Letteratura scientifica selezionata sul tema "ERx"
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Articoli di riviste sul tema "ERx"
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Viswanadhapalli, Suryavathi, Xihui Liu, Uday Pratap, Gangadhara R. Sareddy, Susan T. Weintraub, Ganesh V. Raj, Jung-Mo Ahn e Ratna K. Vadlamudi. "Abstract P6-10-14: Lysosomal acid lipase (LIPA) as a novel therapeutic vulnerability for treating TNBC". Cancer Research 83, n. 5_Supplement (1 marzo 2023): P6–10–14—P6–10–14. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-10-14.
Testo completoAbstract (sommario):
Abstract Background: TNBCs have the highest mortality rate among all BC subtypes. There is thus an urgent and unmet need for effective targeted therapies in TNBC. Recently we, identified a novel agent ERX-41 that showed good efficacy in treating TNBC in preclinical mouse models, however, its molecular action remain unknown. In this study, we identified LIPA as novel molecular target of ERX-41. Methods: We have used CRISPR knockout pooled library and multiple TNBC models for identifying molecular target of ERX-41. Mechanistic studies were performed using LIPA mutants, RNA-seq, Turbo-ID mapping, Mass spectrometry, Immunoprecipitation, and Western blotting. The in vivo efficacy of ERX-41 was examined using four different patient-derived xenograft (PDX) models. We evaluated LIPA protein expression in TNBC using tissue microarray (TMA). Results: To identify the molecular target of ERX-41, we performed an unbiased CRISPR–Cas9 knockout (KO) screen in MDA-MB-231 cells and the results identified LIPA as a top hit. KO of LIPA alone (which encodes lysosomal acid lipase (LAL) abrogated cytotoxic response to ERX-41. Cellular thermal shift assays confirmed that ERX-41 binds to LAL. In silico modelling and mutational studies confirmed that ERX-41 interacts with LAL through residues in its LXXLL domain and that ERX-41 ability to induce ER stress and cell death in TNBC is independent of the lipase activity of LAL. Unbiased RNA-seq studies with and without ERX-41 in parental and LIPA KO SUM-159 cells revealed induction of genes involved in ER stress and UPR response by ERX-41 in parental SUM-159 cells but not in cells with LIPA KO. Ultrastructural studies using live-cell confocal microscopy show that LIPA KO abrogated ER morphological changes at 2 and 4 h after ERX-41 treatment. Further, subcellular localization studies showed LIPA localizes to endoplasmic reticulum (ER). Unbiased proteomic approaches (TurboID and DIA mass spec) identified a core set of proteins that were both LAL binders and affected by ERX-41 treatment. GO analyses of LAL binding proteins confirmed their involvement in protein folding. Tumor micro array (TMA) analyses confirmed that >80% of primary TNBC tumors had significant and detectable LAL protein expression in contrast, normal breast tissue had lower LAL expression. ERX-41 (10 mg/kg body weight) decreased growth of four distinct TNBC patient-derived xenografts (PDXs) in vivo. Conclusions: Our results identified a new molecular target (LAL) for ERX-41 and novel mechanism of action (disruption of protein folding and induction of ER stress) that may have utility in treating patients with TNBC. Citation Format: Suryavathi Viswanadhapalli, Xihui Liu, Uday Pratap, Gangadhara R. Sareddy, Susan T. Weintraub, Ganesh V. Raj, Jung-Mo Ahn, Ratna K. Vadlamudi. Lysosomal acid lipase (LIPA) as a novel therapeutic vulnerability for treating TNBC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-14.
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Viswanadhapalli, Suryavathi, Tae-Kyung Lee, Kara Kassees, Gaurav Sharma, Rahul Gopalam, Karla Parra, Tanner Reese et al. "Abstract 4813: ERX-208 as a novel therapeutic for treating ovarian cancer by enhancing endoplasmic reticulum stress". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 4813. http://dx.doi.org/10.1158/1538-7445.am2023-4813.
Testo completoAbstract (sommario):
Abstract Background: Ovarian cancer (OCa) is the deadliest of all gynecologic cancers in the United States. Despite initial response to chemotherapy, most OCa patients become chemo resistant and progress to metastatic disease. Here, we tested the hypothesis that the high basal level of endoplasmic reticulum stress (ERS) in OCa represents a critical vulnerability and drugs that further aggravate this already engaged system in OCa may exhaust its protective features and contribute to apoptosis induction. The objective of this proposal is to identify a hit compound that enhances ERS in OCa and to conduct mechanistic studies. Methods: We synthesized a small library of >200 chemically distinct oligobenzamide analogs with maintenance of the chemical backbone but altered R groups of ERX-11. We performed the primary screening of this library to evaluate the induction of mRNA levels of two canonical ERS/UPR (unfolded protein response) genes- sXBP1 and CHOP. Biological activity of ERX-208 was validated using multiple OCa cells. Mechanistic studies were conducted using CRISPR/Cas9 KO, Western blotting, reporter gene assays, IHC and RNA-seq analysis. PK (pharmacokinetics) and toxicity studies were done using C57BL/6 mice. Cell line-derived xenografts (CDXs), patient-derived xenografts (PDXs), patient-derived explants (PDEs), and patient-derived organoids (PDO) were used for preclinical evaluation. Results: From a screen of a curated ERX-11 derived oligobenzamide library, we identified a hit compound, ERX-208 that potently (IC50~100nM) induces ERS/UPR and apoptosis in multiple OCa cells in vitro. CRISPR KO screen identified the lysosomal acid lipase A (LIPA) protein as the critical target of ERX-208. LIPA KO abrogates response to ERX-208, while reconstitution of LIPA restores ERX-208 response. The time course studies showed a robust and consistent induction (>15-fold CHOP, and >10-fold sXBP1) by ERX-208 treatment within 24h. We confirmed induction of classic UPR components peIF2α, CHOP and LC3B using Western blotting in multiple OCa cells. Functionally, ERX-208 causes growth inhibition of OCa cells, as noted by MTT cell viability assays using 15 OCa cells with an IC50 of ~50-100nM. The activity of ERX-208 is distinct among oligobenzamides as ERX-11 has limited/no activity against OCa cells. RNA-seq analysis confirmed that ERX-208 induces significant ERS, UPR, and apoptosis. Further, ERX-208 reduced the growth of OCa PDO’s in vitro, PDEs ex vivo and CDXs and PDXs in vivo. ERX-208 treatment did not show any signs of toxicity and body weight of mice was not affected. IHC analyses showed increased activation of ERS/UPR markers such as GRP78, p-PERK and decreased proliferation measured by Ki67. Conclusions: Collectively, our results demonstrated the utility of ERX-208 and will establish a novel therapeutic paradigm in OCa that overcomes tumor heterogeneity by targeting LIPA and enhancing ERS leading to apoptosis. Citation Format: Suryavathi Viswanadhapalli, Tae-Kyung Lee, Kara Kassees, Gaurav Sharma, Rahul Gopalam, Karla Parra, Tanner Reese, Michael Hsieh, Uday P. Pratap, Xue Yang, Behnam Ebrahimi, Chia Yuan Chen, Scott Terry Elmore, Christian Cervantes, Zhenming Xu, Edward Kost, Gangadhara Reddy Sareddy, Rajeshwar Rao Tekmal, Jung-Mo Ann, Ganesh V. Raj, Ratna K. Vadlamudi. ERX-208 as a novel therapeutic for treating ovarian cancer by enhancing endoplasmic reticulum stress. [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 4813.
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Collier, Alexia B., Suryavathi Viswanadhapalli, Tae-Kyung Lee, Kara Kassees, Karla Parra, Gaurav Sharma, Tanner Reese et al. "Abstract 3986: Novel LIPA targeted therapy for treating ovarian cancer". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 3986. http://dx.doi.org/10.1158/1538-7445.am2023-3986.
