Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells

Rhabdomyosarcoma (RMS) is a highly malignant and metastatic pediatric cancer arising from skeletal muscle myogenic progenitors. Recent studies have shown an important role for AKT signaling in RMS progression. Aberrant activation of the PI3K/AKT axis is one of the most frequent events occurring in human cancers and serves to disconnect the control of cell growth, survival, and metabolism from exogenous growth stimuli. In the study reported here, a panel of five compounds targeting the catalytic subunits of the four class I PI3K isoforms (p110α, BYL-719 inhibitor; p110β, TGX-221 inhibitor; p110γ, {"type":"entrez-protein","attrs":{"text":"CZC24832","term_id":"994587862","term_text":"CZC24832"}}CZC24832; p110δ, CAL-101 inhibitor) and the dual p110α/p110δ, AZD8835 inhibitor, were tested on the RMS cell lines RD, A204, and SJCRH30. Cytotoxicity, cell cycle, apoptosis, and the activation of downstream targets were analyzed. Of the individual inhibitors, BYL-719 demonstrated the most anti-tumorgenic properties. BYL-719 treatment resulted in G1/G0 phase cell cycle arrest and apoptosis. When combined with CAL-101, BYL-719 decreased cell viability and induced apoptosis in a synergistic manner, equaling or surpassing results achieved with AZD8835. In conclusion, our findings indicate that BYL-719, either alone or in combination with the p110δ inhibitor, CAL-101, could represent an efficient treatment for human rhabdomyosarcoma presenting with aberrant upregulation of the PI3K signaling pathway.     

Molecular-cluster studies of defects in silicon lattices

Summary Ab initio HF-SCF-LCAO calculations have been performed on Si _n H _2n+n (n=1 to 5) by means of four different basis sets. Total energies, first ionization potentials, minimum-energy geometries and torsional barriers of rotation around the Si−Si bond have been computed in order to test the accuracy of the basis sets used.

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Riassunto Sono stati eseguiti calcoliab initio HF-LCAO-SCF su composti della famiglia dei silani lineari (Si _n H _2n+2 ,n=1, ..., 5) mediate quatro differenti insiemi di funzioni di base. Sono state calcolate energie totali, primi potenziali di ionizzazione, geometrie al minimo di energia e barriere torsionali attorno al legame Si−Si per poter verificare l'accuratezza degl'insiemi di funzioni di base usati.

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Резюме Сначала проводятся вычисления HF-SCF-LCAO в семействе соединений Si _n H _2n+1 (n от 1 до 5), используя четыре различных базисных системы. С целью проверки точнсти использованных базисных систем систем бычислены полные знергии, первые потенциалы ионизации, геометрии с минимльной энергией и барьеры врашения вокруг связи Si−Si.

     

The nonequilibrium Lorentz gas

We study the conductivity of a Lorentz gas system, composed of a regular array of fixed scatterers and a point-like moving particle, as a function of the strength of an applied external field. In order to obtain a nonequilibrium stationary state, the speed of the point particle is fixed by the action of a Gaussian thermostat. For small fields the system is ergodic and the diffusion coefficient is well defined. We show that in this range the Periodic Orbit Expansion can be successfully applied to compute the values of the thermodynamic variables. At larger values of the field we observe a variety of possible dynamics, including the breakdown of ergodic behavior, and later the existence of a single stable trajectory for the largest fields. We also study the behavior of the system as a function of the orientation of the array of scatterers with respect to the external field. Finally, we present a detailed dynamical study of the transitions in the bifurcation sequence in both the elementary cell and the fundamental domain. The consequences of this behavior for the ergodicity of the system are explored. (c) 1995 American Institute of Physics.     

Free‐electron laser multiplex driven by a superconducting linear accelerator

Free‐electron lasers (FELs) generate femtosecond XUV and X‐ray pulses at peak powers in the gigawatt range. The FEL user facility FLASH at DESY (Hamburg, Germany) is driven by a superconducting linear accelerator with up to 8000 pulses per second. Since 2014, two parallel undulator beamlines, FLASH1 and FLASH2, have been in operation. In addition to the main undulator, the FLASH1 beamline is equipped with an undulator section, sFLASH, dedicated to research and development of fully coherent extreme ultraviolet photon pulses using external seed lasers. In this contribution, the first simultaneous lasing of the three FELs at 13.4 nm, 20 nm and 38.8 nm is presented.     

Temporal asymmetry of fluctuations in nonequilibrium steady states: links with correlation functions and nonlinear response

The presence of temporal asymmetries in fluctuation paths of nonequilibrium systems has recently been confirmed numerically in nonequilibrium molecular dynamics simulations of particular deterministic systems. Here we show that this is a common feature of homogeneously driven and thermostatted, reversible, deterministic, chaotic, nonequilibrium systems of interacting particles. This is done by expressing fluctuation paths as correlation functions. The theoretical arguments look rather general, and we expect them to easily extend to other forms of driving and thermostats. The emergence of asymmetry is also justified using the transient time correlation function expression of nonlinear response theory. Numerical simulations are used to verify our arguments.     

Sulle trasformazioni continue

Sunto Si dimostra che ogni trasformazione piana, rappresentata da funzioni assolutamente continue secondoTonelli con dervate parziali prime integrabiliL ²→ α con α>0, sono a variazione limitata e assolutamente continue secondoBanach eVitali. Si danno inoltre esempi effettivi di trasformazioni piane, rappresentate da funzioni assolutamente continue secondoTonelli con derivate parziali prime integrabiliL ², che non sono ne a variazione limitata ne assolutamente continue secondoBanacheVitali. Lavoro eseguito nel Seminario Matematico della R. Scuola Normale Superiore di Pisa.