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Gotowa bibliografia na temat „GLS1”

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Data publikacji: 7 lipca 2024

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Artykuły w czasopismach na temat "GLS1"

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Vidula, Neelima, Christina Yau i Hope S. Rugo. "Glutaminase (GLS) expression in primary breast cancer (BC): Correlations with clinical and tumor characteristics." Journal of Clinical Oncology 37, nr 15_suppl (20.05.2019): 558. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.558.

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558 Background: Tumor cells rely on glutamine for growth. GLS is a mitochondrial enzyme that is necessary for glutamine catabolism, and is present as isoforms GLS1 and GLS2. A GLS1 inhibitor is being studied in triple-negative (TN) BC. We studied GLS1 expression in primary BC to understand associations with clinical and tumor characteristics in publically available databases. Methods: GLS1 mRNA levels were evaluated using expression data from the TCGA (n = 817) dataset, with confirmation in METABRIC (n = 1992). Associations between GLS1 levels and tumor subtype were assessed using ANOVA, followed by the post-hoc Tukey test for pairwise comparisons. Pearson correlations were used to study associations between GLS1 and selected genes. Correlations with overall survival (OS) were studied with Cox proportional hazard model. For all analyses, p < 0.05 was considered significant. Results: In TCGA, the expression of GLS1 and its isoform GLS2 were significantly inversely correlated (r = -0.32). GLS1 expression was highest in TN compared to hormone receptor (HR)+ and HER2+ BC (p < 0.001). In addition, GLS1 expression was higher in basal vs luminal A, luminal B, and HER2 enriched BC (p < 0.001). GLS1 expression was significantly inversely correlated with ER (r = -0.45), PR (r = -0.34), and AR (r = -0.34), and these inverse correlations remained significant when restricted to TNBC (ER: r = -0.25, PR: r = -0.25, AR: r = -0.30). Consistent with previous reports of MYC upregulation of GLS1, GLS1 expression was significantly positively correlated with MYC (r = 0.26). Similarly, in METABRIC, GLS1 was most highly expressed in basal and TNBC, significantly inversely correlated with the expression of GLS2, ER, PR, and AR, and positively correlated with MYC expression. In METABRIC, higher GLS1 expression was associated with better OS (HR 0.91, p = 0.005); this association remained significant in the TN subset (HR 0.83, p = 0.03). Correlations between GLS1 and genes involved in metabolism and immune activation will be presented at the meeting. Conclusions: GLS1 expression is highest in basal and TNBC, is associated with MYC expression, and may have prognostic implications. These findings support ongoing trials of GLS1 inhibition in TNBC.
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Rojas, Livisu Pajares, i Claudia Machicado Rivero. "Abstract 883: Glutaminases expression and viral infection as potential prognostic factors in cervical, head and neck and liver cancers". Cancer Research 83, nr 7_Supplement (4.04.2023): 883. http://dx.doi.org/10.1158/1538-7445.am2023-883.

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Abstract Human Papilloma virus (HPV)-associated Cervical squamous cell carcinoma (CESC-HPV(+)), HPV-associated Head and Neck squamous cell carcinoma (HNSCC-HPV(+)), and Hepatitis Virus B/C (HBV/HCV)-associated Liver hepatocellular carcinoma (LIHC-HBV(+)/LIHC-HCV(+)) present metabolic changes during viral transformation to adjust energy demands of transformed cells. Glutamine is used as an important energy and carbon source by cancer cells through its degradation (glutaminolysis). This latter is regulated by Glutaminases 1 and 2 (GLS1/GLS2) that convert glutamine in glutamate. GLS1/2 expression is altered both in HNSCC and LIHC but it is undetermined in CESC. We aimed to indagate if the expression of GLS1/GLS2 genes and/or status of infection by HPV, HBV, and HCV, are associated to the overall survival (OS) in CESC, HNSCC and LIHC. The Cancer Genome Atlas (TCGA) was mined and both gene expression and copy number variation (CNV) of GLS1/GLS2 was analyzed across the CESC, HNSCC and LIHC cohorts. Changes in gene expression were determined by analyzing the Log2FC and by applying statistical analysis (Welch’s T-test or One-Way ANOVA). To learn if the genomic profile was associated with phenotype, gene status was correlated with demographic and clinical data such as age group, ethnicity, race, gender, BMI, viral subtype, histologic grade, clinical stage, and tobacco/alcohol consumption. We applyed chi-squared, one-way ANOVA, and Welch’s T-tests for those assays. Kaplan Meier (K-M) plots were obtained to figure out the association of genomic and phenotypic data with OS. Our results showed that GLS1/GLS2 had no CNVs across the analyzed cohorts. However, GLS1 was upregulated in cancerous tissues both in HNSCC and LIHC (p&lt;0.05, Log2FC&gt;2) whereas GLS2 was downregulated in cancerous tissues in LIHC (p&lt;0.05, Log2FC=-2). Likewise, GLS1 was upregulated both in HNSCC-HPV(-) and LIHC-HBV/HCV(+) compared with HNSCC-HPV(+) and LIHC-HBV/HCV(-), respectively (p&lt;0.05). Also, GLS2 was over-expressed in CESC-HPV(+) and HNSCC-HPV(+) patients, compared with CESC-HPV(-) and HNSCC-HPV(-) patients, respectively (p&lt;0.05). In the other hand, GLS2 was under-expressed in LIHC-HBV/HCV(+) compared with LIHC-HBV/HCV(-) patients (p&lt;0.05, Log2FC = -2.5). Finally, K-M plots showed that GLS2 expression is associated with OS in CESC patients whereas the HPV subtypes and HBV/HCV infection were associated with OS in HNSCC and LIHC patients, respectively (p&lt;0.05). We concluded that the expression of glutaminases is abnormal in patients with CESC, HNSCC, and LIHC and it depends on the status of viral infection. Since the GLS2 expression and viral infection affects the OS in the analyzed tumors, our research provides with potential prognostic markers of CESC, HNSCC and LIHC that should be validated in future studies. Citation Format: Livisu Pajares Rojas, Claudia Machicado Rivero. Glutaminases expression and viral infection as potential prognostic factors in cervical, head and neck and liver cancers [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 883.
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Bright, Scott J., Rishab Kolachina, Mariam Ben Kacem, Mandira Manandhar, Philip Jones, Timothy A. Yap, Steven H. Lin i Gabriel O. Sawakuchi. "Abstract B030: Modulating mitochondria metabolism to radiosensitize KEAP1 mutated non-small cell lung cancer". Cancer Research 84, nr 1_Supplement (9.01.2024): B030. http://dx.doi.org/10.1158/1538-7445.dnarepair24-b030.

