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| 2. |
- Lee, Hyun-Seob, et al.
(författare)
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Foxa2 and Nurr1 Synergistically Yield A9 Nigral Dopamine Neurons Exhibiting Improved Differentiation, Function, and Cell Survival
- 2010
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 28:3, s. 501-512
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Tidskriftsartikel (refereegranskat)abstract
- Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs) is prerequisite for precursor/stem cell-based therapy of Parkinson's disease (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription factor that can drive DA neuron differentiation from non-dopaminergic NPCs in vitro. However, Nurr1 alone neither induces full neuronal maturation nor expression of proteins found specifically in midbrain DA neurons. In addition, Nurr1 expression is inefficient in inducing DA phenotype expression in NPCs derived from certain species such as mouse and human. We show here that Foxa2, a forkhead transcription factor whose role in midbrain DA neuron development was recently revealed, synergistically cooperates with Nurr1 to induce DA phenotype acquisition, midbrain-specific gene expression, and neuronal maturation. Thus, the combinatorial expression of Nurr1 and Foxa2 in NPCs efficiently yielded fully differentiated nigral (A9)-type midbrain neurons with clearly detectable DA neuronal activities. The effects of Foxa2 in DA neuron generation were observed regardless of the brain regions or species from which NPCs were derived. Furthermore, DA neurons generated by ectopic Foxa2 expression were more resistant to toxins. Importantly, Foxa2 expression resulted in a rapid cell cycle exit and reduced cell proliferation. Consistently, transplantation of NPCs transduced with Nurr1 and Foxa2 generated grafts enriched with midbrain-type DA neurons but reduced number of proliferating cells, and significantly reversed motor deficits in a rat PD model. Our findings can be applied to ongoing attempts to develop an efficient and safe precursor/stem cell-based therapy for PD. STEM CELLS 2010; 28: 501-512
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| 3. |
- Lee, Sang Hoon, et al.
(författare)
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Mapping the spectrum of 3D communities in human chromosome conformation capture data
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Several experiments show that the three dimensional (3D) organization of chromosomes affects genetic processes such as transcription and gene regulation. To better understand this connection, researchers developed the Hi-C method that is able to detect the pairwise physical contacts of all chromosomal loci. The Hi-C data show that chromosomes are composed of 3D compartments that range over a variety of scales. However, it is challenging to systematically detect these cross-scale structures. Most studies have therefore designed methods for specific scales to study foremost topologically associated domains (TADs) and A/B compartments. To go beyond this limitation, we tailor a network community detection method that finds communities in compact fractal globule polymer systems. Our method allows us to continuously scan through all scales with a single resolution parameter. We found: (i) polymer segments belonging to the same 3D community do not have to be in consecutive order along the polymer chain. In other words, several TADs may belong to the same 3D community. (ii) CTCF proteins-a loop-stabilizing protein that is ascribed a big role in TAD formation-are well correlated with community borders only at one level of organization. (iii) TADs and A/B compartments are traditionally treated as two weakly related 3D structures and detected with different algorithms. With our method, we detect both by simply adjusting the resolution parameter. We therefore argue that they represent two specific levels of a continuous spectrum 3D communities, rather than seeing them as different structural entities.
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| 4. |
- Lee, Sang Hoon, 1982-, et al.
(författare)
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Phase-shift inversion in oscillator systems with periodically switching couplings
- 2012
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Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - : American Physical Society. - 1539-3755 .- 1550-2376. ; 85:2, s. 027202-
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Tidskriftsartikel (refereegranskat)abstract
- A system's response to external periodic changes can provide crucial information about its dynamical properties. We investigate the synchronization transition, an archetypical example of a dynamic phase transition, in the framework of such a temporal response. The Kuramoto model under periodically switching interactions has the same type of phase transition as the original mean-field model. Furthermore, we see that the signature of the synchronization transition appears in the relative delay of the order parameter with respect to the phase of oscillating interactions as well. Specifically, the phase shift becomes significantly larger as the system gets closer to the phase transition, so that the order parameter at the minimum interaction density can even be larger than that at the maximum interaction density, counterintuitively. We argue that this phase-shift inversion is caused by the diverging relaxation time, in a similar way to the resonance near the critical point in the kinetic Ising model. Our result, based on exhaustive simulations on globally coupled systems as well as scale-free networks, shows that an oscillator system's phase transition can be manifested in the temporal response to the topological dynamics of the underlying connection structure.
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| 5. |
- Wåhlin, Anna, 1970, et al.
