16,019 research outputs found
Complexity in cancer stem cells and tumor evolution: towards precision medicine
In this review, we discuss recent advances on the plasticity of cancer stem
cells and highlight their relevance to understand the metastatic process and to
guide therapeutic interventions. Recent results suggest that the strict
hierarchical structure of cancer cell populations advocated by the cancer stem
cell model must be reconsidered since the depletion of cancer stem cells leads
the other tumor cells to switch back into the cancer stem cell phenotype. This
plasticity has important implications for metastasis since migrating cells do
not need to be cancer stem cells in order to seed a metastasis. We also discuss
the important role of the immune system and the microenvironment in modulating
phenotypic switching and suggest possible avenues to exploit our understanding
of this process to develop an effective strategy for precision medicine.Comment: 2 Figures, to appear in Seminars in Cancer Biology, Available online
23 February 201
The Laplace-Jaynes approach to induction
An approach to induction is presented, based on the idea of analysing the
context of a given problem into `circumstances'. This approach, fully Bayesian
in form and meaning, provides a complement or in some cases an alternative to
that based on de Finetti's representation theorem and on the notion of infinite
exchangeability. In particular, it gives an alternative interpretation of those
formulae that apparently involve `unknown probabilities' or `propensities'.
Various advantages and applications of the presented approach are discussed,
especially in comparison to that based on exchangeability. Generalisations are
also discussed.Comment: 38 pages, 1 figure. V2: altered discussion on some points, corrected
typos, added reference
Numerical Bayesian state assignment for a three-level quantum system. I. Absolute-frequency data; constant and Gaussian-like priors
This paper offers examples of concrete numerical applications of Bayesian
quantum-state-assignment methods to a three-level quantum system. The
statistical operator assigned on the evidence of various measurement data and
kinds of prior knowledge is computed partly analytically, partly through
numerical integration (in eight dimensions) on a computer. The measurement data
consist in absolute frequencies of the outcomes of N identical von Neumann
projective measurements performed on N identically prepared three-level
systems. Various small values of N as well as the large-N limit are considered.
Two kinds of prior knowledge are used: one represented by a plausibility
distribution constant in respect of the convex structure of the set of
statistical operators; the other represented by a Gaussian-like distribution
centred on a pure statistical operator, and thus reflecting a situation in
which one has useful prior knowledge about the likely preparation of the
system.
In a companion paper the case of measurement data consisting in average
values, and an additional prior studied by Slater, are considered.Comment: 23 pages, 14 figures. V2: Added an important note concerning
cylindrical algebraic decomposition and thanks to P B Slater, corrected some
typos, added reference
Numerical Bayesian quantum-state assignment for a three-level quantum system. II. Average-value data with a constant, a Gaussian-like, and a Slater prior
This paper offers examples of concrete numerical applications of Bayesian
quantum-state assignment methods to a three-level quantum system. The
statistical operator assigned on the evidence of various measurement data and
kinds of prior knowledge is computed partly analytically, partly through
numerical integration (in eight dimensions) on a computer. The measurement data
consist in the average of outcome values of N identical von Neumann projective
measurements performed on N identically prepared three-level systems. In
particular the large-N limit will be considered. Three kinds of prior knowledge
are used: one represented by a plausibility distribution constant in respect of
the convex structure of the set of statistical operators; another one
represented by a prior studied by Slater, which has been proposed as the
natural measure on the set of statistical operators; the last prior is
represented by a Gaussian-like distribution centred on a pure statistical
operator, and thus reflecting a situation in which one has useful prior
knowledge about the likely preparation of the system. The assigned statistical
operators obtained with the first two kinds of priors are compared with the one
obtained by Jaynes' maximum entropy method for the same measurement situation.
In the companion paper the case of measurement data consisting in absolute
frequencies is considered.Comment: 10 pages, 4 figures. V2: added "Post scriptum" under Conclusions,
slightly changed Acknowledgements, and corrected some spelling error
What Moves the Discount on Country Equity Funds?
The paper characterizes several empirical regularities of closed- end fund prices and examines the extent to which a 'sentiment' model of asset prices is consistent with the empirical regularities. We find that after controlling for the effect of cross-border investment restrictions, country funds trade at an average discount. Discounts vary substantially and contribute to a variance in country fund weekly returns which is generally three times greater than the returns on the net asset value (NAV). Regression analysis suggests that discounts have predictive power for fund returns but not for NAV returns, suggesting that investor 'sentiment' is a component of the price of a fund and not its NAV. Estimation of an unobserved components model on the discounts of the funds reveals a significant and strongly persistent common component across fund discounts. Regressions of fund and NAV returns on financial variables reveal that fund prices are 'sticky' with respect to movements in the host country's stock market and overly sensitive to variation in the U.S. and world stock markets. This relation is unaffected when we consider separately funds whose host countries restrict cross-border investment and funds which invest in emerging stock markets.
Protein accumulation in the endoplasmic reticulum as a non-equilibrium phase transition
Several neurological disorders are associated with the aggregation of
aberrant proteins, often localized in intracellular organelles such as the
endoplasmic reticulum. Here we study protein aggregation kinetics by mean-field
reactions and three dimensional Monte carlo simulations of diffusion-limited
aggregation of linear polymers in a confined space, representing the
endoplasmic reticulum. By tuning the rates of protein production and
degradation, we show that the system undergoes a non-equilibrium phase
transition from a physiological phase with little or no polymer accumulation to
a pathological phase characterized by persistent polymerization. A combination
of external factors accumulating during the lifetime of a patient can thus
slightly modify the phase transition control parameters, tipping the balance
from a long symptomless lag phase to an accelerated pathological development.
The model can be successfully used to interpret experimental data on
amyloid-\b{eta} clearance from the central nervous system
Conformational mechanism for the stability of microtubule-kinetochore attachments
Regulating the stability of microtubule(MT)-kinetochore attachments is
fundamental to avoiding mitotic errors and ensure proper chromosome segregation
during cell division. While biochemical factors involved in this process have
been identified, its mechanics still needs to be better understood. Here we
introduce and simulate a mechanical model of MT-kinetochore interactions in
which the stability of the attachment is ruled by the geometrical conformations
of curling MT-protofilaments entangled in kinetochore fibrils. The model allows
us to reproduce with good accuracy in vitro experimental measurements of the
detachment times of yeast kinetochores from MTs under external pulling forces.
Numerical simulations suggest that geometrical features of MT-protofilaments
may play an important role in the switch between stable and unstable
attachments
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