Tumor dormancy: EMT beyond invasion and metastasis.

More than two-thirds of cancer-related deaths are attributable to metastases. In some tumor types metastasis can occur up to 20 years after diagnosis and successful treatment of the primary tumor, a phenomenon termed late recurrence. Metastases arise from disseminated tumor cells (DTCs) that leave the primary tumor early on in tumor development, either as single cells or clusters, adapt to new environments, and reduce or shut down their proliferation entering a state of dormancy for prolonged periods of time. Dormancy has been difficult to track clinically and study experimentally. Recent advances in technology and disease modeling have provided new insights into the molecular mechanisms orchestrating dormancy and the switch to a proliferative state. A new role for epithelial-mesenchymal transition (EMT) in inducing plasticity and maintaining a dormant state in several cancer models has been revealed. In this review, we summarize the major findings linking EMT to dormancy control and highlight the importance of pre-clinical models and tumor/tissue context when designing studies. Understanding of the cellular and molecular mechanisms controlling dormant DTCs is pivotal in developing new therapeutic agents that prevent distant recurrence by maintaining a dormant state

Assortment optimisation under a general discrete choice model: A tight analysis of revenue-ordered assortments

The assortment problem in revenue management is the problem of deciding which subset of products to offer to consumers in order to maximise revenue. A simple and natural strategy is to select the best assortment out of all those that are constructed by fixing a threshold revenue $\pi$ and then choosing all products with revenue at least $\pi$. This is known as the revenue-ordered assortments strategy. In this paper we study the approximation guarantees provided by revenue-ordered assortments when customers are rational in the following sense: the probability of selecting a specific product from the set being offered cannot increase if the set is enlarged. This rationality assumption, known as regularity, is satisfied by almost all discrete choice models considered in the revenue management and choice theory literature, and in particular by random utility models. The bounds we obtain are tight and improve on recent results in that direction, such as for the Mixed Multinomial Logit model by Rusmevichientong et al. (2014). An appealing feature of our analysis is its simplicity, as it relies only on the regularity condition. We also draw a connection between assortment optimisation and two pricing problems called unit demand envy-free pricing and Stackelberg minimum spanning tree: These problems can be restated as assortment problems under discrete choice models satisfying the regularity condition, and moreover revenue-ordered assortments correspond then to the well-studied uniform pricing heuristic. When specialised to that setting, the general bounds we establish for revenue-ordered assortments match and unify the best known results on uniform pricing.Comment: Minor changes following referees' comment

Skill competency development strategies by a contractor

Construction skills are one of the vital aspects of construction work which is growing in importance due to skill gaps and skill shortages during different economic cycles. The aim of this study was to investigate competence development strategies by a traditional construction company within its own pool of skill resources and among its supply chain members. The study was carried out via literature review, empirical studies involving a focus study, analysis of documentary evidence supported by unstructured interviews and a report of skill development/supply chain conference. The study demonstrates how long-term skill development can be achieved through: (a) strategic capacity planning which allows high retention, continuous training, and balanced construction demand and contractor’s supply capacity over the long term; (b) updating and upgrading the knowledge base of the supply chain through conferences and training schemes; (c) strategic investment in the workforce through training, vocational and higher degrees; and (d) acquaintance with different sources of finance. This study will assist small traditional firms in building competencies in skill development and improvement. It will assist an international audience who may face similar issue with their construction firm

Epithelial-mesenchymal plasticity determines estrogen receptor positive breast cancer dormancy and epithelial reconversion drives recurrence

More than 70% of human breast cancers (BCs) are estrogen receptor α-positive (ER+). A clinical challenge of ER+ BC is that they can recur decades after initial treatments. Mechanisms governing latent disease remain elusive due to lack of adequate in vivo models. We compare intraductal xenografts of ER+ and triple-negative (TN) BC cells and demonstrate that disseminated TNBC cells proliferate similarly as TNBC cells at the primary site whereas disseminated ER+ BC cells proliferate slower, they decrease CDH1 and increase ZEB1,2 expressions, and exhibit characteristics of epithelial-mesenchymal plasticity (EMP) and dormancy. Forced E-cadherin expression overcomes ER+ BC dormancy. Cytokine signalings are enriched in more active versus inactive disseminated tumour cells, suggesting microenvironmental triggers for awakening. We conclude that intraductal xenografts model ER + BC dormancy and reveal that EMP is essential for the generation of a dormant cell state and that targeting exit from EMP has therapeutic potential

Superfluid to normal phase transition and extreme regularity of superdeformed bands

We derive the exact semiclassical expression for the second inertial parameter $\cal B$ for the superfluid and normal phases. Interpolation between these limiting values shows that the function ${\cal B}(I)$ changes sign at the spin $I_c$, which is critical for a rotational spectrum. The quantity $\cal B$ turns out to be a sensitive measure of the change in static pairing correlations. The superfluid-to-normal transition reveals itself in the specific variation of the ratio ${\cal B}/{\cal A}$ versus spin $I$ with the plateau characteristic of the normal phase. We find this dependence to be universal for normal deformed and superdeformed bands. The long plateau with a small value ${\cal B}/{\cal A}\sim A^{-8/3}$ explains the extreme regularity of superdeformed bands.Comment: 30 pages in LaTeX, 6 figures (PostScript). To be published in Yadernaya Fizika (Physics of Atomic Nuclei), special edition dedecated to the 90th birthday of Prof. I. I. Gurevit

Long-range Effects on the Pyroelectric Coefficient and Dielectric Susceptibility of a Ferroelectric Bilayer

Long-range effects on the pyroelectric coefficient and susceptibility of a ferroelectric bilayer with a ferroelectric interfacial coupling are investigated by use of the transverse Ising model within the framework of mean-field theory. The effects of the interfacial coupling and the transverse field on the pyroelectric coefficient and susceptibility of the bilayer are investigated by taking into account the long-range interaction. It is found that the pyroelectric coefficient and susceptibility increase with the decrease of the magnitude of the long-range interaction and the interfacial coupling when the temperature is lower than the phase transition temperature. We also find that the strong long-range interaction, the large transverse field and weak interfacial coupling can lead to the disappearance of some of the peaks of the pyroelectric coefficient and susceptibility of the ferroelectric bilayer. The phase transition temperature increases with the increase of the strength of the long-range interaction, which is similar to the results obtained in ferroelectric multi-layers or superlattice.Comment: 23 pages, 11 figure

Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium.

Oestrogen receptor α (ERα) is a transcription factor with ligand-independent and ligand-dependent activation functions (AF)-1 and -2. Oestrogens control postnatal mammary gland development acting on a subset of mammary epithelial cells (MECs), termed sensor cells, which are ERα-positive by immunohistochemistry (IHC) and secrete paracrine factors, which stimulate ERα-negative responder cells. Here we show that deletion of AF-1 or AF-2 blocks pubertal ductal growth and subsequent development because both are required for expression of essential paracrine mediators. Thirty percent of the luminal cells are ERα-negative by IHC but express Esr1 transcripts. This low level ERα expression through AF-2 is essential for cell expansion during puberty and growth-inhibitory during pregnancy. Cell-intrinsic ERα is not required for cell proliferation nor for secretory differentiation but controls transcript levels of cell motility and cell adhesion genes and a stem cell and epithelial mesenchymal transition (EMT) signature identifying ERα as a key regulator of mammary epithelial cell plasticity