Bibliografie tematiche / TEAD COMPLEX

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Letteratura scientifica selezionata sul tema "TEAD COMPLEX"

Autore: Grafiati
Pubblicato: 11 settembre 2023

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Articoli di riviste sul tema "TEAD COMPLEX"

1

Moure, Casey J., Christopher Sondey, Mangeng Cheng, My Mansueto, Rafael Fernandez, Sebastian E. Schneider, Julia V. Ramirez et al. "Abstract 3938: Discovery of a novel small molecule inhibitor of the YAP1/TAZ-TEAD transcriptional complex". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 3938. http://dx.doi.org/10.1158/1538-7445.am2022-3938.

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Abstract (sommario):
Abstract Hippo pathway alterations in human cancers often result in dephosphorylation of yes-associated protein (YAP1) and its paralog TAZ (WWTR1), allowing the formation of an active complex with transcriptional enhanced associate domain transcription factors (TEADs). This complex formation results in the activation of pro-survival and pro-proliferative transcriptional programs in cancer cells. Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of tumors are driven by YAP1/TEAD activity. Although traditionally difficult to drug with small molecules, identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs necessary for YAP1 interaction has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TAZ-TEAD complex formation and transcriptional activity. We report the discovery and characterization of the novel YAP1/TAZ-TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TAZ-TEAD activity. In biochemical thermal shift assays, MRK-A caused a concentration-dependent melting temperature shift of 8-12.5 and 0.6-1.5 degrees for TEAD1 and TEAD2, respectively, indicating direct binding to TEAD protein. In cellular assays, MRK-A demonstrated inhibition of a TEAD-based reporter assay, with little to no activity in multiple orthogonal off-target reporter assays such as WNT, NF-KB, TGFB and PPARG (8.4 nM vs. >10000 nM), which is consistent with the exquisite selectivity profile of this molecule (>1000x selectivity against 350+ measured kinases and other common off-targets). In the NF2-deficient mesothelioma cell line H226, MRK-A suppressed the transcription of endogenous YAP/TAZ-TEAD target genes CYR61, ERBB3, ANKRD1 and CTGF (50-75% inhibition at 100 nM), but not LATS1, a non-TEAD regulated Hippo pathway gene. In co-immunoprecipitation assays, MRK-A disrupted the interaction of YAP1 and TEAD in H226 cells at concentrations consistent with inhibition of target genes. In addition, MRK-A potently blocked the clonogenic growth and viability of H226 cells in a dose-dependent manner (maximal response at 1 µM compound >90% growth inhibition), while sparing the Hippo wild-type mesothelioma cell line H28. Furthermore, structurally similar control compounds, MRK-B and MRK-C, without the ability to block TEAD-mediated transcription (TEAD reporter MCF7 assay IC50 > 10000 nM), did not impact the clonogenic growth of H226 cells. In vivo, MRK-A did not show acute tolerability signals in mice and demonstrated pharmacokinetics suitable for daily oral dosing in efficacy studies. In summary, we report the structure and characterization of MRK-A demonstrating potent and specific inhibition of YAP1/TAZ-TEAD mediated transcriptional responses, with potential implications for treating malignancies driven by altered Hippo signaling. Citation Format: Casey J. Moure, Christopher Sondey, Mangeng Cheng, My Mansueto, Rafael Fernandez, Sebastian E. Schneider, Julia V. Ramirez, Brian Long, Erin DiMauro, Brandon Vara, Charles Yeung, Abe Achab, Jongwon Lim, Ronald Kim, Cayetana Zarate, Jonathan Bennett, Rachel Palte, Robert Foti, Vladimir Simov, Evan Barry. Discovery of a novel small molecule inhibitor of the YAP1/TAZ-TEAD transcriptional complex [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3938.
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2

Pobbati, Ajaybabu V., e Brian P. Rubin. "Protein-Protein Interaction Disruptors of the YAP/TAZ-TEAD Transcriptional Complex". Molecules 25, n. 24 (18 dicembre 2020): 6001. http://dx.doi.org/10.3390/molecules25246001.

Testo completo
Abstract (sommario):
The identification of protein-protein interaction disruptors (PPIDs) that disrupt the YAP/TAZ-TEAD interaction has gained considerable momentum. Several studies have shown that YAP/TAZ are no longer oncogenic when their interaction with the TEAD family of transcription factors is disrupted. The transcriptional co-regulator YAP (its homolog TAZ) interact with the surface pockets of TEADs. Peptidomimetic modalities like cystine-dense peptides and YAP cyclic and linear peptides exploit surface pockets (interface 2 and interface 3) on TEADs and function as PPIDs. The TEAD surface might pose a challenge for generating an effective small molecule PPID. Interestingly, TEADs also have a central pocket that is distinct from the surface pockets, and which small molecules leverage exclusively to disrupt the YAP/TAZ-TEAD interaction (allosteric PPIDs). Although small molecules that occupy the central pocket belong to diverse classes, they display certain common features. They are flexible, which allows them to adopt a palmitate-like conformation, and they have a predominant hydrophobic portion that contacts several hydrophobic residues and a small hydrophilic portion that faces the central pocket opening. Despite such progress, more selective PPIDs that also display favorable pharmacokinetic properties and show tolerable toxicity profiles are required to evaluate the feasibility of using these PPIDs for cancer therapy.
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3

Che, Kepeng, Ajaybabu V. Pobbati, Caleb N. Seavey, Yuriy Fedorov, Anton A. Komar, Ashley Burtscher, Shuang Ma e Brian P. Rubin. "Aurintricarboxylic acid is a canonical disruptor of the TAZ-TEAD transcriptional complex". PLOS ONE 17, n. 4 (13 aprile 2022): e0266143. http://dx.doi.org/10.1371/journal.pone.0266143.

