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| 3. |
- Liu, Jin-ming, et al.
(författare)
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Mid-term effects of lung volume reduction surgery on pulmonary function in patients with chronic obstructive pulmonary disease
- 2007
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 120:8, s. 658-662
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Tidskriftsartikel (refereegranskat)abstract
- Background Now lung volume reduction surgery (LVRS) has become one of the most effective methods for the management of some cases of severe chronic obstructive pulmonary disease (COPD). We evaluated the mid-term effects of LVRS on pulmonary function in patients with severe COPD. Methods Ten male patients with severe COPD aged 38-70 years underwent LVRS and their pulmonary function was assessed before, 3 months and 3 years after surgery. The spirometric and gas exchange parameters included residual volume, total lung capacity, inspiratory capacity, forced vital capacity, forced expiratory volume in one second, diffusion capacity for CO, and arterial blood gas. A 6-minute walk distance (6MWD) test was performed. Results As to preoperative assessment, most spirometric parameters and 6MWD were significantly improved after 3 months and slightly 3 years after LVRS. Gas exchange parameters were significantly improved 3 months after surgery, but returned to the preoperative levels after 3 years. Conclusions LVRS may significantly improve pulmonary function in patients with severe COPD indicating for LVRS. Mid-term pulmonary function 3 years after surgery can be decreased to the level at 3 months after surgery. Three years after LVRS, lung volume and pulmonary ventilation function can be significantly improved, but the improvement in gas exchange function was not significant.
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- Chandramohan, Arun, et al.
(författare)
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Design-Rules for Stapled Alpha-Helical Peptides with On-Target In Vivo Activity: Application to Mdm2/X dual antagonists
- 2023
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Ingår i: Nature Communications. - : Cold Spring Harbor Laboratory. - 2041-1723.
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Tidskriftsartikel (refereegranskat)abstract
- Stapled α-helical peptides can bind to and modulate historically intractable targets while addressing the traditional liabilities associated with peptide therapeutics. However, their pipeline advancement has been impeded by the challenges of identifying peptides with sufficient cellular uptake to engage the target protein while lacking off-target toxicities. Here, we advance the field to arrive at a workflow for identifying advanced stapled peptide lead molecules with on-target in vivo activity with no off-target cell proliferation effects. Specifically, we generated a >350-member library based on ATSP-7041, a stapled peptide Mdm2(X) antagonist with validated on-target cellular effects but with significant off-target activity. Key insights from library analysis include 1) a clear correlation between lipophilicity and permeability, 2) removal of positive charge to avoid off-target toxicities, 3) judicious placement of anionic residues to enhance peptide solubility/behavior, 4) optimization of C-terminal length and helicity to enhance cell activity, 5) optimization of staple type/number to avoid polypharmacology. Incorporation of one or more of these attributes led to molecules with improved in vitro and in vivo activities (up to a >292x improved cell proliferation EC50). A subset of peptides were devoid of off-target cell proliferation effects in cell lines lacking wild-type p53 protein (up to a >3800x on-target index). This latter improvement contrasted with clinical Mdm2 antagonistic molecules. Application of these ‘design rules’ to a distinct Mdm2(X) peptide series resulted in rapid improvement in cellular activity (>150x) and removal of off-target toxicities. Overall, the detailed workflow outlined here should help researchers identify stapled α-helical peptides for therapeutic impact.
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| 6. |
- Chandramohan, Arun, et al.
(författare)
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Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these ‘design rules’ to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.
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| 7. |
- Kristan, Matej, et al.
(författare)
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The Ninth Visual Object Tracking VOT2021 Challenge Results
- 2021
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Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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| 9. |
- Termeer, Catrien J. A. M., et al.
(författare)
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Institutions and the resilience of biobased production systems : the historical case of livestock intensification in the Netherlands
- 2019
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Ingår i: Ecology and Society. - : The Resilience Alliance. - 1708-3087. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- Disconnects between farming and urban systems are widely seen as impairing the resilience of biobased production systems (BBPSs). However, the institutional mechanisms that underlie these resilience problems are not well understood. In this explorative paper, which integrates elements from institutional and resilience theory, we develop a framework to analyze how institutionally shaped patterns of connects and disconnects affect the resilience of BBPs along the dimensions of robustness, adaptability, and transformability. This framework is applied to the historical case of pig livestock intensification in the Netherlands from 1870 to 2017. The case shows that institutions, successfully established in earlier periods, shape connects and disconnects in subsequent periods, thereby enabling and constraining resilience. A combination of perturbations, institutional layering, and shifts in ideational power is an important institutional mechanism for resilience. We conclude that building resilience requires a variety of reconnecting institutions and refraining from a focus on local reconnects or certification only.
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| 10. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 11. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :1
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :9
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Tidskriftsartikel (refereegranskat)
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