| 1. |
- Andersson, Mats, et al.
(author)
-
Global search strategies for solving multilinear least-squares problems
- 2012
-
In: Sultan Qaboos University Journal for Science. - : Sultan Qaboos University. - 1027-524X. ; 17:1, s. 12-21
-
Journal article (peer-reviewed)abstract
- The multilinear least-squares (MLLS) problem is an extension of the linear leastsquares problem. The difference is that a multilinear operator is used in place of a matrix-vector product. The MLLS is typically a large-scale problem characterized by a large number of local minimizers. It originates, for instance, from the design of filter networks. We present a global search strategy that allows for moving from one local minimizer to a better one. The efficiency of this strategy is illustrated by results of numerical experiments performed for some problems related to the design of filter networks.
|
|
| 2. |
- Andersson, Mats, et al.
(author)
-
Global Search Strategies for Solving Multilinear Least-squares Problems
- 2011
-
Reports (other academic/artistic)abstract
- The multilinear least-squares (MLLS) problem is an extension of the linear least-squares problem. The difference is that a multilinearoperator is used in place of a matrix-vector product. The MLLS istypically a large-scale problem characterized by a large number of local minimizers. It originates, for instance, from the design of filter networks. We present a global search strategy that allows formoving from one local minimizer to a better one. The efficiencyof this strategy isillustrated by results of numerical experiments performed forsome problems related to the design of filter networks.
|
|
| 3. |
- Andersson, Mats, et al.
(author)
-
Sparsity Optimization in Design of Multidimensional Filter Networks
- 2013
-
Reports (other academic/artistic)abstract
- Filter networks is a powerful tool used for reducing the image processing time, while maintaining its reasonably high quality.They are composed of sparse sub-filters whose low sparsity ensures fast image processing.The filter network design is related to solvinga sparse optimization problem where a cardinality constraint bounds above the sparsity level.In the case of sequentially connected sub-filters, which is the simplest network structure of those considered in this paper, a cardinality-constrained multilinear least-squares (MLLS) problem is to be solved. If to disregard the cardinality constraint, the MLLS is typically a large-scale problem characterized by a large number of local minimizers. Each of the local minimizers is singular and non-isolated.The cardinality constraint makes the problem even more difficult to solve.An approach for approximately solving the cardinality-constrained MLLS problem is presented.It is then applied to solving a bi-criteria optimization problem in which both thetime and quality of image processing are optimized. The developed approach is extended to designing filter networks of a more general structure. Its efficiency is demonstrated by designing certain 2D and 3D filter networks. It is also compared with the existing approaches.
|
|
| 4. |
- Andersson, Mats, et al.
(author)
-
Sparsity Optimization in Design of Multidimensional Filter Networks
- 2015
-
In: Optimization and Engineering. - : Springer. - 1389-4420 .- 1573-2924. ; 16:2, s. 259-277
-
Journal article (peer-reviewed)abstract
- Filter networks are used as a powerful tool used for reducing the image processing time and maintaining high image quality.They are composed of sparse sub-filters whose high sparsity ensures fast image processing.The filter network design is related to solvinga sparse optimization problem where a cardinality constraint bounds above the sparsity level.In the case of sequentially connected sub-filters, which is the simplest network structure of those considered in this paper, a cardinality-constrained multilinear least-squares (MLLS) problem is to be solved. Even when disregarding the cardinality constraint, the MLLS is typically a large-scale problem characterized by a large number of local minimizers, each of which is singular and non-isolated.The cardinality constraint makes the problem even more difficult to solve.An approach for approximately solving the cardinality-constrained MLLS problem is presented.It is then applied to solving a bi-criteria optimization problem in which both thetime and quality of image processing are optimized. The developed approach is extended to designing filter networks of a more general structure. Its efficiency is demonstrated by designing certain 2D and 3D filter networks. It is also compared with the existing approaches.
|
|
| 5. |
- Burdakov, Oleg, 1953-, et al.
(author)
-
On Efficiently Combining Limited-Memory and Trust-Region Techniques
- 2017
-
In: Mathematical Programming Computation. - : Springer. - 1867-2949 .- 1867-2957. ; 9:1, s. 101-134
-
Journal article (peer-reviewed)abstract
- Limited-memory quasi-Newton methods and trust-region methods represent two efficient approaches used for solving unconstrained optimization problems. A straightforward combination of them deteriorates the efficiency of the former approach, especially in the case of large-scale problems. For this reason, the limited-memory methods are usually combined with a line search. We show how to efficiently combine limited-memory and trust-region techniques. One of our approaches is based on the eigenvalue decomposition of the limited-memory quasi-Newton approximation of the Hessian matrix. The decomposition allows for finding a nearly-exact solution to the trust-region subproblem defined by the Euclidean norm with an insignificant computational overhead as compared with the cost of computing the quasi-Newton direction in line-search limited-memory methods. The other approach is based on two new eigenvalue-based norms. The advantage of the new norms is that the trust-region subproblem is separable and each of the smaller subproblems is easy to solve. We show that our eigenvalue-based limited-memory trust-region methods are globally convergent. Moreover, we propose improved versions of the existing limited-memory trust-region algorithms. The presented results of numerical experiments demonstrate the efficiency of our approach which is competitive with line-search versions of the L-BFGS method.
|
|
| 6. |
- Burdakov, Oleg, 1953-, et al.
