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Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes.
Adult mammalian cardiomyocytes exit the cell cycle during the neonatal period, commensurate with the loss of regenerative capacity in adult mammalian hearts. We established conditions for long-term culture of adult mouse cardiomyocytes that are genetically labeled with fluorescence. This technique permits reliable analyses of proliferation of pre-existing cardiomyocytes without complications from cardiomyocyte marker expression loss due to dedifferentiation or significant contribution from cardiac progenitor cell expansion and differentiation in culture. Using this system, we took a candidate gene approach to screen for fetal-specific proliferative gene programs that can induce proliferation of adult mouse cardiomyocytes. Using pooled gene delivery and subtractive gene elimination, we identified a novel functional interaction between E2f Transcription Factor 2 (E2f2) and Brain Expressed X-Linked (Bex)/Transcription elongation factor A-like (Tceal) superfamily members Bex1 and Tceal8. Specifically, Bex1 and Tceal8 both preserved cell viability during E2f2-induced cell cycle re-entry. Although Tceal8 inhibited E2f2-induced S-phase re-entry, Bex1 facilitated DNA synthesis while inhibiting cell death. In sum, our study provides a valuable method for adult cardiomyocyte proliferation research and suggests that Bex family proteins may function in modulating cell proliferation and death decisions during cardiomyocyte development and maturation
The transition temperature of the dilute interacting Bose gas for internal degrees of freedom
We calculate explicitly the variation of the Bose-Einstein
condensation temperature induced by weak repulsive two-body interactions
to leading order in the interaction strength. As shown earlier by general
arguments, is linear in the dimensionless product
to leading order, where is the density and the scattering length. This
result is non-perturbative, and a direct perturbative calculation of the
amplitude is impossible due to infrared divergences familiar from the study of
the superfluid helium lambda transition. Therefore we introduce here another
standard expansion scheme, generalizing the initial model which depends on one
complex field to one depending on real fields, and calculating the
temperature shift at leading order for large . The result is explicit and
finite. The reliability of the result depends on the relevance of the large
expansion to the situation N=2, which can in principle be checked by systematic
higher order calculations. The large result agrees remarkably well with
recent numerical simulations.Comment: 10 pages, Revtex, submitted to Europhysics Letter
Private Matchings and Allocations
We consider a private variant of the classical allocation problem: given k
goods and n agents with individual, private valuation functions over bundles of
goods, how can we partition the goods amongst the agents to maximize social
welfare? An important special case is when each agent desires at most one good,
and specifies her (private) value for each good: in this case, the problem is
exactly the maximum-weight matching problem in a bipartite graph.
Private matching and allocation problems have not been considered in the
differential privacy literature, and for good reason: they are plainly
impossible to solve under differential privacy. Informally, the allocation must
match agents to their preferred goods in order to maximize social welfare, but
this preference is exactly what agents wish to hide. Therefore, we consider the
problem under the relaxed constraint of joint differential privacy: for any
agent i, no coalition of agents excluding i should be able to learn about the
valuation function of agent i. In this setting, the full allocation is no
longer published---instead, each agent is told what good to get. We first show
that with a small number of identical copies of each good, it is possible to
efficiently and accurately solve the maximum weight matching problem while
guaranteeing joint differential privacy. We then consider the more general
allocation problem, when bidder valuations satisfy the gross substitutes
condition. Finally, we prove that the allocation problem cannot be solved to
non-trivial accuracy under joint differential privacy without requiring
multiple copies of each type of good.Comment: Journal version published in SIAM Journal on Computation; an extended
abstract appeared in STOC 201
Live-Learn Cal Poly: A New-Urbanist Vision for a More Livable and Sustainable Campus
Universities across the nation have begun a mixed-use initiative in an effort to densify campuses and diversify retail and housing choices to increase student residency on campus. The movement to model the built environment after traditional mixed-use urbanism has been shown to improve capital flow within the local submarket on campus, foster flexible learning environments to support student success, and reduce automobile dependency. In order to reflect Cal Poly’s Master Plan moving forward, this report intends to follow the guiding principles outlined in the Master Plan while proposing sustainable and efficient land use designs to accommodate future growth at Cal Poly
Quantum phase transition in an atomic Bose gas near a Feshbach resonance
We study the quantum phase transition in an atomic Bose gas near a Feshbach
resonance in terms of the renormalization group. This quantum phase transition
is characterized by an Ising order parameter. We show that in the low
temperature regime where the quantum fluctuations dominate the low-energy
physics this phase transition is of first order because of the coupling between
the Ising order parameter and the Goldstone mode existing in the bosonic
superfluid. However, when the thermal fluctuations become important, the phase
transition turns into the second order one, which belongs to the
three-dimensional Ising universality class. We also calculate the damping rate
of the collective mode in the phase with only a molecular Bose-Einstein
condensate near the second-order transition line, which can serve as an
experimental signature of the second-order transition.Comment: 8 pages, 2 figures, published version in Phys. Rev.
FPT-Algorithms for the l-Matchoid Problem with Linear and Submodular Objectives
We design a fixed-parameter deterministic algorithm for computing a maximum
weight feasible set under a -matchoid of rank , parameterized by
and . Unlike previous work that presumes linear representativity of
matroids, we consider the general oracle model. Our result, combined with the
lower bounds of Lovasz, and Jensen and Korte, demonstrates a separation between
the -matchoid and the matroid -parity problems in the setting of
fixed-parameter tractability.
Our algorithms are obtained by means of kernelization: we construct a small
representative set which contains an optimal solution. Such a set gives us much
flexibility in adapting to other settings, allowing us to optimize not only a
linear function, but also several important submodular functions. It also helps
to transform our algorithms into streaming algorithms.
In the streaming setting, we show that we can find a feasible solution of
value and the number of elements to be stored in memory depends only on
and but totally independent of . This shows that it is possible to
circumvent the recent space lower bound of Feldman et al., by parameterizing
the solution value. This result, combined with existing lower bounds, also
provides a new separation between the space and time complexity of maximizing
an arbitrary submodular function and a coverage function in the value oracle
model
Typing tumors using pathways selected by somatic evolution.
Many recent efforts to analyze cancer genomes involve aggregation of mutations within reference maps of molecular pathways and protein networks. Here, we find these pathway studies are impeded by molecular interactions that are functionally irrelevant to cancer or the patient's tumor type, as these interactions diminish the contrast of driver pathways relative to individual frequently mutated genes. This problem can be addressed by creating stringent tumor-specific networks of biophysical protein interactions, identified by signatures of epistatic selection during tumor evolution. Using such an evolutionarily selected pathway (ESP) map, we analyze the major cancer genome atlases to derive a hierarchical classification of tumor subtypes linked to characteristic mutated pathways. These pathways are clinically prognostic and predictive, including the TP53-AXIN-ARHGEF17 combination in liver and CYLC2-STK11-STK11IP in lung cancer, which we validate in independent cohorts. This ESP framework substantially improves the definition of cancer pathways and subtypes from tumor genome data
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