Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update

Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15–20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents

Theta dependence of the vacuum energy in the SU(3) gauge theory from the lattice

We report on a precise computation of the topological charge distribution in the SU(3) Yang--Mills theory. It is carried out on the lattice with high statistics Monte Carlo simulations by employing the definition of the topological charge suggested by Neuberger's fermions. We observe significant deviations from a Gaussian distribution. Our results disfavour the theta behaviour of the vacuum energy predicted by instanton models, while they are compatible with the expectation from the large Nc expansion.Comment: Plain latex, 4 pages, 2 figure

Bipartite quantum states and random complex networks

We introduce a mapping between graphs and pure quantum bipartite states and show that the associated entanglement entropy conveys non-trivial information about the structure of the graph. Our primary goal is to investigate the family of random graphs known as complex networks. In the case of classical random graphs we derive an analytic expression for the averaged entanglement entropy $\bar S$ while for general complex networks we rely on numerics. For large number of nodes $n$ we find a scaling $\bar{S} \sim c \log n +g_e$ where both the prefactor $c$ and the sub-leading O(1) term $g_e$ are a characteristic of the different classes of complex networks. In particular, $g_e$ encodes topological features of the graphs and is named network topological entropy. Our results suggest that quantum entanglement may provide a powerful tool in the analysis of large complex networks with non-trivial topological properties.Comment: 4 pages, 3 figure

Validation of landslide hazard assessment by means of GPS monitoring technique ? a case study in the Dolomites (Eastern Alps, Italy)

International audienceIn the last years a research project aimed at the assessment of the landslide hazard and susceptibility in the high Cordevole river basin (Eastern Dolomites, Italy) have been carried out. The hazard map was made adopting the Swiss Confederation semi-deterministic approach that takes into account parameters such as velocity, geometry and frequency of landslides. Usually these parameters are collected by means of geological and morphological surveys, historical archive researches, aerophotogrammetric analysis etc. In this framework however the dynamics of an instable slope can be difficult to determine. This work aims at illustrating some progress in landslide hazard assessment using a modified version of the Swiss Confederation semi-deterministic approach in which the values of some parameters have been refined in order to accomplish more reliable results in hazard assessment. A validation of the accuracy of these new values, using GPS and inclinometric measurements, has been carried out on a test site located inside the high Cordevole river basin

Adiabatic quantum algorithm for search engine ranking

We propose an adiabatic quantum algorithm for generating a quantum pure state encoding of the PageRank vector, the most widely used tool in ranking the relative importance of internet pages. We present extensive numerical simulations which provide evidence that this algorithm can prepare the quantum PageRank state in a time which, on average, scales polylogarithmically in the number of webpages. We argue that the main topological feature of the underlying web graph allowing for such a scaling is the out-degree distribution. The top ranked $\log(n)$ entries of the quantum PageRank state can then be estimated with a polynomial quantum speedup. Moreover, the quantum PageRank state can be used in "q-sampling" protocols for testing properties of distributions, which require exponentially fewer measurements than all classical schemes designed for the same task. This can be used to decide whether to run a classical update of the PageRank.Comment: 7 pages, 5 figures; closer to published versio

Site investigation and modelling at "La Maina" landslide (Carnian Alps, Italy)

International audienceThe Sauris reservoir is a hydroelectric basin closed downstream by a 136 m high, double arc concrete dam. The dam is firmly anchored to a consistent rock (Dolomia dello Schlern), but the Lower Triassic clayey formations, cropping out especially in the lower part of the slopes, have made the whole catchment basin increasingly prone to landslides. In recent years, the "La Maina landslide" has opened up several joints over a surface of about 100 000 m2, displacing about 1 500 000 m3 of material. Particular attention is now being given to the evolution of the instability area, as the reservoir is located at the foot of the landslide. Under the commission of the Regional Authority for Civil Protection a numerical modelling simulation in a pseudo-time condition of the slope was developed, in order to understand the risk for transport infrastructures, for some houses and for the reservoir and to take urgent mesaures to stabilize the slope. A monitoring system consisting of four inclinometers, three wire extensometers and ten GPS bench-mark pillars was immediately set up to check on surface and deep displacements. The data collected and the geological and geomorphological evidences was used to carry out a numerical simulation. The reliability of the results was checked by comparing the model with the morphological evidence of the movement. The mitigation measures were designed and realised following the indications provided by the model

Relativistic MHD Simulations of Jets with Toroidal Magnetic Fields

This paper presents an application of the recent relativistic HLLC approximate Riemann solver by Mignone & Bodo to magnetized flows with vanishing normal component of the magnetic field. The numerical scheme is validated in two dimensions by investigating the propagation of axisymmetric jets with toroidal magnetic fields. The selected jet models show that the HLLC solver yields sharper resolution of contact and shear waves and better convergence properties over the traditional HLL approach.Comment: 12 pages, 5 figure

An algorithm of the wildfire classification by its acoustic emission spectrum using Wireless Sensor Networks

Crown fires are extremely dangerous as the speed of their distribution is dozen times higher compared to surface fires. Therefore, it is important to classify the fire type as early as possible. A method for forest fires classification exploits their computed acoustic emission spectrum compared with a set of samples of the typical fire acoustic emission spectrum stored in the database. This method implies acquisition acoustic data using Wireless Sensors Networks (WSNs) and their analysis in a central processing and a control center. The paper deals with an algorithm which can be directly implemented on a sensor network node that will allow reducing considerably the network traffic and increasing its efficiency. It is hereby suggested to use the sum of the squares ratio, with regard to amplitudes of low and high frequencies of the wildfire acoustic emission spectrum, as the indicator of a forest fire type. It is shown that the value of the crown fires indicator is several times higher than that of the surface ones. This allows classifying the fire types (crown, surface) in a short time interval and transmitting a fire type indicator code alongside with an alarm signal through the network

Migration of dendritic cells across blood and lymphatic endothelial barriers.

7openopenDel Prete A; Locati M; Otero K; Riboldi E; Mantovani A; Vecchi A; Sozzani S.DEL PRETE, Annalisa; Locati, M; Otero, K; Riboldi, E; Mantovani, A; Vecchi, A; Sozzani, Silvan