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Abstract (sommario):
Disrupting the formation of the oncogenic YAP/TAZ-TEAD transcriptional complex holds substantial therapeutic potential. However, the three protein interaction interfaces of this complex cannot be easily disrupted using small molecules. Here, we report that the pharmacologically active small molecule aurintricarboxylic acid (ATA) acts as a disruptor of the TAZ-TEAD complex. ATA was identified in a high-throughput screen using a TAZ-TEAD AlphaLISA assay that was tailored to identify disruptors of this transcriptional complex. We further used fluorescence polarization assays both to confirm disruption of the TAZ-TEAD complex and to demonstrate that ATA binds to interface 3. We have previously shown that cell-based models that express the oncogenic TAZ-CAMTA1 (TC) fusion protein display enhanced TEAD transcriptional activity because TC functions as an activated form of TAZ. Utilizing cell-based studies and our TC model system, we performed TC/TEAD reporter, RNA-Seq, and qPCR assays and found that ATA inhibits TC/TEAD transcriptional activity. Further, disruption of TC/TEAD and TAZ/TEAD interaction by ATA abrogated anchorage-independent growth, the phenotype most closely linked to dysregulated TAZ/TEAD activity. Therefore, this study demonstrates that ATA is a novel small molecule that has the ability to disrupt the undruggable TAZ-TEAD interface.
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4

Gallego-Gutiérrez, Helios, Laura González-González, Leticia Ramírez-Martínez, Esther López-Bayghen e Lorenza González-Mariscal. "Tight junction protein ZO-2 modulates the nuclear accumulation of transcription factor TEAD". Molecular Biology of the Cell 32, n. 15 (15 luglio 2021): 1347–58. http://dx.doi.org/10.1091/mbc.e20-07-0470.

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Abstract (sommario):
ZO-2 interaction with TEAD regulates TEAD movement in and out of the nucleus. nPKCδ blocks formation of ZO-2/TEAD complex. PKA blocks ZO-2 nuclear import. nPKCε activates a NES of ZO-2 and TEAD exportation in a complex with ZO-2 or alone.
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5

Li, Z., B. Zhao, P. Wang, F. Chen, Z. Dong, H. Yang, K. L. Guan e Y. Xu. "Structural insights into the YAP and TEAD complex". Genes & Development 24, n. 3 (1 febbraio 2010): 235–40. http://dx.doi.org/10.1101/gad.1865810.

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6

Kim, Jisook, Seung Hyun Jung, Seon Yeong Han, Jihee Yoon, Minjeong Kim, Jooyun Byun, Heesun Moon et al. "Abstract 1614: Antitumor activity of novel and potent YAP/TAZ-TEAD inhibitorstargeting the Hippo pathway in solid tumors". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 1614. http://dx.doi.org/10.1158/1538-7445.am2023-1614.

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Abstract (sommario):
Abstract The Hippo pathway is evolutionarily conserved and known to regulate diverse cellular processes, including cell survival, proliferation, differentiation, migration, and organ size. The key regulator of Hippo pathway is transcriptional enhanced associate domain (TEAD) transcription factors, which directly bind with YAP/TAZ and then drive the multiple signaling by activating target gene expression on nuclear. Loss-of-function mutations in the upstream activators, NF2-LATS1/2-MST1/2, trigger YAP/TAZ nuclear translocation and target gene transcription (Hippo-off state). This YAP/TAZ-TEAD complex is overexpressed and leads to metastatic progression in various cancers including malignant mesothelioma, NSCLC, ovarian cancer or cholangiocarcinoma. A recent development in targeting the Hippo pathway has been focused on the discovery of a central lipophilic pocket in TEAD amenable to the small-molecule binding site of autopalmitoylation. Within this lipophilic palmitate pocket, post-translational S-palmitoylation of TEAD at a conserved catalytic cysteine (Cys) residue (e.g., C380) leads to TEAD stabilization and is believed to be critical for maintaining appropriate protein folding to enable the formation of the transcriptionally active YAP/TAZ -TEAD complex. Therefore, targeting the palmitate pocket with allosteric small molecules inhibitor disrupt the formation of the YAP/TAZ-TEAD complex and modulate YAP/TAZ-TEAD driven gene transcription. We have identified a series of novel, potent small-molecule inhibitors of the YAP/TAZ-TEAD transcriptional complex. It showed under 20 nM of potency in the inhibition of TEAD luciferase reporter assay in MCF7-TEAD-luc cells. These TEAD inhibitors inhibited YAP/TAZ-TEAD protein-protein interaction in H226 cells harboring neurofibromin 2 (NF2) alteration. In addition, our lead compounds exhibited dose-dependent growth inhibitory effects in Hippo pathway-altered cancer cell lines and reduced the YAP/TAZ-TEAD target gene expression, CTGF, and CYR61 in H226 cells. Our lead compounds, singled out and optimized based on in vitro functional assay, displayed favorable pharmacokinetic and safety profiles. Furthermore, orally administered lead compound effectively suppressed tumor growth within tolerable doses in xenograft mice with tumors harboring NF2 alteration as a major upstream molecule of the Hippo pathway. In summary, we pointed our novel YAP/TAZ-TEAD inhibitors that showed excellent efficacy in Hippo-altered mutant cancer in vitro and in vivo xenograft models. These data best support a therapeutic option for the treatment of cancers with amplified or overexpressed YAP, TAZ, or TEAD genes. Further preclinical studies will be performed and reported soon after the establishment of a preclinical candidate. Citation Format: Jisook Kim, Seung Hyun Jung, Seon Yeong Han, Jihee Yoon, Minjeong Kim, Jooyun Byun, Heesun Moon, Eunyoung Lee, Yu-Yon Kim, Hyunjin Park, So-Ye Jeon, Young Gil Ahn, Young Hoon Kim, Kwee Hyun Suh. Antitumor activity of novel and potent YAP/TAZ-TEAD inhibitorstargeting the Hippo pathway in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1614.
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7