Testo completoAbstract (sommario):
Abstract BACKGROUND: Ovarian cancer (OCa) is the deadliest of all gynecologic cancers in the United States. Currently approved therapies have improved OCa survival for clinically localized disease, however, the majority (~90%) of patients with high-grade serous OCa (HGSOC) experience relapse with incurable metastases. There is a dire need for new therapeutic approaches. We hypothesized that the high basal endoplasmic reticulum stress (ERS) in OCa represents a critical and targetable vulnerability and may overcome the tumor heterogeneity. The objective of this project is to exploit increased ERS in ovarian cancer cells by engaging the novel target LIPA using the unique compound ERX-41. METHODS: The utility of ERX-41 as a new therapy was evaluated using MTT and CellTiter-Glo Cell Viability Assays. We used multiple established and patient derived OCa cell lines. The effect of ERX-41 on the Cell viability of patient-derived organoids (PDO) was measured using CellTiter-Glo 3D Assay. Long term effects of ERX-41 on cell survival were measured using colony formation assays. Apoptosis was measured using Annexin V and Caspase-Glo® 3/7 Assays. Cell cycle analysis was analyzed by Flow Cytometry. Mechanistic studies were done using LIPA knockout (KO) cells, RT-qPCR, and western blotting. Status of LIPA in OCa was determined using TNMplot database. In vivo efficacy of ERX-41 was tested using both cell line derived (CDX) and patient derived (PDXs) xenografts. RESULTS: TNM plot results showed that LIPA is highly expressed in OCa tumors compared to normal tissues and LIPA expression correlated with clinical grade. Kaplan-Meier plotter analyses of TCGA data revealed that LIPA expression is negatively correlated with overall survival in OCa patients. MTT and CellTitre-Glo assay results showed that ERX-41 significantly reduced the cell viability of both established and primary OCa cells, and PDO’s with an IC50 of ~500nM. ERX-41 treatment also significantly reduced the cell survival, increased S-phase arrest, and promoted apoptosis of OCa cells. A time course study revealed a robust and consistent induction of ERS markers (CHOP and sXBP1) in OCa cells by ERX-41 within 4h. Western blotting analyses also confirmed increased expression of ERS markers including CHOP, elF2α, PERK, and ATF4 upon ERX-41 treatment confirming that ERX-41 induces ERS. In xenograft studies, ERX-41 treatment resulted in ~66% reduction of tumor volume measured by Xenogen-IVIS. Further, in studies using PDX tumors, treatment with ERX-41 resulted in a significant reduction (~60%) of tumor volume and tumor weight. CONCLUSION: Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of action and implicate ERX-41 binding to LIPA induces ER stress, and apoptosis of OCa cells. Further molecular characterization of how ERX-41 binding to LIPA induces ER stress in OCa cells is ongoing. Citation Format: Alexia B. Collier, Suryavathi Viswanadhapalli, Tae-Kyung Lee, Kara Kassees, Karla Parra, Gaurav Sharma, Tanner Reese, Michael Hsieh, Xihui Liu, Xue Yang, Behnam Ebrahimi, Uday P. Pratap, Rahul Gopalam, Chia Yuan Chen, Scott Terry Elmore, Gangadhara Reddy Sareddy, Edward R. Kost, Jung-Mo Ahn, Ganesh V. Raj, Ratna K. Vadlamudi. Novel LIPA targeted therapy for treating ovarian cancer. [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 3986.
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Viswanadhapalli, Suryavathi, Tae-Kyung Lee, Scott Elmore, Gaurav Sharma, Rahul Gopalam, Karla Parra, Tanner Reese et al. "Abstract 394: Preclinical evaluation of ERX-208, a potent inducer of ER stress for the treatment of ovarian cancer". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 394. http://dx.doi.org/10.1158/1538-7445.am2024-394.
Testo completoAbstract (sommario):
Abstract Background: Ovarian cancer (OCa) is the deadliest kind of gynecologic cancer in the United States. The long-term survival rate for OCa is less than 20% after five years. Intra-tumoral and inter-tumoral heterogeneity is implicated in tumor resistance to conventional therapies and the unsatisfactory clinical outcomes. Addressing these issues necessitates innovative therapies that target intrinsic common vulnerabilities within OCa. Recent studies have highlighted that high basal level of endoplasmic reticulum stress (ERS) in OCa as a critical vulnerability. We have identified a promising compound, ERX-208 that potently induces ERS in cancer cells. The objective of this study is to characterize the mechanisms and activity of ERX-208 using preclinical models. Methods: The biological activity of ERX-208 was examined across 17 distinct OCa cells, representing 5 diverse OCa subtypes. Mechanistic studies utilized Western blotting, immunohistochemistry (IHC), RNA-Seq analysis, and CRISPR/Cas9 knockouts (KO). Pharmacokinetics (PK) and toxicity studies were performed on C57BL/6 mice. Comprehensive preclinical assessments were carried out through cell line-derived xenografts (CDXs), patient-derived xenografts (PDXs), organoids (PDOs) and explants (PDEs). Results: ERX-208 demonstrated an IC50 of approximately 50-100 nM inducing ERS and reducing cell viability in OCa cells. Conversely, normal ovarian surface epithelial cells exhibited minimal effects from ERX-208. In vitro experiments revealed strong ERX-208-induced apoptosis in OCa cell lines. Mechanistic studies employing RNA sequencing, Western blotting, and RT-qPCR, confirmed activation of ERS pathways observed as early as 5 hours post-ERX-208 treatment. Our studies identified LIPA as a potential target, and KO of LIPA significantly diminished ERX-208 activity. Moreover, LIPA KO substantially impeded in vivo OCa tumor growth. ERX-208 up to a dose of 25 mg/kg showed no observable organ toxicity and had no effect on the mice's body weight. Dose range studies identified 10 mg/kg intraperitoneal as the minimal effective dose, achieving more than 50% tumor reduction. In preclinical models, ERX-208 inhibited the growth of OCa CDXs, PDXs, and ex vivo PDEs and PDO’s. IHC analyses indicated reduced proliferation (Ki-67) and increased activation of ERS markers, such as GRP78 and p-PERK. Conclusions: Collectively, our findings underscore the preclinical promise of ERX-208 as a potential therapeutic agent for treating OCa. Conflict: The patents surrounding ERX-208 are licensed to EtiraRx. Citation Format: Suryavathi Viswanadhapalli, Tae-Kyung Lee, Scott Elmore, Gaurav Sharma, Rahul Gopalam, Karla Parra, Tanner Reese, Michael Hsieh, Uday P. Pratap, Xue Yang, Behnam Ebrahimi, Henry Neal, Chia-Yuan Chen, Kara Kassees, Christian Cervantes, Zhenming Xu, Edward Kost, Gangadhara Reddy Sareddy, Rajeshwar R. Tekmal, Jung-Mo Ahn, Ganesh V. Raj, Ratna K. Vadlamudi. Preclinical evaluation of ERX-208, a potent inducer of ER stress for the treatment of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 394.
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Collier, Alexia B., Suryavathi Viswanadhapalli, Rahul Gopalam, Tae-Kyung Lee, Kara Kassees, Karla Parra, Gaurav Sharma et al. "Novel LIPA-Targeted Therapy for Treating Ovarian Cancer". Cancers 16, n. 3 (24 gennaio 2024): 500. http://dx.doi.org/10.3390/cancers16030500.
Testo completoAbstract (sommario):
Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa.
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Fuentes, Zenaida, Rahul Gopalam, Bianca A. Romo, Khaled Mohamed Nassar, Xue Yang, Behnam Ebrahimi, Paulina Ramirez et al. "Abstract 2100: Novel LIPA targeted therapy for treating inflammatory breast cancer". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 2100. http://dx.doi.org/10.1158/1538-7445.am2024-2100.
Testo completoAbstract (sommario):
Abstract Background: Inflammatory breast cancer (IBC) is a rare but incredibly aggressive subtype of breast cancer (BC). IBC accounts for 2-4% of all occurrences of breast cancer and results in 7-10% of breast cancer-related deaths. IBC is only partially treatable with current therapies such as chemotherapy, surgery, and radiotherapy. Identification of novel therapeutic targets is urgently required. The main organelle for the synthesis, folding, and modification of proteins is called the endoplasmic reticulum (ER). Since elevated basal ER stress (ERS) is usually found in many cancers including IBC, our hypothesis was that the high basal ERS in IBC constitutes a serious vulnerability that can be targeted. Recently, we developed a small molecule ERX41 that promotes ER stress by blocking Lysosomal acid lipase A (LIPA) function in ER of cancer cells. The goal of the project is to test the utility of ERX-41 in treating IBC. Methods: To study the effect of ERX-41, we have used three well-established IBC model cells. We evaluated the efficacy of ERX-41 as a novel therapeutic for treating IBC using cell viability assays. The long-term effects of ERX-41 on IBC cell survival were evaluated using colony formation assays. Annexin V assays were used to measure apoptosis. Reporter assays, splicing assays, RT-qPCR, and Western blotting were used in mechanistic investigations. The effectiveness of ERX-41 was examined in vivo using KPL4 cell-based xenografts. Results: ERX-41 significantly decreased the viability of all three IBC model cells (SUM149, SUM190PT, and KPL4), with an IC50 of about 125 nM in MTT assay. Additionally, ERX-41 treatment significantly decreased IBC cells capacity to form colonies and promoted apoptosis. Specificity of the ERX41 mediated actions were confirmed using LIPA KO cells. Using RTqPCR based splicing assays, we demonstrated increased splicing of XBP1 as early as 6 hours after ERX41 treatment. Western analyses showed robust induction of stress markers (CHOP, PERK, ATF4) in IBC cells upon treatment with ERX-41. In KPL4 xenograft studies, ERX-41 showed significant reduction in the tumor volume. IHC analyses confirmed decreased proliferation marker and increased ER stress markers. Conclusions: Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of action and implicate ERX-41 binding to LIPA induces ER stress and promotes apoptosis of IBC cells. Citation Format: Zenaida Fuentes, Rahul Gopalam, Bianca A. Romo, Khaled Mohamed Nassar, Xue Yang, Behnam Ebrahimi, Paulina Ramirez, Chia-Yuan Chen, Scott Elmore, Harika Nagandla, Uday Pratap, Christoforos Thomas, Suryavathi Viswanadhapalli, Jung-Mo Ahn, Ganesh Raj, Ratna K. Vadlamudi. Novel LIPA targeted therapy for treating inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2100.
