On random primitive sets, directable NDFAs and the generation of slowly synchronizing DFAs

We tackle the problem of the randomized generation of slowly synchronizing deterministic automata (DFAs) by generating random primitive sets of matrices. We show that when the randomized procedure is too simple the exponent of the generated sets is O(n log n) with high probability, thus the procedure fails to return DFAs with large reset threshold. We extend this result to random nondeterministic automata (NDFAs) by showing, in particular, that a uniformly sampled NDFA has both a 2-directing word and a 3-directing word of length O(n log n) with high probability. We then present a more involved randomized algorithm that manages to generate DFAs with large reset threshold and we finally leverage this finding for exhibiting new families of DFAs with reset threshold of order $\Omega(n^2/4)$.Comment: 31 pages, 9 figures. arXiv admin note: text overlap with arXiv:1805.0672

The Synchronizing Probability Function for Primitive Sets of Matrices

Motivated by recent results relating synchronizing DFAs and primitive sets, we tackle the synchronization process and the related longstanding \v{C}ern\'{y} conjecture by studying the primitivity phenomenon for sets of nonnegative matrices having neither zero-rows nor zero-columns. We formulate the primitivity process in the setting of a two-player probabilistic game and we make use of convex optimization techniques to describe its behavior. We develop a tool for approximating and upper bounding the exponent of any primitive set and supported by numerical results we state a conjecture that, if true, would imply a quadratic upper bound on the reset threshold of a new class of automata.Comment: 24 pages, 9 figures. Submitted to DLT 2018 Special Issu

Cholesterol impairment contributes to neuroserpin aggregation

Intraneural accumulation of misfolded proteins is a common feature of several neurodegenerative pathologies including Alzheimer's and Parkinson's diseases, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). FENIB is a rare disease due to a point mutation in neuroserpin which accelerates protein aggregation in the endoplasmic reticulum (ER). Here we show that cholesterol depletion induced either by prolonged exposure to statins or by inhibiting the sterol regulatory binding-element protein (SREBP) pathway also enhances aggregation of neuroserpin proteins. These findings can be explained considering a computational model of protein aggregation under non-equilibrium conditions, where a decrease in the rate of protein clearance improves aggregation. Decreasing cholesterol in cell membranes affects their biophysical properties, including their ability to form the vesicles needed for protein clearance, as we illustrate by a simple mathematical model. Taken together, these results suggest that cholesterol reduction induces neuroserpin aggregation, even in absence of specific neuroserpin mutations. The new mechanism we uncover could be relevant also for other neurodegenerative diseases associated with protein aggregation.Comment: 7 figure

Chacterization of CU tube filled with Al alloy foam by means of X-ray computer tomography

Copper tubes filled with aluminium foams were prepared by directly foaming metal powder compacts inside them. Compressive behaviour and foam-shell interface, that characterizes mechanical properties of reinforced tubes, were investigated by means of variable focus X-ray computer tomography. Compression tests were performed on empty and filled samples at increasing deformation steps: at each stage the samples were observed by tomography. A geometric evaluation of porosity on 2D sections was performed by calculating, for each pore, its area, equivalent diameter and circularity

Oligodendroglioma cells lack glutamine synthetase and are auxotrophic for glutamine, but do not depend on glutamine anaplerosis for growth

In cells derived from several types of cancer, a transcriptional program drives high consumption of glutamine (Gln), which is used for anaplerosis, leading to a metabolic addiction for the amino acid. Low or absent expression of Glutamine Synthetase (GS), the only enzyme that catalyzes de novo Gln synthesis, has been considered a marker of Gln-addicted cancers. In this study, two human cell lines derived from brain tumors with oligodendroglioma features, HOG and Hs683, have been shown to be GS-negative. Viability of both lines depends from extracellular Gln with EC of 0.175 ± 0.056 mM (Hs683) and 0.086 ± 0.043 mM (HOG), thus suggesting that small amounts of extracellular Gln are sufficient for OD cell growth. Gln starvation does not significantly affect the cell content of anaplerotic substrates, which, consistently, are not able to rescue cell growth, but causes hindrance of the Wnt/β-catenin pathway and protein synthesis attenuation, which is mitigated by transient GS expression. Gln transport inhibitors cause partial depletion of intracellular Gln and cell growth inhibition, but do not lower cell viability. Therefore, GS-negative human oligodendroglioma cells are Gln-auxotrophic but do not use the amino acid for anaplerosis and, hence, are not Gln addicted, exhibiting only limited Gln requirements for survival and growth