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Abstract Glutamine is the most abundant amino acid in the body. Glutamine is metabolized by the enzyme Glutaminase-1 (GLS1), and results in the formation of glutamate. Glutamate is essential for redox homeostasis, energy production, tricarboxylic acid (TCA) cycle anaplerosis, and synthesis of amino acids, lipids and nucleotides. Genetic alterations in cancer cells like in the protein Kelch-like ECH-associated protein 1 (KEAP1), can rewire cell metabolism creating greater dependency on metabolites such as glutamine. KEAP1-mutant cells rely critically on GLS1 to maintain adequate glutamate levels, TCA cycle fueling and antioxidant production. Notably, 15-20% of non-small cell lung cancers (NSCLC) have mutations in KEAP1. Therefore, GLS1 is a promising target that should show specificity in KEAP1 mutated tumors with relatively limited effects in normal tissue in a significant patient population. GLS1 inhibitors (GLS1i) are being tested in several clinical trials as a monotherapy or in combination. One combination of relevance is radiotherapy (RT)+GLS1i. GLS1 products (lipids, nucleotides, ATP or antioxidants) are heavily implicated in RT response to neutralize radiation-induced reactive oxygen species (ROS) or to serve as substrates to repair radiation-induced DNA damage. Our preliminary data indicate that a novel GLS1 inhibitor (IACS-6274) profoundly sensitizes lung cancer cell lines including KEAP1-mutant and wild type cells exposed to RT+IACS-6274, including proton RT where we saw an increase in the relative biological effectiveness. We also observed significantly more mitochondrial ROS in RT treated groups in the presence of IACS-6274, and that the radiosensitizing effects could be rescued by resupplying cells with α-ketoglutarate, the ROS scavenger N-acetyl cysteine or the ferroptosis inhibitor, ferrostatin 1. Thus, the combination of RT+IACS-6274 may offer a unique treatment combination, that could be further optimized using proton therapy. Maximizing the efficacy of RT+IACS-6274 requires identifying the mechanisms by which GLS1 inhibition sensitizes cells exposed to RT, which are currently unclear. Our findings indicate that radiation induces permanent mitochondria dysfunction, resulting in persistent higher levels of ROS which in turn can be amplified by IACS-6274 treatment. Also, in addition to increased oxidative stress as a result of reduced antioxidants, GLS1 inhibition significantly sensitizes cells to radiation by altering TCA cycle metabolism. In summary, we have identified a patient population (KEAP1 mutated NSCLC) with poorer survival and greater levels of local recurrence that may show profound sensitivity to a novel treatment strategy that exploits tumor metabolic rewiring combined with the unique physical characteristics of RT. Citation Format: Scott J. Bright, Rishab Kolachina, Mariam Ben Kacem, Mandira Manandhar, Philip Jones, Timothy A. Yap, Steven H. Lin, Gabriel O. Sawakuchi. Modulating mitochondria metabolism to radiosensitize KEAP1 mutated non-small cell lung cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B030.
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Xiao, Yangbo, Rong Huang, Shenping Cao, Dafang Zhao, Zhuangwen Mao, Chuchu Xiao, Zhehua Xu i in. "Molecular Characterization and Dietary Regulation of Glutaminase 1 (gls1) in Triploid Crucian Carp (Carassius auratus)". Fishes 7, nr 6 (7.12.2022): 377. http://dx.doi.org/10.3390/fishes7060377.

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Kidney-type glutaminase, encoded by the gls1 gene, plays a critical role in glutamate production and improvement of meat flavor. In this study, a gls1 gene encoding 595 amino acids was cloned from triploid crucian carp (Carassius auratus) (TCC) and showed a high similarity with the gls1 gene found in Cyprinus carpio, Sinocyclocheilus rhinocerous and Puntigrus tetrazona. Comparing the abundance of gls1 in different tissues, we found its expression level in the brain and liver were significantly higher than that in heart, gut, kidney, spleen and muscle. gls1 expression in the brain reached the highest value. In addition, the expression levels of gls1 also appeared different in diurnal variation, with the highest expression seen at 9:00, while it was low at 3:00, 6:00, 15:00 and 24:00. Furthermore, dietary regulation of gls1 expression was investigated in our study. In each feeding trial, each diet was randomly assigned to triplicate tanks. Fish were fed one of the tested diets up to satiation twice daily. The results showed that gls1 expression increased in 32% protein group and decreased in 35–41% protein group. The results of different protein source experiments showed that the expression of gls1 gene in the mixed protein group (the control group) was significantly higher than that in the fish meal and soybean meal groups. Glutamate treatment revealed that appropriate concentrations (0.10 mg/mL in vivo and 2.00% in vitro) of glutamate remarkably improved the expression of gls1. Besides, diets supplemented with 0.80–1.60% lysine-glutamate dipeptide exhibited a down regulatory impact on gls1 expression. In conclusion, this study demonstrated that the expression of gls1 in TCC was increased by 32% protein diet, mixed protein source diet and diet with 2.00% glutamate concentration, while decreased by 0.80–1.60% lysine-glutamate dipeptide. The findings of this study provide a reference for the regulation of gls1 and have a potential application in the optimization of dietary formula in aquaculture.
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Myint, Zin W., Ramon C. Sun, Patrick J. Hensley, Andrew C. James, Peng Wang, Stephen E. Strup, Robert J. McDonald, Donglin Yan, William H. St. Clair i Derek B. Allison. "Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters". Cancers 13, nr 9 (29.04.2021): 2157. http://dx.doi.org/10.3390/cancers13092157.

