Revealing the Nonequilibrium Nature of a Granular Intruder: The Crucial Role of Non-Gaussian Behavior.

The characterization of the distance from equilibrium is a debated problem in particular in the treatment of experimental signals. If the signal is a one-dimensional time series, such a goal becomes challenging. A paradigmatic example is the angular diffusion of a rotator immersed in a vibro-fluidized granular gas. Here, we experimentally observe that the rotator's angular velocity exhibits significant differences with respect to an equilibrium process. Exploiting the presence of two relevant timescales and non-Gaussian velocity increments, we quantify the breakdown of time-reversal asymmetry, which would vanish in the case of a 1D Gaussian process. We deduce a new model for the massive probe, with two linearly coupled variables, incorporating both Gaussian and Poissonian noise, the latter motivated by the rarefied collisions with the granular bath particles. Our model reproduces the experiment in a range of densities, from dilute to moderately dense, with a meaningful dependence of the parameters on the density. We believe the framework proposed here opens the way to a more consistent and meaningful treatment of out-of-equilibrium and dissipative systems.

The genomics of mycobacteria.

The species Mycobacterium bovis and Mycobacterium avium subspecies paratuberculosis are the causal agents, respectively, of tuberculosis and paratuberculosis in animals. Both mycobacteria, especially M. bovis, are also important to public health because they can infect humans. In recent years, this and the impact of tuberculosis and paratuberculosis on animal production have led to significant advances in knowledge about both pathogens and their host interactions. This article describes the contribution of genomics and functional genomics to studies of the evolution, virulence, epidemiology and diagnosis of both these pathogenic mycobacteria.

Les mycobactéries Mycobacterium bovis et Mycobacterium avium subsp. paratuberculosis sont les agents étiologiques de la tuberculose et de la paratuberculose, respectivement. En outre, les deux mycobactéries (mais plus particulièrement M. bovis) peuvent infecter l'être humain et jouent donc un rôle en santé publique. En raison de cette importance et des effets de la tuberculose et de la paratuberculose sur la production animale, de grands efforts ont été déployés pour faire avancer nos connaissances sur ces deux agents pathogènes et sur leurs interactions avec leurs hôtes. Les auteurs décrivent la contribution de la génomique et de la génomique fonctionnelle dans les études sur l'évolution, la virulence, l'épidémiologie et le diagnostic de ces deux mycobactéries pathogènes.

Las especies Mycobacterium bovis y Mycobacterium avium subsp. paratuberculosis son los agentes causales de la tuberculosis y la paratuberculosis en animales, respectivamente. Además, ambas micobacterias, pero fundamentalmente M. bovis, son importantes para la salud pública, ya que pueden infectar a los humanos. Debido a esto último y al impacto de la tuberculosis y la paratuberculosis en la producción animal, en los últimos años se ha producido un avance significativo en los conocimientos de ambos agentes patógenos y de la interacción con sus hospedadores. En este artículo describiremos la contribución de la genómica y la genómica funcional a los estudios de evolución, virulencia, epidemiología y diagnóstico de ambas micobacterias patógenas.

Diffusion of individual birds in starling flocks.

Flocking is a paradigmatic example of collective animal behaviour, where global order emerges out of self-organization. Each individual has a tendency to align its flight direction with those of neighbours, and such a simple form of interaction produces a state of collective motion of the group. When compared with other cases of collective ordering, a crucial feature of animal groups is that the interaction network is not fixed in time, as each individual moves and continuously changes its neighbours. The possibility to exchange neighbours strongly enhances the stability of global ordering and the way information is propagated through the group. Here, we assess the relevance of this mechanism in large flocks of starlings (Sturnus vulgaris). We find that birds move faster than Brownian walkers both with respect to the centre of mass of the flock, and with respect to each other. Moreover, this behaviour is strongly anisotropic with respect to the direction of motion of the flock. We also measure the amount of neighbours reshuffling and find that neighbours change in time exclusively as a consequence of the random fluctuations in the individual motion, so that no specific mechanism to keep one's neighbours seems to be enforced. On the contrary, our findings suggest that a more complex dynamical process occurs at the border of the flock.

Interaction ruling animal collective behavior depends on topological rather than metric distance: evidence from a field study.

Numerical models indicate that collective animal behavior may emerge from simple local rules of interaction among the individuals. However, very little is known about the nature of such interaction, so that models and theories mostly rely on aprioristic assumptions. By reconstructing the three-dimensional positions of individual birds in airborne flocks of a few thousand members, we show that the interaction does not depend on the metric distance, as most current models and theories assume, but rather on the topological distance. In fact, we discovered that each bird interacts on average with a fixed number of neighbors (six to seven), rather than with all neighbors within a fixed metric distance. We argue that a topological interaction is indispensable to maintain a flock's cohesion against the large density changes caused by external perturbations, typically predation. We support this hypothesis by numerical simulations, showing that a topological interaction grants significantly higher cohesion of the aggregation compared with a standard metric one.