Critical role for prokineticin 2 in CNS autoimmunity

Objective: To investigate the potential role of prokineticin 2 (PK2), a bioactive peptide involved in multiple biological functions including immune modulation, in CNS autoimmune demyelinating disease. Methods: We investigated the expression of PK2 in mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), and in patients with relapsing-remitting MS. We evaluated the biological effects of PK2 on expression of EAE and on development of T-cell response against myelin by blocking PK2 in vivo with PK2 receptor antagonists. We treated with PK2 immune cells activated against myelin antigen to explore the immune-modulating effects of this peptide in vitro. Results: Pk2 messenger RNA was upregulated in spinal cord and lymph node cells (LNCs) of mice with EAE. PK2 protein was expressed in EAE inflammatory infiltrates and was increased in sera during EAE. In patients with relapsing-remitting MS, transcripts for PK2 were significantly increased in peripheral blood mononuclear cells compared with healthy controls, and PK2 serum concentrations were significantly higher. A PK2 receptor antagonist prevented or attenuated established EAE in chronic and relapsing-remitting models, reduced CNS inflammation and demyelination, and decreased the production of interferon (IFN)-γ and interleukin (IL)-17A cytokines in LNCs while increasing IL-10. PK2 in vitro increased IFN-γ and IL-17A and reduced IL-10 in splenocytes activated against myelin antigen. Conclusion: These data suggest that PK2 is a critical immune regulator in CNS autoimmune demyelination and may represent a new target for therapy

Fe-periclase reactivity at Earth's lower mantle conditions: Ab-initio geochemical modelling

Intrinsic and extrinsic stability of the (Mg,Fe)O solid mixture in the Fe-Mg-Si-O system at high P, T conditions relevant to the Earth\u2019s mantle is investigated by the combination of quantum mechanical calculations (Hartree- 26 Fock/DFT hybrid scheme), cluster expansion techniques and statistical thermodynamics. Iron in the (Mg,Fe)O binary mixture is assumed to be either in the low spin (LS) or in the high spin (HS) state. Un-mixing at solid state is observed only for the LS condition in the 23\u201342 GPa pressure range, whereas HS does not give rise to un-mixing. LS (Mg,Fe)O un-mixings are shown to be able to incorporate iron by subsolidus reactions with a reservoir of a virtual bridgmanite composition, for a maximum total enrichment of 0.22 FeO. At very high P (up to 130/3150 GPa/K), a predominant (0.7 phase proportion), iron-rich Fe-periclase mixture (Mg0.50Fe0.50)O is formed, and it coexists, at constrained phase composition conditions, with two iron-poor assemblages [(Mg0.90Fe0.10)O and (Mg0.825Fe0.175)O]. These theoretical results agree with the compositional variability and frequency of occurrence observed in lower mantle Fe-periclase from diamond inclusions and from HP-HT synthesis products. The density difference among the Fe-periclase phases increases up to 10%, between 24 and 130 GPa. The calculated bulk Fe/Mg partitioning coefficient between the bridgmanite reservoir and Fe-periclase, Kd, is 0.64 at 24 GPa; it then drops to 0.19 at 80 GPa, and becomes quasi-invariant (0.18\u20130.16) in the lowermost portion of the Earth\u2019s mantle (80\u2013 130 GPa). These Kd-values represent an approximate estimate for the Fe/Mg-partitioning between actual bridgmanite and Fe-periclase. Consequently, our Kd-values agree with experimental measurements and theoretical determinations, hinting that iron preferentially dissolves in periclase with respect to all the other iron-bearing phases of the lower mantle. The continuous change up to 80 GPa (2000 km depth) of the products (compositions and phase proportions) over the MgO-FeO binary causes geochemical heterogeneities throughout the lower mantle, but it does not give rise to any sharp discontinuity. In this view, anomalies like the ULVZs, explained with a local and abrupt change of density, do not seem primarily ascribable to the mixing behavior and reactivity of (Mg,Fe)O at subsolidus

Activity and Rotation in the young cluster h Per

We study the stellar rotation-activity relation in the crucial age at which stars reach the fastest rotation. To this aim we have analyzed data of the young cluster h Per, very rich and compact, located at 2300 pc, that at an age of 13 Myr should be mainly composed of stars that have ended their contraction phase and that have not lost significant angular momentum viamagnetic breaking. To constrain the activity level of h Per members we have analyzed a deep Chandra/ACIS-I observation. Rotational periods of h Per members have been derived by Moraux et al. (2013) in the framework of the MONITOR project (Aigrain et al. 2007; Irwin et al. 2007). In the Chandra observation we have detected 1010 X-ray sources located in the central field of h Persei. Assuming a distance of 2300 pc their X-ray luminosity ranges between 2x10^29 and 6x10^31 erg/s. Among the 1010 x-ray sources ~600 have as optical counterpart candidate members of the cluster with masses ranging down to 0.3 solar mass, and ˜150 have also measured rotational period. For this sample of ˜150 h Per members we have compared X-ray luminosity and rotational periods for different mass ranges. We have found that solar type stars (~1.3 solar mass) show evidence of supersaturation for short periods. This phenomenon is unobserved for lower mass stars