Lauriola, Angela, Elisa Uliassi, Matteo Santucci, Maria Laura Bolognesi, Marco Mor, Laura Scalvini, Gian Marco Elisi et al. "Identification of a Quinone Derivative as a YAP/TEAD Activity Modulator from a Repurposing Library". Pharmaceutics 14, n. 2 (10 febbraio 2022): 391. http://dx.doi.org/10.3390/pharmaceutics14020391.

Testo completo
Abstract (sommario):
The transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif) are the major downstream effectors in the Hippo pathway and are involved in cancer progression through modulation of the activity of TEAD (transcriptional enhanced associate domain) transcription factors. To exploit the advantages of drug repurposing in the search of new drugs, we developed a similar approach for the identification of new hits interfering with TEAD target gene expression. In our study, a 27-member in-house library was assembled, characterized, and screened for its cancer cell growth inhibition effect. In a secondary luciferase-based assay, only seven compounds confirmed their specific involvement in TEAD activity. IA5 bearing a p-quinoid structure reduced the cytoplasmic level of phosphorylated YAP and the YAP–TEAD complex transcriptional activity and reduced cancer cell growth. IA5 is a promising hit compound for TEAD activity modulator development.
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8

Sheldon, Caroline, Aaron Farley, Qing Ma, William T. Pu e Zhiqiang Lin. "Depletion of VGLL4 Causes Perinatal Lethality without Affecting Myocardial Development". Cells 11, n. 18 (10 settembre 2022): 2832. http://dx.doi.org/10.3390/cells11182832.

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Abstract (sommario):
Congenital heart disease is one of the leading causes of pediatric morbidity and mortality, thus highlighting the importance of deciphering the molecular mechanisms that control heart development. As the terminal transcriptional effectors of the Hippo–YAP pathway, YAP and TEAD1 form a transcriptional complex that regulates the target gene expression and depletes either of these two genes in cardiomyocytes, thus resulting in cardiac hypoplasia. Vestigial-like 4 (VGLL4) is a transcriptional co-factor that interacts with TEAD and suppresses the YAP/TEAD complex by competing against YAP for TEAD binding. To understand the VGLL4 function in the heart, we generated two VGLL4 loss-of-function mouse lines: a germline Vgll4 depletion allele and a cardiomyocyte-specific Vgll4 depletion allele. The whole-body deletion of Vgll4 caused defective embryo development and perinatal lethality. The analysis of the embryos at day 16.5 revealed that Vgll4 knockout embryos had reduced body size, malformed tricuspid valves, and normal myocardium. Few whole-body Vgll4 knockout pups could survive up to 10 days, and none of them showed body weight gain. In contrast to the whole-body Vgll4 knockout mutants, cardiomyocyte-specific Vgll4 knockout mice had no noticeable heart growth defects and had normal heart function. In summary, our data suggest that VGLL4 is required for embryo development but dispensable for myocardial growth.
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9

Zhang, Wenxiang, Jinjin Xu, Jinhui Li, Tong Guo, Dan Jiang, Xue Feng, Xueyan Ma et al. "The TEA domain family transcription factor TEAD4 represses murine adipogenesis by recruiting the cofactors VGLL4 and CtBP2 into a transcriptional complex". Journal of Biological Chemistry 293, n. 44 (12 settembre 2018): 17119–34. http://dx.doi.org/10.1074/jbc.ra118.003608.