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High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.
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Yang, Jianqiang, Fanghui Chen, Fan Yang i Yong Teng. "Abstract 3061: A positive feedback loop between GLS1 and c-Myc drives tumor aggressiveness". Cancer Research 84, nr 6_Supplement (22.03.2024): 3061. http://dx.doi.org/10.1158/1538-7445.am2024-3061.

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Abstract Both GLS1 and c-Myc are upregulated in head and neck squamous cell carcinoma (HNSCC) primary tumors and further increased in metastatic tumors. However, the regulation between these two molecules remains largely unknown. GLS1 is a critical enzyme that regulates glutamate, which plays an important role in cancer metabolism that supports cancer growth and survival. Our bioinformatic analysis of the TCGA HNSCC cohort revealed a strong correlation between c-Myc and GLS1 expression. We describe the importance of c-Myc in regulating GLS1 and vice versa. c-Myc protein directly binds to the promoter of the GLS1 gene and upregulates its expression at the transcriptional level. Interestingly, blocking GLS1 signaling in HNSCC cells by lentiviral shRNA knockdown or CB-839 treatment downregulates USP1, one of the best characterized human DUBs, which in turn reduces c-Myc protein stability via the ubiquitin-proteasome pathway. The GLS1-c-Myc axis thus represents a novel positive feedback loop that is critical for driving the aggressiveness of HNSCC. As the treatment of HNSCC remains a major challenge, these novel findings provide the molecular basis for combining GLS1-specific inhibitors with c-Myc-targeted therapy for the treatment of HNSCC patients. Citation Format: Jianqiang Yang, Fanghui Chen, Fan Yang, Yong Teng. A positive feedback loop between GLS1 and c-Myc drives tumor aggressiveness [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 3061.
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Ahmed, Shanzay, Peter John, Rehan Zafar Paracha, Attya Bhatti i Monica Guma. "Docking and Molecular Dynamics Study to Identify Novel Phytobiologics from Dracaena trifasciata against Metabolic Reprogramming in Rheumatoid Arthritis". Life 12, nr 8 (29.07.2022): 1148. http://dx.doi.org/10.3390/life12081148.

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Enhancement of glycolysis and glutaminolysis are the two most common modalities associated with metabolic reprogramming in rheumatoid arthritis (RA). This enhancement is concomitant to the upregulation of hexokinase 2 (HK2) and glutaminase 1 (GLS1). Hence, the current study was undertaken to identify potential phytobiological inhibitors against HK2 and GLS1, from Dracaena (Sansevieria) trifasciata, an indigenous ethnomedicinal plant found in Pakistan, using computational analysis. Phytobiologics from Dracaena trifasciata were assessed for their ability to co-inhibit HK2 and GLS1 via molecular docking and molecular dynamics simulations. The results underscored seven phytobiologics with promising binding affinities for both HK2 and GLS1. Molecular dynamics simulations further elucidated that all seven identified phytobiologics inhibited HK2 by forming stable complexes but only five amongst the seven had the potential to form stable complexes with GLS1 in real time, thereby implying the potential of co-inhibition for these five compounds. Compound 28MS exhibited an equally strong binding profile for both HK2 (−8.19 kcal/mol) and GLS1 (−8.99 kcal/mol). Furthermore, it exhibited a similar trend in stability during simulation for both targets. Our results serve as a primer for a more lucid understanding towards co-inhibition of HK2 and GLS1 using multiple computational approaches. The identified phytobiologics should undergo in-vitro and in-vivo validation to corroborate their therapeutic potential in RA.
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Kono, Michihito, Nobuya Yoshida, Kayaho Maeda i George C. Tsokos. "Transcriptional factor ICER promotes glutaminolysis and the generation of Th17 cells". Proceedings of the National Academy of Sciences 115, nr 10 (20.02.2018): 2478–83. http://dx.doi.org/10.1073/pnas.1714717115.

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Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in the glutaminolysis pathway. Both pharmacological and siRNA-based selective inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR-mediated increase of the mammalian target of rapamycin complex 1 activity. Treatment of mice with a Gls1 inhibitor ameliorated experimental autoimmune encephalomyelitis. Furthermore, RAG1-deficient mice that received Gls1-shRNA–transfected 2D2 T cells had reduced experimental autoimmune encephalomyelitis scores compared with those that received control-shRNA–treated cells. Next we found that T cells deficient in inducible cAMP early repressor (ICER), a transcriptional factor known to promote Th17 differentiation, display reduced activity of oxidative phosphorylation rates in the presence of glutamine and reduced Gls1 expression, both of which could be restored by ICER overexpression. Finally, we demonstrate that ICER binds to the gls1 promoter directly and increases its activity. These findings demonstrate the importance of glutaminolysis in the generation of Th17 and the direct control of Gls1 activity by the IL-17–promoting transcription factor ICER. Pharmaceutical modulation of the glutaminolysis pathway should be considered to control Th17-mediated pathology.
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Beręsewicz-Haller, Małgorzata, Olga Krupska, Paweł Bochomulski, Danuta Dudzik, Anita Chęcińska, Wojciech Hilgier, Coral Barbas, Krzysztof Zablocki i Barbara Zablocka. "Mitochondrial Metabolism behind Region-Specific Resistance to Ischemia-Reperfusion Injury in Gerbil Hippocampus. Role of PKCβII and Phosphate-Activated Glutaminase". International Journal of Molecular Sciences 22, nr 16 (7.08.2021): 8504. http://dx.doi.org/10.3390/ijms22168504.

