102,058 research outputs found
Special issue on effective methods in algebraic geometry - (MEGA 2005) - Foreword from the editors
No full textSpecial Issue on Effective Methods in Algebraic Geometry (MEGA 2005
The conundrum challenges for Research Software and Research Data in Open Science
No full textInternational audienceAbstractThe Borgman's conundrum challenges [1] have been initially formulated concerning the difficulties to share Research Data: which Research Data might be shared, by whom, with whom, under what conditions, why, and to what effects.In our previous work, we have proposed a Research Software Definition [2] with a formulation that we have adapted in order to propose a Research Data definition [3,4]. We have thus constructed a framework to understand and to explain Research Software and Research Data in the Open Science context [5].This framework is constructed in three stages: definition, dissemination, and evaluation of these research outputs [2,3,4], and it is now completed with answers to the Borgman's conundrum challenges for Research Data [3] and for Research Software [6].In this talk we will present our answers to the Borgman's conundrum challenges, and we will explain the comparison methodologies that we have developed in order to construct and to complete this Open Science framework.It is our understanding that to provide correct and clear answers to the conundrum questions will have, as a consequence, the improvement of Research Software and Research Data sharing and dissemination practices, which, in turn, will enhance trustworthiness, correctness, rigor, reproducibility, reusability and transparency in the research endeavor.This FOSDEM'25 presentation follows and extends our previous talks at FOSDEM: [FOSDEM'21] Free/Open source Research Software production at the Gaspard-Monge Computer Science laboratory. Lessons learnt. https://archive.fosdem.org/2021/schedule/event/open_research_gaspard_monge/ [FOSDEM'22] On the dissemination/evaluation loop for Research Software. https://archive.fosdem.org/2022/schedule/event/open_research_cdur/ ReferencesBorgman, C.L. The conundrum of sharing research data. J Am Soc Inf Sci Tec 2012, 63, 1059–1078. https://doi.org/10.1002/asi.22634 Gomez-Diaz, T.; Recio, T. On the evaluation of research software: the CDUR procedure [version 2; peer review: 2 approved]. F1000Research 2019, 8 1353. https://doi.org/10.12688/f1000research.19994.2Gomez-Diaz, T.; Recio, T. Research Software vs. Research Data I: Towards a Research Data definition in the Open Science context. [version 2; peer review: 3 approved]. F1000Research 2022, 11 118. https://doi.org/10.12688/f1000research.78195.2 Gomez-Diaz, T.; Recio, T. Research Software vs. Research Data II: Protocols for Research Data dissemination and evaluation in the Open Science context. [version 2; peer review: 2 approved]. F1000Research 2022, 11 117. https://doi.org/10.12688/f1000research.78459.2 Gomez-Diaz, T.; Recio, T. Towards an Open Science definition as a political and legal framework: on the sharing and dissemination of research outputs. POLIS 2020, N. 19. https://doi.org/10.58944/yuro5734. Version 3, 2021, available at https://zenodo.org/doi/10.5281/zenodo.4577065 Gomez-Diaz, T.; Recio, T. The conundrum challenges for Research Software in Open Science, Computers, 2024, 13(11), 302. https://doi.org/10.3390/computers13110302</ol
The conundrum challenges for Research Software and Research Data in Open Science
