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

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

Investigation of a generalized Obukhov Model for Turbulence

We introduce a generalization of Obukhov's model [A.M. Obukhov, Adv. Geophys. 6, 113 (1959)] for the description of the joint position-velocity statistics of a single fluid particle in fully developed turbulence. In the presented model the velocity is assumed to undergo a continuous time random walk. This takes into account long time correlations. As a consequence the evolution equation for the joint position-velocity probability distribution is a Fokker-Planck equation with a fractional time derivative. We determine the solution of this equation in the form of an integral transform and derive a relation for arbitrary single time moments. Analytical solutions for the joint probability distribution and its moments are given.Comment: 10 page

Legal determinants of external finance revisited : the inverse relationship between investor protection and societal well-being

This paper investigates relationships between corporate governance traditions and quality of life as measured by a number of widely reported indicators. It provides an empirical analysis of indicators of societal health in developed economies using a classification based on legal traditions. Arguably the most widely cited work in the corporate governance literature has been the collection of papers by La Porta et al. which has shown, inter alia, statistically significant relationships between legal traditions and various proxies for investor protection. We show statistically significant relationships between legal traditions and various proxies for societal health. Our comparative evidence suggests that the interests of investors may not be congruent with the interests of wider society, and that the criteria for judging the effectiveness of approaches to corporate governance should not be restricted to financial metrics

Mechanical Properties of Growing Melanocytic Nevi and the Progression to Melanoma

Melanocytic nevi are benign proliferations that sometimes turn into malignant melanoma in a way that is still unclear from the biochemical and genetic point of view. Diagnostic and prognostic tools are then mostly based on dermoscopic examination and morphological analysis of histological tissues. To investigate the role of mechanics and geometry in the morpholgical dynamics of melanocytic nevi, we study a computation model for cell proliferation in a layered non-linear elastic tissue. Numerical simulations suggest that the morphology of the nevus is correlated to the initial location of the proliferating cell starting the growth process and to the mechanical properties of the tissue. Our results also support that melanocytes are subject to compressive stresses that fluctuate widely in the nevus and depend on the growth stage. Numerical simulations of cells in the epidermis releasing matrix metalloproteinases display an accelerated invasion of the dermis by destroying the basal membrane. Moreover, we suggest experimentally that osmotic stress and collagen inhibit growth in primary melanoma cells while the effect is much weaker in metastatic cells. Knowing that morphological features of nevi might also reflect geometry and mechanics rather than malignancy could be relevant for diagnostic purpose

The Future is Now

No abstract available DOI: http://dx.doi.org/10.5564/mjia.v0i5.361 The Mongolian Journal of International Affairs; Number 5, 1998, Pages 3-1