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Ischemic episodes are a leading cause of death worldwide with limited therapeutic interventions. The current study explored mitochondrial phosphate-activated glutaminase (GLS1) activity modulation by PKCβII through GC-MS untargeted metabolomics approach. Mitochondria were used to elucidate the endogenous resistance of hippocampal CA2-4 and dentate gyrus (DG) to transient ischemia and reperfusion in a model of ischemic episode in gerbils. In the present investigation, male gerbils were subjected to bilateral carotids occlusion for 5 min followed by reperfusion (IR). Gerbils were randomly divided into three groups as vehicle-treated sham control, vehicle-treated IR and PKCβII specific inhibitor peptide βIIV5-3-treated IR. Vehicle or βIIV5-3 (3 mg/kg, i.v.) were administered at the moment of reperfusion. The gerbils hippocampal tissue were isolated at various time of reperfusion and cell lysates or mitochondria were isolated from CA1 and CA2-4,DG hippocampal regions. Recombinant proteins PKCβII and GLS1 were used in in vitro phosphorylation reaction and organotypic hippocampal cultures (OHC) transiently exposed to NMDA (25 μM) to evaluate the inhibition of GLS1 on neuronal viability. PKCβII co-precipitates with GAC (GLS1 isoform) in CA2-4,DG mitochondria and phosphorylates GLS1 in vitro. Cell death was dose dependently increased when GLS1 was inhibited by BPTA while inhibition of mitochondrial pyruvate carrier (MPC) attenuated cell death in NMDA-challenged OHC. Fumarate and malate were increased after IR 1h in CA2-4,DG and this was reversed by βIIV5-3 what correlated with GLS1 activity increases and earlier showed elevation of neuronal death (Krupska et al., 2017). The present study illustrates that CA2-4,DG resistance to ischemic episode at least partially rely on glutamine and glutamate utilization in mitochondria as a source of carbon to tricarboxylic acid cycle. This phenomenon depends on modulation of GLS1 activity by PKCβII and remodeling of MPC: all these do not occur in ischemia-vulnerable CA1.
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Myint, Zin, Patrick J. Hensley, Andrew Callaway James, Peng Wang, Stephen Strup, Donglin Yan, William H. St Clair, Robert S. DiPaola i Derek B. Allison. "Immunohistochemical evaluation of glutaminase expression in prostate adenocarcinoma and correlation with clinicopathologic parameters." Journal of Clinical Oncology 39, nr 6_suppl (20.02.2021): 251. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.251.

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251 Background: Glutaminolysis plays a significant role in the metabolic reprogramming of cancer cell growth and proliferation. Glutaminase (GLS1), the rate-limiting enzyme of the glutamine pathway, is frequently dysregulated in cancer. High GLS1 expression is reported in colorectal and breast cancers and has been found to correlate with the tumor stage and disease progression. Furthermore, a new orally bioavailable glutaminase inhibitor (CB-839) is in early phase clinical trials in select tumors. The purpose of this study is to investigate the status of GLS1 expression in prostate cancer (PCa) and to correlate expression levels with clinicopathologic parameters. Methods: Radical prostatectomy samples from 154 patients with prostate adenocarcinoma were retrospectively reviewed and used to evaluate GLS1 expression by immunohistochemistry (IHC). The IHC expression score was calculated by multiplying the intensity of the stain by the proportion of cells staining; cases were then segmented into negative, low, or high expression groups. In addition, 41 samples of benign prostate tissue were used as a control. Associations between GLS1 levels and clinicopathologic parameters were analyzed by Pearson’s chi-squared and Log-rank tests. Results: GLS1 expression in the benign controls were negative, low, and high in 59%, 41%, 0% of cases, respectively, compared to 53%, 21.5%, 25.5%, respectively, in PCa (p < 0.003). Most PCa patients were age < 60 (55.8%), white (78.6%), stage T2 (52.9%), node negative (80.5%), Grade Group 3 (44%), and non-smokers (63.6%). There was no difference between GLS1 expression and age, race, Gleason score, stage, node status, and smoking status by univariate analysis. The median biochemical-progression free survival for negative, low, and high expression was 10, 9, and 10 years, respectively (p = 0.7). Conclusions: In our study, PCa samples were more likely to have GLS1 expression compared to benign controls. Although GLS1 expression did not appear to be a prognostic marker, our cohort was enriched for cases with localized disease and low-to-intermediate grade PCa. As a result, future studies are warranted to evaluate the expression levels in high grade and advanced PCa cases to determine a role for prognostic and or therapeutic implication to justify future preclinical studies with CB-839.
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Rozprawy doktorskie na temat "GLS1"

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Hasan, Bou Issa Lama. "Étude des dépendances génomiques dans le myélome multiple surexprimant MYC". Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS011.