No full textInternational audienceAbstractThe Borgman's conundrum challenges [1] have been initially formulated concerning the difficulties to share Research Data: which Research Data might be shared, by whom, with whom, under what conditions, why, and to what effects.In our previous work, we have proposed a Research Software Definition [2] with a formulation that we have adapted in order to propose a Research Data definition [3,4]. We have thus constructed a framework to understand and to explain Research Software and Research Data in the Open Science context [5].This framework is constructed in three stages: definition, dissemination, and evaluation of these research outputs [2,3,4], and it is now completed with answers to the Borgman's conundrum challenges for Research Data [3] and for Research Software [6].In this talk we will present our answers to the Borgman's conundrum challenges, and we will explain the comparison methodologies that we have developed in order to construct and to complete this Open Science framework.It is our understanding that to provide correct and clear answers to the conundrum questions will have, as a consequence, the improvement of Research Software and Research Data sharing and dissemination practices, which, in turn, will enhance trustworthiness, correctness, rigor, reproducibility, reusability and transparency in the research endeavor.This FOSDEM'25 presentation follows and extends our previous talks at FOSDEM: [FOSDEM'21] Free/Open source Research Software production at the Gaspard-Monge Computer Science laboratory. Lessons learnt. https://archive.fosdem.org/2021/schedule/event/open_research_gaspard_monge/ [FOSDEM'22] On the dissemination/evaluation loop for Research Software. https://archive.fosdem.org/2022/schedule/event/open_research_cdur/ ReferencesBorgman, C.L. The conundrum of sharing research data. J Am Soc Inf Sci Tec 2012, 63, 1059–1078. https://doi.org/10.1002/asi.22634 Gomez-Diaz, T.; Recio, T. On the evaluation of research software: the CDUR procedure [version 2; peer review: 2 approved]. F1000Research 2019, 8 1353. https://doi.org/10.12688/f1000research.19994.2Gomez-Diaz, T.; Recio, T. Research Software vs. Research Data I: Towards a Research Data definition in the Open Science context. [version 2; peer review: 3 approved]. F1000Research 2022, 11 118. https://doi.org/10.12688/f1000research.78195.2 Gomez-Diaz, T.; Recio, T. Research Software vs. Research Data II: Protocols for Research Data dissemination and evaluation in the Open Science context. [version 2; peer review: 2 approved]. F1000Research 2022, 11 117. https://doi.org/10.12688/f1000research.78459.2 Gomez-Diaz, T.; Recio, T. Towards an Open Science definition as a political and legal framework: on the sharing and dissemination of research outputs. POLIS 2020, N. 19. https://doi.org/10.58944/yuro5734. Version 3, 2021, available at https://zenodo.org/doi/10.5281/zenodo.4577065 Gomez-Diaz, T.; Recio, T. The conundrum challenges for Research Software in Open Science, Computers, 2024, 13(11), 302. https://doi.org/10.3390/computers13110302</ol
Role of Methylation in Modulating MAPK Signaling. Implications in Melanoma. Papel de la metilación como modulador de la señalización en MAPK. Implicaciones en melanoma.
No full text1. General Overview
MTAP is a key enzyme in the methionine salvage pathway and controls the levels of methylthioadenosine (MTA). Lost of MTAP, which is frequent in melanoma, results in higher intra and extracellular MTA levels. As MTA is an inhibitor of methylation reactions within the cell, we decided to further investigate the role of methylation in the progression of cancer and how the main signaling pathway involved in melanoma (RAS-RAF-MEK-ERK pathway) can be affected in the presence or absence of methylation inhibitors.
2. Results
• Exogenous addition of MTA (and therefore blocking of methylation reactions) to melanoma cells increased total activity of the RAS-ERK pathway, highlighting a new role of methylation into controlling the amplitude of the signal transduction.
• We found out that PRMT5, a protein arginine methyl transferase enzyme, binds to CRAF, a key component of the RAS-ERK pathway. In vitro and in vivo experiments showed that PRMT5 methylates CRAF and thus modifies the pathway’s output. We identified CRAF arginine 563 as the target of PRMT5 methyl transferase activity. Furthermore, in vitro kinase assays and siRNA technology experiments showed that methylation at arginine 563 can modify the kinase activity of CRAF protein, therefore modulating the total activity of the RAS-ERK pathway.
