Design and Synthesis of New Withaferin A Inspired Hedgehog Pathway Inhibitors

Withanolides constitute a well-known family of plant-based alkaloids characterised by widespread biological properties, including the ability of interfering with Hedgehog (Hh) signalling pathway. Following our interest in natural products and in anticancer compounds, we report here the synthesis of a new class of Hh signalling pathway inhibitors, inspired by withaferin A, the first isolated member of withanolides. The decoration of our scaffolds was rationally supported by in silico studies, while functional evaluation revealed promising candidates, confirming once again the importance of natural products as inspiration source for the discovery of novel bioactive compounds. A stereoselective approach, based on Brown chemistry, allowed the obtainment and the functional evaluation of the enantiopure hit compounds.     

Mediterranean diet in a Sicilian student population. Second part: breakfast and its nutritional profile

Abstract

Breakfast habits affect the nutritional status and health of people, in particular children and adolescents. This is the second part a previous study about the adherence to the Mediterranean diet in a Sicilian (Italy) student population. The investigation analysed both normal weight and overweight subjects in order to understand how eating habits, number of meals and daily calorie intakes could affect their body mass indexes (BMI). The aim of this second part was to analyse the breakfast nutritional profiles of this student population. The results highlighted that breakfast was regularly consumed by a percentage ranging from a maximum of 84% (in normal subjects) to a minimum value of 57.4% (in overweight/obese students). Milk, yoghurt, sugar, bread/rusk and tea contributed as main foods to the breakfast composition. The results highlighted that subjects who consumed breakfast showed lower BMI values with significant differences between normal and overweight/obese students.     

A Continuous-Time Random Walk Extension of the Gillis Model

We consider a continuous-time random walk which is the generalization, by means of the introduction of waiting periods on sites, of the one-dimensional non-homogeneous random walk with a position-dependent drift known in the mathematical literature as Gillis random walk. This modified stochastic process allows to significantly change local, non-local and transport properties in the presence of heavy-tailed waiting-time distributions lacking the first moment: we provide here exact results concerning hitting times, first-time events, survival probabilities, occupation times, the moments spectrum and the statistics of records. Specifically, normal diffusion gives way to subdiffusion and we are witnessing the breaking of ergodicity. Furthermore we also test our theoretical predictions with numerical simulations.     

Chaos control by using Motor Maps

In this paper a new method for chaos control is proposed, consisting of an unsupervised neural network, namely a Motor Map. In particular a feedback entrainment scheme is adopted: a chaotic system with a given parameter set generates the reference trajectory for another chaotic system with different parameters to be controlled: the Motor Map is required to provide the appropriate time-varying gain value for the feedback signal. The state of the controlled system is considered as input to the Motor Map. Particular efforts have been paid to the feasibility of the implementation. Indeed, the simulations performed have been oriented to design a Motor Map suitable for an hardware realization, thus some restrictive hypotheses, such as for example a low number of neurons, have been assumed. A huge number of simulations has been carried out by considering as system to be controlled a Double Scroll Chua Attractor as well as other chaotic attractors. Several reference trajectories have also been considered: a limit cycle generated by a Chua's circuit with different parameters values, a double scroll Chua attractor, a chaotic attractor of the family of the Chua's circuit attractors. In all the simulations instead of controlling the whole state space, only two state variables have been fed back. Good results in terms of settling time (namely, the period in which the map learns the control task) and steady state errors have been obtained with a few neurons. The Motor Map based adaptive controller offers high performances, specially in the case when the reference trajectory is switched into another one. In this case, a specialization of the neurons constituting the Motor Map is observed: while a group of neurons learns the appropriate control law for a reference trajectory, another group specializes itself to control the system when the other trajectory is used as a reference. A discrete components electronic realization of the Motor Map is presented and experimental results confirming the simulation results are shown. (c) 2002 American Institute of Physics.     