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Le myélome multiple (MM), une hémopathie maligne qui représente environ 13% des cancers hématologiques, est caractérisée par la prolifération de plasma cells tumoraux au niveau de la moelle osseuse. Le MM évolue à partir de stades précurseurs, à savoir la gammapathie monoclonale de signification indéterminée (MGUS) et le myélome multiple asymptomatique (SMM), vers la forme symptomatique, le MM. C’est une hémopathie maligne incurable dont l’hétérogénéité et l’évolution clonale permettent l’échappement aux traitements et la progression de la maladie. Les altérations de MYC ont un rôle essentiel dans cette progression. Cependant, MYC n'est pas ciblable thérapeutiquement en raison de sa localisation nucléaire et de la courte demi-vie de la protéine.Pour surmonter cela, nous avons fait l’hypothèse que l’avantage prolifératif induit par la surexpression de MYC crée des dépendances des cellules tumorales vis-à-vis d’autres voies de signalisation qui deviennent indispensables à la survie de ces cellules. Pour tester cette hypothèse, nous avons appliqué une nouvelle méthodologie utilisant la carte de dépendance (Achilles) et effectué un screening de 2000 petites molécules afin d'identifier les vulnérabilités génomiques induites par MYC. Si elles sont identifiées, ces vulnérabilités offrent une possibilité de traitement ciblé des cancers ayant une surexpression de MYC. Nos analyses démontrent la dépendance des lignées cellulaires surexprimant MYC pour le métabolisme de la glutamine, spécifiquement les gène GLS1 (glutaminase). Nous avons validé et délimité fonctionnellement cette dépendance in vitro à partir des différentes approches.Par l’analyse de notre criblage de 1869 composés chimiques, nous avons observé que les inhibiteurs de la synthèse de NAD avaient un effet préférentiel sur la prolifération des cellules surexprimant MYC. Considérant que les rôles métaboliques du glutamine sont liés à ceux du NAD, nous avons ensuite exploré un effet synergique potentiel entre les inhibiteurs du GLS1 et du NAMPT. Nous avons démontré l'efficacité de cette nouvelle combinaison synergique pour cibler les cellules MM surexprimant MYC in vitro et in vivo.Ces résultats établissent une base méthodologique solide utilisable pour développer de nouvelles approches thérapeutiques afin de répondre à des besoins thérapeutiques non satisfaits pour cibler le MYC dans le MM
Multiple myeloma (MM) is a hematological malignancy that accounts for around 13% of hematological cancers and is characterized by the uncontrolled proliferation of malignant plasma cells in the bone marrow. MM progresses from precursor stages, known as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), to the symptomatic form, MM. It is an incurable malignancy in which heterogeneity and clonal evolution allow treatment escape and disease progression. MYC alterations play an essential role in this progression. However, MYC is not therapeutically targetable due to its nuclear localization and the protein's short half-life.To overcome this, we hypothesized that the proliferative advantage induced by MYC overexpression creates genomic dependencies on other signalling pathways that become essential for cell survival. To test this hypothesis, we applied a novel approach by leveraging large-scale loss of function screen (Achilles) and 1869 small molecules screen to identify MYC-induced genomic vulnerabilities. When identified, these vulnerabilities offer an opportunity to selectively target cancer cells harbouring this overexpression and spare normal cells.Our analyses demonstrate the dependence of MYC overexpressing cells on glutamine metabolism, in particular on the GLS1 (glutaminase). We validated and functionally delineated this dependence in vitro using different approaches.Our small molecule screen highlighted that NAD synthesis inhibitors had a preferential effect on the proliferation of MYC overexpressing cells. Considering that glutamine and NAD have closely interlinked metabolic networks, we investigated the possibility of a potential synergistic effect between GLS1 and NAMPT inhibitors. We demonstrated the effectiveness of this new synergistic combination to target MYC-driven MM cells in vitro and in vivo.These results establish a solid methodological basis that can be used to develop new therapeutic approaches to address unmet therapeutic needs to target MYC in MM
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Schippel-Coressel, Katja [Verfasser], i Matthias [Akademischer Betreuer] Frank. "GLP1 als Therapieoption bei Adipositas (kurz- und langwirksame GLP1 Analoga im klinischen Vergleich) / Katja Schippel-Coressel ; Betreuer: Matthias Frank". Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2018. http://d-nb.info/115209534X/34.

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Li, Xingnan. "Regulation of [beta]-catenin by Gli1 in epithelial transformation". Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2006. http://www.mhsl.uab.edu/dt/2007p/li_xingnan.pdf.

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Seytanoglu, Adil. "Investigation of the effects of gle1 depletion in zebrafish". Thesis, University of Sheffield, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.632835.

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Hutschenreuther, Antje, Marina Bigl, Nasr Y. A. Hemdan, Tewodros Debebe, Frank Gaunitz i Gerd Birkenmeier. "Modulation of GLO1 expression affects malignant properties of cells". Universitätsbibliothek Leipzig, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-217965.

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The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect) characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO). Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1) that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.
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Hutschenreuther, Antje, Marina Bigl, Nasr Y. A. Hemdan, Tewodros Debebe, Frank Gaunitz i Gerd Birkenmeier. "Modulation of GLO1 expression affects malignant properties of cells". MDPI, 2016. https://ul.qucosa.de/id/qucosa%3A15256.

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The energy metabolism of most tumor cells relies on aerobic glycolysis (Warburg effect) characterized by an increased glycolytic flux that is accompanied by the increased formation of the cytotoxic metabolite methylglyoxal (MGO). Consequently, the rate of detoxification of this reactive glycolytic byproduct needs to be increased in order to prevent deleterious effects to the cells. This is brought about by an increased expression of glyoxalase 1 (GLO1) that is the rate-limiting enzyme of the MGO-detoxifying glyoxalase system. Here, we overexpressed GLO1 in HEK 293 cells and silenced it in MCF-7 cells using shRNA. Tumor-related properties of wild type and transformed cells were compared and key glycolytic enzyme activities assessed. Furthermore, the cells were subjected to hypoxic conditions to analyze the impact on cell proliferation and enzyme activities. Our results demonstrate that knockdown of GLO1 in the cancer cells significantly reduced tumor-associated properties such as migration and proliferation, whereas no functional alterations where found by overexpression of GLO1 in HEK 293 cells. In contrast, hypoxia caused inhibition of cell growth of all cells except of those overexpressing GLO1. Altogether, we conclude that GLO1 on one hand is crucial to maintaining tumor characteristics of malignant cells, and, on the other hand, supports malignant transformation of cells in a hypoxic environment when overexpressed.
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Lee, Jaehoon Ph D. Massachusetts Institute of Technology. "Studies of superconformal field theories using GLSM and conformal bootstrap". Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/99308.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Physics, 2015.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 273-288).
In this thesis, we study strongly interacting superconformal field theories in two and three dimensions. In two dimensions, we investigate N = (0, 2) gauge theories using the gauged linear sigma models (GLSM). In those theories, we identify simple mechanism by which worldsheet description of H-flux satisfying Green-Schwarz Bianchi identity arises. Under the renormalization group flow, we argue that these models flow into superconformal fixed points describing string theory compactifications backgrounds with non-trivial H-flux turned on. By analyzing quantum-consistency of effective theories with such mechanism, we identify conditions under which these theories to become interacting superconformal field theories in the infrared. In three dimensions, we study maximally supersymmetric (N = 8) conformal field theories by conformal bootstrap approach. We focus on studying the four-point function of stress-tensor multiplet. The superconformal blocks for the four-point function are computed by analyzing superconformal Ward identity. Using these blocks, we study crossing symmetry constraints both numerically and analytically. Doing so, we obtain universal bounds and exact relations of N = 8 superconformal field theory data.
by Jaehoon Lee.
Ph. D.
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Mora, Saavedra Aquiles Andrés. "Plan de Marketing para un Bar GLS". Tesis, Universidad de Chile, 2010. http://www.repositorio.uchile.cl/handle/2250/102472.