(author)
-
On Efficiently Combining Limited Memory and Trust-Region Techniques
- 2013
-
Reports (other academic/artistic)abstract
- Limited memory quasi-Newton methods and trust-region methods represent two efficient approaches used for solving unconstrained optimization problems. A straightforward combination of them deteriorates the efficiency of the former approach, especially in the case of large-scale problems. For this reason, the limited memory methods are usually combined with a line search. We show how to efficiently combine limited memory and trust-region techniques. One of our approaches is based on the eigenvalue decomposition of the limited memory quasi-Newton approximation of the Hessian matrix. The decomposition allows for finding a nearly-exact solution to the trust-region subproblem defined by the Euclidean norm with an insignificant computational overhead compared with the cost of computing the quasi-Newton direction in line-search limited memory methods. The other approach is based on two new eigenvalue-based norms. The advantage of the new norms is that the trust-region subproblem is separable and each of the smaller subproblems is easy to solve. We show that our eigenvalue-based limited-memory trust-region methods are globally convergent. Moreover, we propose improved versions of the existing limited-memory trust-region algorithms. The presented results of numerical experiments demonstrate the efficiency of our approach which is competitive with line-search versions of the L-BFGS method.
|
|
| 7. |
- Camsund, Daniel, 1980-, et al.
(author)
-
Time-resolved imaging-based CRISPRi screening
- 2020
-
In: Nature Methods. - : NATURE PUBLISHING GROUP. - 1548-7091 .- 1548-7105. ; 17:1, s. 86-92
-
Journal article (peer-reviewed)abstract
- DuMPLING (dynamic mu-fluidic microscopy phenotyping of a library before in situ genotyping) enables screening of dynamic phenotypes in strain libraries and was used here to study genes that coordinate replication and cell division in Escherichia coli. Our ability to connect genotypic variation to biologically important phenotypes has been seriously limited by the gap between live-cell microscopy and library-scale genomic engineering. Here, we show how in situ genotyping of a library of strains after time-lapse imaging in a microfluidic device overcomes this problem. We determine how 235 different CRISPR interference knockdowns impact the coordination of the replication and division cycles of Escherichia coli by monitoring the location of replication forks throughout on average >500 cell cycles per knockdown. Subsequent in situ genotyping allows us to map each phenotype distribution to a specific genetic perturbation to determine which genes are important for cell cycle control. The single-cell time-resolved assay allows us to determine the distribution of single-cell growth rates, cell division sizes and replication initiation volumes. The technology presented in this study enables genome-scale screens of most live-cell microscopy assays.
|
|
| 8. |
|
|
| 9. |
- Lüking, Malin, et al.
(author)
-
Molecular Origins of Kinetics and Selectivity in the lac operon
-
Other publication (other academic/artistic)abstract
- We address the question of specificity in protein-DNA interactions using the E. colitranscription factor LacI as an example. Switching between two conformations, one fornon-specific, transient and another for specific, long-lived interaction with DNA, has beensuggested to help DNA-binding proteins solve the conflict between fast search andstable, specific binding. We tested this idea by changing the ability of LacI to switchconformations. We used molecular simulation to select LacI variants with altered flexibilityin the region that is involved in LacI’s conformational change, the hinge helix. We thenused fluorescent microscopy to study the wild-type LacI and LacI variants when binding tonon-operator and operator-DNA in vivo. In fact, LacI with a more flexible hinge helix is aweaker binder that exhibits less off-target site binding. A more stable helix, in contrast,enhances the formation of long-lived protein-DNA complexes also with non-operatorDNA. We examined the effects of two allosteric factors of LacI, the inducer IPTG, whichreduces DNA affinity, and the ligand ONPG, which enhances DNA binding according toour finding. We found that wild-type LacI is optimised for high stability of the specificcomplex and sensitivity to induction.
|
|
| 10. |
- Marklund, Emil, et al.
(author)
-
Sequence specificity in DNA binding is mainly governed by association
- 2022
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6579, s. 442-445
-
Journal article (peer-reviewed)abstract
- Sequence-specific binding of proteins to DNA is essential for accessing genetic information. We derive a model that predicts an anticorrelation between the macroscopic association and dissociation rates of DNA binding proteins. We tested the model for thousands of different lac operator sequences with a protein binding microarray and by observing kinetics for individual lac repressor molecules in single-molecule experiments. We found that sequence specificity is mainly governed by the efficiency with which the protein recognizes different targets. The variation in probability of recognizing different targets is at least 1.7 times as large as the variation in microscopic dissociation rates. Modulating the rate of binding instead of the rate of dissociation effectively reduces the risk of the protein being retained on nontarget sequences while searching.
|
|