Testo completo
Abstract (sommario):
The Hippo signaling pathway is known to play an important role in multiple physiological processes, including adipogenesis. However, whether the downstream components of the Hippo pathway are involved in adipogenesis remains unknown. Here we demonstrate that the TEA domain family (TEAD) transcription factors are essential for adipogenesis in murine 3T3-L1 preadipocytes. Knockdown of TEAD1–4 stimulated adipogenesis and increased the expression of adipocyte markers in these cells. Interestingly, we found that the TEAD4 knockdown–mediated adipogenesis proceeded in a Yes-associated protein (YAP)/TAZ (Wwtr1)–independent manner and that adipogenesis suppression in WT cells involved formation of a ternary complex comprising TEAD4 and the transcriptional cofactors C-terminal binding protein 2 (CtBP2) and vestigial-like family member 4 (VGLL4). VGLL4 acted as an adaptor protein that enhanced the interaction between TEAD4 and CtBP2, and this TEAD4–VGLL4–CtBP2 ternary complex dynamically existed at the early stage of adipogenesis. Finally, we verified that TEAD4 directly targets the promoters of major adipogenesis transcription factors such as peroxisome proliferator–activated receptor γ (PPARγ) and adiponectin, C1Q, and collagen domain–containing (Adipoq) during adipogenesis. These findings reveal critical insights into the role of the TEAD4–VGLL4–CtBP2 transcriptional repressor complex in suppression of adipogenesis in murine preadipocytes.
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10

Gnedeva, Ksenia, Xizi Wang, Melissa M. McGovern, Matthew Barton, Litao Tao, Talon Trecek, Tanner O. Monroe et al. "Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal". Proceedings of the National Academy of Sciences 117, n. 24 (1 giugno 2020): 13552–61. http://dx.doi.org/10.1073/pnas.2000175117.

Testo completo
Abstract (sommario):
Precise control of organ growth and patterning is executed through a balanced regulation of progenitor self-renewal and differentiation. In the auditory sensory epithelium—the organ of Corti—progenitor cells exit the cell cycle in a coordinated wave between E12.5 and E14.5 before the initiation of sensory receptor cell differentiation, making it a unique system for studying the molecular mechanisms controlling the switch between proliferation and differentiation. Here we identify the Yap/Tead complex as a key regulator of the self-renewal gene network in organ of Corti progenitor cells. We show that Tead transcription factors bind directly to the putative regulatory elements of many stemness- and cell cycle-related genes. We also show that the Tead coactivator protein, Yap, is degraded specifically in the Sox2-positive domain of the cochlear duct, resulting in down-regulation of Tead gene targets. Further, conditional loss of theYapgene in the inner ear results in the formation of significantly smaller auditory and vestibular sensory epithelia, while conditional overexpression of a constitutively active version ofYap,Yap5SA, is sufficient to prevent cell cycle exit and to prolong sensory tissue growth. We also show that viral gene delivery ofYap5SAin the postnatal inner ear sensory epithelia in vivo drives cell cycle reentry after hair cell loss. Taken together, these data highlight the key role of the Yap/Tead transcription factor complex in maintaining inner ear progenitors during development, and suggest new strategies to induce sensory cell regeneration.
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Più fonti

Tesi sul tema "TEAD COMPLEX"

1

Stapleton, James L. "Joint effects of team composition and team decision mode on complex decision quality /". Available to subscribers only, 2006. http://proquest.umi.com/pqdweb?did=1147183151&sid=11&Fmt=2&clientId=1509&RQT=309&VName=PQD.

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2

Rovira, Asenjo Núria. "Complex network approaches to small team analysis. Conflict and gender". Doctoral thesis, Universitat Rovira i Virgili, 2014. http://hdl.handle.net/10803/130926.

Testo completo
Abstract (sommario):
En un contexto donde los equipos juegan un papel cada vez más importante, es de gran importancia entender el conflicto y desarrollar herramientas de diagnóstico para evitarlo. Aquí, investigamos empíricamente si es posible predecir cuantitativamente futuros conflictos en equipos pequeños utilizando modelos de estructura de red social. Analizamos los datos de 16 equipos pequeños. Encontramos que los modelos basados en redes complejas anticipan el conflicto exitosamente mientras que los modelos utilizados tradicionalmente no lo hacen. También presentamos un estudio sobre las diferencias de género en el liderazgo. Este estudio tiene como objetivo entender los mecanismos detrás del proceso de evaluación del liderazgo. Analizamos los datos de 45 evaluaciones de líderes (33% mujeres). Encontramos que las mujeres líderes son mejor evaluadas que los líderes masculinos al principio. Más tarde, esta ventaja se desvanece junto con el efecto sorprendente de tener una líder femenino. También encontramos que la agrupación de la red de líderes mujeres crece significativamente más que la agrupación de líderes hombres.
In a context where teams play an increasingly important role, it is of major importance to understand conflict and to develop diagnostic tools to avert it. Here, we investigate empirically whether it is possible to quantitatively predict future conflict in small teams using models of social network structure. We analyze data of 16 small teams. We find that models based on complex networks successfully anticipate conflict whereas traditionally used models do not. We also present a study about gender differences on leadership. This study aims to understand the mechanisms behind the leadership evaluation process. We analyze data of 45 leader evaluations (33% women). We find that female leaders are better evaluated than male leaders at the beginning. Later, this advantage vanishes together with the surprising effect of having a female leader. We also find that the network clustering of female leaders grows significantly more than the clustering of male leaders.
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3

Stevenson, David M. "Decision making skill and complex problem solving in team sports". Thesis, University of Stirling, 2013. http://hdl.handle.net/1893/20389.

