| 1. |
|
|
| 2. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 3. |
|
|
| 4. |
- Rodriguez Prieto, Juan Manuel, et al.
(författare)
-
Generation of segmental chips in metal cutting modeled with the PFEM
- 2018
-
Ingår i: Computational Mechanics. - : Springer. - 0178-7675 .- 1432-0924. ; 61:6, s. 639-655
-
Tidskriftsartikel (refereegranskat)abstract
- The Particle Finite Element Method, a lagrangian finite element method based on a continuous Delaunay re-triangulation of the domain, is used to study machining of Ti6Al4V. In this work the method is revised and applied to study the influence of the cutting speed on the cutting force and the chip formation process. A parametric methodology for the detection and treatment of the rigid tool contact is presented. The adaptive insertion and removal of particles are developed and employed in order to sidestep the difficulties associated with mesh distortion, shear localization as well as for resolving the fine-scale features of the solution. The performance of PFEM is studied with a set of different two-dimensional orthogonal cutting tests. It is shown that, despite its Lagrangian nature, the proposed combined finite element-particle method is well suited for large deformation metal cutting problems with continuous chip and serrated chip formation.
|
|
| 5. |
- Carraminana, Albert, et al.
(författare)
-
Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV)
- 2019
-
Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
|
|
| 6. |
|
|
| 7. |
- Rodriguez, Juan Manuel, et al.
(författare)
-
Continuous chip formation in metal cutting processes using the Particle Finite Element Method (PFEM)
- 2017
-
Ingår i: International Journal of Solids and Structures. - : Elsevier. - 0020-7683 .- 1879-2146. ; 120, s. 81-102
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents a study on the metal cutting simulation with a particular numerical technique, the Particle Finite Element Method (PFEM) with a new modified time integration algorithm and incorporating a contact algorithm capability . The goal is to reproduce the formation of continuous chip in orthogonal machining. The paper tells how metal cutting processes can be modelled with the PFEM and which new tools have been developed to provide the proper capabilities for a successful modelling. The developed method allows for the treatment of large deformations and heat conduction, workpiece-tool contact including friction effects as well as the full thermo-mechanical coupling for contact. The difficulties associated with the distortion of the mesh in areas with high deformation are solved introducing new improvements in the continuous Delaunay triangulation of the particles. The employment of adaptative insertion and removal of particles at every new updated configuration improves the mesh quality allowing for resolution of finer-scale features of the solution. The performance of the method is studied with a set of different two-dimensional tests of orthogonal machining. The examples consider, from the most simple case to the most complex case, different assumptions for the cutting conditions and different material properties. The results have been compared with experimental tests showing a good competitiveness of the PFEM in comparison with other available simulation tools.
|
|