[Pilot study to assess and compare the eating habits and nutrition knowledge in school-age Italians and Finns, using specific questionnaires]. / Studio pilota per la valutazione ed il confronto delle abitu- dini alimentari e dello stile di vita di un gruppo di ragazzi italiani ed un gruppo di ragazzi finlandesi grazie all'ausilio di specifici questionari.

In recent decades, the American diet has emerged in our country as a reference model food, particularly among young people, to the detriment of the Mediterranean diet, an healthy eating pattern rich in fruits and vegetables, olive oil, whole grains and fish. Even in Europe, North American habits are widespread at the expense of traditional northern nutritional powers, characterized by a lot of fish, wild game meat that are much thinner than from farm animals, rye, oats, cabbage, root vegetables. Given this background, in Pavia (Italy) and Tampere (Finland) we conducted a pilot study with the objective to assess and compare the eating habits and nutrition knowledge in school-age children using 2 questionnaires entitled "what do you eat?" and "what do you know about diet and health?". The results of the first questionnaire clearly shows that, among young people of both countries, there is the loss of traditional food: the Mediterranean and the Finnish diet. All the boys wear it with a low frequency fish, fruit and vegetables, and instead a high frequency of adverse health foods, such as potato chips and sweet drinks. The answers to questions which relate to nutrients and their properties, show that children of all groups have little knowledge about these topics. The use of questionnaires, such as those administered by us, can be easily performed to investigate the dietary habits and the nutritional level of culture, due to make nutrition education interventions aimed at correcting poor eating habits.

Vicsek model by time-interlaced compression: A dynamical computable information density.

Collective behavior, both in real biological systems and in theoretical models, often displays a rich combination of different kinds of order. A clear-cut and unique definition of "phase" based on the standard concept of the order parameter may therefore be complicated, and made even trickier by the lack of thermodynamic equilibrium. Compression-based entropies have been proved useful in recent years in describing the different phases of out-of-equilibrium systems. Here, we investigate the performance of a compression-based entropy, namely, the computable information density, within the Vicsek model of collective motion. Our measure is defined through a coarse graining of the particle positions, in which the key role of velocities in the model only enters indirectly through the velocity-density coupling. We discover that such entropy is a valid tool in distinguishing the various noise regimes, including the crossover between an aligned and misaligned phase of the velocities, despite the fact that velocities are not explicitly used. Furthermore, we unveil the role of the time coordinate, through an encoding recipe, where space and time localities are both preserved on the same ground, and find that it enhances the signal, which may be particularly significant when working with partial and/or corrupted data, as is often the case in real biological experiments.

A histochemical approach to the evaluation of the in vivo cytotoxicity of the nitrobutadienes (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate in mice liver and kidney.

Two new molecules (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1-Naph-DNB) and (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) in previous studies showed interesting antiproliferative activity in vitro. Furthermore, toxicological tests and histological analysis provided promising results, in particular for 1-Naph-NMCB that displayed lower toxic activity both in terms of lethal effect and tissue damage of the main organs. Finally, studies of the antitumour activity in vivo confirmed the efficacy of both molecules, though with some differences in tumour selectivity and levels of activity. In this investigation the activities of some specific enzymes, acid phosphatase (AcPase), alkaline phosphatase (AlkPase), catalase (Cat), succinic dehydrogenase (SDH), glucose-6-phosphatase (G6Pase) and K+ p-nitrophenyl phosphatase (K+ pNPPase) were studied in the liver and kidney as histopathological biomarkers, to assess the effects of the two compounds in organs generally involved in the metabolism and excretion of different drugs. As oxidative stress may also develop as a consequence of the toxic effect of chemicals, reactive oxygen species (ROS) production was evaluated by a histochemical method. The results indicated that some enzyme activities and ROS expression changed in a dose-related manner. Nevertheless, neither in the liver nor in the kidney were dramatic toxic effects evident. By contrast, the variations of some enzyme activities (AlkPase, AcPase, Cat, K+ pNPPase) were interpreted as possible defensive mechanisms for tolerating high dosage of the compounds.

Comparative effects of paclitaxel and docetaxel on the metabolism and pharmacokinetics of epirubicin in breast cancer patients.

