Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection‐based delivery of insulin. Neonatal Fc receptor (FcRn)‐mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn‐targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH‐responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH‐sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn‐targeted NPs. Overall, these FcRn‐targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.     

Discrimination between accelerated life models via Approximate Bayesian Computation

Accelerated life testing (ALT) is widely used in high-reliability product estimation to get relevant information about an item's performance and its failure mechanisms. To analyse the observed ALT data, reliability practitioners need to select a suitable accelerated life model based on the nature of the stress and the physics involved. A statistical model consists of (i) a lifetime distribution that represents the scatter in product life and (ii) a relationship between life and stress. In practice, several accelerated life models could be used for the same failure mode and the choice of the best model is far from trivial. For this reason, an efficient selection procedure to discriminate between a set of competing accelerated life models is of great importance for practitioners. In this paper, accelerated life model selection is approached by using the Approximate Bayesian Computation (ABC) method and a likelihood-based approach for comparison purposes. To demonstrate the efficiency of the ABC method in calibrating and selecting accelerated life model, an extensive Monte Carlo simulation study is carried out using different distances to measure the discrepancy between the empirical and simulated times of failure data. Then, the ABC algorithm is applied to real accelerated fatigue life data in order to select the most likely model among five plausible models. It has been demonstrated that the ABC method outperforms the likelihood-based approach in terms of reliability predictions mainly at lower percentiles particularly useful in reliability engineering and risk assessment applications. Moreover, it has shown that ABC could mitigate the effects of model misspecification through an appropriate choice of the distance function.     

The use of coevolution and the artificial immune system for ensemble learning

This paper presents two new approaches for constructing an ensemble of neural networks (NN) using coevolution and the artificial immune system (AIS). These approaches are extensions of the CLONal Selection Algorithm for building ENSembles (CLONENS) algorithm. An explicit diversity promotion technique was added to CLONENS and a novel coevolutionary approach to build neural ensembles is introduced, whereby two populations representing the gates and the individual NN are coevolved. The former population is responsible for defining the ensemble size and selecting the members of the ensemble. This population is evolved using the differential evolution algorithm. The latter population supplies the best individuals for building the ensemble, which is evolved by AIS. Results show that it is possible to automatically define the ensemble size being also possible to find smaller ensembles with good generalization performance on the tested benchmark regression problems. More interestingly, the use of the diversity measure during the evolutionary process did not necessarily improve generalization. In this case, diverse ensembles may be found using only implicit diversity promotion techniques.     

Indexing and querying segmented web pages: the BlockWeb Model

We present in this paper a model for indexing and querying web pages, based on the hierarchical decomposition of pages into blocks. Splitting up a page into blocks has several advantages in terms of page design, indexing and querying such as (i) blocks of a page most similar to a query may be returned instead of the page as a whole (ii) the importance of a block can be taken into account, as well as (iii) the permeability of the blocks to neighbor blocks: a block b is said to be permeable to a block b?? in the same page if b?? content (text, image, etc.) can be (partially) inherited by b upon indexing. An engine implementing this model is described including: the transformation of web pages into blocks hierarchies, the definition of a dedicated language to express indexing rules and the storage of indexed blocks into an XML repository. The model is assessed on a dataset of electronic news, and a dataset drawn from web pages of the ImagEval campaign where it improves by 16% the mean average precision of the baseline.     

A memetic algorithm for the multi-compartment vehicle routing problem with stochastic demands

The multi-compartment vehicle routing problem (MC-VRP) consists of designing transportation routes to satisfy the demands of a set of customers for several products that, because of incompatibility constraints, must be loaded in independent vehicle compartments. Despite its wide practical applicability the MC-VRP has not received much attention in the literature, and the few existing methods assume perfect knowledge of the customer demands, regardless of their stochastic nature. This paper extends the MC-VRP by introducing uncertainty on what it is known as the MC-VRP with stochastic demands (MC-VRPSD). The MC-VRPSD is modeled as a stochastic program with recourse and solved by means of a memetic algorithm. The proposed memetic algorithm couples genetic operators and local search procedures proven to be effective on deterministic routing problems with a novel individual evaluation and reparation strategy that accounts for the stochastic nature of the problem. The algorithm was tested on instances of up to 484 customers, and its results were compared to those obtained by a savings-based heuristic and a memetic algorithm (MA/SCS) for the MC-VRP that uses a spare capacity strategy to handle demand fluctuations. In addition to effectively solve the MC-VRPSD, the proposed MA/SCS also improved 14 best known solutions in a 40-problem testbed for the MC-VRP.     

Product interface design: A participatory approach based on virtual reality

The usability of the user interface is a key aspect for the success of several industrial products. This assumption has led to the introduction of numerous design methodologies addressed to evaluate the user-friendliness of industrial products. Most of these methodologies follow the participatory design approach to involve the user in the design process. Virtual Reality is a valid tool to support Participatory Design, because it facilitates the collaboration among designers and users.The present study aims to evaluate the feasibility and the efficacy of an innovative Participatory Design approach where Virtual Reality plays a ‘double role’: a tool to evaluate the usability of the virtual product interface, and a communication channel that allows users to be directly involved in the design process as co-designers.In order to achieve these goals, we conducted three experiments: the purpose of the first experiment is to determine the influence of the virtual interface on the usability evaluation by comparing “user–real product” interaction and “user–virtual product” interaction. Subsequently, we tested the effectiveness of our approach with two experiments involving users (directly or through their participation in a focus group) in the redesign of a product user interface. The experiments were conducted with two typologies of consumer appliances: a microwave oven and a washing machine.