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Abstract (sommario):
This thesis aimed to enhance understanding of the nature of knowledge bases possessed by elite sports performers which underpin perceptual-cognitive and decision making skills. Two main theories were considered; Active Control of Thought (ACT*) and Representational Redescription (RR). The purpose of Study 1 was to examine the anticipatory ability of elite and non-elite players in football and hockey. The results indicated that elite players in both sports were quicker and more accurate in their expectation of pass destination. Study 2 aimed to understand the extent to which knowledge is transferable. The results indicated that elite players’ knowledge is relatively domain specific although some elements of underlying task strategy may transfer. The objective of Study 3 was to explore the means by which elite and non-elite players in football and hockey identify and differentiate between possible decisions. Results showed elite players’ rationale was based on deeper theoretical principles whilst non-experts utilised relatively superficial information and naïve theories. Study 4 focussed on problem representations of elite and non-elite football players. Results revealed elite players’ representations were more pertinent, connected and articulated in a more effective manner. Overall, the findings from the current thesis provide advanced understanding of the knowledge bases responsible for perceptual-cognitive and decision making skill, and such understanding may assist attempts to enhance athletes’ performance and support future research.
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4

Gibault, Floriane. "Conception, synthèse et évaluation d’inhibiteurs du complexe protéique YAP-TEAD à visée anticancéreuse". Thesis, Lille 1, 2017. http://www.theses.fr/2017LIL10097.

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Abstract (sommario):
La voie Hippo, découverte chez la Drosophile et conservée chez les mammifères, a été identifiée comme un élément essentiel dans le contrôle de la taille des organes. Cette cascade de kinases régule la phosphorylation de l’effecteur terminal YAP (ou de son paralogue TAZ), un coactivateur transcriptionnel reconnu comme oncogène. Sa fonction est médiée par sa translocation nucléaire et son interaction avec les facteurs de transcription TEAD, pour former le complexe YAP-TEAD qui active l’expression des gènes cibles responsable de la prolifération cellulaire et de la croissance des organes. La surexpression des protéines YAP/TAZ/TEAD dans de nombreux cancers perturbe l’équilibre de la voie Hippo et favorise la formation du complexe protéique causant une hyperprolifération et la propagation des cellules cancéreuses. Inhiber cette interaction protéine-protéine est une cible thérapeutique prometteuse pour concevoir de nouveaux anticancéreux. Dans cette optique, le laboratoire a considéré deux stratégies. La première consiste à cibler la protéine YAP en synthétisant des dipyrrines, représentant des fragments de la Vertéporfine dans le but de définir le motif minimal requis pour conserver l’activité biologique. Une seconde approche implique la synthèse de ligands de TEAD capable de se positionner au sein de l’interface 3. Basée sur des études de modélisation moléculaire, une famille avec un noyau central triazolique a été optimisée pour établir des relations structure-activité. Les molécules synthétisées sont actuellement en cours d’évaluation, grâce à la mise au point des tests biologiques et physicochimiques, et les premiers résultats ont permis d’identifier un composé prometteur
The Hippo pathway, firstly described in Drosophila and highly conserved in mammals, has been demonstrated to play a crucial role in the organ size control. This kinase cascade regulates the phosphorylation of the downstream effector YAP (or its paralogue TAZ), a transcriptional coactivator with oncogenic activity. Its function is mediated by its nuclear translocation and interaction with the transcriptional factor TEAD, to form YAP-TEAD complex which activates the genes expression in charge of cell proliferation triggering organ growth. Overexpression of YAP/TAZ/TEAD protein in several cancers disrupts the Hippo pathway balance and urges on YAP-TEAD complex formation causing excessive proliferation and cancer development. Inhibiting this protein-protein interaction is thus a promising therapeutic target for the design of new anti-cancer drugs. In this goal, the laboratory has considered two strategies. The first one consists in targeting the YAP protein by synthesizing dipyrrins, representing Verteporfin fragments to define the minimal requirement yielding the expected biological activity. A second approach involves synthesizing TEAD ligands able to fit in specific interface 3. Based on molecular modeling, a triazole scaffold family was optimized to establish structure-activity relationship. Thanks to the biological and binding tests development, synthesized molecules evaluation is still in progress and the present first results have already allowed identifying a promising compound
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5

Sperling, Brian Keith. "Information Sharing Strategies To Improve Team Mental Models In Complex Systems". Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/6975.

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Abstract (sommario):
This thesis hypothesizes that providing task specific information to individual team members will improve coordination and decision-making, and therefore team performance, at time critical tasks. Major themes addressed in this research include teams and team processes, mental models, team mental models, work domain analysis, and hierarchical task analysis. Furthermore, the theory behind the development of complementary models is introduced. A unique method to identify the information sources and requirements in a complex team environment is first discussed in general and then specifically applied in two domains. The findings are presented of two experiments examining the effects of imposing different information distribution strategies that range from no complementariness to full complementariness of information. Team communication, team and individual task performance, workload, and timeliness and effectiveness of team decision making were assessed in nominal and off-nominal conditions. The first experiment used an automobile simulator and examined team navigation while driving. A second experiment was designed to incorporate additional measures to more specifically investigate individual performance, team workload, and clarity of information requirements using a UH-60 Black Hawk helicopter simulator. The procedures used for both experiments provided for dynamic yet controlled environments through which critical factors that influence team process and performance could be evaluated accurately. Results of these experiments provide empirical evidence that providing task relevant information to individual team members in a time critical environment, while limiting their access to non-relevant information, improves individual and team performance. Furthermore, there is evidence of increased individual performance that indicates this method of distributing information among team members may provide individual crewmembers with a more accurate task relevant mental model of their own environment. This research provides new insight into how the distribution of information among team members effects the development of mental models, information requirements, team and individual performance, and communications, and highlights several directions for future research. The information distribution design principles presented in this thesis address the heterogeneity of teams; teams cannot be thought of as groups of identical individuals. The results concerning the communication, workload, performance and team of mental models were consistent across the domains in this research.
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6

Obanda, Aston Martin. "The oxidation of simple and complex polyphenols by laccase". Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46476.

