| 1. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Doll, Jim, et al.
(författare)
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Thermodynamic integration methods, infinite swapping and the calculation of generalized averages
- 2017
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- In the present paper we examine the risk-sensitive and sampling issues associated with the problem of calculating generalized averages. By combining thermodynamic integration and Stationary Phase Monte Carlo techniques, we develop an approach for such problems and explore its utility for a prototypical class of applications.
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| 3. |
- Budhiraja, Amarjit, et al.
(författare)
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Quasistationary distributions and ergodic control problems
- 2022
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Ingår i: Stochastic Processes and their Applications. - : Elsevier BV. - 0304-4149 .- 1879-209X. ; 145, s. 143-164
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Tidskriftsartikel (refereegranskat)abstract
- We introduce and study the basic properties of two ergodic stochastic control problems associated with the quasistationary distribution (QSD) of a diffusion process X relative to a bounded domain. The two problems are in some sense dual, with one defined in terms of the generator associated with X and the other in terms of its adjoint. Besides proving wellposedness of the associated Hamilton-Jacobi- Bellman equations, we describe how they can be used to characterize important properties of the QSD. Of particular note is that the QSD itself can be identified, up to normalization, in terms of the cost potential of the control problem associated with the adjoint.
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| 4. |
- Doll, Jim, et al.
(författare)
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A large deviation analysis of certain qualitative properties of parallel tempering and infinite swapping algorithms
- 2018
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Ingår i: Applied mathematics and optimization. - : Springer. - 0095-4616 .- 1432-0606. ; 78:1, s. 103-144
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Tidskriftsartikel (refereegranskat)abstract
- Parallel tempering, or replica exchange, is a popular method for simulating complex systems. The idea is to run parallel simulations at different temperatures, and at a given swap rate exchange configurations between the parallel simulations. From the perspective of large deviations it is optimal to let the swap rate tend to infinity and it is possible to construct a corresponding simulation scheme, known as infinite swapping. In this paper we propose a novel use of large deviations for empirical measures for a more detailed analysis of the infinite swapping limit in the setting of continuous time jump Markov processes. Using the large deviations rate function and associated stochastic control problems we consider a diagnostic based on temperature assignments, which can be easily computed during a simulation. We show that the convergence of this diagnostic to its a priori known limit is a necessary condition for the convergence of infinite swapping. The rate function is also used to investigate the impact of asymmetries in the underlying potential landscape, and where in the state space poor sampling is most likely to occur.
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