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Viswanadhapalli, Suryavathi, Karla Parra, Tae-Kyung Lee, Rahul Gopalam, Kara Kassees, Tanner Reese, Gaurav Sharma et al. "Abstract PO3-26-11: Enhancing endoplasmic reticulum stress for treating endocrine therapy resistant breast cancers driven by mutant estrogen receptors". Cancer Research 84, n. 9_Supplement (2 maggio 2024): PO3–26–11—PO3–26–11. http://dx.doi.org/10.1158/1538-7445.sabcs23-po3-26-11.
Testo completoAbstract (sommario):
Abstract Background: Estrogen receptor alpha (ERα) mutations are common (30-40%) in metastatic endocrine therapy-resistant breast cancers (ETR-BC), enable resistance to endocrine therapies and are the molecular drivers of ETR-BC. We had previously shown that an oligobenzamide, ERX-41, could enhance endoplasmic reticulum stress in ETR-BCs driven by mutant (MT) ERα, resulting in cancer cell death in vitro and and in vivo. To enable clinical translation of ERX-41, we performed lead optimization, followed by preclinical and IND-enabling studies. Methods: Over 2000 oligo-benzamides were designed, synthesized and tested in multiple BC models including those that express WT-ERα (MCF7, and ZR75) and BC models with acquired resistance (MCF7-Tam, and MCF7-LTLT) and engineered models that express MT-ERα (MCF7-ERα-D538G, MCF7-ERα-Y537S, ZR75-ERα-D538G, ZR75-ERα-Y537S). For our lead compound, mechanistic validation studies were performed using CRISPR LIPA mutants, RT-qPCR and Western blotting. Explants, organoids, cell line-(CDX) and patient-derived (PDX) xenografts were used to test the ex vivo and in vivo effectiveness of our lead compound as a monotherapy and in combination with abemaciclib. Results: Testing of >2000 synthesized oligo-benzamides identified a lead compound, ERX-315, that had broad and potent activity (IC50 between 20-100 nM) against both WT and MT (mutant) ERα-driven BC cells in in vitro assays. CRISPR KO of LIPA (which encodes lysosomal acid lipase (LAL) in BC cells abrogated cytotoxic response to ERX-315, validating LIPA as the molecular target of ERX-315. Ultrastructural and molecular studies confirm that ERX-315 induces significant endoplasmic reticulum stress, leading to a shutdown of de novo protein synthesis and apoptotic cell death in BC. Importantly, ERX-315 does not induce endoplasmic reticulum stress or cell death in normal cells and is non-toxic in animal models. We have shown that this capacity of ERX-315 to induce endoplasmic reticulum stress is unique among drugs targeting ERα, including selective ERα modulators and degraders, such as GDC-0180, AZD-9496 and fulvestrant. ERX-315 has potent anti-proliferative activity against MT-ERα-driven BC, as seen in genetically modified cell lines both grown as monolayer or spheroids in vitro, patient derived explants (PDEs) ex vivo and cell line derived (CDX) and patient-derived (PDX) xenografts in vivo. The combination of ERX-315 and CDK4/6 inhibitor abemaciclib was synergistic in decreasing the proliferation of both endocrine therapy-sensitive and endocrine therapy-resistant BC cells, in vitro, in xenograft models in vivo, and in primary patient-derived explants ex vivo. We are currently optimizing both the synthesis of ERX-315 using GMP process for kilogram scale production and validated methods for pharmacokinetic studies. We have developed formulations for both intravenous and oral administration with favorable pharmacokinetic parameters and proven utility of the formulated ERX-315 against CDX and PDX tumors in vivo. Toxicity studies in dogs and rodents have demonstrated >8-fold therapeutic to toxicity window. A phase I clinical trial is planned to be open to enrollment by Q1 2024. Conclusions: We have identified a lead compound ERX-315, which represents a novel class of agent that induce catastrophic levels of ER stress resulting in cancer cell death and that can effectively work against multiple forms of ETR-BC, including those driven by MT-ERα. Preclinical studies, GMP manufacturing, formulation and IND-enabling studies are being completed in time for the commencement of the phase I clinical trial by Q1 2024. Citation Format: Suryavathi Viswanadhapalli, Karla Parra, Tae-Kyung Lee, Rahul Gopalam, Kara Kassees, Tanner Reese, Gaurav Sharma, Xihui Liu, Xue Yang, ChiaYuan Chen, Carlos Roggero, Liping Chen, Sautam Bhattacharya, Uday Pratap, Russell Hayward, Sharron Gargosky, Jung-Mo Ahn, Ganesh V. Raj, Ratna Vadlamudi. Enhancing endoplasmic reticulum stress for treating endocrine therapy resistant breast cancers driven by mutant estrogen receptors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-26-11.
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Devarakonda, S., e R. Govindan. "TRAC(ERx)-ing lung cancer evolution". Annals of Oncology 28, n. 8 (agosto 2017): 1690–92. http://dx.doi.org/10.1093/annonc/mdx313.
Testo completo
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Nobrega, Rayssa Lourenna Trigueiro, Rony Lucas Silva Viana, Marianna Barros Silva, Luciana Duarte Martins Matta, Giulianna Paiva Viana Andrade Souza, Hugo Alexandre Oliveira Rocha e Raniere Fagundes Melo-Silveira. "Evaluation of the Pharmacological Activities of a Xylan from Corn Cobs". Polysaccharides 6, n. 1 (1 febbraio 2025): 9. https://doi.org/10.3390/polysaccharides6010009.
Testo completoAbstract (sommario):
Xylans, polysaccharides abundantly derived from agricultural byproducts, have shown potential pharmacological properties, making them a subject of increasing research interest. This study aimed to expand the understanding of xylans’ pharmacological properties and relate them to their composition. A method combining ultrasound and alkaline media for xylan extraction from corn cobs (ERX) was used, resulting in a significant increase in final yield compared to other methodologies. The physicochemical characterization of ERX was carried out, and its antioxidant, cytotoxic, anticoagulant, and immunomodulatory properties were evaluated. ERX demonstrated significant antioxidant activity with metal-chelating properties and induced apoptosis in HeLa tumor cells (p < 0.0001). It also reduced nitric oxide (NO) production by activated macrophages and extended the blood coagulation time, as assessed by the APTT assay (p < 0.0001). Further fractionation of ERX using various organic solvents resulted in multiple xylan subfractions. Among them, the ethanol-derived subfraction E1.4 exhibited remarkable pharmacological activities, including metal-chelation, cytotoxicity against HeLa cells via apoptosis, reduced NO production (p < 0.0001), and prolonged coagulation times (p < 0.0001). E1.4 is heteroxylan with a molecular weight of approximately 100 kDa. These findings suggest that corn cobs could be a promising source of pharmacologically significant molecules, particularly the heteroxylan E1.4. Future studies should focus on the structural characterization of this xylan to understand the relationship between structure and biological activity and explore the therapeutic potential of E1.4 in vivo models.
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SCHNEIDER, MARY ELLEN. "Clock Is Ticking Toward Medicare eRx Penalties". Family Practice News 42, n. 9 (maggio 2012): 1–3. http://dx.doi.org/10.1016/s0300-7073(12)70382-1.
Testo completoTesi sul tema "ERx"
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Miček, David. "Genetické algoritmy". Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2009. http://www.nusl.cz/ntk/nusl-218215.
Testo completoAbstract (sommario):
This thesis presents description of Genetic algorithm. The description begins with theory of complexity and following basic theory of genetic algorithm. Next part explains the principle of all three tasks – travelling salesman problem, knapsack problem and evolution of algorithm for five-in-a-row. The main focus was on developing the algorithm for five-in-a-row. The results were tested with other similar algorithms from internet. In case of travelling salesman problem and knapsack problem, the results were compared with gradient optimization methods.
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Delcour, Clémence. "Exploration des mécanismes étiopathogéniques des pathologies de la puberté". Electronic Thesis or Diss., Université Paris Cité, 2024. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=6023&f=74391.