PURPOSE: To investigate whether paclitaxel and docetaxel influence the pharmacokinetics and metabolism of epirubicin. PATIENTS AND METHODS: We studied the pharmacokinetics and biotransformation patterns of epirubicin in 27 cycles and 20 breast cancer patients. Four patients received epirubicin alone 90 mg/m(2) by intravenous (IV) bolus; eight patients received the same dose of epirubicin followed immediately by paclitaxel 175 mg/m(2) in a 3-hour infusion; the other eight patients received epirubicin 90 mg/m(2) followed immediately by docetaxel 70 mg/m(2) in a 1-hour infusion. Epirubicin and its metabolites, epirubicinol (EOL) and 7-deoxydoxorubicinone (7d-Aone), were identified by high-pressure liquid chromatography. RESULTS: No pharmacokinetic interaction between the parent compound epirubicin and taxanes was detected. Conversely, a significant effect on epirubicin metabolism by both paclitaxel and docetaxel was found. Epirubicin given with paclitaxel or docetaxel yielded areas under the plasma concentration-time curves (AUC) for 7d-Aone 1. 7-fold and 1.9-fold higher (P <.05), respectively, than epirubicin alone. The appearance of two polar metabolites sensitive to glucuronidase was also significantly greater in both taxane groups. Quantitatively different metabolic rates and patterns for EOL were observed in the paclitaxel and docetaxel combinations. The EOL AUC after paclitaxel treatment (1,521 +/- 150 ng/mL*h) was significantly higher (P <.01) than the corresponding values after epirubicin administered either as a single agent (692 +/- 46 ng/mL*h) or in combination with docetaxel (848 +/- 237 ng/mL*h). CONCLUSION: There is no apparent pharmacokinetic interaction between the parent compound epirubicin and paclitaxel or docetaxel. A different pattern of interaction between these taxanes and epirubicin metabolism is clearly evident.

Sequence effect of epirubicin and paclitaxel treatment on pharmacokinetics and toxicity.

PURPOSE: Sequence-dependent clinical and pharmacokinetic interactions between paclitaxel and doxorubicin have been reported. Some data have shown an influence of paclitaxel on epirubicin metabolism, but no data are available about the effect of diverse sequences of these drugs. We investigated whether reversing the sequence of epirubicin and paclitaxel affects the pattern or degree of toxicity and pharmacokinetics. PATIENTS AND METHODS: Patients receiving epirubicin 90 mg/m(2) by intravenous bolus followed by paclitaxel 175 mg/m(2) over 3-hour infusion or the opposite sequence every 3 weeks for four cycles were eligible. Toxicity was recorded at nadir. Pharmacokinetic data were evaluated at the first and the second cycle and were correlated with toxicity parameters. RESULTS: Thirty-nine consecutive stage II breast cancer patients were treated. Twenty-one patients received epirubicin followed by paclitaxel (ET group), and 18 received the opposite sequence (TE group). No significant difference in nonhematologic toxicity was seen. A lower neutrophil and platelet nadir and a statistically significant slower neutrophil recovery was observed in the TE group. Area under the concentration-time curve (AUC) of epirubicin was higher in the TE group (2,346 ng/mL. h v 1,717 ng/mL. h; P =.002). An inverse linear correlation between epirubicin AUC and neutrophil recovery was also observed (P =.012). No difference was detected in paclitaxel pharmacokinetics. CONCLUSION: Our results support a sequence-dependent effect of paclitaxel over epirubicin pharmacokinetics that is associated with increased myelotoxicity. Because schedule modifications of anthracyclines and paclitaxel can have clinical consequences, the classical way of administration (ie, anthracyclines followed by paclitaxel) should be maintained in clinical practice.

Expression of CD44v6 correlates with cell proliferation and cellular atypia in urothelial carcinoma cell lines 5637 and HT1197.

CD44 comprises a family of membrane adhesion molecules encoded by a single gene and diversified by alternative splicing and extensive posttranslational modifications. Alterations of CD44 expression patterns are linked to tumour invasion and formation of metastases. However, CD44 expression and its relation to the biological properties of tumours vary depending on the tumour type and origin. In transitional cell carcinoma of the urinary bladder, low CD44 expression is linked to enhanced tumour aggressiveness. We studied CD44 expression in two urothelial cancer cell lines, HT1197 and 5637. CD44s and a v6 variable exon-containing splice variants were detected in both cell lines by reverse transcription-PCR and by commercially available monoclonal antibodies. In both cell lines, Western blot analysis detected immunoreactive proteins with approximate sizes 70-85 kD, 95-110 kD, and 120-140 kD with CD44v6 antibody and weak bands with size 70-98 kD with CD44s antibody. At the cellular level, the pattern of CD44 immunoreactivity correlated with a lower level of cell differentiation and a higher degree of cell proliferation. In HT1197 cells, the CD44v6 was detected predominantly in small proliferating cells and in large multinuclear atypical cells. CD44s and CD44v6 displayed low immunoreactivity in HT1197 cells with a higher degree of epithelial differentiation. The 5637 cells expressed CD44v6 strongly and CD44s weakly. We conclude that CD44v6 expression correlates with a higher proliferative activity and with a stem cell-like phenotype in both cell lines and with cellular atypia in HT1197 cells.