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7

Krishnaswami, Ram 1966. "System team composition for a complex system to enable integration and attribute management". Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/34799.

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Abstract (sommario):
Thesis (S.M.)--Massachusetts Institute of Technology, System Design & Management Program, June 2004.
"May 2004."
Includes bibliographical references (p. 89).
The automatic transmission is a very complex system in a modern automobile with several hundred components performing mechanical, hydraulic and electronic functions. System integration and attribute management are key challenges in the design and development of an automatic transmission. The system and sub system team structure can play a key part in the success of this development. A properly structured team can enhance the communication between the engineers designing the individual components, ensure that all interfaces between the components are properly managed and appropriate design actions are in place for best in class attributes. This thesis analyzes the current team structure and composition that is in place in the Automatic Transmission Division at Ford Motor Company and offers recommendations to improve the composition to better align the sub system teams with the actual workings of the transmission. The main tool that is used to enable this work is the Design Structure Matrix (DSM). Communication between individual team members is compared to components that physically touch or exchange energy through hydraulic means, or exchange electrical signals and preferred team compositions for effectively engineering these sub systems are proposed. The efficacy of these teams to manage attributes like noise and shift quality is also discussed.
by Ram Krishnaswami.
S.M.
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8

Williams, Alicia, Millie Wykoff, Ryan Tewell, Jodi Polaha e Jim Holt. "Harmonizing Clinical, Research, and Teaching Aims: Team Care for Patients with Complex Needs". Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/6447.

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Abstract (sommario):
At the conclusion of this session, the participants will be able to: 1. Describe a team-based approach to addressing complex patients’ needs. 2. Develop engaged and experiential methods for teaching interprofessional learners about team-care for complex patients. 3. Demonstrate familiarity with an evaluation strategy and preliminary outcomes data for a team approach for complex patients.
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Kim, Youngmok. "Factors influencing antioxidant phytochemical stability of teas". [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-3172.

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Buselmeier, Billy, e Jodi Polaha. "A Team Approach to Patients With Complex Health and Social Needs in Primary Care". Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etsu-works/6554.

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Libri sul tema "TEAD COMPLEX"

1

1983-, Medina Paco, Checchetto Marco, Vlasco Juan, Curiel David colorist, Rosenberg Rachelle e Caramagna Joe, a cura di. Superior Spider-Man team-up: Superiority complex. New York: Marvel Worldwide, 2013.

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Jiang, Silis Y. A Team-Based Approach to Studying Complex Healthcare Processes. [New York, N.Y.?]: [publisher not identified], 2017.

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Eduardo, Salas, Goodwin Gerald F e Burke C. Shawn, a cura di. Team effectiveness in complex organizations: Cross-disciplinary perspectives and approaches. New York, NY: Psychology Press, 2008.

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L' affaire Lindros: Dossier complexe et peu reluisant. Laval, Québec, Canada: Guy Saint-Jean, 1992.

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The team selling solution: Creating and managing teams that win the complex sale. New York: McGraw-Hill, 2004.

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Washington State Library. Gateways Team. [Academic library statistics] / compiled by Washington State Library Gateways Team. [Olympia, Wash.]: Washington State Library, 1996.

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Ted, Weiss, e United States. General Accounting Office. Human Resources Division, a cura di. Homelessness: A complex problem and the federal response : report to the Honorable Ted Weiss, House of Representatives. Washington, D.C: The Office, 1985.

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1970-, Murphy Naomi, e McVey Des 1962-, a cura di. Treating personality disorder: Creating robust services for people with complex mental health needs. Hove, East Sussex: Routledge, 2010.

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Limbrick, Peter. Early support for children with complex needs: Team around the child and the multi-agency keyworker : a manual for service development. Worcester: Interconnections, 2004.

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Limbrick, Peter. The team around the child: Multi-agency service coordination for children with complex needs and their families : a manual for service development. Manchester: Interconnections, 2001.

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Capitoli di libri sul tema "TEAD COMPLEX"

1

Coumbe-Lilley, John E. "Team toughness". In Complex Cases in Sport Psychology, 150–57. Milton Park, Abingdon, Oxon : New York, NY : Routledge, 2018.: Routledge, 2018. http://dx.doi.org/10.4324/9781315178882-17.

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Coumbe-Lilley, John E. "Team building". In Complex Cases in Sport Psychology, 158–67. Milton Park, Abingdon, Oxon : New York, NY : Routledge, 2018.: Routledge, 2018. http://dx.doi.org/10.4324/9781315178882-18.

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Coumbe-Lilley, John E. "Team development". In Complex Cases in Sport Psychology, 168–77. Milton Park, Abingdon, Oxon : New York, NY : Routledge, 2018.: Routledge, 2018. http://dx.doi.org/10.4324/9781315178882-19.

