Retinoic acid-induced differentiation sensitizes myeloid progenitors cells to ER stress

The clonal expansion of hematopoietic myeloid precursors blocked at different stages of differentiation characterizes the acute myeloid leukemia (AML) phenotype. A subtype of AML, acute promyelocytic leukemia (APL), characterized by the chimeric protein PML-RARα is considered a paradigm of differentiation therapy. In this leukemia subtype the all-trans-retinoic acid (RA)-based treatments are able to induce PML-RARα degradation and leukemic blast terminal differentiation [1-2]. Granulocytic differentiation of APL cells driven by RA triggers a physiological Unfolded Protein Response (UPR), a series of pathways emanating from the ER in case of ER stress, which ensues when higher protein folding activity is required as during differentiation. We show here that, although mild, the ER stress induced by RA is sufficient to render human APL cell lines and primary blasts very sensitive to low doses of Tunicamycin (Tm), an ER stress inducing drug, at doses that are not toxic in the absence of RA. Importantly only human progenitors cells derived from APL patients resulted sensitive to the combined treatment with RA and Tm whereas those obtained from healthy donors were not affected. We also show that the UPR pathway downstream of PERK plays a major protective role against ER stress in differentiating cells and, by using a specific PERK inhibitor, we potentiated the toxic effect of the combination of RA and Tm. In conclusion, our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML

Efficacy and safety of trabeculectomy vs nonpenetrating surgical procedures: a systematic review and meta-analysis

To date, only a few studies have directly compared nonpenetrating surgery (NPS) and trabeculectomy (TE). Therefore, there is no strong evidence as to which surgical technique leads to the best results in terms of ocular hypotensive effect and safety

Intermediate hepatocellular carcinoma: current treatments and future perspectives

Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment of Barcelona-Clinic Liver Cancer (BCLC)-B patients. However, the long-term survival outcomes of patients managed with this technique do not appear fully satisfactory; in addition, intermediate-stage hepatocellular carcinoma (HCC) includes a heterogeneous population of patients with varying tumour burdens, liver function and disease aetiology. Therefore, not all patients with intermediate-stage HCC may derive similar benefit from TACE, and some patients may benefit from other treatment options, which are currently approved or being explored. These include different TACE modalities, such as selective TACE or drug-eluting beads TACE and radioembolization. The introduction of sorafenib in the therapeutic armamentarium for HCC has provided a new therapeutic option for the treatment of BCLC-B patients who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity. In addition, clinical trials aimed at investigating the potential role of this molecule in the treatment of patients with intermediate-stage HCC within combination therapeutic regimens are ongoing. This narrative review will present and discuss the most recent evidence on the locoregional or medical treatment with sorafenib in patients with intermediate-stage HC

Theory of continuum percolation I. General formalism

The theoretical basis of continuum percolation has changed greatly since its beginning as little more than an analogy with lattice systems. Nevertheless, there is yet no comprehensive theory of this field. A basis for such a theory is provided here with the introduction of the Potts fluid, a system of interacting $s$-state spins which are free to move in the continuum. In the $s \to 1$ limit, the Potts magnetization, susceptibility and correlation functions are directly related to the percolation probability, the mean cluster size and the pair-connectedness, respectively. Through the Hamiltonian formulation of the Potts fluid, the standard methods of statistical mechanics can therefore be used in the continuum percolation problem.Comment: 26 pages, Late

A Renormalization Proof of the KAM Theorem for Non-Analytic Perturbations

We shall use a Renormalization Group (RG) scheme in order to prove the classical KAM result in the case of a non-analytic perturbation (the latter will be assumed to have continuous derivatives up to a sufficiently large order). We shall proceed by solving a sequence of problems in which the perturbations are analytic approximations of the original one. We shall finally show that the sequence of the approximate solutions will converge to a differentiable solution of the original problem.Comment: 33 pages, no figure

Acción urbana: ¿acción profesional?

El debate “¿Acción urbana: acción profesional?” se celebró el 30 de abril de 2014 en el marco del programa radiofónico “¿Qué está paz-ando? Una mirada reflexiva con los actores que construyen ciudadanía”, del Instituto de Paz de la Universidad Distrital de Bogotá, (Colombia). En él se trató el tema de las acciones urbanas desde distintas visiones, con invitados tanto académicos como profesionales provenientes del I Foro Internacional de Acciones Urbanas, organizado por la Universidad de Los Andes. Se tuvo especial atención a la participación desde Twitter a través del hashtag #D_accion, transmitiendo temas y preguntas a los distintos invitado

Dynamics of the Wang-Landau algorithm and complexity of rare events for the three-dimensional bimodal Ising spin glass

We investigate the performance of flat-histogram methods based on a multicanonical ensemble and the Wang-Landau algorithm for the three-dimensional +/- J spin glass by measuring round-trip times in the energy range between the zero-temperature ground state and the state of highest energy. Strong sample-to-sample variations are found for fixed system size and the distribution of round-trip times follows a fat-tailed Frechet extremal value distribution. Rare events in the fat tails of these distributions corresponding to extremely slowly equilibrating spin glass realizations dominate the calculations of statistical averages. While the typical round-trip time scales exponential as expected for this NP-hard problem, we find that the average round-trip time is no longer well-defined for systems with N >= 8^3 spins. We relate the round-trip times for multicanonical sampling to intrinsic properties of the energy landscape and compare with the numerical effort needed by the genetic Cluster-Exact Approximation to calculate the exact ground state energies. For systems with N >= 8^3 spins the simulation of these rare events becomes increasingly hard. For N >= 14^3 there are samples where the Wang-Landau algorithm fails to find the true ground state within reasonable simulation times. We expect similar behavior for other algorithms based on multicanonical sampling.Comment: 9 pages, 12 figure

Optical properties of atomic Mott insulators: from slow light to dynamical Casimir effects

We theoretically study the optical properties of a gas of ultracold, coherently dressed three-level atoms in a Mott insulator phase of an optical lattice. The vacuum state, the band dispersion and the absorption spectrum of the polariton field can be controlled in real time by varying the amplitude and the frequency of the dressing beam. In the weak dressing regime, the system shows unique ultra-slow light propagation properties without absorption. In the presence of a fast time modulation of the dressing amplitude, we predict a significant emission of photon pairs by parametric amplification of the polaritonic zero-point fluctuations. Quantitative considerations on the experimental observability of such a dynamical Casimir effect are presented for the most promising atomic species and level schemes

Multi-scale analysis of lung computed tomography images

A computer-aided detection (CAD) system for the identification of lung internal nodules in low-dose multi-detector helical Computed Tomography (CT) images was developed in the framework of the MAGIC-5 project. The three modules of our lung CAD system, a segmentation algorithm for lung internal region identification, a multi-scale dot-enhancement filter for nodule candidate selection and a multi-scale neural technique for false positive finding reduction, are described. The results obtained on a dataset of low-dose and thin-slice CT scans are shown in terms of free response receiver operating characteristic (FROC) curves and discussed.Comment: 18 pages, 12 low-resolution figure