Testo completoAbstract (sommario):
Le développement de l'axe gonadotrope (HHG) débute pendant la vie foetale mais ne s'achève qu'une fois la puberté terminée. De nombreux acteurs interviennent à chaque étape et le défaut de l'un d'entre eux peut mener à des pathologies de la puberté ou des troubles de la fertilité à l'âge adulte. Les facteurs génétiques ont une place centrale dans le développement de l'axe HHG et l'étude génétique des pathologies de la puberté a permis des avancées majeures dans la compréhension des mécanismes moléculaires sous-jacents, bien qu'il subsiste toujours de nombreuses inconnues. Pour mon travail de thèse, j'ai choisi d'explorer la génétique des maladies de la puberté afin de mieux comprendre les mécanismes étiopathogéniques de ces maladies complexes. Dans un premier temps, j'ai eu l'opportunité d'étudier une famille consanguine au sein de laquelle deux soeurs présentaient une absence de puberté associée à une augmentation des concentrations d'oestradiol et des gonadotrophines. Nous avons mis en évidence un variant rare à l'état homozygote dans le récepteur alpha de l'oestradiol (ERalpha). L'étude in vitro du récepteur muté a montré une diminution de son activité régulatrice sur un promoteur contenant des éléments de réponse à l'oestradiol ainsi qu'une activation paradoxale ligand-indépendante du promoteur de KISS1. L'étude de ces cas permet de mieux comprendre les conséquences des mutations perte de fonction de ERalpha ainsi que les mécanismes de régulation exercés par l'oestradiol via ERalpha. Dans un second temps, je me suis intéressée à la génétique de la puberté précoce centrale (PPC) et particulièrement au gène MKRN3 (Makorin ring finger protein 3) puisqu'il s'agit de la cause génétique la plus fréquente de la PPC. MKRN3 est un gène soumis à empreinte maternel dont la fonction protéique n'est pas connue. La détermination de la pathogénicité des variants faux-sens associés à la PPC repose presque exclusivement sur les analyses in silico. Dans cette partie de mon travail, j'ai montré que les outils usuels d'analyse in silico ne sont pas performants pour déterminer la pathogénicité des variants faux-sens rares de MKRN3. J'ai également proposé une nouvelle approche pour annoter la pathogénicité des variants basée sur l'analyse de la contrainte mutationnelle de MKRN3 et la conservation des acides aminés au sein de la famille des protéines MKRN. Les PPC avec transmission maternelle représentent la majorité des PPC familiales et ne sont pas expliquées par une mutation de MKRN3. J'ai cherché à identifier de nouveaux gènes impliqués dans la PPC de transmission maternelle, en partant de l'hypothèse qu'il pourrait exister un gène majeur selon un modèle monogénique. Pour cela, j'ai sélectionné 27 patients provenant de 18 familles chez qui l'analyse d'un panel de gènes associés à la PPC n'était pas contributive. L'analyse des variants sur les régions codantes combinée à l'analyse des variations du nombre de copies (CNV) sur l'ensemble du génome m'a permis d'identifier des gènes candidats dont la fréquence a été évaluée sur une cohorte réplicative de 48 patients par séquençage à haut débit (NGS). Cette analyse n'a pas permis d'identifier un gène majeur. Toutefois, nous avons identifié des variants perte de fonction dans deux gènes pour lesquels l'analyse de l'expression hypothalamique chez la souris a montré une diminution pendant la phase juvénile, suggérant leur implication dans le contrôle post-natal de la maturation de l'axe HHG. Cette troisième partie indique que la PPC est une maladie génétique complexe. Ce travail de thèse permet de mieux comprendre les conséquences cliniques et biologiques de la perte de fonction de ERalpha. Il confirme la complexité du contrôle génétique du développement et de la maturation de l'axe HHG. Finalement, il montre que l'annotation des variants pour les maladies de la puberté est complexe et que les analyses in-silico actuelles ne sont pas adaptées à l'étude de la PPCThe development of the gonadotropic axis (HHG) begins during fetal life but is not completed until puberty. Numerous players are involved at each stage, and a defect in any one of them can lead to pubertal pathologies or fertility disorders in adulthood. Genetic factors play a central role in the development of the HHG axis, and the genetic study of pubertal pathologies has led to major advances in our understanding of the underlying molecular mechanisms, although there are still many unknowns. For my thesis work, I chose to explore the genetics of pubertal diseases in order to better understand the etiopathogenic mechanisms of these complex disorders. First, I had the opportunity to study a consanguineous family in which two sisters showed an absence of puberty associated with increased concentrations of estradiol and gonadotropins. We identified a rare homozygous variant in the estradiol receptor alpha (ERalpha). In vitro study of the mutated receptor showed a decrease of its regulatory activity on a promoter containing Estradiol Response Elements, as well as a paradoxical ligand-independent activation of the KISS1 promoter. The study of these cases provides a better understanding of the consequences of ERalpha loss-of-function mutations and the regulatory mechanisms exerted by estradiol via ERalpha. Next, I focused on the genetics of central precocious puberty (CPP), and in particular the MKRN3 (Makorin ring finger protein 3) gene, since its mutations are the most common genetic cause of CPP. MKRN3 is a maternally imprinted gene whose protein function is unknown. Determining the pathogenicity of CPP-associated missense variants relies almost exclusively on in silico analyses. In this part of my work, I have shown that the usual in silico analysis tools do not efficiently determine the pathogenicity of rare MKRN3 missense variants. I have also proposed a new approach to annotate the pathogenicity of variants based on the analysis of MKRN3 mutational constraint and amino acid conservation within the MKRN protein family. Maternally inherited CPP accounts for the majority of familial CPP and is not explained by a mutation in MKRN3. I aimed to identify new genes involved in maternally inherited CPP, based on the hypothesis that a major gene might exist in a monogenic model. For this purpose, I selected 27 patients from 18 families in whom analysis of a panel of genes associated with CPP was non-contributory. Analysis of variants in coding regions combined with genome-wide copy number variation (CNV) analysis led to the identification of candidate genes whose frequency was assessed on a replicative cohort of 48 patients by high-throughput sequencing (NGS). This analysis failed to identify a major gene. However, we did identify loss-of-function variants in two genes for which mouse hypothalamic expression analysis showed a decrease during the juvenile phase, suggesting their involvement in the post-natal control of HHG axis maturation. This study shows that CPP is a complex genetic disease. My research provides a better understanding of the clinical and biological consequences of loss of ERalpha function. It confirms the complexity of genetic control of development and maturation of the HHG axis. Finally, it shows that the annotation of variants for pubertal diseases is complex and that current in-silico analyses are not adapted to the study of CPP
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Bonifácio, Paulo Ricardo Corrêa. "Estudo da sincronização e dessincronização cortical em EEG associada a movimento de membros inferiores". Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/3/3142/tde-05092006-143720/.
Testo completoAbstract (sommario):
Bonifácio, P.R.C. Estudo da sincronização e dessincronização cortical em EEG associada a movimento de membros inferiores. 84 f. Dissertação (Mestrado) Escola Politécnica, Universidade de São Paulo, São Paulo, 2006. Quando o ser humano prepara a execução de um movimento conhecido e treinado, é possível identificar as fases desta preparação no sinal eletrencefalográfico (EEG), sobre as faixas de freqüência delta, mu, beta e gama. A preparação do movimento dos membros inferiores pode ser antecipada em milhares de milissegundos e a facilitação descendente no sistema nervoso central pode ser identificada. Este trabalho sistematiza um processo de aquisição para o sinal de preparação motora baseado no EEG, em área associada a membros inferiores, como subsídio à identificação de Sincronização e Dessincronização corticais, nas faixas de freqüência acima de 13Hz, como reflexo da interação funcional de alças córtico-talâmicas, para movimento conhecido e treinado, em tarefa de retardo instruído. Buscou-se comprovar a possibilidade de uso de um número reduzido de cinco canais de EEG para monitorar esta preparação cortical, bem como formalizar a possibilidade de usar o sinal processado nas faixas beta e gama. Foram obtidos resultados coerentes com a literatura, com dessincronização mu e beta com todos os sujeitos e sincronização gama evidenciada em metade dos sujeitos. Como resultado principal ficou evidenciado que: o uso de cinco canais suportando a coleta de EEG apresenta-se cabível e possui uma boa capacidade de discriminação dos fenômenos de ERS/ERD nas faixas de interesse, para o monitoramento da atividade cortical pré-movimento para membros inferiores; que é possível identificar, no paradigma empregado, os períodos de envio de informação para os tratos descendentes, e quais são as condições mínimas para realizar o monitoramento com a preparação ambiental adequada para evitar os distratores mais conhecidos.The analysis of the electroencephalogram (EEG) enables the identification of a pre-movement activity associated with the execution of a known and pre-trained movement. The main frequency bands to achieve this identification are the delta, mu, beta and gamma. The initiation of the movement of the legs can be anticipated by thousands of milliseconds by a suitable analysis of the EEG. The objective of this work is to develop signal acquisition and signal processing methodologies associated with the scalp EEG during pre-movement trials. The EEG recordings are concentrated over the leg cortical area with the objective of identifying cortical synchronization and desynchronization (ERS/ERD) associated with trained movements. The number of available EEG channels was limited to five and one task was to investigate if this low number of channels would be enough for the purposes of monitoring cortical preparation. The results were consistent with those presented in the literature. In all subjects mu and beta desynchronization were observed and in half (four) of them the gamma band showed synchronization. One conclusion was that the cortical ERS/ERD associated with the lower limbs are recognizable using only five EEG channels. Several aspects of the experimental paradigm and the signal processing were adjusted for optimal results. members, foot, leg.