Equatorial Plane Circular Orbits in the Taub-NUT Spacetime

Accelerated circular orbits in the equatorial plane of the Taub-NUT spacetime are analyzed to investigate the effects of its gravitomagnetic monopole source. The effect of a small gravitomagnetic monopole on these orbits is compared to the corresponding orbits pushed slightly off the equatorial plane in the absence of the monopole.     

Transmission of HIV in sexual networks in sub-Saharan Africa and Europe

We are reviewing the literature regarding sexual networks and HIV transmission in sub-Saharan Africa and Europe. On Likoma Island in Malawi, a sexual network was reconstructed using a sociometric survey in which individuals named their sexual partners. The sexual network identified one giant component including half of all sexually active individuals. More than 25% of respondents were linked through independent chains of sexual relations. HIV was more common in the sparser regions of the network due to over-representation of groups with higher HIV prevalence. A study from KwaZulu-Natal in South-Africa collected egocentric data about sexual partners and found that new infections in women in a particular area was associated with the number of life-time partners in men. Data about sexual networks and HIV transmission are not reported in Europe. It is, however, found that the annual number of sexual partners follows a scale-free network. Phylogenetic studies that determine genetic relatedness between HIV isolates obtained from infected individuals, found that patients in the early stages of infections explain a high number of new infections. In conclusion, the limited information that is available suggest that sexual networks play a role in spread of HIV. Obtaining more information about sexual networks can be of benefit for modeling studies on HIV transmission and prevention.     

Sulle formole per la composizione di più movimenti finiti

Rendiconti del Circolo Matematico di Palermo Series 1 -     

The effect of post-irradiation annealing on the crosslinking of high-density polyethylene induced by gamma-radiation

Samples of two high-density polyethylenes having different crystallinity levels were gamma irradiated under vacuum at doses ranging from 20 to 300 kGy. Subsequently, the vials containing the irradiated samples were exposed to different post-irradiation treatments. Parts of the specimens were annealed while still under vacuum. The annealing time was 4 h and the annealing temperatures 110 °C or 150 °C. Others were exposed directly to air opening the vials without any thermal treatment. It was verified that in all cases the dosage to produce an incipient gel increases with the crystallinity of the initial sample. The amount of gel produced after exposing specimens of the same polymer to a given dose increases with the annealing temperature. The largest increment in the amount of gel produced at the completion of the post-irradiation treatment was found on the samples with the highest initial crystallinity level.Evidence of oxidation was found in all irradiated samples. The extent of oxidation depends on the initial crystallinity of the sample, the irradiation dose and the type of post-irradiation treatment. The heat of fusion measured in the annealed samples decreases with the gel content while the fusion temperature was slightly affected. Ductile or brittle behaviors were observed after testing specimens under tensile stress. The yield stress increases proportionally to the crystallinity level that, in turn, depends on the total dosage applied to the samples. The extensibility of ductile samples is determined by the amount of gel produced regardless of the degree of initial crystallinity and the type of annealing process applied to each sample.     

Extraction methods of red blood cell membrane proteins for Multidimensional Protein Identification Technology (MudPIT) analysis

Since red blood cells (RBCs) lack nuclei and organelles, cell membrane is their main load-bearing component and, according to a dynamic interaction with the cytoskeleton compartment, plays a pivotal role in their functioning. Even if erythrocyte membranes are available in large quantities, the low abundance and the hydrophobic nature of cell membrane proteins complicate their purification and detection by conventional 2D gel-based proteomic approaches. So, in order to increase the efficiency of RBC membrane proteome identification, here we took advantage of a simple and reproducible membrane sub-fractionation method coupled to Multidimensional Protein Identification Technology (MudPIT). In addition, the adoption of a stringent RBC filtration strategy from the whole blood, permitted to remove exhaustively contaminants, such as platelets and white blood cells, and to identify a total of 275 proteins in the three RBC membrane fractions collected and analysed. Finally, by means of software for the elaboration of the great quantity of data obtained and programs for statistical analysis and protein classification, it was possible to determine the validity of the entire system workflow and to assign the proper sub-cellular localization and function for the greatest number of the identified proteins.