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Cangini, Loris. "Modern OpenGL e linguaggio GLSL per lo sviluppo di shader grafici". Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2017.

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OpenGL ha subito, nel corso del tempo, diverse evoluzioni, cambiando il suo funzionamento. Con il seguente elaborato si vuole capire come e quanto l’introduzione degli shader ha migliorato l’API, e perché questa innovazione ha permesso lo sviluppo di applicazioni più liberamente rispetto a quanto era possibile fare con le prime versioni. Si vedranno quali sono, e per quali ragioni sono state introdotte, le migliorie che hanno portato al Modern OpenGL, verranno trattati i principali tipi di shader utilizzati e le strutture dati che devono essere usate per poter comunicare eᨴcientemente con la scheda video, dove verranno eseguiti gli shader e calcolato il rendering della scena da noi descritta. Verranno usati anche esempi pratici per vedere come le cose funzionano nel concreto; si partirà da semplici scene 2D, aggiungendo man mano concetti in modo da ottenere rese sempre più realistiche, permettendo così a chiunque di provare con le proprie mani a creare shader ed applicazioni graᨴche.
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McMellon, Hannah. "Structure-function studies on putative Gly1 homologues in gram-negative bacteria". Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/12921/.

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Książki na temat "GLS1"

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Jali. Pl*xi*gls. Bilbao: Astiberri, 2004.

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Ripardo, Sérgio. Guia GLS - São Paulo. São Paulo: Publifolha, 2007.

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Lindenberg, Cariê. GLS, entenda as entendidas. Rio de Janeiro: Gryphus Editora, 2005.

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Ripardo, Sérgio. Guia GLS - São Paulo. São Paulo: Publifolha, 2007.

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Nyarko, Philomena. Ghana living standards survey: Report on the second round (GLSS 2), October 1988-September 1989 (with corresponding tables from GLSS 1). Accra: Ghana Statistical Service, 1996.

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Linton, Oliver. Small sample properties of adaptive GLS estimators. Oxford: Nuffield College, 1992.

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Dohmen, Caspar. Good Bank: Das Modell der GLS Bank. Freiburg: Orange Press, 2011.

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Abbud, red. Triunfo dos pêlos e outros contos gls. São Paulo, SP: Edições GLS, 2000.

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Ghana living standards survey round 6 (GLSS 6): Community facilities. Accra: Ghana Statistical Service, 2014.

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Ghana living standards survey round 6 (GLSS 6): Child labour report. Accra: Ghana Statistical Service, 2014.

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Części książek na temat "GLS1"

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Colubri, Andrés. "GLSL Shaders". W Processing for Android, 269–301. Berkeley, CA: Apress, 2023. http://dx.doi.org/10.1007/978-1-4842-9585-4_15.

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Ala’Aldeen, Aryan, David L. Marks, Rachel L. O. Olson i Martin E. Fernandez-Zapico. "Glioma-Associated Oncogene 1 (GLI1)". W Encyclopedia of Signaling Molecules, 2088–98. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_101890.

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Meyr, Herbert. "Das GLSP mit Rüstzeiten (GLSPST)". W Simultane Losgrößen- und Reihenfolgeplanung für kontinuierliche Produktionslinien, 129–58. Wiesbaden: Deutscher Universitätsverlag, 1999. http://dx.doi.org/10.1007/978-3-322-89140-2_6.

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Ala’Aldeen, Aryan, David L. Marks, Rachel L. O. Olson i Martin E. Fernandez-Zapico. "Glioma-Associated Oncogene 1 (GLI1)". W Encyclopedia of Signaling Molecules, 1–11. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4614-6438-9_101890-1.

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Wee, Lionel. "Globalization". W Handbook of Pragmatics, 91–106. Amsterdam: John Benjamins Publishing Company, 2022. http://dx.doi.org/10.1075/hop.25.glo1.

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Cronin, Michael. "Globalization and translation". W Handbook of Translation Studies, 134–40. Amsterdam: John Benjamins Publishing Company, 2010. http://dx.doi.org/10.1075/hts.1.glo1.

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Schneeweiss, Eva. "GLS Bank: Successfully Sustainable". W Banking with Integrity, 107–14. London: Palgrave Macmillan UK, 2012. http://dx.doi.org/10.1057/9780230346499_8.

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Meyr, Herbert. "Das GLSP bei parallelen Linien (GLSPPL)". W Simultane Losgrößen- und Reihenfolgeplanung für kontinuierliche Produktionslinien, 159–201. Wiesbaden: Deutscher Universitätsverlag, 1999. http://dx.doi.org/10.1007/978-3-322-89140-2_7.

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Schips, Bernd. "Verallgemeinerte Kleinst-Quadrate-Schätzfunktionen (GLS)". W Beiträge zur psychologischen Forschung, 135–44. Wiesbaden: Gabler Verlag, 1990. http://dx.doi.org/10.1007/978-3-322-89329-1_15.

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Knottnerus, Paul. "GLS Estimation by Kalman Filtering". W Lecture Notes in Economics and Mathematical Systems, 55–95. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-48383-7_4.

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Streszczenia konferencji na temat "GLS1"

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Henry, Christophe, Karine Berthelot, Christophe Lanneau, Cécile Orsini, Dimitri Gorge-Bernat, Isabelle Meaux, Dorine Chassin i in. "Abstract 242: Identification of biomarkers predicting sensitivity to GLS1 inhibition using a CRISPR screen". W 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.am2020-242.

