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- Ghaddar, N, et al.
(författare)
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The integrated stress response is tumorigenic and constitutes a therapeutic liability in KRAS-driven lung cancer
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 4651-
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Tidskriftsartikel (refereegranskat)abstract
- The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. Here we demonstrate that ISR is pivotal in lung adenocarcinoma (LUAD) development, the most common histological type of lung cancer and a leading cause of cancer death worldwide. Increased phosphorylation of the translation initiation factor eIF2 (p-eIF2α), the focal point of ISR, is related to invasiveness, increased growth, and poor outcome in 928 LUAD patients. Dissection of ISR mechanisms in KRAS-driven lung tumorigenesis in mice demonstrated that p-eIF2α causes the translational repression of dual specificity phosphatase 6 (DUSP6), resulting in increased phosphorylation of the extracellular signal-regulated kinase (p-ERK). Treatments with ISR inhibitors, including a memory-enhancing drug with limited toxicity, provides a suitable therapeutic option for KRAS-driven lung cancer insofar as they substantially reduce tumor growth and prolong mouse survival. Our data provide a rationale for the implementation of ISR-based regimens in LUAD treatment.
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| 2. |
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| 3. |
- Keblawi, A., et al.
(författare)
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Chilled ceiling displacement ventilation design charts correlations to employ in optimized system operation for feasible load ranges
- 2009
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Ingår i: Energy and Buildings. - : Elsevier BV. - 1872-6178 .- 0378-7788. ; 41:11, s. 1155-1164
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Tidskriftsartikel (refereegranskat)abstract
- This paper expands Ghaddar et al. [N. Ghaddar, K. Ghali, R. Saadeh, A. Keblawi, Design charts for combined chilled ceiling displacement ventilation system (1438-RP), ASHRAE Transactions, 143 (2) (2008) 574-587] design charts of combined chilled ceiling (CC) displacement ventilation (DV) system to operating sensible load ranges from 40 W/m(2) to 100 W/m(2). It develops a global correlation of system load and operational parameters, with comfort measured by vertical temperature gradient and indoor air quality measured by the stratification height. The correlations are used for a known transient load profile in generating optimal settings of the CC/DV system operational parameters and associated energy consumption. An example is illustrated to show how the correlation could be used to size the system and to provide optimized control of the CC/DV system operation at low computational cost. Results of the current model are compared to the published case study of an optimized operation based on transient simulations of the space thermal model to achieve minimum operation cost [M. Mossolly, N. Ghaddar, K. Ghali, L Jensen, Optimized operation of combined chilled ceiling displacement ventilation system using genetic algorithm, ASHRAE Transactions, 143 (2) (2008) 541-554]. The design correlations resulted in good agreement with published data (within 3% error in energy consumption and average 6% error in predictions of comfort and stratification height) at 1/4 of the computational time. The presented methodology provides an alternative for using the correlation for supervisory online controllers for the CC/DV system based on physically derived correlations. (C) 2009 Elsevier B.V. All rights reserved.
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