Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Stimuli-Responsive Nanocomposite Hydrogels for Biomedical Applications

The complex tissue-specific physiology that is orchestrated from the nano- to the macroscale, in conjugation with the dynamic biophysical/biochemical stimuli underlying biological processes, has inspired the design of sophisticated hydrogels and nanoparticle systems exhibiting stimuli-responsive features. Recently, hydrogels and nanoparticles have been combined in advanced nanocomposite hybrid platforms expanding their range of biomedical applications. The ease and flexibility of attaining modular nanocomposite hydrogel constructs by selecting different classes of nanomaterials/hydrogels, or tuning nanoparticle-hydrogel physicochemical interactions widely expands the range of attainable properties to levels beyond those of traditional platforms. This review showcases the intrinsic ability of hybrid constructs to react to external or internal/physiological stimuli in the scope of developing sophisticated and intelligent systems with application-oriented features. Moreover, nanoparticle-hydrogel platforms are overviewed in the context of encoding stimuli-responsive cascades that recapitulate signaling interplays present in native biosystems. Collectively, recent breakthroughs in the design of stimuli-responsive nanocomposite hydrogels improve their potential for operating as advanced systems in different biomedical applications that benefit from tailored single or multi-responsiveness.     

Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.     

Addition of ferulic acid,ethyl ferulate,and feruloylated monoacyl- and diacylglycerols to salad oils and frying oils

To determine antioxidative effects of ferulic acid and esterified ferulic acids, these compounds were added to soybean oils (SBO), which were evaluated for oxidative stability and frying stability. Additives included feruloylated MAG and DAG (FMG/FDG), ferulic acid, ethyl ferulate, and TBHQ. After frying tests with potato chips, oils were analyzed for retention of additives and polar compounds. Chips were evaluated for hexanal and rancid odor. After 15 h frying, 71% of FMG/FDG was retained, whereas 55% of ethyl ferulate was retained. TBHQ and ferulic acid levels were 6% and <1%, respectively. Frying oils with ethyl ferulate or TBHQ produced significantly less polar compounds than SBO with no additives. Chips fried in SBO with TBHQ or ferulic acid had significantly lower amounts of hexanal and significantly less rancid odor after 8 d at 60°C than other samples. Oils were also aged at 60°C, and stability was analyzed by PV, hexanal, and rancid odor. Oils with TBHQ or FMG/FDG had significantly less peroxides and hexanal, and a lower rancid odor intensity than the control. FMG/FDG inhibited deterioration at 60°C, whereas ethyl ferulate inhibited the formation of polar compounds in frying oil. Ferulic acid acted as an antioxidant in aged fried food. TBHQ inhibited oil degradation at both temperatures. Presented at the 94th AOCS Meeting & Expo, Kansas City, MO, May 4–7, 2003.     

Generating Rare Association Rules Using the Minimal Rare Itemsets Family

Rare association rules correspond to rare, or infrequent, itemsets, as opposed to frequent ones that are targeted by conventional pattern miners. Rare rules reflect regularities of local, rather than global, scope that can nevertheless provide valuable insights to an expert, especially in areas such as genetics and medical diagnosis where some specific deviations/illnesses occur only in a small number of cases. The work presented here is motivated by the long-standing open question of efficiently mining strong rare rules, i.e., rules with high confidence and low support. We also propose an efficient solution for finding the set of minimal rare itemsets. This set serves as a basis for generating rare association rules.     

A survey on offline scheduling with rejection

In classical deterministic scheduling problems, it is assumed that all jobs have to be processed. However, in many practical cases, mostly in highly loaded make-to-order production systems, accepting all jobs may cause a delay in the completion of orders which in turn may lead to high inventory and tardiness costs. Thus, in such systems, the firm may wish to reject the processing of some jobs by either outsourcing them or rejecting them altogether. The field of scheduling with rejection provides schemes for coordinated sales and production decisions by grouping them into a single model. Since scheduling problems with rejection are very interesting both from a practical and a theoretical point of view, they have received a great deal of attention from researchers over the last decade. The purpose of this survey is to offer a unified framework for offline scheduling with rejection by presenting an up-to-date survey of the results in this field. Moreover, we highlight the close connection between scheduling with rejection and other fields of research such as scheduling with controllable processing times and scheduling with due date assignment, and include some new results which we obtained for open problems.     

Approximation Bounds for Minimum Information Loss Microaggregation

The NP-hard microaggregation problem seeks a partition of data points into groups of minimum specified size k, so as to minimize the sum of the squared euclidean distances of every point to its group's centroid. One recent heuristic provides an O(k³) guarantee for this objective function and an O(k²) guarantee for a version of the problem that seeks to minimize the sum of the distances of the points to its group's centroid. This paper establishes approximation bounds for another microaggregation heuristic, providing better approximation guarantees of O(k²) for the squared distance measure and O(k) for the distance measure.     

Engineering an efficient two‐phase local search algorithm for the co‐rotating twin‐screw extruder configuration problem

The twin‐screw configuration problem arises during polymer extrusion and compounding. It consists in defining the location of a set of pre‐defined screw elements along the screw axis in order to optimize different, typically conflicting objectives. In this paper, we present a simple yet effective stochastic local search (SLS) algorithm for this problem. Our algorithm is based on efficient single‐objective iterative improvement algorithms, which have been developed by studying different neighborhood structures, neighborhood search strategies, and neighborhood restrictions. These algorithms are embedded into a variation of the two‐phase local search framework to tackle various bi‐objective versions of this problem. An experimental comparison with a previously proposed multi‐objective evolutionary algorithm shows that a main advantage of our SLS algorithm is that it converges faster to a high‐quality approximation to the Pareto front.     

A stabilized difference scheme for deformable porous media and its numerical resolution by multigrid methods

This paper deals with the 2D system of incompressible poroelasticity equations in which an artificial stabilization term has been added to the discretization on collocated grids. Two issues are discussed: It is proved and shown that the additional term indeed brings stability and does not spoil the second order accurate convergence. Secondly, various smoothers are examined in order to find an optimal multigrid method for the discrete system of equations. Numerical experiments confirm the stability and the second order accuracy, as well as fast multigrid convergence for a realistic poroelasticity experiment. This research has been partially supported by the INTAS project 03-50-4395, the Spanish project MEC/FEDER MTM 2004-019051, the Diputación General de Aragón and the Dutch program BSIK: knowledge and research capacity, in the ICT project BRICKS (http://www.bsik-bricks.nl), theme MSV1.