MicroRNAs in cancer: from developmental genes in worms to their clinical application in patients

Several discoveries have paved the way to personalise cancer medicine and a tremendous gain of knowledge in genomics and molecular mechanisms of cancer progression cumulated over the last years. Big stories in biology commonly start in a simple model system. No wonder microRNAs have been identified as regulators of embryonic development in the nematode Caenorhabditis elegans. From the first identification in worms to the first-in-man microRNA-based clinical trial in humans, almost 20 years passed. In this review we follow the story of understanding microRNA alterations in cancer, describe recent developments in the microRNA field and critically discuss their potential as diagnostic, prognostic and therapeutics factors in cancer medicine. We will explain the rationale behind the use of microRNAs in cancer diagnosis and prognosis prediction, but also discuss the limitations and pitfalls associated with this. Novel developments of combined microRNA/siRNA pharmacological approaches will be discussed and most recently data about MXR34, the first-tested microRNA drug will be described

Trimer states with ℤ₃ topological order in Rydberg atom arrays.

Trimers are defined as two adjacent edges on a graph. We study the quantum states obtained as equal-weight superpositions of all trimer coverings of a lattice, with the constraint of having a trimer on each vertex: the so-called trimer resonating-valence-bond (tRVB) states. Exploiting their tensor network representation, we show that these states can host $\mathbb{Z}_3$ topological order or can be gapless liquids with $\mathrm{U}(1) \times \mathrm{U}(1)$ local symmetry. We prove that this continuous symmetry emerges whenever the lattice can be tripartite such that each trimer covers all the three sublattices. In the gapped case, we demonstrate the stability of topological order against dilution of maximal trimer coverings, which is relevant for realistic models where the density of trimers can fluctuate. Furthermore, we clarify the connection between gapped tRVB states and $\mathbb{Z}_3$ lattice gauge theories by smoothly connecting the former to the $\mathbb{Z}_3$ toric code, and discuss the non-local excitations on top of tRVB states. Finally, we analyze via exact diagonalization the zero-temperature phase diagram of a diluted trimer model on the square lattice and demonstrate that the ground state exhibits topological properties in a narrow region in parameter space. We show that a similar model can be implemented in Rydberg atom arrays exploiting the blockade effect. We investigate dynamical preparation schemes in this setup and provide a viable route for probing experimentally $\mathbb{Z}_3$ quantum spin liquids

Answer Set Solving with Bounded Treewidth Revisited

Parameterized algorithms are a way to solve hard problems more efficiently, given that a specific parameter of the input is small. In this paper, we apply this idea to the field of answer set programming (ASP). To this end, we propose two kinds of graph representations of programs to exploit their treewidth as a parameter. Treewidth roughly measures to which extent the internal structure of a program resembles a tree. Our main contribution is the design of parameterized dynamic programming algorithms, which run in linear time if the treewidth and weights of the given program are bounded. Compared to previous work, our algorithms handle the full syntax of ASP. Finally, we report on an empirical evaluation that shows good runtime behaviour for benchmark instances of low treewidth, especially for counting answer sets.Comment: This paper extends and updates a paper that has been presented on the workshop TAASP'16 (arXiv:1612.07601). We provide a higher detail level, full proofs and more example

Central bank independence and the monetary instrument problem

We study the monetary instrument problem in a model of optimal discretionary fiscal and monetary policy. The policy problem is cast as a dynamic game between the central bank, the fiscal authority, and the private sector. We show that, as long as there is a conflict of interest between the two policy-makers, the central bank's monetary instrument choice critically affects the Markov-perfect Nash equilibrium of this game. Focusing on a scenario where the fiscal authority is impatient relative to the monetary authority, we show that the equilibrium allocation is typically characterized by a public spending bias if the central bank uses the nominal money supply as its instrument. If it uses instead the nominal interest rate, the central bank can prevent distortions due to fiscal impatience and implement the same equilibrium allocation that would obtain under cooperation of two benevolent policy authorities. Despite this property, the welfare-maximizing choice of instrument depends on the economic environment under consideration. In particular, the money growth instrument is to be preferred whenever fiscal impatience has positive welfare effects, which is easily possible under lack of commitment

Optimal Fiscal and Monetary Policy Without Commitment

This paper studies optimal fiscal and monetary policy in a stochastic economy with imperfectly competitive product markets and a discretionary government. We find that, in the flexible price economy, optimal time-consistent policy implements the Friedman rule independently of the degree of imperfect competition. This result is in contrast to the Ramsey literature, where the Friedman rule emerges as the optimal policy only if markets are perfectly competitive. Second, once nominal rigidities are introduced, the Friedman rule ceases to be optimal, inflation rates are low and stable, and tax rates are relatively volatile. Finally, optimal time-consistent policy under sticky prices does not generate the near-random walk behavior of taxes and real debt that can be observed under optimal policy in the Ramsey problem. A common reason for these results is that the discretionary government, in an effort to asymptotically eliminate its time-consistency problem, accumulates a large net asset position such that it can finance its expenditures via the associated interest earnings

Inflation dynamics under optimal discretionary fiscal and monetary policies

We examine the dynamic properties of inflation in a model of optimal discretionary fiscal and monetary policies. The lack of commitment and the presence of nominally risk-free debt provide the government with an incentive to implement policies which induce positive and persistent inflation rates. We show that this property obtains already in an environment with flexible prices and perfectly competitive product markets. Introducing nominal rigidities and imperfect competition has no qualitative but important quantitative implications. In particular, with a modest degree of price stickiness our model generates inflation dynamics very similar to those experienced in the U.S. since the Volcker disinflation of the early 1980s

New bulk scalar field solutions in brane worlds

We use nonlinear perturbation theory to obtain new solutions for brane world models that incorporate a massive bulk scalar field. We then consider tensor perturbations and show that Newtonian gravity is recovered on the brane for both a light scalar field and for a bulk field with large negative mass. This latter result points to the viability of higher-derivative theories of gravity in the context of bulk extra dimensions.Comment: 4+\epsilon pages, no figure