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.     

Potential science-technology spillovers in regions: An insight on geographic co-location of knowledge activities in the EU

This article depicts some features of the geography of science and technology outputs in the EU, with a particular attention to regional “co-location” of these two pillars of the “knowledge-based society”. Economists have, for a decade, paid great attention to local “spillovers” stating that industrial firms often draw advantages from the presence of nearby academic centres. The presence in the same areas of strong academic and technological resources is both a condition and a result of science-technology interactions. Concentrating on publications and patents as proxies of the science and technology level in regions, we built a typology of regions according to their commitment to the two knowledge-base activities and then analysed the co-locations of science and technology from several points of view. A fine-grain lattice, mainly based on standard Nuts3 level, was used. Co-location, at the EU level, is not a general rule. A strong potential for spillover/ interaction does exist in the top-class regions which concentrate a high proportion of European S and T output. But for regions with a small/medium level of S&T activity, a divergence of orientations appears between a science-oriented family and a technology-oriented family, indicating an imbalance between local S and T resources. If we look at the S-oriented regions, whilst controlling for underlying factors, such as population and regional economic product, a significant geographic linkage between T and S appears. This suggests a trajectory of science-based technological development. A careful examination of S&T thematic alignments and specialisation is necessary to develop the hypothesis that fostering academic resources could increase the technological power along a growth path. This revised version was published online in August 2006 with corrections to the Cover Date.     

A DSS for Production Planning

This paper presents a decision support system designed to aid the production planner in choosing the values of the principle parameters governing just-in-time manufacturing. The DSS uses a knowledge base composed of data from simulations of the production of the entire product line under systematically varied conditions. The planners may add data from actual production experience as it is obtained. The stochastic dominance outranking method of Martel and Zaras allows the identification of clusters of parameters that respect the preferences of the decision maker. When launching an order for a product, the decision maker may judge certain sets of parameters to be equivalent. A visual interactive simulation model will then allow their comparison according to three performance criteria.     

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.     

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

Hybrid crafting: towards an integrated practice of crafting with physical and digital components

With current digital technologies, people have large archives of digital media, such as images and audio files, but there are only limited means to include these media in creative practices of crafting and making. Nevertheless, studies have shown that crafting with digital media often makes these media more cherished and that people enjoy being creative with their digital media. This paper aims to open up the way for novel means for crafting, which include digital media in integrations with physical construction, here called ‘hybrid crafting’. Notions of hybrid crafting were explored to inform the design of products or systems that may support these new crafting practices. We designed ‘Materialise’—a building set that allows for the inclusion of digital images and audio files in physical constructions by using tangible building blocks that can display images or play audio files, alongside a variety of other physical components—and used this set in four hands-on creative workshops to gain insight into how people go about doing hybrid crafting; whether hybrid crafting is desirable; what the characteristics of hybrid crafting are; and how we may design to support these practices. By reflecting on the findings from these workshops, we provide concrete guidelines for the design of novel hybrid crafting products or systems that address craft context, process and result. We aim to open up the design space to designing for hybrid crafting because these new practices provide interesting new challenges and opportunities for future crafting that can lead to novel forms of creative expression.     

A fast compound algorithm for mining generators,closed itemsets,and computing links between equivalence classes

In pattern mining and association rule mining, there is a variety of algorithms for mining frequent closed itemsets (FCIs) and frequent generators (FGs), whereas a smaller part further involves the precedence relation between FCIs. The interplay of these three constructs and their joint computation have been studied within the formal concept analysis (FCA) field yet none of the proposed algorithms is scalable. In frequent pattern mining, at least one suite of efficient algorithms has been designed that exploits basically the same ideas and follows the same overall computational schema. Based on an in-depth analysis of the aforementioned interplay that is rooted in a fundamental duality from hypergraph theory, we propose a new schema that should enable for a more parsimonious computation. We exemplify the new schema in the design of Snow-Touch, a concrete FCI/FG/precedence miner that reuses an existing algorithm, Charm, for mining FCIs, and completes it with two original methods for mining FGs and precedence, respectively. The performance of Snow-Touch and of its closest competitor, Charm-L, were experimentally compared using a large variety of datasets. The outcome of the experimental study suggests that our method outperforms Charm-L on dense data while on sparse one the trend is reversed. Furthermore, we demonstrate the usefulness of our method and the new schema through an application to the analysis of a genome dataset. The initial results reported here confirm the capacity of the method to focus on significant associations.     

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.