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Suzuki, Erika, Jennifer Molina, Nakia D. Spencer, Christopher A. Bristow, Angela L. Harris, Ningping Feng, Mikhila Mahendra i in. "Abstract 2338: The GLS1 inhibitor IPN60090 enhances antitumor immune response through metabolic reprogramming of T cells and impacts on the tumor microenvironment". W 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.am2021-2338.

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Spencer, Nakia D., Christopher A. Bristow, Virginia Giulani, Meredith A. Miller, Alessandro Carugo, Angela L. Harris, Rosalba Minelli i in. "Abstract 87: Asparagine synthetase (ASNS) expression predicts response to the GLS1 inhibitor IPN60090 in ovarian cancer through selective modulation of redox homeostasis". W 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.am2021-87.

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Mittal, Mukul K., i Gautam Chaudhuri. "Abstract LB-112: Increase in glutaminase (GLS1) levels through SLUG-induced repression of hsa-miR-23a in triple negative breast cancer cells." W Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-lb-112.

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Scott, Gary K., Justine Rutter, Katya Frazier, Daniel Rothschild, Christina Yau i Christopher Benz. "Abstract 5402: A new anticancer strategy based on inhibiting mitochondrial proline dehydrogenase (PRODH) and exploiting synthetic lethal interactions with p53 restoration and/or glutaminase (GLS1) inhibition". W Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-5402.

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Palant, Wladimir, Carsten Griwodz i Pål Halvorsen. "GLS". W the 14th annual ACM international conference. New York, New York, USA: ACM Press, 2006. http://dx.doi.org/10.1145/1180639.1180818.

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Chen, Feng, Chang-Tien Lu i Arnold P. Boedihardjo. "GLS-SOD". W the 16th ACM SIGKDD international conference. New York, New York, USA: ACM Press, 2010. http://dx.doi.org/10.1145/1835804.1835939.

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Tornai, Robert, Ildiko Papp i Roland Kunkli. "GLSL in batch image processing". W 2014 5th IEEE Conference on Cognitive Infocommunications (CogInfoCom). IEEE, 2014. http://dx.doi.org/10.1109/coginfocom.2014.7020407.

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Gomes, Thiago, Luiz Estevao, Rodrigo de Toledo i Paulo Roma Cavalcanti. "A Survey of GLSL Examples". W 2012 XXV SIBGRAPI Conference on Graphics, Patterns and Images Tutorials (SIBGRAPI-T). IEEE, 2012. http://dx.doi.org/10.1109/sibgrapi-t.2012.11.

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Li, Sen, Zunce Wang, Yan Xu, Fengxia Lv, Yuejuan Yan i Yujie Song. "Numerical Simulation of Compressible Flow in Gas Liquid Separator". W ASME 2010 29th International Conference on Ocean, Offshore and Arctic Engineering. ASMEDC, 2010. http://dx.doi.org/10.1115/omae2010-21039.

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The Gas Liquid Separator (GLS) has been widely used by petroleum industry, chemical engineering, the area of environmental protection, etc. A large quantity of works on the GLS available in literature includes experimental data, numerical simulations and field applications. However, previous studies on the GLS were based on gas incompressible circumstances. In fact, the gas flows from high to low pressure area that it lead to the density fluctuations of gas in separator, the changes of density cause volume expansion of gas, so that separation performance of the GLS is reduced. Numerical simulation for the GLS was developed based on compressible and incompressible flow. Research results show that flow field of two ways and separation performance were different.
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Raporty organizacyjne na temat "GLS1"

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Ghosal, Samit, i Binayak Sinha. The cardiovascular benefits of GLP1-RA are directly related to their positive effect on glycaemic control: A meta-regression analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, styczeń 2022. http://dx.doi.org/10.37766/inplasy2022.1.0071.

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Review question / Objective: P (patient population) = Type 2 diabetes patients with high CV risk or established atherosclerotic cardiovascular disease; I (intervention) = Received drugs: GLP1-RA; C (control group) = Compared to a control group that received a placebo; O (outcome) = Outcomes of interest included primary CV outcomes (MACE, CV death, MI, and Stroke). Condition being studied: To explore whether the heterogeneity associated with the primary outcomes benefits can be attributed to the metabolic improvements associated with GLP1-RA. The plan is to use HBA1c, weight, and SBP reduction as moderators attempting to explain any variance between the true and observed effect size.
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Deo, Salil, David McAllister, Naveed Sattar i Jill Pell. The time-varying cardiovascular benefits of glucagon like peptide-1 agonist (GLP-RA)therapy in patients with type 2 diabetes mellitus: A meta-analysis of multinational randomized trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, lipiec 2021. http://dx.doi.org/10.37766/inplasy2021.7.0097.

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Review question / Objective: P - patients with type 2 diabetes melllitus already receiving routine medical therapy; I - patients receiving glucagon like peptide 1 receptor agonist (GLP1 receptor agonist) therapy (semaglutide, dulaglutide, liraglutide, exenatide, lixisenatide, efpeglenatide, abiglutide); C - patients receiving standard therapy for diabetes mellitus but not receiving GLP1 agonist therapy; O - composite end point as per invididual trial, cardiovascular mortality, all-cause mortality, myocardial infarction, stoke. Condition being studied: Type 2 diabetes mellitus. Study designs to be included: Randomised controlled trials which enroll a large number of patients (defined as > 500) and are multinational in origin. Studies included will need to have published Kaplan and Meier curves for the end-points presented in the manuscript.
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Qiu, Mei, Liang-Liang Ding i Hai-Rong Zhou. Impact of SGLT2 inhibitors and GLP1 receptor agonists on respiratory infections: a meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, styczeń 2021. http://dx.doi.org/10.37766/inplasy2021.1.0092.