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Pinhão, Sara Filipa Pereira. "Neurociência aplicada à comunicação: avaliação do impacto das campanhas publicitárias sobre a emoção de voluntários saudáveis". Master's thesis, Faculdade de Ciências e Tecnologia, 2011. http://hdl.handle.net/10362/6284.
Testo completoAbstract (sommario):
Dissertação de Mestrado em Engenharia Biomédica, realizada no Laboratório de
Processamento de Imagens e Sinais da Universidade Federal do Rio de Janeiro, para obtenção do título de Mestre em Engenharia Biomédica na Faculdade de Ciências e Tecnologia da Universidade Nova de LisboaNeste estudo foi investigado o impacto da atenção e emocional dos anúncios publicitários através da aplicação de técnicas de processamento digital de sinais EEG. Os sinais EEG de 32 voluntários saudáveis foram adquiridos durante 300s de olhos fechados (OF) e durante a visualização de um filme composto por trechos de um documentário e por seis anúncios de diversos produtos. Com base nas respostas ao questionário, no qual os sujeitos emitiram a sua opinião, foram seleccionados o anúncio B (EVB) e o anúncio C (EVC) para análise por serem,respectivamente, o que menos gostaram e despertou emoções negativas ou o preferido e,portanto, o que despertou emoções positivas. A análise de sincronismo entre os sinais de EEG da actividade durante a estimulação (EVB e EVC) e a actividade de olhos fechados (OF), em torno de ±1Hz do pico de ALFA (BPA) para as derivações parieto-temporo-occipitais, foi realizada utilizando-se o índice event related dessynchronization / synchronization, ERD/ERS(f). Por um lado, os resultados do índice ERD/ERS(f), para α=0,05 com correcção de Bonferroni, e do Teste de Wilcoxon (α=0,05) indicaram dessincronismo na BPA com distribuição topográfica homogénea, tanto para EVB como EVC. Por outro lado, o Teste de Wilcoxon aplicado ao grau médio de sincronismo da BPA, indicou somente as regiões parieto-temporais esquerdas como as de maior dessincronismo quando os sujeitos eram estimulados pelo anúncio C, ou seja, o anúncio preferido e considerado pelos mesmos como de impacto emocional mais positivo. Tais resultados indicam a potencialidade do uso do índice ERD/ERS(f) na avaliação da resposta electrofisiológica cortical à publicidade e propaganda, em particular no que concerne à ligação emocional.
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Giroux, Véronique. "Rôle de la famille des récepteurs à l'oestrogène dans l'épithélium intestinal et les pathologies associées". Thèse, Université de Sherbrooke, 2013. http://hdl.handle.net/11143/6659.
Testo completoAbstract (sommario):
Plusieurs études animales et cellulaires suggèrent un rôle protecteur pour l’oestrogène dans les maladies inflammatoires intestinales. L'oestrogène agit principalement via l’interaction avec ses récepteurs ER? et ER?. Puisqu'ER? est l’isoforme prédominant dans l'épithélium colique, celui-ci devrait y être le médiateur des effets de l'oestrogène. Dans cette étude, nous avons tout d'abord démontré que la perte d’ER? chez la souris augmente les signes d'inflammation dans un modèle murin de colite. Également, l’activation sélective d’ER? avec le diarylpropionitrile (DPN) réduit les signes de colite dans le même modèle. L'expression de la cytokine inflammatoire TNF? était réduite alors que celle des cytokines anti-inflammatoires TGF?1, TGF?2 et TGF?3 était augmentée dans le côlon des souris traitées au DPN. Des études réalisées dans les cellules cancéreuses du côlon LS1034 ont démontré que le DPN augmente la signalisation du TGF? et que cette régulation contribue en partie à l’effet anti-inflammatoire du DPN dans ces mêmes cellules. Bref, ces résultats suggèrent que l'activation pharmacologique d’ER? réduit l’inflammation intestinale en partie via la régulation de la voie du TGF? dans les cellules épithéliales intestinales. Le récepteur nucléaire ERR?, un régulateur clé du métabolisme énergétique, possède une forte homologie avec les ERs bien que celui-ci ne peut lier l’oestrogène. Son activité est plutôt régulée par la disponibilité des coactivateurs ainsi que par des modifications post-traductionnelles. La découverte d'un variant d'épissage pour ERR? (ERR? ?5) a soulevé un nouveau mécanisme de régulation d'ERR?. En effet, puisqu'ERR? ?5 ne pourrait interagir avec les coactivateurs, il pourrait donc agir comme dominant négatif sur l’activité d'ERR?. Dans cette étude, nous avons démontré qu'ERR? et ERR? ?5 colocalisent au noyau en plus d’interagir physiquement De plus, ERR? ?5 réduit l'activité transcriptionnelle d'ERR? ainsi que l'expression de ses gènes cibles. Tout comme ERR?, ERR? ?5 est exprimé dans une multitude de lignées normales et cancéreuses du côlon ainsi que dans des cellules ou tissus provenant de d'autres organes et de d’autres espèces animales. Par contre, la protéine ERR? ?5 est exprimée plus faiblement qu'ERR? puisqu’elle est instable et rapidement dégradée par le protéasome. Néanmoins, la surexpression d'ERR? ?5 réduit la croissance cellulaire et possiblement l'adhésion cellulaire. Bref, nos résultats démontrent qu’ERR? ?5 agit comme dominant négatif sur ERR? et que son expression transitoire pourrait donc affecter l’activité d'ERR? ainsi que ses fonctions biologiques. [symboles non conformes]
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Cederberg, Lisa. "Felaktig alternativ splicing: Vissa mutationer i BRCA1, BRCA2, ERα och ERβ är starkt förknippade med bröstcancer". Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-69551.
Testo completoAbstract (sommario):
Alternative splicing is a process that partly rejects the common definition of a gene – that one gene codes for one specific protein. By variable combination of coding regions (exons) and exclusion of non-coding regions (introns), formation of several different mRNA-transcripts, and consequently several different proteins, can derive from the same gene. Alternative splicing is an important condition for the development of complex life forms, but it is also a highly sensitive process and inaccurate splicing is the cause of approximately 15 % of mutations that cause genetic diseases. This article presents four genes, BRCA1, BRCA2, ERα and ERβ, and inaccurate splicing of these genes increases the risk of developing cancer, particularly breast cancer and ovarian cancer. Breast cancer is the second most common form of lethal cancer among women. After identifying the cancerogenic mutations, women of high-risk families can undergo genetic testing and preventive therapy can reduce the morbidity and mortality. The article also presents a short discussion around the ethical problems of genetic testing, and the social and psychological dilemmas women of high-risk families are facing when they are given the option to undergo genetic testing.
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Pecorelli, Margherita. "Effetti della tDCS sui pattern ERS/ERD indotti da immaginazione motoria: stato dell'arte". Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/11307/.
Testo completoAbstract (sommario):
I sistemi BCI EEG-based sono un mezzo di comunicazione diretto tra il cervello e un dispositivo esterno il quale riceve comandi direttamente da segnali derivanti dall'attività elettrica cerebrale.
Le features più utilizzate per controllare questi dispositivi sono i ritmi sensorimotori, ossia i ritmi mu e beta (8-30 Hz). Questi ritmi hanno la particolare proprietà di essere modulati durante l'immaginazione di un movimento generando così delle desincronizzazioni e delle sincronizzazioni evento correlate, ERD e ERS rispettavamente. Tuttavia i destinatari di tali sistemi BCI sono pazienti con delle compromissioni corticali e non sono sempre in grado di generare dei pattern ERD/ERS stabili. Per questo motivo, negli ultimi anni, è stato proposto l'uso di tecniche di stimolazione cerebrale non invasiva, come la tDCS, da abbinare al training BCI. In questo lavoro ci si è focalizzati sugli effetti della tDCS sugli ERD ed ERS neuronali indotti da immaginazione motoria attraverso un'analisi dei contributi presenti in letteratura. In particolare, sono stati analizzati due aspetti, ossia: i) lo studio delle modificazioni di ERD ed ERS durante (online) o in seguito (offline) a tDCS e ii) eventuali cambiamenti in termini di performance/controllo del sistema BCI da parte del soggetto sottoposto alla seduta di training e tDCS.
