A cellular automaton for the factor of safety field in landslides modeling

Landslide inventories show that the statistical distribution of the area of recorded events is well described by a power law over a range of decades. To understand these distributions, we consider a cellular automaton to model a time and position dependent factor of safety. The model is able to reproduce the complex structure of landslide distribution, as experimentally reported. In particular, we investigate the role of the rate of change of the system dynamical variables, induced by an external drive, on landslide modeling and its implications on hazard assessment. As the rate is increased, the model has a crossover from a critical regime with power-laws to non power-law behaviors. We suggest that the detection of patterns of correlated domains in monitored regions can be crucial to identify the response of the system to perturbations, i.e., for hazard assessment.Comment: 4 pages, 3 figure

Evaluating 5-nitrofurans as trypanocidal agents

The nitroheterocycle nifurtimox, as part of a nifurtimox-eflornithine combination therapy, represents one of a limited number of treatments targeting Trypanosoma brucei, the causative agent of human African trypanosomiasis. The mode of action of this prodrug involves an initial activation reaction catalysed by a type I nitroreductase (NTR), an enzyme found predominantly in prokaryotes, leading to the formation of a cytotoxic unsaturated open chain nitrile metabolite. Here, we evaluate the trypanocidal activity of a library of other 5-nitrofurans against bloodstream form T. brucei as a preliminary step in the identification of additional nitroaromatic compounds that could potentially partner eflornithine. Biochemical screening against purified enzyme revealed that all 5-nitrofurans were effective substrates for TbNTR with the preferred compounds having apparent kcat/KM values approximately 50-fold greater than nifurtimox. For several compounds, in vitro reduction by this nitroreductase yielded products characterized by mass spectroscopy as either unsaturated or saturated open chain nitriles. When tested against bloodstream form T. brucei, many of the derivatives displayed significant growth inhibitory properties with the most potent compounds generating IC50 values around 200 nM. The anti-parasitic activity of the most potent agents was demonstrated to be NTR dependent as parasites having reduced levels of the enzyme displayed resistance to the compounds while parasites over expressing TbNTR showed hypersensitivity. We conclude that other members of the 5-nitrofurans class of nitroheterocycles have potential to treat human African trypanosomiasis perhaps as an alternative partner prodrug to nifurtimox in the next generation of eflornithine-based combinational therapies

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Finite driving rate and anisotropy effects in landslide modeling

In order to characterize landslide frequency-size distributions and individuate hazard scenarios and their possible precursors, we investigate a cellular automaton where the effects of a finite driving rate and the anisotropy are taken into account. The model is able to reproduce observed features of landslide events, such as power-law distributions, as experimentally reported. We analyze the key role of the driving rate and show that, as it is increased, a crossover from power-law to non power-law behaviors occurs. Finally, a systematic investigation of the model on varying its anisotropy factors is performed and the full diagram of its dynamical behaviors is presented.Comment: 8 pages, 9 figure

Conceptual design of the enhanced coolant purification systems for the European HCLL and HCPB test blanket modules

The Coolant Purification Systems (CPSs) is one of the most relevant ancillary systems of European Helium Cooled Lead Lithium (HCLL) and Helium Cooled Pebble Bed (HCPB) Test Blanket Modules (TBMs) which are currently in the preliminary design phase in view of their installation and operation in ITER. The CPS implements mainly two functions: the extraction and concentration of the tritium permeated from the TBM modules into the primary cooling circuit and the chemistry control of helium primary coolant. During the HCLL and HCPB-TBSs (Test Blanket Systems) Conceptual Design Review (CDR) in 2015 it was recognized the need of reducing the tritium permeation into the Port Cell #16 of ITER. To achieve this and, then, to lower the tritium partial pressure in the Helium Cooling Systems in normal operation, the helium flow-rate treated by each CPS has been increased of almost one order of magnitude. In 2017, to satisfy the CDR outcomes and the new design requirements requested by Fusion for Energy (F4E, the European Domestic Agency for ITER), ENEA performed a preliminary design of the “enhanced” CPSs. This paper presents the current design of the “enhanced” CPSs, focusing on design requirements, assumptions, selection of technologies and preliminary components sizing