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 European M&A industry: Trends, patterns and shortcomings

This paper provides a comprehensive overview of the process of European mergers and acquisitions. We characterize the main features of M&A activity in Europe in the period 2001-2007. We review the process of M&A regulatory integration and patterns of activity. Most European M&As still take place among domestic firms, although cross-border transactions are larger in value and have been slightly increasing, especially in regulated industries. Transactions are likely to be friendly, partially negotiated via public tender offers and private deals, and paid in cash, especially for smaller deals. Competing bids are still fairly rare and less likely to be completed. Target shareholders obtain an average premium of around 20% and this premium is slightly declining with deal size. Regulatory differences are large, particularly in the application of takeover regulations, and uncertainty persists in the predictability of the national regulatory agencies.European cross-border; domestic merger; acquisitions; M&A trends;

Completeness on the worm domain and the M\"untz-Sz\'asz problem for the Bergman space

In this paper we are concerned with the problem of completeness in the Bergman space of the worm domain $\mathcal{W}_\mu$ and its truncated version $\mathcal{W}'_\mu$. We determine some orthogonal systems and show that they are not complete, while showing that the union of two particular of such systems is complete. In order to prove our completeness result we introduce the Muentz-Szasz problem for the 1-dimensional Bergman space of the disk $\{\zeta : |\zeta-1|<1\}$ and find a sufficient condition for its solution.Comment: 14 pages, Author Accepted Manuscrip

A Convex Framework for Optimal Investment on Disease Awareness in Social Networks

We consider the problem of controlling the propagation of an epidemic outbreak in an arbitrary network of contacts by investing on disease awareness throughout the network. We model the effect of agent awareness on the dynamics of an epidemic using the SAIS epidemic model, an extension of the SIS epidemic model that includes a state of "awareness". This model allows to derive a condition to control the spread of an epidemic outbreak in terms of the eigenvalues of a matrix that depends on the network structure and the parameters of the model. We study the problem of finding the cost-optimal investment on disease awareness throughout the network when the cost function presents some realistic properties. We propose a convex framework to find cost-optimal allocation of resources. We validate our results with numerical simulations in a real online social network.Comment: IEEE GlobalSIP Symposium on Network Theor

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

Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli

Behavioral responses to painful stimuli require peripheral sensory neurons called nociceptors. Electrophysiological studies show that most C-fiber nociceptors are polymodal (i.e., respond to multiple noxious stimulus modalities, such as mechanical and thermal); nevertheless, these stimuli are perceived as distinct. Therefore, it is believed that discrimination among these modalities only occurs at spinal or supraspinal levels of processing. Here, we provide evidence to the contrary. Genetic ablation in adulthood of unmyelinated sensory neurons expressing the G protein-coupled receptor Mrgprd reduces behavioral sensitivity to noxious mechanical stimuli but not to heat or cold stimuli. Conversely, pharmacological ablation of the central branches of TRPV1+ nociceptors, which constitute a nonoverlapping population, selectively abolishes noxious heat pain sensitivity. Combined elimination of both populations yielded an additive phenotype with no additional behavioral deficits, ruling out a redundant contribution of these populations to heat and mechanical pain sensitivity. This double-dissociation suggests that the brain can distinguish different noxious stimulus modalities from the earliest stages of sensory processing

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

The Bohlmann–Rahtz pyridine synthesis and the Hantzsch dihydropyridine synthesis can be carried out in a microwave flow reactor or using a conductive heating flow platform for the continuous processing of material. In the Bohlmann–Rahtz reaction, the use of a Brønsted acid catalyst allows Michael addition and cyclodehydration to be carried out in a single step without isolation of intermediates to give the corresponding trisubstituted pyridine as a single regioisomer in good yield. Furthermore, 3-substituted propargyl aldehydes undergo Hantzsch dihydropyridine synthesis in preference to Bohlmann–Rahtz reaction in a very high yielding process that is readily transferred to continuous flow processing

Class of PPT bound entangled states associated to almost any set of pure entangled states

We analyze a class of entangled states for bipartite $d \otimes d$ systems, with $d$ non-prime. The entanglement of such states is revealed by the construction of canonically associated entanglement witnesses. The structure of the states is very simple and similar to the one of isotropic states: they are a mixture of a separable and a pure entangled state whose supports are orthogonal. Despite such simple structure, in an opportune interval of the mixing parameter their entanglement is not revealed by partial transposition nor by the realignment criterion, i.e. by any permutational criterion in the bipartite setting. In the range in which the states are Positive under Partial Transposition (PPT), they are not distillable; on the other hand, the states in the considered class are provably distillable as soon as they are Nonpositive under Partial Transposition (NPT). The states are associated to any set of more than two pure states. The analysis is extended to the multipartite setting. By an opportune selection of the set of multipartite pure states, it is possible to construct mixed states which are PPT with respect to any choice of bipartite cuts and nevertheless exhibit genuine multipartite entanglement. Finally, we show that every $k$-positive but not completely positive map is associated to a family of nondecomposable maps.Comment: 12 pages, 3 figures. To appear in Phys. Rev.