Le ricerche effettuate tramite studi offline o online o con entrambe le modalità, hanno portato a risultati contrastanti e nuovi studi sarebbero necessari per chiarire meglio i meccanismi cerebrali che sottendono alla modulazione di ERD ed ERS indotta dalla tDCS. Si è infine provato ad ipotizzare un protocollo sperimentale per chiarire alcuni di questi aspetti.
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Pugazhendhi, Dhamayanthi. "Role of ERα and ERβ in oestrogen action in human breast cancer cells". Thesis, University of Reading, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494000.
Testo completoAbstract (sommario):
The role of ERα in hormone responsive breast cancer is well established but that of ERβ remains to be determined. In this thesis, the effects of overexpression of ERβlong have been studied in MCF7 human breast cancer cells which possess high endogenous levels of ERα . Stable overexpression of ERβlong protein (2-fold) resulted in reduced fold induction (from 2.6 to 1.8) of an ERE-CAT reporter gene with 10-8M 17β-oestradiol but enhanced fold induction (from 1.18 to 2.12) by 10-5M genistein and an increased induction (from 4.4 to 11.4) of growth with 10-4M methylparaben.
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Cerri, Marion. "Régulation et fonctions de facteurs de transcription ERF ERN au cours de la symbiose entre Medicago truncatula et Sinorhizobium meliloti". Thesis, Toulouse, INSA, 2013. http://www.theses.fr/2013ISAT0042/document.
Testo completoAbstract (sommario):
Les légumineuses sont capables de s’associer en symbiose avec des bactéries du sol Rhizobium. Cette interaction culmine par la formation d’un nouvel organe racinaire appelé nodule, à l’intérieur duquel les bactéries différentiées fixent l’azote atmosphérique sous une forme assimilable par la plante hôte. La mise en place de cette association repose sur un dialogue moléculaire entre les deux partenaires, faisant intervenir des signaux bactériens lipo-chitooligosaccharidiques appelés Facteurs Nod (FNods). Chez la légumineuse modèle Medicago truncatula, la perception de ces signaux symbiotiques au niveau de l’épiderme racinaire, initie une voie de signalisation qui conduit à des oscillations calciques nécessaires pour l`activation de gènes de la plante hôte, tel le gène marqueur ENOD11. Il a été montré que les facteurs de transcription ERF ERN1/ERN2, étroitement apparentés, agissent comme des activateurs directs de la transcription d’ENOD11, via leur liaison à la séquence cis régulatrice NFbox. Le mutant ern1 est de manière cohérente requis pour l’activation d’ENOD11 en réponse aux FNods mais également au cours des étapes suivantes d’infection et de développement nodulaire. Cependant, ce mutant présente un phénotype symbiotique partiel soulevant la question d’une redondance fonctionnelle, qui pourrait être attribuée à la présence du facteur ERN2, étroitement apparenté. Ainsi, au cours de ma thèse, j’ai étudié la relation fonctionnelle entre les facteurs ERN1/ERN2 par de approches diverses visant à déterminer leur expression et fonctions relatives au cours de la symbiose rhizobienne. Mon travail de thèse a dans tout d’abord porté sur l’étude des profils d’expression spatio-temporels de gènes ERN au cours de la symbiose rhizobienne, corroborée par la dynamique de localisation cellulaire des protéines de fusions ERN. Ces facteurs sont exprimés de manière séquentielle mais aussi conjointe aux cours de la signalisation FNods et l’infection rhizobienne. Par la suite, des expériences de complémentation croisée, dans le fond mutant ern1, ont montré qu’ERN2 peut remplacer ERN1 pour l’induction d’ENOD11 en réponse aux FNods et pour la formation de nodules, dès lors qu’il est exprimé sous le contrôle du promoteur d’ERN1. Ceci indique que ces facteurs ont des activités biologiques similaires et suggère que l’absence de complémentation d’ern1 par le facteur endogène ERN2 est probablement liée à une régulation transcriptionnelle différentielle de la part de leurs promoteurs. Enfin, nous avons initié la caractérisation phénotypique de nouvelles lignées mutées au niveau du gène ERN2, dans le but d’identifier les fonctions spécifiques de ce facteur au cours de la nodulation. A travers l’analyse d’une lignée Tilling (ern2.1) présentant une mutation ponctuelle dans le domaine de liaison à l’ADN, nous avons mis en évidence un rôle d’ERN2 dans la progression des cordons d’infection au niveau du cortex racinaire. Des études moléculaires ont permis de montrer que l’acide aminé muté est un résidu conservé et important pour la topologie du domaine de liaison à l’ADN, mais également pour l’activité transcriptionnelle d’ERN2 sur ENOD11. Contrairement à ern1, le mutants ern2.1 et ern2.2 (mutant d’insertion) sont capables de former des nodules. Néanmoins, l’infection nodulaire apparait dans les deux cas parfois défectueuse, conduisant à une sénescence précoce. Ces résultats démontrent qu’ERN2 remplit aussi des rôles spécifiques au cours de la nodulation, qui ne sont pas entièrement complémentés par ERN1. Il semblerait donc que les facteurs ERN contrôlent des étapes communes et divergentes de l‘infection rhizobienne, ERN1 ayant un rôle prépondérant dans l`initiation et progression de l’infection tandis qu’ERN2 aurait un rôle secondaire, plus centré dans la progression des cordons. La lignée double mutant ern1ern2.1, ouvre de nouvelles perspectives pour l’étude de la redondance fonctionnelle entre ces deux facteurs au cours des symbioses racinairesLegumes are able to associate in symbiosis with Rhizobia bacteria in the soil, which culminates in the formation of a new organ referred to as the root nodule, within which differentiated bacteria fix nitrogen to the benefit of the host plant. The establishment of this association relies on a molecular dialogue between the two partners, involving bacterial lipo-chitooligosaccharide signals called Nod factors (NF). In the model legume Medicago truncatula, the perception of these symbiotic signals in the root epidermis, initiates a signaling pathway that leads to calcium oscillation responses required for the activation of downstream genes such as the well-characterized ENOD11. Previously, ERN1 and the closely-related ERN2 transcription factors (TFs) were reported as direct activators of ENOD11 via binding to the NFbox regulatory unit. In addition, phenotypic analysis of the ern1 knockout mutant has confirmed the importance of ERN1 not only during NF signaling but also throughout subsequent infection and nodule development stages. Nevertheless, the ern1 mutant displays a less severe phenotype compared to plants mutated in other NF signaling genes, raising the question of a possible functional redundancy with the endogenous closely-related ERN2 factor. My PhD project was focused on the study of the functional relationship between ERN1 and ERN2 TFs. By using a variety of strategies we aimed at determining both ERN expression profiles and relative functions during nodulation. We first examined the spatio-temporal expression profiles of these genes during rhizobial symbiosis and correlated this with the dynamics of cellular localization of ERN fusion proteins. These analyses revealed that these factors possess both common and distinct expression profiles, correlated with cell-type specific and dynamic in vivo protein accumulation, tightly associated with rhizobial pre-infection and subsequent infection stages in M. truncatula. Further cross-complementation studies in the ern1 mutant background showed that, when ERN2 is expressed under the control of the ERN1 promoter, it can fully restore the ern1 phenotype regarding NF-elicited ENOD11 activation and nodule formation. This indicates that these factors have similar biological activities and suggests that the incapacity of endogenous ERN2 to complement the ern1 mutant is mainly due to differences in their promoter activities. Finally, we also initiated a phenotypic characterization of M. truncatula ern2 mutant lines, in order to get a better insight into ERN2 specific functions during nodulation. The phenotypic analysis of a Tilling line (ern2.1) carrying a point mutation in a conserved amino acid in the ERN2 DNA binding domain, revealed a role for ERN2 during infection thread progression in the root cortex. Further molecular studies demonstrated that this mutated amino acid in the Tilling line is conserved and required for optimal DNA binding domain topology and transcriptional activity of ERN2 on its target ENOD11 gene. In addition, the ern2.1 line and a second ern2.2 insertional mutant line are both capable of forming nodules, in contrast to the ern1 mutant. Nevertheless, these nodules are partly infection defective leading to premature senescence. These findings provide evidence that ERN2 possesses specialized functions during nodulation that cannot be fully complemented by ERN1. This suggests that ERN possess common and divergent functions, ERN1 having a predominant role in rhizobial infection initiation and progression while ERN2 having a secondary and more centered role during infection thread progression. The ern1ern2.1 double mutant line, recently generated during my PhD, opens new perspectives to further study the functional relationship between ERN TFs during root endosymbioses
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Mattsson, Anna. "Roles of ERα and ERβ in Normal and Disrupted Sex Differentiation in Japanese Quail". Doctoral thesis, Uppsala universitet, Ekotoxikologi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8921.