(författare)
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Variability of Warm Deep Water Inflow in a Submarine Trough on the Amundsen Sea Shelf
- 2013
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Ingår i: Journal of Physical Oceanography. - 0022-3670 .- 1520-0485. ; 43:10, s. 2054-2070
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Tidskriftsartikel (refereegranskat)abstract
- The ice shelves in the Amundsen Sea are thinning rapidly, and the main reason for their decline appears to be warm ocean currents circulating below the ice shelves and melting these from below. Ocean currents transportwarm densewater ontothe shelf,channeledby bathymetric troughs leadingto the deep inner basins. A hydrographic mooring equipped with an upward-looking ADCP has been placed in one of these troughs on the central Amundsen shelf. The two years (2010/11) of mooring data are here used to characterize the inflow of warm deep water to the deep shelf basins. During both years, the warm layer thickness and temperature peaked in austral fall. The along-trough velocity is dominated by strong fluctuations that do not vary in the vertical. These fluctuations are correlated with the local wind, with eastward wind over the shelf and shelf break giving flow toward the ice shelves. In addition, there is a persistent flow of dense lower Circumpolar Deep Water (CDW) toward the ice shelves in the bottom layer. This bottom-intensified flow appears to be driven by buoyancy forces rather than the shelfbreak wind. The years of 2010 and 2011 were characterized by a comparatively stationary Amundsen Sea low, and hence there were no strong eastward winds during winter that could drive an upwelling of warm water along the shelf break. Regardless of this, there was a persistent flow of lower CDW in the bottom layer during the two years. The average heat transport toward the ice shelves in the trough was estimated from the mooring data to be 0.95 TW.
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| 6. |
- Yu, Jung-Hoon, et al.
(författare)
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Structuring Poly(3,4-ethylenedioxythiophene) : Poly(styrenesulfonate) Towards Enhancing Hole Collection Efficiency
- 2014
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Ingår i: Journal of Nanoscience and Nanotechnology. - : American Scientific Publishers. - 1533-4880 .- 1533-4899. ; 14:12, s. 9489-9492
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Tidskriftsartikel (refereegranskat)abstract
- To date, organic photovoltaic devices (OPVs) have obtained relatively low power conversion efficiency, mostly because of the low charge carrier mobility of the polymers to be used. This limits the optimal film thickness for efficient absorption of the solar spectrum. The capability of efficient charge carrier collections is a main factor for utilizing thick OPVs, consequently enhancing the power conversion efficiency. In this report, we demonstrate a facile approach for enhancing the hole carrier collection by possibly shortening the hole collection path via structuring poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), which is widely used as a hole collecting intermediate layer in OPVs. For structuring the PEDOT:PSS, the nanosphere lithographic method was used. Furthermore, the effects of the structuring of PEDOT:PSS on optical properties were also investigated.
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| 7. |
- Baek, Yongjoo, et al.
(författare)
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Market behavior and performance of different strategy evaluation schemes
- 2010
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Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - : American Physical Society. - 1063-651X .- 1095-3787. ; 82:026109
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Tidskriftsartikel (refereegranskat)abstract
- Strategy evaluation schemes are a crucial factor in any agent-based market model, as they determine the agents’ strategy preferences and consequently their behavioral pattern. This study investigates how the strategy evaluation schemes adopted by agents affect their performance in conjunction with the market circumstances. We observe the performance of three strategy evaluation schemes, the history-dependent wealth game, the trend-opposing minority game, and the trend-following majority game, in a stock market where the price is exogenously determined. The price is either directly adopted from the real stock market indices or generated with a Markov chain of order ≤2. Each scheme’s success is quantified by average wealth accumulated by the traders equipped with the scheme. The wealth game, as it learns from the history, shows relatively good performance unless the market is highly unpredictable. The majority game is successful in a trendy market dominated by long periods of sustained price increase or decrease. On the other hand, the minority game is suitable for a market with persistent zigzag price patterns. We also discuss the consequence of implementing finite memory in the scoring processes of strategies. Our findings suggest under which market circumstances each evaluation scheme is appropriate for modeling the behavior of real market traders.
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| 8. |
- Bernenko, Dolores, et al.