• The previous results provided the first known evidence of methylation as a key modulator of the activity in MAPKs pathways, so we looked for a biological significance of this new regulatory mechanism. We used the well-established PC12 cell line system (EGF growth factor triggers proliferation whereas NGF promotes differentiation): as we had shown that PRMT5-catalyzed methylation can modify the kinase activity of the RAS-ERK pathway, we wondered whether this regulation could be part of a general mechanism controlling cell behavior. In order to test this, we tried to mimic the differentiating effect of NGF using EGF to activate the pathway in the presence of MTA or after PRMT5 siRNA. Interestingly, when triggering the cells with EGF after PRMT5 depletion or MTA treatment, they differentiated in a manner indistinguishable from that induced by NGF. Moreover, we observed that cells transfected with CRAFR563K mutant underwent differentiation, instead proliferation, when treating the cells with EGF. Together these data demonstrate a central role of methylation in the growth factors-elicited biological responses.
• RAS-ERK pathway plays a key role into controlling development and maintenance of melanoma. There is a clear correlation between the activity of the pathway and melanoma growth and proliferation, so we wondered how methylation reactions could affect melanoma progression. In order to address this question we performed in vitro assays in a variety of melanoma cell lines and we found out that MTA inhibited cell proliferation and viability. Next, we injected these cells in a melanoma xenograft mouse model to induce tumoral growth: mice treated with MTA showed a significant decrease (47%) in the tumor volume with no apparent toxic effects, indicating that MTA is effective blocking melanoma in vivo tumor growth. Besides, we have been able to proof that MTA inhibitory effect was due to citostatic MTA capability rather than a pro-apoptotic effect.
3. Discussion
In our reports we demonstrate that methylation is an important mechanism modulating signal transduction through the RAS-ERK pathway in response to specific growth factors. Our data implicate a specific PRMT5 methylation motif (GRG) that is conserved in all RAF proteins and we demonstrate that methylation appears to be a critical posttranslational modification controlling the RAF input to the downstream activity.
We have shown that methylation is controlling ERK signal amplitude in response to specific growth factors in cells from different species. We also have identified PRMT5 as the protein performing the methylation reaction. Our results provide clues about the possible fine-tuning mechanism by which methylation regulates the total signal, indicating that PRMT5 methylates CRAF at arginine 563.
Our research shows that protein arginine methylation is a universal mechanism that modulates signal transduction in response to specific growth factors and we demonstrate that PRMT5 is the methyltransferase involved in the process regulating the total CRAF kinase activity within the pathway. The mechanism we describe provides the means by which cells can modulate the time profile of ERK activation for which a particular biological response is evoked. More importantly, because cancer cells tend to heavily rely on oncogenic signalling through the RAS-RAF-MEK-ERK pathway, this additional level of signal transduction regulation identifies novel candidate targets for therapeutical intervention.
Finally, we have tested the potential of the methylation inhibitor MTA regarding to tumour progression: our experiments have demonstrated that MTA inhibits, in vitro, cell proliferation and viability in a dose dependent manner in a variety of mouse and human melanoma cell lines. Importantly, MTA was also effective inhibiting in vivo tumour growth in a mouse melanoma xenograft model. In summary, here we show the therapeutic potential of the natural occurring nucleoside MTA and we demonstrate that MTA can inhibit melanoma cell proliferation and in vivo tumour growth at non-toxic rates, supporting the use of MTA in antitumoral therapies and presenting protein methylation reactions as potential targets when developing new antitumoral strategies
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
Emergent literacy across languages: using stories and technology to teach English to three and four year old Spanish children in a foreign language context
No full textHandwritten biographical information on Paulina T. McClung Merritt
No full textA handwritten biography of Paulina T. McClung Merritt by an unknown author, 1892.
Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Pelevin’s Trinity in the novel “t”: author – protagonist – reader
No full textThe article attempts to interpret Pelevin's artistic strategy in the novel "T" by exploring its subject organization and addressing the key problems of the author, the protagonist, and the reader as they are seen by the researcher. The article analyzes the peculiarities of constructing the narrative reality in the novel "T", and goes on to discuss Pelevin's philosophic models of the development of the humankind, and the emergence of his new anthropology
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