Testo completoAbstract (sommario):
Exposure to xenoestrogens during development has been shown to impair sexual differentiation in various species. The major aim of this thesis was to elucidate the respective roles of the two estrogen receptors ERα and ERβ in normal and disrupted differentiation of sex organs and copulatory behavior in the Japanese quail (Coturnix japonica). The expression of ERα mRNA was much stronger than that of ERβ mRNA in the gonads and Müllerian ducts (embryonic oviducts) in early embryos. By contrast, ERβ seemed to be predominantly expressed in regions of the embryonic brain that are associated with male sexual behavior. Embryos were exposed to the selective ERα agonists propyl-pyrazole-triol (PPT) and 16α-lactone-estradiol (16α-LE2). The estrogens 17β-estradiol (E2) and 17α-ethynylestradiol (EE2), which activate both ERα and ERβ, were used as positive controls. All substances impaired reproductive organ differentiation. The effects observed included oviductal malformations in females and partial development of oviducts in males. All substances also induced testis feminization (ovotestis) in male embryos. The male copulatory behavior was severely impaired by the positive controls but was unaffected by PPT and 16α-LE2 at doses that disrupted sex organ differentiation. A higher dose of 16α-LE2 significantly suppressed the behavior. However, it is possible that this effect was caused by cross-activation of ERβ. The substances also induced hepatic expression of mRNA encoding the egg-yolk proteins vitellogenin II and very low-density apolipoprotein II, which are commonly used as indicators of estrogen exposure. In conclusion, the results suggest that ERα is important for female reproductive organ differentiation. Excess activation of ERα by xenoestrogens impairs differentiation in both females and males and induces hepatic expression of egg-yolk proteins. The results also indicate that ERα alone cannot mediate demasculinization of male copulatory behavior in quail, although further studies are needed to test this hypothesis.
Libri sul tema "ERx"
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Niarchos, Thanase s. Th. Ero s ero tas. 2a ed. Athe na: Kastanio te, 1986.
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Shtub, Avraham, e Reuven Karni. ERP. Boston, MA: Springer US, 2010. http://dx.doi.org/10.1007/978-0-387-74526-8.
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Capmany, Maria Aurèlia. Això era i no era. Barcelona (Espanya): Planeta, 1989.
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Headley, Marc Morgan. Blown for Good: Behind the Iron Curtain of Scientology. Burbank, CA: BFG Books, 2009.
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Monika, Doppert, a cura di. Ni era vaca ni era caballo. 3a ed. Caracas, Venezuela: Ediciones Ekaré, 1998.
Cerca il testo completoCapitoli di libri sul tema "ERx"
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Psaila, Giuseppe. "ERX-QL: Querying an Entity-Relationship DB to Obtain XML Documents". In Database Programming Languages, 281–99. Berlin, Heidelberg: Springer Berlin Heidelberg, 2002. http://dx.doi.org/10.1007/3-540-46093-4_17.
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Psaila, Giuseppe. "ERX: An Experience in Integrating Entity-Relationship Models, Relational Databases, and XML Technologies". In XML-Based Data Management and Multimedia Engineering — EDBT 2002 Workshops, 242–65. Berlin, Heidelberg: Springer Berlin Heidelberg, 2002. http://dx.doi.org/10.1007/3-540-36128-6_14.
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Pfurtscheller, Gert, e Christa Neuper. "Movement and ERD/ERS". In The Bereitschaftspotential, 191–206. Boston, MA: Springer US, 2003. http://dx.doi.org/10.1007/978-1-4615-0189-3_12.
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Relvas, Vânia, J. Miguel Sanches e Patrícia Figueiredo. "Scalp EEG Continuous Space ERD/ERS Quantification". In Pattern Recognition and Image Analysis, 616–23. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-38628-2_73.
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Wortmann, Johan C., e Kristian Peters. "Future of ERP: Challenges and Opportunities in the SaaS-era". In Progress in Pattern Recognition, Image Analysis, Computer Vision, and Applications, 383–90. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-662-44733-8_48.
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Gronwald, Klaus-Dieter. "ERP". In Integrierte Business-Informationssysteme, 59–79. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-662-43720-9_10.
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Ellenbroek, Bart, Alfonso Abizaid, Shimon Amir, Martina de Zwaan, Sarah Parylak, Pietro Cottone, Eric P. Zorrilla et al. "ERP". In Encyclopedia of Psychopharmacology, 490. Berlin, Heidelberg: Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/978-3-540-68706-1_6016.
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Horneck, Gerda. "ERA". In Encyclopedia of Astrobiology, 745–46. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-662-44185-5_531.
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Proske, Uwe, David L. Morgan, Tamara Hew-Butler, Kevin G. Keenan, Roger M. Enoka, Sebastian Sixt, Josef Niebauer et al. "ERK". In Encyclopedia of Exercise Medicine in Health and Disease, 303. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-540-29807-6_2360.
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Horneck, Gerda. "ERA". In Encyclopedia of Astrobiology, 502–3. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-11274-4_531.
Testo completoAtti di convegni sul tema "ERx"
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Psaila, Giuseppe. "ERX". In the 2000 ACM symposium. New York, New York, USA: ACM Press, 2000. http://dx.doi.org/10.1145/338407.338680.
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Viswanadhapalli, Suryavathi, Mengxing Li, Shi-Hong Ma, Gangadhara Reddy Sareddy, Tae-Kyung Lee, Mei Zhou, Yiliao Liu et al. "Abstract 21: Generation and characterization of potent analogues of ERX-11". In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-21.
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Viswanadhapalli, Suryavathi, Mengxing Li, Shi-Hong Ma, Gangadhara Reddy Sareddy, Tae-Kyung Lee, Mei Zhou, Yiliao Liu et al. "Abstract 21: Generation and characterization of potent analogues of ERX-11". In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-21.
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Viswanadhapalli, Suryavathi, Xihui Liu, Shi-Hong Ma, Tae-Kyung Lee, Mengxing Li, Weiwei Tang, Junhao Liu et al. "Abstract 1237: Preclinical evaluation of ERX-41 in triple negative breast cancer". In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1237.
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Koike, Y., K. Hirota, H. Qiu, S. Kimoto, K. Kato, M. Yoshimura e M. Nakajima. "The observation of spin reorientation phase transition in Sm1-x Erx FeO3". In 2019 44th International Conference on Infrared, Millimeter, and Terahertz Waves (IRMMW-THz). IEEE, 2019. http://dx.doi.org/10.1109/irmmw-thz.2019.8873998.
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Lichtenfels, Martina, Gilberto Schwartsmann e Stefan Wiemann. "ESTROGEN RECEPTOR β AND AS A POSSIBLE BIOMARKER OF TAMOXIFEN RESISTANCE". In Scientifc papers of XXIII Brazilian Breast Congress - 2021. Mastology, 2021. http://dx.doi.org/10.29289/259453942021v31s1048.
Testo completoAbstract (sommario):
Introduction: Approximately two-thirds of all breast cancer patients overexpress hormonal receptors and are treated with endocrine therapy, being tamoxifen (TAM) the standard treatment. However, many of the initial responders to TAM as first-line experience relapse. Several mechanisms have been proposed to explain the occurrence of acquired TAM resistance. Previous studies showed that estrogen receptor β (ERβ) expression is associated with better response to tamoxifen treatment, as the co-expression of ERα and ERβ is associated with TAM antiproliferative effects. Moreover, there is a growing interest about the cross talk between ERs and ErbB family in response to endocrine therapy. Objectives: The aim of the present study was to evaluate the expression of ERβ and the relation of ERβ with ERα and ErbB family in response to TAM treatment and in TAM resistant cells. Methods: ERβ expression was analyzed in two different databases of breast cancer patients. The mRNA levels of ER, HER receptors and PTEN and MAPK signal pathways were measured after TAM treatment, in TAM resistance cells and in cells silenced for ER genes. The cellular viability was also measured after TAM treatment, in TAM resistance cells and in cells silenced for ER genes. Results: Breast cancer patients presented reduced ERβ expression, and the ERα-positive breast cancer subtypes presented lower ERβ levels when compared to ERα-negative breast cancer subtypes. Cells expressing moderate levels of ERβ presented a better response to TAM treatment. Downregulation of ERs induced by TAM treatment was accompanied by an increase in ErbB2 and ErbB3, MAPK3 mRNA levels and increased PTEN levels. TAM–resistant cells expressed decreased ERs, PTEN and MAPK3 mRNA levels and increased EGFR, ErbB3 and ErbB4 levels. In accordance to the resistance finding, cells silenced for ERβ presented decreased MAPK3 and cells silenced for ERα showed an increased EGFR. Conclusions: These results provide additional data indicating the importance of ERβ as a possible biomarker of endocrine resistance and highlighted the interaction between ERα and EGFR as a mechanism of TAM resistance.