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Qiu, Mei, Liang-Liang Ding i Hai-Rong Zhou. Effects of SGLT2 inhibitors and GLP1 receptor agonists on risk of various arrhythmias: a meta-analysis of large randomized trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, styczeń 2021. http://dx.doi.org/10.37766/inplasy2021.1.0102.

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Qiu, Mei, Liang-Liang Ding i Hai-Rong Zhou. Effects of SGLT2 inhibitors and GLP1 receptor agonists on risk of various fractures: a meta-analysis of large randomized trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, styczeń 2021. http://dx.doi.org/10.37766/inplasy2021.1.0103.

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AUGUSTONI, ARNOLD L. Laser Safety Evaluation of the Oscmar M203PI Grenade Launcher Simulator (GLS) and the Associated Umpire Control Gun. Office of Scientific and Technical Information (OSTI), czerwiec 2002. http://dx.doi.org/10.2172/801000.

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Pinkus, Alan R., i Harry L. Task. Interlaboratory Study (ILS) on the Standard Test Method for Measuring Grid Line Slope (GLS) in Aerospace Transparencies. Fort Belvoir, VA: Defense Technical Information Center, maj 2001. http://dx.doi.org/10.21236/ada387935.

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Simakov, S. Evaluation of the Prompt Gamma-ray Spectrum from Spontaneous Fission of 252Cf. IAEA Nuclear Data Section, luty 2024. http://dx.doi.org/10.61092/iaea.bz1p-e3yc.

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The energy spectra, multiplicities and average energies of the prompt, total and delayed γ-rays accompanying the spontaneous fission of 252Cf were collected from the literature and dedicated databases. They were carefully analysed for consistency with a view to producing reference data for usage in various applications. This could be accomplished for the prompt fission gamma ray spectrum up to 20 MeV since dozens of measurements exist and reasonably agree. The prompt fission gamma ray spectrum (PFGS) was non-model evaluated by fitting the preselected experimental data with the help of the generalized least-squares (GLS) code GMA. The resulting spectrum could be considered as a reference for the γ-ray energies from 0.1 to 20 MeV with uncertainties varying between ≈ 3 and 25%. This reference gamma spectrum will be a substantial contribution to the precise and complete characterisation of the 252Cf source since the prompt fission neutron spectrum (PFNS), which has been accepted as a standard for a long time, has comparable uncertainties. The average gamma multiplicity and energy were also surveyed and used to derive the recommended values. The prompt X- and γ-ray energy spectra below ≈ 100 keV and delayed photon spectra in the whole energy range, as well as their multiplicities, are still seldomly and incompletely measured, that excepts an evaluation based on experimental data. The comparison with existing theoretical prompt and delayed 252Cf(s.f.) γ-spectra or with those presented in the major evaluated cross section libraries explored their incompleteness or deviations from the evaluated PFGS. The existing measurements of the pionic and muonic radioactivity of 252Cf(s.f.) and 235U(nth,f) were reviewed and the potential impact of gammas from the π0 decay on the high energy part of the PFGS was investigated.
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Lui, Mortimer i Wood. PR-273-0323-R02 Corrosion Assessment Guidance for High Strength Steels (Phase 2). Chantilly, Virginia: Pipeline Research Council International, Inc. (PRCI), listopad 2009. http://dx.doi.org/10.55274/r0010703.

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Phase 2 report from GL for assessment of high strength steel affected by corrosion. This work supplements the prior Phase 1 Report (GL Report R9017), issued in August 2009 and incorprates burst test data not previously reported. Extensive research has been carried out for many years by Pipeline Research Council International, Inc. (PRCI) and others to develop methods for assessing the remaining strength of corroded pipelines. This has led to the development of assessment methods such as ASME B31G and RSTRENG. Research by Germanischer Lloyd (hereafter GL1, formerly Advantica) has developed new criteria such as the LPC method and extended the range of assessment methods to include numerical analysis. While there has been substantial progress, there remain areas where existing criteria require improvements. The needed improvements identified include limitations on the interaction of closely spaced defects; the effects of external loading, and cyclic pressure loading. Furthermore, as operators start to use higher strength materials there will be an increasing need to assess the integrity of corroded high strength pipelines and to further validate the application of existing criteria and models to these materials. Phase 1 of the work was conducted to investigate the application of existing assessment methods to high strength pipelines and is described in GL Report R9017. PRCI, the Pipeline and Hazardous Materials Safety Administration (PHMSA) and BP Exploration have funded research to address these issues in recent years. A method for extending the assessment of corroded pipelines of strength grade up to X65, subject to combined internal pressure and external loading, to assess corrosion damage in pipelines subject to cyclic pressure loading, is described in GL Report R9068. In GL Reports R9107, R7702 and, work was undertaken to investigate the performance of methods such as ASME B31G, RSTRENG and LPC when applied to the assessment of higher strength pipeline materials (API 5L/ISO 3183 grade L555/X80 and L690M/X100M). In addition to this work, GL has been commissioned by BP Exploration to conduct an operational trial using 48-inch diameter grade X100 pipe. The operational trial will generate substantial data on long term performance by testing sections of X100 pipeline in near real world conditions. An accelerated operational period will be simulated by two years of pressure cycling, equivalent to forty years operation. This large scale trial will be complemented by a range of laboratory scale tests. During the course of the trial a substantial amount of data related to the assessment of corrosion defects in X100 grade pipe will be gathered. This report presents the results of a program of work that builds on the development work being conducted for PHMSA/PRCI Project #153 and for the corrosion defect assessment section of the BP X100 operational trial.
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Long-term youth suicide prevention programs can have sustained effects. ACAMH, wrzesień 2019. http://dx.doi.org/10.13056/acamh.10652.

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The Garrett Lee Smith (GLS) Memorial Suicide Prevention Act was passed in 2004 to address the public health issue of suicide in the USA. Since then, numerous programs have been funded via the GLS program to provide comprehensive, community-based suicide prevention programs to adolescents and emerging adults aged 10-24 years.
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