(författare)
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Exploring 3D community inconsistency in human chromosome contact networks
- 2023
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Ingår i: Journal of physics. Complexity. - : Institute of Physics (IOP). - 2632-072X. ; 4:3
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Researchers developed chromosome capture methods such as Hi-C to better understand DNA's 3D folding in nuclei. The Hi-C method captures contact frequencies between DNA segment pairs across the genome. When analyzing Hi-C data sets, it is common to group these pairs using standard bioinformatics methods (e.g., PCA). Other approaches handle Hi-C data as weighted networks, where connected node represent DNA segments in 3D proximity. In this representation, one can leverage community detection techniques developed in complex network theory to group nodes into mesoscale communities containing similar connection patterns. While there are several successful attempts to analyze Hi-C data in this way, it is common to report and study the most typical community structure. But in reality, there are often several valid candidates. Therefore, depending on algorithm design, different community detection methods focusing on slightly different connectivity features may have differing views on the ideal node groupings. In fact, even the same community detection method may yield different results if using a stochastic algorithm. This ambiguity is fundamental to community detection and shared by most complex networks whenever interactions span all scales in the network. This is known as community inconsistency. This paper explores this inconsistency of 3D communities in Hi-C data for all human chromosomes. We base our analysis on two inconsistency metrics, one local and one global, and quantify the network scales where the community separation is most variable. For example, we find that TADs are less reliable than A/B compartments and that nodes with highly variable node-community memberships are associated with open chromatin. Overall, our study provides a helpful framework for data-driven researchers and increases awareness of some inherent challenges when clustering Hi-C data into 3D communities.
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| 9. |
- Bernenko, Dolores, et al.
(författare)
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Mapping the semi-nested community structure of 3D chromosome contact networks
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Mammalian DNA folds into 3D structures that facilitate and regulate genetic processes such as transcription, DNA repair, and epigenetics. Several insights derive from chromosome capture methods, such as Hi-C, which allow researchers to construct contact maps depicting 3D interactions among all DNA segment pairs. These maps show a complex cross-scale organization spanning megabase-pair compartments to short-ranged DNA loops. To better understand the organizing principles, several groups analyzed Hi-C data assuming a Russian-doll-like nested hierarchy where DNA regions of similar sizes merge into larger and larger structures. Apart from being a simple and appealing description, this model explains, e.g., the omnipresent chequerboard pattern seen in Hi-C maps, known as A/B compartments, and foreshadows the co-localization of some functionally similar DNA regions. However, while successful, this model is incompatible with the two competing mechanisms that seem to shape a significant part of the chromosomes’ 3D organization: loop extrusion and phase separation. This paper aims to map out the chromosome’s actual folding hierarchy from empirical data. To this end, we take advantage of Hi-C experiments and treat the measured DNA-DNA interactions as a weighted network. From such a network, we extract 3D communities using the generalized Louvain algorithm. This algorithm has a resolution parameter that allows us to scan seamlessly through the community size spectrum, from A/B compartments to topologically associated domains (TADs). By constructing a hierarchical tree connecting these communities, we find that chromosomes are more complex than a perfect hierarchy. Analyzing how communities nest relative to a simple folding model, we found that chromosomes exhibit a significant portion of nested and non-nested community pairs alongside considerable randomness. In addition, by examining nesting and chromatin types, we discovered that nested parts are often associated with active chromatin. These results highlight that crossscale relationships will be essential components in models aiming to reach a deep understanding of the causal mechanisms of chromosome folding.
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| 10. |
- Bernenko, Dolores, et al.
(författare)
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Mapping the semi-nested community structure of 3D chromosome contact networks
- 2023
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Ingår i: PloS Computational Biology. - : Public Library of Science (PLoS). - 1553-734X .- 1553-7358. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian DNA folds into 3D structures that facilitate and regulate genetic processes such as transcription, DNA repair, and epigenetics. Several insights derive from chromosome capture methods, such as Hi-C, which allow researchers to construct contact maps depicting 3D interactions among all DNA segment pairs. These maps show a complex cross-scale organization spanning megabase-pair compartments to short-ranged DNA loops. To better understand the organizing principles, several groups analyzed Hi-C data assuming a Russian-doll-like nested hierarchy where DNA regions of similar sizes merge into larger and larger structures. Apart from being a simple and appealing description, this model explains, e.g., the omnipresent chequerboard pattern seen in Hi-C maps, known as A/B compartments, and foreshadows the co-localization of some functionally similar DNA regions. However, while successful, this model is incompatible with the two competing mechanisms that seem to shape a significant part of the chromosomes' 3D organization: loop extrusion and phase separation. This paper aims to map out the chromosome's actual folding hierarchy from empirical data. To this end, we take advantage of Hi-C experiments and treat the measured DNA-DNA interactions as a weighted network. From such a network, we extract 3D communities using the generalized Louvain algorithm. This algorithm has a resolution parameter that allows us to scan seamlessly through the community size spectrum, from A/B compartments to topologically associated domains (TADs). By constructing a hierarchical tree connecting these communities, we find that chromosomes are more complex than a perfect hierarchy. Analyzing how communities nest relative to a simple folding model, we found that chromosomes exhibit a significant portion of nested and non-nested community pairs alongside considerable randomness. In addition, by examining nesting and chromatin types, we discovered that nested parts are often associated with active chromatin. These results highlight that cross-scale relationships will be essential components in models aiming to reach a deep understanding of the causal mechanisms of chromosome folding.
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