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Kaven, Emily, Ilana Kaven, Diego Gómez-Zará, Leslie DeChurch e Noshir Contractor. "Assessing How Team Task Influences Team Assembly Through Network Analysis". In Complex Networks & Their Applications IX, 322–34. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65351-4_26.

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Chong, Aun-Yeong, Terry Meadows e David Glineur. "Complex Coronary Revascularization Heart Team". In Heart Teams for Treatment of Cardiovascular Disease, 11–22. Cham: Springer International Publishing, 2019. http://dx.doi.org/10.1007/978-3-030-19124-5_2.

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Coumbe-Lilley, John E. "Staying with or leaving a team". In Complex Cases in Sport Psychology, 65–73. Milton Park, Abingdon, Oxon : New York, NY : Routledge, 2018.: Routledge, 2018. http://dx.doi.org/10.4324/9781315178882-8.

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Bowers, Clint, e Janis Cannon-Bowers. "Cognitive Readiness for Complex Team Performance". In Teaching and Measuring Cognitive Readiness, 301–23. Boston, MA: Springer US, 2013. http://dx.doi.org/10.1007/978-1-4614-7579-8_16.

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Aungurenci, Sorin, e Aurel Chiriac. "Integrated Product Team in Large Scale and Complex Systems". In Complex Systems Design & Management, 335–47. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-02812-5_24.

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Keir, Denise. "Rehabilitation — complex values of a limitless team". In Rehabilitation of Older People, 42–53. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4899-2987-7_4.

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Smith-Jentsch, Kimberly A., Joan H. Johnston e Stephanie C. Payne. "Measuring team-related expertise in complex environments." In Making decisions under stress: Implications for individual and team training., 61–87. Washington: American Psychological Association, 1998. http://dx.doi.org/10.1037/10278-003.

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Atti di convegni sul tema "TEAD COMPLEX"

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Hossain, Mohammad Abul. "Sorption Dynamics of Cr(VI) on Used Black Tea Leaves". In SLOW DYNAMICS IN COMPLEX SYSTEMS: 3rd International Symposium on Slow Dynamics in Complex Systems. AIP, 2004. http://dx.doi.org/10.1063/1.1764183.

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Hunt, Paul, e Sophie Skellett. "12 Improving teamwork in a paediatric clinical emergency team". In GOSH Conference 2019, Care of the Complex Child. BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health, 2019. http://dx.doi.org/10.1136/archdischild-2019-gosh.12.

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Carff, John, Matthew Johnson, Eman M. El-Sheikh e Jerry E. Pratt. "Human-robot team navigation in visually complex environments". In 2009 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2009). IEEE, 2009. http://dx.doi.org/10.1109/iros.2009.5354321.

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Kieras, David E., e Thomas P. Santoro. "Computational GOMS modeling of a complex team task". In the 2004 conference. New York, New York, USA: ACM Press, 2004. http://dx.doi.org/10.1145/985692.985705.

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Sancho-Parramon, Jordi, Vesna Janicki, Matej Bubaš, Ivana Fabijanić, Elizabeth Hedl, Vesna Blažek Bregović e Željko Samec. "Tuning the optical response of complex metal islands films for near infrared coatings". In Optical Interference Coatings. Washington, D.C.: Optica Publishing Group, 2022. http://dx.doi.org/10.1364/oic.2022.tea.3.

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Different approaches for tailoring the effective optical constants of complex island films in the near-infrared range are presented. Nearly-percolated films with finely tuned optical properties may be used as highly-lossy materials in novel optical coatings.
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Torres, M. R. Martinez, S. L. Toral, M. Perales e F. Barrero. "Analysis of the Core Team Role in Open Source Communities". In 2011 International Conference on Complex, Intelligent and Software Intensive Systems (CISIS). IEEE, 2011. http://dx.doi.org/10.1109/cisis.2011.25.

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Moore, Tamara, Heidi Diefes-Dux e P. K. Imbrie. "Assessment of Team Effectiveness During Complex Mathematical Modeling Tasks". In Proceedings. Frontiers in Education. 36th Annual Conference. IEEE, 2006. http://dx.doi.org/10.1109/fie.2006.322481.

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Wang, Juan-Ru, e Jin Yang. "Study on Knowledge Integration of Complex Product Development Team". In 2010 International Conference on Management and Service Science (MASS 2010). IEEE, 2010. http://dx.doi.org/10.1109/icmss.2010.5577176.

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Vlasceanu, Emilian, Dan Popescu e Loretta Ichim. "Aerial Robotic Team for Complex Monitoring in Precision Agriculture". In 2019 15th International Conference on Distributed Computing in Sensor Systems (DCOSS). IEEE, 2019. http://dx.doi.org/10.1109/dcoss.2019.00044.

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Reardon, Christopher, e Jonathan Fink. "Air-ground robot team surveillance of complex 3D environments". In 2016 IEEE International Symposium on Safety, Security, and Rescue Robotics (SSRR). IEEE, 2016. http://dx.doi.org/10.1109/ssrr.2016.7784322.

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Rapporti di organizzazioni sul tema "TEAD COMPLEX"

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Terranova, M. Team-computer interfaces in complex task environments. Office of Scientific and Technical Information (OSTI), settembre 1990. http://dx.doi.org/10.2172/6427485.