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Viswanadhapalli, Suryavathi, Shihong Ma, Tae Kyung Lee, Xihui Liu, Kara Kassees, Uday P. Pratap, Junhao Liu et al. "Abstract 5676: Preclinical evaluation of estrogen receptor coregulator binding inhibitor ERX-245 in breast cancer". In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-5676.
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Viswanadhapalli, Suryavathi, Gangadhara Reddy Sareddy, Shi-Hong Ma, Tae-Kyung Lee, Rajeshwar Rao Tekmal, Jung-Mo Ahn, Ganesh Raj e Ratna K. Vadlamudi. "Abstract 4148: Novel ERX-11 and CDK4/6 inhibitor combination therapy for treating therapy resistant breast cancer". In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-4148.
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Vadlamudi, Ratna, Suryavathi Viswanadhapalli, Xihui Liu, Tae-Kyung Lee, Gangadhara R. Sareddy, Shihong Ma, Mengxing Li et al. "Abstract P6-04-05: ERX-41, a novel drug to target and block mutant-ERα-coregulator driven signaling". In Abstracts: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, Texas. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.sabcs19-p6-04-05.
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Liu, X., S. Viswanadhapalli, S. Ma, T.-K. Lee, GR Sareddy, DN Ekoue, EM Blatt et al. "Abstract P4-07-01: A small molecule inhibitor (ERX-41) induces endoplasmic reticulum stress in triple negative breast cancer". In Abstracts: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-p4-07-01.
Testo completoRapporti di organizzazioni sul tema "ERx"
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Salonen, Hilma. Umbætur, ekki bara skaðabætur: Tækifæri í stefnumótun í þágu réttlátra grænna umskipta. Nordregio, febbraio 2025. https://doi.org/10.6027/pb2025:16.2001-3876.
Testo completoAbstract (sommario):
Vaxandi áhrif loftslagsbreytinga, breyttur efnahagslegur og pólitískur veruleiki og nýleg orkukreppa hafa gert það að verkum að flestir Norðurlandabúar telja græn umskipti nauðsynleg. Framleiðsla endurnýjanlegrar orku er dreifðari en framleiðsla á jarðefnaeldsneyti eða kjarnorku og því hefur hún veruleg áhrif á landslag og landnotkun. Fyrir vikið eru norræn dreifbýlissvæði mikilvæg þegar kemur að því að uppfylla markmið um græn umskipti. Þó eru nú þegar teikn á lofti um að umbreytingarferlið muni hafa misjöfn áhrif í þéttbýli annars vegar og dreifbýli hins vegar og skilja svæði sem nú þegar eru jaðarsett enn frekar eftir. Hvernig getum við tryggt réttlátari græn umskipti í dreifbýli? Með tillögum þessa stefnuyfirlits er leitast við að svara þessari spurningu í því augnamiði að yfirstíga algeng vandamál sem tengjast grænum orkuverkefnum og jafnframt að stuðla að því að heimafólk upplifi réttlæti.
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Bogason, Ágúst, e Elin Slätmo. Veiting grunnþjónustu og aðgengi að þjónustu í dreifbýli á Norðurlöndum. Nordregio, febbraio 2025. https://doi.org/10.6027/pb2025:11.2001-3876.
Testo completoAbstract (sommario):
Þjónustuveiting er einn þeirra lykilþátta sem gera dreifbýlissvæði eftirsóknarverð og lífvænleg. Þættir á borð við fólksflutninga, stafvæðingu og loftslagsbreytingar hafa áhrif á bæði aðgengi að þjónustu og það hvaða þjónusta er álitin nauðsynleg fyrir daglegt líf í dreifbýli. Í þessu stefnuyfirliti er fjallað um niðurstöður verkefnisins Service Provision and Access to Services In Nordic Rural Areas – Secure, Trusted And For All Ages auk þess sem settar eru fram tillögur að stefnumótun.
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Kamp, Bart, Carmen Vallverdu e Eduardo Sisti . Kataluniako industria enpresen arteko negozioaren zerbitizazioa. A cura di Patricia Canto. Universidad de Deusto, 2023. http://dx.doi.org/10.18543/vtme3963.
Testo completoAbstract (sommario):
Zerbitizazio kontzeptuak manufaktura-enpresek beren negozioak ekoiztutako ondasunetan ez ezik, zerbitzuetan ere oinarritzeko duten joerari egiten dio erreferentzia. Horrek esan nahi du balio proposamenen zorroak handitu eta soluzio oso gisa integratu eta lotu behar direla. Era berean, zerbitzuak emateagatik edota produktuengatik zerbitzuak balira bezala kobratzeagatik diru-sarrerak sortzea dakar. Azterlan honek zerbitizazioaren fenomenoa kontzeptualizatzen du, Kataluniako industriaren egoera aurkezten du (ikuspegi mesoekonomikoa) eta Kataluniako 8 enpresaren esperientziak biltzen ditu (ikuspegi mikroekonomikoa) zerbitizazioaren oztopoak eta onurak aztertzeko.
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Canto, Patricia, a cura di. Enpresa taldeak Euskal Autonomia Erkidegoan. Universidad de Deusto, 2023. http://dx.doi.org/10.18543/mqns1140.
Testo completoAbstract (sommario):
"Enpresa-taldeak Euskadin" txostenak Euskadiko enpresen akziodunen egitura deskribatzen du, enpresa-taldeen garrantzia erakutsiz. Era berean, Euskadin dauden enpresa-talde horiek identifikatzeko eta sailkatzeko metodologia bat proposatzen du. Horrela, 2022rako talde horien argazkia erakusten da, 4.136 enpresa-talde identifikatuz, haien ezaugarriak jatorrizko enpresaren kokapenaren arabera deskribatuz eta Euskadiko, Espainiako (EAEtik kanpokoak) eta atzerriko taldeak bereiziz. Tipologia bakoitzerako, enpresa-taldeei buruzko literaturak garrantzitsutzat jotzen dituen zenbait ezaugarri aztertzen dira: estrategien sofistikazioa, sektore-dibertsifikazioa edo talde barruko finantzaketa-mekanismoak. EAEn enplegu gehien sortzen duten enpresa-taldeen xehetasunak ere ematen dira.
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Cavicchia, Rebecca, Jonas Kačkus Tybjerg e Hilma Salonen. Grænt flug – Stefnumiðaður vegvísir um innleiðingu rafknúins flugs á Norðurlöndum. Nordregio, febbraio 2025. https://doi.org/10.6027/pb2025:6.2001-3876.
Testo completoAbstract (sommario):
Fluggeirinn stendur frammi fyrir þeirri áskorun að draga úr loftslagsáhrifum sínum, og rafknúnar flugsamgöngur (Electric Aviation, EA) hafa komið fram sem álitlegur kostur í þeim efnum. Norðurlöndin leitast við að vera í fararbroddi í innleiðingu þessarar nýju tækni og hafa sett sér metnaðarfull markmið um að gera hana að raunveruleika á næstu árum. En ýmsar spurningar þarf enn að svara og margar áskoranir að leysa áður en rafknúnar flugsamgöngur verða að veruleika. Er pólitískur stuðningur á Norðurlöndum nægilegur til að knýja þessar breytingar áfram? Hvaðan á nauðsynlegt fjármagn að koma? Eru innviðir og tæknilegir möguleikar til staðar? Þessar áskoranir og mögulegar lausnir eru til umfjöllunar í þessu stefnuyfirliti.
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V., Ingram, Mala W., Awono A. e Schure J. Eru in Cameroon. Center for International Forestry Research (CIFOR), 2010. http://dx.doi.org/10.17528/cifor/004639.
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Lamb, Kyle E. Trinity Era Storage. Office of Scientific and Technical Information (OSTI), febbraio 2015. http://dx.doi.org/10.2172/1169674.
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Meyer, Brent, Emil Mihaylov, Jose Maria Barrero, Steven Davis, David Altig e Nicholas Bloom. Pandemic-Era Uncertainty. Cambridge, MA: National Bureau of Economic Research, aprile 2022. http://dx.doi.org/10.3386/w29958.
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Jain, A. R&D ERL: Magnetic measurements of the ERL magnets. Office of Scientific and Technical Information (OSTI), agosto 2010. http://dx.doi.org/10.2172/1013499.
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Meot, Francois, V. Litvinenko e T. Roser. Polarization Transport in the ERL-ERL FCC e+e- Collider. Office of Scientific and Technical Information (OSTI), dicembre 2022. http://dx.doi.org/10.2172/2246894.
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