Drug delivery: Logic‐Embedded Vectors for Intracellular Partitioning,Endosomal Escape,and Exocytosis of Nanoparticles (Small 23/2010)

A new generation of nanocarriers, logic‐embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, thus creating an opportunity for synergistic control of redundant or dual‐hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface‐tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, amine‐functionalized nanoparticles are sorted into multiple vesicular bodies that form novel membrane‐bound compartments compatible with cellular secretion, while chitosan‐coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface‐tailored properties, and enhances endosomal escape of chitosan‐coated nanoparticles. Thus, LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.     

Mean stress and plasticity effect prediction on notch fatigue and crack growth threshold,combining the theory of critical distances and multiaxial fatigue criteria

In the present work, we propose a robust calibration of some bi‐parametric multiaxial fatigue criteria applied in conjunction with the theory of critical distances (TCD). This is based on least‐square fitting fatigue data generated using plain and sharp‐notched specimens tested at two different load ratios and allows for the estimation of the critical distance according to the point and line method formulation of TCD. It is shown that this combination permits to incorporate the mean stress effect into the fatigue strength calculation, which is not accounted for in the classical formulation of TCD based on the range of the maximum principal stress. It is also shown that for those materials exhibiting a low fatigue‐strength‐to‐yield‐stress ratio σ_fl,R = ?1/σ_YS, such as 7075‐T6 (σ_fl,R = ?1/σ_YS = 0.30), satisfactorily accurate predictions are obtained assuming a linear‐elastic stress distribution, even at the tip of sharp notches and cracks. Conversely, for any materials characterized by higher values of this ratio, as quenched and tempered 42CrMo4 (σ_fl,R = ?1/σ_YS = 0.54), it is recommended to consider the stabilized elastic‐plastic stress/strain distribution, also for plain and blunt‐notched samples and even in the high cycle fatigue regime still with the application of the TCD.     

Synchronisation control of electric motors through adaptive disturbance cancellation

A master–slave synchronisation control problem is addressed for current-fed DC and permanent magnet synchronous motors with all uncertain parameters. A measurable exogenous rotor position reference signal, which belongs to the class of biased sinusoidal signals with uncertain bias, amplitude, angular frequency, phase, is to be tracked without assuming its a priori knowledge. An innovative modification of disturbance cancellation techniques allows to prove that an output feedback adaptive nonlinear control scheme, which simply generalises the classical internal-model-based input law, solves the aforementioned problem, with an overall stability proof concerning the entire closed-loop system. The practical effectiveness of the proposed approach is illustrated by experimental results.     

Logic-embedded vectors for intracellular partitioning, endosomal escape, and exocytosis of nanoparticles

A new generation of nanocarriers, logic-embedded vectors (LEVs), is endowed with the ability to localize components at multiple intracellular sites, thus creating an opportunity for synergistic control of redundant or dual-hit pathways. LEV encoding elements include size, shape, charge, and surface chemistry. In this study, LEVs consist of porous silicon nanocarriers, programmed for cellular uptake and trafficking along the endosomal pathway, and surface-tailored iron oxide nanoparticles, programmed for endosomal sorting and partitioning of particles into unique cellular locations. In the presence of persistent endosomal localization of silicon nanocarriers, amine-functionalized nanoparticles are sorted into multiple vesicular bodies that form novel membrane-bound compartments compatible with cellular secretion, while chitosan-coated nanoparticles escape from endosomes and enter the cytosol. Encapsulation within the porous silicon matrix protects these nanoparticle surface-tailored properties, and enhances endosomal escape of chitosan-coated nanoparticles. Thus, LEVs provide a mechanism for shielded transport of nanoparticles to the lesion, cellular manipulation at multiple levels, and a means for targeting both within and between cells.     

Open shop scheduling problem with a multi-skills resource constraint: a genetic algorithm and an ant colony optimisation approach

The continuous evolution of manufacturing environments leads to a more efficient production process that controls an increasing number of parameters. Production resources usually represent an important constraint in a manufacturing activity, specially talking about the management of human resources and their skills. In order to study the impact of this subject, this paper considers an open shop scheduling problem based on a mechanical production workshop to minimise the total flow time including a multi-skill resource constraint. Then, we count with a number of workers that have a versatility to carry out different tasks, and according to their assignment a schedule is generated. In that way, we have formulated the problem as a linear as and a non-linear mathematical model which applies the classic scheduling constraints, adding some different resources constraints related to personnel staff competences and their availability to execute one task. In addition, we introduce a genetic algorithm and an ant colony optimisation (ACO) method to solve large size problems. Finally, the best method (ACO) has been used to solve a real industrial case that is presented at the end.     

Early nitrogen supply as an alternative management for a cover crop-maize sequence under a no-till system

Nutrient Cycling in Agroecosystems - The use of a controlled-release fertilizer (CRF) was studied in a traditional rainfed olive grove in a Mediterranean climate where precipitation is very...     

The ultra-modulating gas boiler as an opportunity for domestic energy saving

ABSTRACT

Domestic gas boilers on the market are able to modulate up to a modulation ratio equal to 10; in the present work the convenience of adopting modulation ratios up to 40 has been assessed. A methane condensing domestic boiler has been set up to work over the nominal modulation range up to 15, so that a consumption and efficiency experimental characterisation has been carried out and numerically extended to 40. A bin-method-based model has been implemented in order to estimate the modified boiler consumption for different scenarios. An increasing in the modulation ratio improves the overall boiler efficiency by reducing cycling losses yet rises the operating time and the electrical consumption; accordingly, in the present work a comprehensive analysis has been performed to identify optimal ‘ultra-modulating’ ratios for different climates and buildings.     

Forecasting lava flow hazards during the 2006 Etna eruption: Using the MAGFLOW cellular automata model

The MAGFLOW cellular automata (CA) model was able to fairly accurately reproduce the time of the lava flow advance during the 2006 Etna eruption, leading to very plausible flow predictions. MAGFLOW is intended for use in emergency response situations during an eruption to quickly forecast the lava flow path over some time interval from the immediate future to a long-time forecast. Major discrepancies between the observed and simulated paths occurred in the early phase of the 2006 eruption due to an underestimation of the initial flow rate, and at the time of the overlapping with the 2004–2005 lava flow. Very good representations of the areas likely to be inundated by lava flows were obtained when we adopt a time-varying effusion rate and include the 2004–2005 lava flow field in the Digital Elevation Model (DEM) of topography.     

Identification of Structural Features of 2‐Alkylidene‐1,3‐Dicarbonyl Derivatives that Induce Inhibition and/or Activation of Histone Acetyltransferases KAT3B/p300 and KAT2B/PCAF

Dysregulation of the activity of lysine acetyltransferases (KATs) is related to a variety of diseases and/or pathological cellular states; however, their role remains unclear. Therefore, the development of selective modulators of these enzymes is of paramount importance, because these molecules could be invaluable tools for assessing the importance of KATs in several pathologies. We recently found that diethyl pentadecylidenemalonate (SPV106) possesses a previously unobserved inhibitor/activator activity profile against protein acetyltransferases. Herein, we report that manipulation of the carbonyl functions of a series of analogues of SPV106 yielded different activity profiles against KAT2B and KAT3B (pure KAT2B activator, pan‐inhibitor, or mixed KAT2B activator/KAT3B inhibitor). Among the novel compounds, a few derivatives may be useful chemical tools for studying the mechanism of lysine acetylation and its implications in physiological and/or pathological processes.