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Sperling, Brian K., Amy Pritchett, Arthur Estrada e Gina E. Adam. Information Distribution in Complex Systems to Improve Team Performance. Fort Belvoir, VA: Defense Technical Information Center, gennaio 2006. http://dx.doi.org/10.21236/ada442749.

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Ntuen, Celestine A. An Experiment in Collaborative Team Decision Making in Complex Information Processing Environments. Fort Belvoir, VA: Defense Technical Information Center, febbraio 2006. http://dx.doi.org/10.21236/ada445386.

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Beshouri, Greg. PR-309-14212-R01 Field Demonstration of Fully Integrated NSCR System. Chantilly, Virginia: Pipeline Research Council International, Inc. (PRCI), gennaio 2019. http://dx.doi.org/10.55274/r0011545.

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Abstract (sommario):
Local, state and federal regulations in the United Sates tend to favor NSCR as the emissions control technology of choice for lower output internal combustion (IC) engines. The technology can achieve extremely low emissions levels for NOx, CO and total hydrocarbons (THC). Theoretically an end user can add it on to any rich burn engine at relatively low cost and the technology scales down to the smallest IC engines. While superficially a "simple and proven" technology, NSCR control is in fact extremely complex, far more complex than the control of lean burn engines. The underlying problems with NSCR control are well documented. Using a systems approach an AETC/HOERBIGER team analyzed each component of the system and identified the core problems and possible solutions. Ultimately the team identified the need for a fully integrated system utilizing linear sensors and actuators. The team then theorized such a system could be controlled by an off the shelf PLC with typical PI control loops. Based on this conclusion HOERBIGER developed an integrated NSCR system utilizing linear sensors and actuators and controlled by an off the shelf PLC. Called the Advanced Richburn Control (ARC), HOERBIGER installed the system on six KVG-410 engines operating in pipeline compression and recorded performance for a year. Those results confirmed the system satisfied the performance requirements and validated the design concept. This report has a related webinar.
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Day, Eric A., Jr Arthur, Bell Winfred, Edwards Suzanne T., Bennett Bryan D., Winston Jr., Jorge L. Mendoza e Travis C. Tubre. Assessing the Impact of Ability-Based Pairing Strategies in Team Training of a Complex Skill. Fort Belvoir, VA: Defense Technical Information Center, gennaio 2005. http://dx.doi.org/10.21236/ada472611.

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Shanteau, James, Clive J. Fullagar e Scott Hemenover. Selecting and Classifying the Good Sailor Exploring the Non-Cognitive Predictors of Expert Team Performance in Complex Technological Contexts. Fort Belvoir, VA: Defense Technical Information Center, settembre 2002. http://dx.doi.org/10.21236/ada409067.

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Worley, D. R. Challenges to Train, Organize, and Equip the Complete Combined Arms Team: The Joint Task Force. Fort Belvoir, VA: Defense Technical Information Center, settembre 1998. http://dx.doi.org/10.21236/ada372524.

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Knox, Sally, Kïrsten Way e Alex Haslam. Are identity leadership and shared social identity associated with the highly reliable behaviour of military personnel? Protocol for a systematic review. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, maggio 2022. http://dx.doi.org/10.37766/inplasy2022.5.0063.

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Abstract (sommario):
Review question / Objective: Are identity leadership and shared social identity associated with the highly reliable behaviour of military personnel? Information sources: Searches will be conducted in the following databases: PsychInfo, Web of Sciences, Proquest Social Science Database, PTSDpubs, PubMed, Business Source Complete, and SCOPUS. To ensure literature saturation, the eligible papers and reviews identified through the search will be used for reference mining. A bibliography of the eligible papers will be circulated to the systematic review team and social identity experts identified by the team to ensure all relevant material has been captured.
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Lees-Deutsch, Liz, Mark Ellis e Andy Aldridge. Reducing in Hospital Length of Stay (RiHLOS) of Alliance 16 Report. Coventry University, dicembre 2021. http://dx.doi.org/10.18552/rihw/2021/0001.

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Abstract (sommario):
Introduction This paper evaluates the Alliance 16 (A16) collaborative led by Emergency Care Implementation Support Team (ECIST) during 2021, which had the aim of reducing in hospital length of stay (RiHLOS). A16 was a centrally funded programme managed collaborative, with sixteen sites selected for inclusion through regional nomination from each of the seven regions. The work focused on measures to improve patient discharge from hospital and length of stay. Evaluation of any measures on this scale is relatively complex due to the heterogeneity differences of the hospital sites, clinical areas involved, and improvement measures selected by sites.
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Morais, Carla, António Coelho, Alexandre Jacinto e Marta Varzim, a cura di. The I SEA Project: Digital Publications. Faculdade de Ciências da Universidade do Porto, ottobre 2020. http://dx.doi.org/10.24840/2020/978-989-746-279-5.

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The I SEA project aimed at the development of a non-obtrusive, valid and replicable method to evaluate audience attitudes about science communication projects through an immersive virtual reality environment that can improve exhibitions while educating and empowering citizens. To achieve the objectives of this highly complex, highly interdisciplinary, and innovative project, a permanent articulation of the scientific approach with the technical and design development took place, aiming the construction of the non- invasive evaluation method. Because it is an intricate project, it required constant iterations and interactions among the team members. So, we’ve learned somehow to consider limitations as engines for developing the project, instead of seeing them as obstacles.
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