675 research outputs found
Statistical Inference in a Directed Network Model with Covariates
Networks are often characterized by node heterogeneity for which nodes
exhibit different degrees of interaction and link homophily for which nodes
sharing common features tend to associate with each other. In this paper, we
propose a new directed network model to capture the former via node-specific
parametrization and the latter by incorporating covariates. In particular, this
model quantifies the extent of heterogeneity in terms of outgoingness and
incomingness of each node by different parameters, thus allowing the number of
heterogeneity parameters to be twice the number of nodes. We study the maximum
likelihood estimation of the model and establish the uniform consistency and
asymptotic normality of the resulting estimators. Numerical studies demonstrate
our theoretical findings and a data analysis confirms the usefulness of our
model.Comment: 29 pages. minor revisio
SUMO chain-induced dimerization activates RNF4
Dimeric RING E3 ligases interact with protein substrates and conformationally restrain the ubiquitin-E2-conjugating enzyme thioester complex such that it is primed for catalysis. RNF4 is an E3 ligase containing an N-terminal domain that binds its polySUMO substrates and a C-terminal RING domain responsible for dimerization. To investigate how RNF4 activity is controlled, we increased polySUMO substrate concentration by ablating expression of SUMO protease SENP6. Accumulation of SUMO chains in vivo leads to ubiquitin-mediated proteolysis of RNF4. In vitro we demonstrate that at concentrations equivalent to those found in vivo RNF4 is predominantly monomeric and inactive as an ubiquitin E3 ligase. However, in the presence of SUMO chains, RNF4 is activated by dimerization, leading to both substrate ubiquitylation and autoubiquitylation, responsible for degradation of RNF4. Thus the ubiquitin E3 ligase activity of RNF4 is directly linked to the availability of its polySUMO substrates
N-Cadherin Expression Level Distinguishes Reserved versus Primed States of Hematopoietic Stem Cells
SummaryOsteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherinhi) are not stem cells, being largely devoid of a Lineage−Sca1+cKit+ population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherinint) or low (N-cadherinlo) levels. The minority N-cadherinlo population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherinint population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherinint cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations
Nuclear dependence of the transverse-single-spin asymmetry for forward neutron production in polarized collisions at GeV
During 2015 the Relativistic Heavy Ion Collider (RHIC) provided collisions of
transversely polarized protons with Au and Al nuclei for the first time,
enabling the exploration of transverse-single-spin asymmetries with heavy
nuclei. Large single-spin asymmetries in very forward neutron production have
been previously observed in transversely polarized collisions at
RHIC, and the existing theoretical framework that was successful in describing
the single-spin asymmetry in collisions predicts only a moderate
atomic-mass-number () dependence. In contrast, the asymmetries observed at
RHIC in collisions showed a surprisingly strong dependence in
inclusive forward neutron production. The observed asymmetry in Al
collisions is much smaller, while the asymmetry in Au collisions is a
factor of three larger in absolute value and of opposite sign. The interplay of
different neutron production mechanisms is discussed as a possible explanation
of the observed dependence.Comment: 315 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for
publication in Phys. Rev. Lett. Plain text data tables for the points plotted
in figures for this and previous PHENIX publications are (or will be)
publicly available at http://www.phenix.bnl.gov/papers.htm
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