A characterization of (regular) circular languages generated by monotone complete splicing systems

Circular splicing systems are a formal model of a generative mechanism of circular words, inspired by a recombinant behaviour of circular DNA. Some unanswered questions are related to the computational power of such systems, and finding a characterization of the class of circular languages generated by circular splicing systems is still an open problem. In this paper we solve this problem for monotone complete systems, which are finite circular splicing systems with rules of a simpler form. We show that a circular language L is generated by a monotone complete system if and only if the set Lin(L) of all words corresponding to L is a pure unitary language generated by a set closed under the conjugacy relation. The class of pure unitary languages was introduced by A. Ehrenfeucht, D. Haussler, G. Rozenberg in 1983, as a subclass of the class of context-free languages, together with a characterization of regular pure unitary languages by means of a decidable property. As a direct consequence, we characterize (regular) circular languages generated by monotone complete systems. We can also decide whether the language generated by a monotone complete system is regular. Finally, we point out that monotone complete systems have the same computational power as finite simple systems, an easy type of circular splicing system defined in the literature from the very beginning, when only one rule of a specific type is allowed. From our results on monotone complete systems, it follows that finite simple systems generate a class of languages containing non-regular languages, showing the incorrectness of a longstanding result on simple systems.     

Estimation of predictive accuracy in survival analysis using R and S-PLUS

When the purpose of a survival regression model is to predict future outcomes, the predictive accuracy of the model needs to be evaluated before practical application. Various measures of predictive accuracy have been proposed for survival data, none of which has been adopted as a standard, and their inclusion in statistical software is disregarded. We developed the surev library for R and S-PLUS, which includes functions for evaluating the predictive accuracy measures proposed by Schemper and Henderson. The library evaluates the predictive accuracy of parametric regression models and of Cox models. The predictive accuracy of the Cox model can be obtained also when time-dependent covariates are included because of non-proportional hazards or when using Bayesian model averaging. The use of the library is illustrated with examples based on a real data set.     

Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling,reduces energy efficiency and improves antioxidant and antiinflammatory defences in rats

Dietary PUFA, mainly those of the n‐3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low‐fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso‐energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF‐α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione‐S‐transferase NADH quinone oxidoreductase) in DM‐treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid‐related factor 2 pathway.     

Human iPSC-Derived Astrocytes: A Powerful Tool to Study Primary Astrocyte Dysfunction in the Pathogenesis of Rare Leukodystrophies

Astrocytes are very versatile cells, endowed with multitasking capacities to ensure brain homeostasis maintenance from brain development to adult life. It has become increasingly evident that astrocytes play a central role in many central nervous system pathologies, not only as regulators of defensive responses against brain insults but also as primary culprits of the disease onset and progression. This is particularly evident in some rare leukodystrophies (LDs) where white matter/myelin deterioration is due to primary astrocyte dysfunctions. Understanding the molecular defects causing these LDs may help clarify astrocyte contribution to myelin formation/maintenance and favor the identification of possible therapeutic targets for LDs and other CNS demyelinating diseases. To date, the pathogenic mechanisms of these LDs are poorly known due to the rarity of the pathological tissue and the failure of the animal models to fully recapitulate the human diseases. Thus, the development of human induced pluripotent stem cells (hiPSC) from patient fibroblasts and their differentiation into astrocytes is a promising approach to overcome these issues. In this review, we discuss the primary role of astrocytes in LD pathogenesis, the experimental models currently available and the advantages, future evolutions, perspectives, and limitations of hiPSC to study pathologies implying astrocyte dysfunctions.     

Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against Candida spp. Clinical Isolates

The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP Chionodracine. We determined their interaction with anionic and zwitterionic membrane-mimicking vesicles and their structure during this interaction. We then investigated their cytotoxic and hemolytic activity against mammalian cells. Lipidated peptides showed a broad spectrum of activity against a relevant panel of pathogen fungi belonging to Candida spp., including the multidrug-resistant C. auris. The antifungal activity was also observed vs. biofilms of C. albicans, C. tropicalis, and C. auris. Finally, a pilot efficacy study was conducted on the in vivo model consisting of Galleria mellonella larvae. Treatment with the most-promising myristoylated peptide was effective in counteracting the infection from C. auris and C. albicans and the death of the larvae. Therefore, this myristoylated peptide is a potential candidate to develop antifungal agents against human fungal pathogens.     

Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury

Acute kidney injury (AKI) is a public health problem worldwide. Sirtuins are a family of seven NAD+-dependent deacylases, Overexpression of Sirtuin 1, 3, and 5 protect against AKI. However, the role of Sirtuin 7 (Sirt7) in AKI is not known. Here, we analyzed how Sirt7 deficient mice (KO-Sirt7) were affected by AKI. As expected, wild-type and Sirt7 heterozygotes mice that underwent renal ischemia/reperfusion (IR) exhibited the characteristic hallmarks of AKI: renal dysfunction, tubular damage, albuminuria, increased oxidative stress, and renal inflammation. In contrast, the KO-Sirt7+IR mice were protected from AKI, exhibiting lesser albuminuria and reduction in urinary biomarkers of tubular damage, despite similar renal dysfunction. The renoprotection in the Sirt7-KO+IR group was associated with reduced kidney weight, minor expression of inflammatory cytokines and less renal infiltration of inflammatory cells. This anti-inflammatory effect was related to diminished p65 expression and in its active phosphorylation, as well as by a reduction in p65 nuclear translocation. Sirt7 deficient mice are protected from AKI, suggesting that this histone deacetylase promotes tubular damage and renal inflammation. Therefore, our findings indicate that Sirt7 inhibitors may be an attractive therapeutic target to reduce NFκB signaling.     

Growth/no growth interfaces of Bacillus cereus, Staphylococcus aureus and Salmonella enteritidis in model systems based on water activity, pH, temperature and ethanol concentration

This study focuses its attention on the boundary between the growth and no growth of three strains ofSalmonella enteritidis , Bacillus cereus and Staphylococcus aureus in the presence of growth controlling factors such as temperature, pH, water activity (A_w) and ethanol concentration. Preliminarly, the minimal values of pH, A_wand temperature, and the maximum ethanol concentrations allowing the growth of the considered micro-organisms were determined. The calculation of these values enabled the use of logistic model to evaluate the growth/no growth boundary for the bacteria in relation to the considered independent variables. The location of the growth/no-growth boundaries for S. enteritidis and Staph. aureus were strongly affected, at the same ethanol concentration, by temperature, pH and A_w. Among the considered species, Staph. aureus was endowed with the highest sensitivity to low pH values whileB. cereus's growth/no growth interface, was quite unaffected by the combination of the stresses, when the physico–chemical conditions were above the minimum for growth. The effects of temperature, A_wand ethanol on the limitation of growth of the considered species were not merely additive. It was possible to identify the combinations of such factors preventing the growth of Salmonella enteritidis, Staph. aureus and B. cereus.     

Interactions between high pressure homogenization and antimicrobial activity of lysozyme and lactoperoxidase

It was the objective of this work to evaluate the effect of high pressure homogenization on the activity of antimicrobial enzymes such as lysozyme and lactoperoxidase against a selected group of Gram positive and Gram negative species inoculated in skim milk. Lactobacillus helveticus, Lactobacillus plantarum and Listeria monocytogenes were the most pressure resistant species while Bacillus subtilis, Pseudomonas putida, Salmonella typhimurium, Staphylococcus aureus, Proteus vulgaris and Salmonella enteritidis were found to be very sensitive to the hyperbaric treatment. The enzyme addition enhanced the instantaneous pressure efficacy on almost all the considered species as indicated by their instantaneous viability loss following the treatment. Moreover, the combination of the enzyme and high pressure homogenization significantly affected the recovery and growth dynamics of several of the considered species. Although L. monocytogenes was slightly sensitive to pressure, the combination of the two stress factors induced a significant viability loss within 3 h and an extension of lag phases in skim milk during incubation at 37 degrees C. The hypothesis formulated in this work is that the interaction of high pressure homogenization and lysozyme or lactoperoxidase is associated to conformational modifications of the two proteins with a consequent enhancement of their activity. This hypothesis is supported by the experimental results also regarding the increased antimicrobial activity against L. plantarum of the previously pressurised lysozyme with respect to that of the native enzyme.     

Optical properties of high-density dispersions of particles: application to intralipid solutions

We propose to study the scattering properties of dense distributions of spherical scatterers by resorting to an iterative solution of the Foldy-Twersky equation for the propagation of the coherent field. As a result of the first step of the iterative procedure, the host medium is substituted by an effective medium of complex refractive index to account for the multiple-scattering processes that occur among the particles. Although we truncate the above-mentioned iterative procedure to the second step, the results of our calculations are in excellent agreement with previous experimental results of Zaccanti et al. ("Measurement of optical properties of high-density media," to be published in Applied Optics) for the scattering coefficient of Intralipid solutions up to a volume density of 15% and show a limited disagreement at a volume density of 22%.     

Synthesis of an Al-ZrO2 composite by infiltration of Zr-chelates into an Al matrix

Aluminium-based matrix composites were prepared by infiltration with an ammoniacal zirconium chelate within an Al matrix synthesized via Aluminium powder compactation. After infiltration, this chelate can be transformed in situ by sol-gel method that leads to tetragonal phases in zirconia, which in turn, transforms to monoclinic structure on heating. Based on Differential Thermal Analysis (DTA), Fourier Transformed Infrared (FTIR), X-Ray Diffraction (XRD), and Scanning Electron Microscopy (SEM), we confirm the reaction sequence to obtain the tetramer, the phase transformation sequence within the Al matrix, and the development of phases that leads to the synthesis of the Al-ZrO₂ composite.