493 research outputs found

    A Semidefinite Approach for Truncated K-Moment Problems

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    A truncated moment sequence (tms) of degree d is a vector indexed by monomials whose degree is at most d. Let K be a semialgebraic set.The truncated K-moment problem (TKMP) is: when does a tms y admit a positive Borel measure supported? This paper proposes a semidefinite programming (SDP) approach for solving TKMP. When K is compact, we get the following results: whether a tms y of degree d admits a K-measure or notcan be checked via solving a sequence of SDP problems; when y admits no K-measure, a certificate will be given; when y admits a K-measure, a representing measure for y would be obtained from solving the SDP under some necessary and some sufficient conditions. Moreover, we also propose a practical SDP method for finding flat extensions, which in our numerical experiments always finds a finitely atomic representing measure for a tms when it admits one

    Interactions and Tradeoffs Between Cell Recruitment, Proliferation, and Differentiation Affect CNS Regeneration

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    AbstractRegeneration of central nervous system (CNS) lesions requires movement of progenitor cells and production of their differentiated progeny. Although damage to the CNS clearly promotes these two processes, the interplay between these complex events and how it affects a response remains elusive. Here, we use spatial stochastic modeling to show that tradeoffs arise between production and recruitment during regeneration. Proper spatial control of cell cycle timing can mitigate these tradeoffs, maximizing recruitment, improving infiltration into the lesion, and reducing wasteful production outside of it. Feedback regulation of cell lineage dynamics alone however leads to spatial defects in cell recruitment, suggesting a novel, to our knowledge, hypothesis for the aggregation of cells to the periphery of a lesion in multiple sclerosis. Interestingly, stronger chemotaxis does not correct this aggregation and instead, substantial random cell motions near the site of the lesion are required to improve CNS regeneration

    The Interplay between Wnt Mediated Expansion and Negative Regulation of Growth Promotes Robust Intestinal Crypt Structure and Homeostasis

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    The epithelium of the small intestinal crypt, which has a vital role in protecting the underlying tissue from the harsh intestinal environment, is completely renewed every 4–5 days by a small pool of stem cells at the base of each crypt. How is this renewal controlled and homeostasis maintained, particularly given the rapid nature of this process? Here, based on the recent observations from in vitro “mini gut” studies, we use a hybrid stochastic model of the crypt to investigate how exogenous niche signaling (from Wnt and BMP) combines with auto-regulation to promote homeostasis. This model builds on the sub-cellular element method to account for the three-dimensional structure of the crypt, external regulation by Wnt and BMP, internal regulation by Notch signaling, as well as regulation by internally generated diffusible signals. Results show that Paneth cell derived Wnt signals, which have been observed experimentally to sustain crypts in cultured organs, have a dramatically different influence on niche dynamics than does mesenchyme derived Wnt. While this signaling can indeed act as a redundant backup to the exogenous gradient, it introduces a positive feedback that destabilizes the niche and causes its uncontrolled expansion. We find that in this setting, BMP has a critical role in constraining this expansion, consistent with observations that its removal leads to crypt fission. Further results also point to a new hypothesis for the role of Ephrin mediated motility of Paneth cells, specifically that it is required to constrain niche expansion and maintain the crypt’s spatial structure. Combined, these provide an alternative view of crypt homeostasis where the niche is in a constant state of expansion and the spatial structure of the crypt arises as a balance between this expansion and the action of various sources of negative regulation that hold it in check

    The Impact of Female Leadership in Collegial Courts on Time to Render Merits Decisions: Evidence from the Norwegian Supreme Court

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    What is the effect of gender on the deliberative process of judging? Drawing on previous research on female leaders’ inclination to foster a more inclusive and collaborative decision-making process, we argue that decision making takes more time in a collegial court when female justices preside over decisional panels. Analyzing an original data set on cases decided by the Norwegian Supreme Court between 2008 and 2019, we find that when a woman is the presiding justice, the duration of case disposition time increases. This effect, however, persists for only eight days. Our finding suggests that institutional practices take effect over gendered effects.publishedVersio

    Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.

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    The fusion of digits or toes, syndactyly, can be part of complex syndromes, including van der Woude syndrome. A subset of van der Woude cases is caused by dominant-negative mutations in the epithelial transcription factor Grainyhead like-3 (GRHL3), and Grhl3-/-mice have soft-tissue syndactyly. Although impaired interdigital cell death of mesenchymal cells causes syndactyly in multiple genetic mutants, Grhl3-/- embryos had normal interdigital cell death, suggesting alternative mechanisms for syndactyly. We found that in digit separation, the overlying epidermis forms a migrating interdigital epithelial tongue (IET) when the epithelium invaginates to separate the digits. Normally, the non-adhesive surface periderm allows the IET to bifurcate as the digits separate. In contrast, in Grhl3-/- embryos, the IET moves normally between the digits but fails to bifurcate because of abnormal adhesion of the periderm. Our study identifies epidermal developmental processes required for digit separation

    Evaluation of Gene Association Methods for Coexpression Network Construction and Biological Knowledge Discovery

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    Background Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. Methods and Results In this study, we compared eight gene association methods – Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding\u27s D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson – and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. Conclusions We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction
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