity science and ecology, freely accessible via the Internet. BioVeL includes functions for accessing and analysing data through curated Web services; for performing complex in silico analysis through exposure of R programs, workflows, and batch processing functions; for on-line collaboration through sharing of workflows and workflow runs; for experiment documentation through reproducibility and repeatability; and for computational support via seamless connections to supporting computing infrastructures. We developed and improved more than 60 Web services with significant potential in many different kinds of data analysis and modelling tasks. We composed reusable workflows using these Web services, also incorporating R programs. Deploying these tools into an easy-to-use and accessible 'virtual laboratory', free via the Internet, we applied the workflows in several diverse case studies. We opened the virtual laboratory for public use and through a programme of external engagement we actively encouraged scientists and third party application and tool developers to try out the services and contribute to the activity. Conclusions: Our work shows we can deliver an operational, scalable and flexible Internet-based virtual laboratory to meet new demands for data processing and analysis in biodiversity science and ecology. In particular, we have successfully integrated existing and popular tools and practices from different scientific disciplines to be used in biodiversity and ecological research.
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| 4. |
- Koureas, Dimitrios, et al.
(author)
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Unifying European Biodiversity Informatics (Bio Unify)
- 2016
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In: Research Ideas and Outcomes. - : Pensoft Publishers. - 2367-7163. ; 2:e7787, s. 1-23
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Journal article (peer-reviewed)abstract
- In order to preserve the variety of life on Earth, we must understand it better. Biodiversity research is at a pivotal point with research projects generating data at an ever increasing rate. Structuring, aggregating, linking and processing these data in a meaningful way is a major challenge. The systematic application of information management and engineering technologies in the study of biodiversity (biodiversity informatics) help transform data to knowledge. However, concerted action is required to be taken by existing e-infrastructures to develop and adopt common standards, provisions for interoperability and avoid overlapping in functionality. This would result in the unification of the currently fragmented landscape that restricts European biodiversity research from reaching its full potential. The overarching goal of this COST Action is to coordinate existing research and capacity building efforts, through a bottom-up trans-disciplinary approach, by unifying biodiversity informatics communities across Europe in order to support the long-term vision of modelling biodiversity on earth. BioUnify will: 1. specify technical requirements, evaluate and improve models for efficient data and workflow storage, sharing and re-use, within and between different biodiversity communities; 2. mobilise taxonomic, ecological, genomic and biomonitoring data generated and curated by natural history collections, research networks and remote sensing sources in Europe; 3. leverage results of ongoing biodiversity informatics projects by identifying and developing functional synergies on individual, group and project level; 4. raise technical awareness and transfer skills between biodiversity researchers and information technologists; 5. formulate a viable roadmap for achieving the long-term goals for European biodiversity informatics, which ensures alignment with global activities and translates into efficient biodiversity policy.
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| 5. |
- Megyesfalvi, Zsolt, et al.
(author)
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Unfolding the secrets of small cell lung cancer progression : Novel approaches and insights through rapid autopsies
- 2023
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In: Cancer Cell. - 1535-6108. ; 41:9, s. 1535-1540
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Journal article (peer-reviewed)abstract
- The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.
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| 6. |
- Rozsas, Anita, et al.
(author)
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Erythropoietin Receptor Expression Is a Potential Prognostic Factor in Human Lung Adenocarcinoma
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Journal article (peer-reviewed)abstract
- Recombinant human erythropoietins (rHuEPOs) are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR) signaling in human non-small cell lung cancer (NSCLC) also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC) and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPO alpha were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPO alpha with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC) proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU) incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPO alpha treatment (either alone or in combination with gemcitabine) did not alter ADC cell proliferation in vitro. However, rHuEPO alpha significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPO alpha treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.
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| 7. |
- Szucs, Edina, et al.
(author)
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Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
- 2020
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In: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
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Journal article (peer-reviewed)abstract
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
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| 8. |
- Valko, Zsuzsanna, et al.
(author)
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Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer
- 2023
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 128:10, s. 1850-1861
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Journal article (peer-reviewed)abstract
- Background: No targeted drugs are currently available against small cell lung cancer (SCLC). BCL-2 family members are involved in apoptosis regulation and represent therapeutic targets in many malignancies. Methods: Expression of BCL-2 family members in 27 SCLC cell lines representing all known four SCLC molecular subtypes was assessed by qPCR, Western blot and mass spectrometry-based proteomics. BCL-2 and MCL-1 inhibition (venetoclax and S63845, respectively) was assessed by MTT assay and flow cytometry and in mice bearing human SCLC tumours. Drug interactions were calculated using the Combenefit software. Ectopic BAX overexpression was achieved by expression plasmids. Results: The highest BCL-2 expression levels were detected in ASCL1- and POU2F3-driven SCLC cells. Although sensitivity to venetoclax was reflected by BCL-2 levels, not all cell lines responded consistently despite their high BCL-2 expression. MCL-1 overexpression and low BAX levels were both characteristic for venetoclax resistance in SCLC, whereas the expression of other BCL-2 family members did not affect therapeutic efficacy. Combination of venetoclax and S63845 resulted in significant, synergistic in vitro and in vivo anti-tumour activity and apoptosis induction in double-resistant cells; however, this was seen only in a subset with detectable BAX. In non-responding cells, ectopic BAX overexpression sensitised to venetoclax and S63845 and, furthermore, induced synergistic drug interaction. Conclusions: The current study reveals the subtype specificity of BCL-2 expression and sheds light on the mechanism of venetoclax resistance in SCLC. Additionally, we provide preclinical evidence that combined BCL-2 and MCL-1 targeting is an effective approach to overcome venetoclax resistance in high BCL-2-expressing SCLCs with intact BAX.
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