Evaluation of direct light processing for the fabrication of bioactive ceramic scaffolds: Effect of pore/strut size on manufacturability and mechanical performance

Bioactive ceramic scaffolds for bone regeneration consisting of a three-dimensional mesh of interpenetrating struts with square section were fabricated via Digital Light Processing (DLP). The ability of the technique to manufacture 3D porous structures from β-tricalcium phosphate (β-TCP) powders with different dimensions of struts and pores was evaluated, identifying the possibilities and limitations of the manufacturing process. Small pore sizes were found to seriously complicate the elimination of excess slurry from the scaffold’s innermost pores. The effect of the strut/pore size on the mechanical performance of the scaffolds under compressive stresses was also evaluated, but no significant influence was found. Under compressive stresses, the structures resulted weaker when tested perpendicularly to the printing plane due to interlayer shear failure. Interlayer superficial grooves are proposed as potential failure-controlling defects, which could also explain the lack of a Weibull size effect on the mechanical strength of the fabricated DLP scaffolds.     

Validation of scientific topic models using graph analysis and corpus metadata

Probabilistic topic modeling algorithms like Latent Dirichlet Allocation (LDA) have become powerful tools for the analysis of large collections of documents (such as papers, projects, or funding applications) in science, technology an innovation (STI) policy design and monitoring. However, selecting an appropriate and stable topic model for a specific application (by adjusting the hyperparameters of the algorithm) is not a trivial problem. Common validation metrics like coherence or perplexity, which are focused on the quality of topics, are not a good fit in applications where the quality of the document similarity relations inferred from the topic model is especially relevant. Relying on graph analysis techniques, the aim of our work is to state a new methodology for the selection of hyperparameters which is specifically oriented to optimize the similarity metrics emanating from the topic model. In order to do this, we propose two graph metrics: the first measures the variability of the similarity graphs that result from different runs of the algorithm for a fixed value of the hyperparameters, while the second metric measures the alignment between the graph derived from the LDA model and another obtained using metadata available for the corresponding corpus. Through experiments on various corpora related to STI, it is shown that the proposed metrics provide relevant indicators to select the number of topics and build persistent topic models that are consistent with the metadata. Their use, which can be extended to other topic models beyond LDA, could facilitate the systematic adoption of this kind of techniques in STI policy analysis and design.

     

Quality enhancement of the abundant under‐valued crustacean,lobster krill (Munida spp.), during its chilled storage

Lobster krill (Munida genus) represents an under‐valued crustacean frequently caught on European fishing banks. In this work, its sensory, microbiological and biochemical qualities were evaluated during chilled storage. Additionally, the effects of a prestorage antimelanosic treatment consisting of soaking in sodium metabisulphite (SMB) solutions at two different concentrations (0.25% and 0.75%) were also studied. SMB prestorage treatment provided lobster specimens that still exhibited acceptable sensory quality after 10 days of storage, while control specimens were unacceptable at that time. SMB treatment also resulted in a significant (P < 0.05) inhibition of microbial growth, mainly of Enterobacteriaceae, psychrotrophes and proteolytic bacteria. Low lipid oxidation levels were observed for all batches; however, a significantly higher (P < 0.05) retention of polyunsaturated fatty acids was found in SMB‐treated lobster, especially in the 0.75% SMB batch. The results presented here open the way to the potential commercialisation of currently under‐utilised lobster krill as a chilled product.     

Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

Bioinformatic characterization of the extracellular lipases from Kluyveromyces marxianus

Lipases are hydrolytic enzymes that break the ester bonds of triglycerides, generating free fatty acids and glycerol. Extracellular lipase activity has been reported for the nonconventional yeast Kluyveromyces marxianus, grown in olive oil as a substrate, and the presence of at least eight putative lipases has been detected in its genome. However, to date, there is no experimental evidence on the physiological role of the putative lipases nor their structural and catalytic properties. In this study, a bioinformatic analysis of the genes of the putative lipases from K. marxianus L-2029 was performed, particularly identifying and characterizing the extracellular expected enzymes, due to their biotechnological relevance. The amino acid sequence of 10 putative lipases, obtained by in silico translation, ranged between 389 and 773 amino acids. Two of the analysed putative proteins showed a signal peptide, 25 and 33 amino acids long for KmYJR107Wp and KmLIP3p, and a molecular weight of 44.53 and 58.23 kDa, respectively. The amino acid alignment of KmLIP3p and KmYJR107Wp with the crystallized lipases from a patatin and the YlLip2 lipase from Yarrowia lipolytica, respectively, revealed the presence of the hydrolase characteristic motifs. From the 3D models of putative extracellular K. marxianus L-2029 lipases, the conserved pentapeptide of each was determined, being GTSMG for KmLIP3p and GHSLG for KmYJR107Wp; besides, the genes of these two enzymes (LIP3 and YJR107W) are apparently regulated by oleate response elements. The phylogenetic analysis of all K. marxianus lipases revealed evolutionary affinities with lipases from abH15.03, abH23.01, and abH23.02 families.     

Generation of Technology-Independent Retargetable Analog Blocks

This paper introduces a complete methodology for retargeting of analog cells to different sets of specifications. This methodology is technology-independent, thus allowing the migration, from one technology to another, of the circuit under retargeting. Careful integration of the device sizing and layout generation tasks via the incorporation of layout constraints during the sizing process allows to generate fully functional designs in a few minutes. The methodology is illustrated via the retargeting of a fully-differential Miller-compensated two-stage operational amplifier for a new set of specifications and two different technological processes.An erratum to this article can be found at     

A Symbolic Pole/Zero Extraction Methodology Based on Analysis of Circuit Time-Constants

This paper introduces a methodology for symbolic pole/zero extraction based on the formulation of the time-constant matrix of the circuits. This methodology incorporates approximation techniques specifically devoted to achieve an optimum trade-off between accuracy and complexity of the symbolic root expressions. The capability to efficiently handle even large circuits will be demonstrated through several practical circuits.     

Inhibition of acid rock drainage from uranium ore waste using a conventional neutralization and precipitation treatment

Glass columns (length 50 cm, i.d. 4 cm) containing 900 g of uranium ore waste were subjected to a three-step process: (1) acid drainage generation, (2) neutralization and precipitation treatment and, again, (3) acid drainage generation. In the first acid generation step, lasting about one year, different variables (pyrite addition, inoculation and irrigation solution) were tested by measuring effluent pH, redox potential, total iron and sulphate. Conditions of acid generation were satisfactorily reproduced, reaching stable pH values around 2.0 that were determined mainly by pyrite addition and the type of irrigation solution used (distilled water or ferrous sulphate). The neutralization and precipitation treatment consisted of alternating irrigations of a neutralizing solution (CaO saturated plus NaOH) and a precipitating solution (ferric sulphate saturated). This treatment caused accumulation of basic iron sulphate and iron oxide precipitates according to SEM studies. After this treatment, the barrier effect created by the reaction products was checked, using irrigation solutions similar to the first step. The effluents collected showed higher pH and lower redox potential, total iron and sulphate values than those observed before the treatment, evidencing inhibition of acid drainage generation.     

Molecular weight effect on the obtainment of parallel and perpendicular orientation in thermotropic poly(diethylene glycol <Emphasis Type="Italic">p,p′</Emphasis>-bibenzoate)

Summary The effect of molecular weight on the uniaxial orientation process has been analyzed in two samples of thermotropic poly(diethylene glycol p,p′-bibenzoate), evaluating the influence of that parameter on the type of orientation obtained. Several strain rates and deformation temperatures have been tested in order to map out the conditions for obtaining the two different kinds of orientation. The results show that in the lower molecular weight PDEB sample (M_w=31200) it is rather easy to get exclusively perpendicular “anomalous” orientation, with the molecular axes aligned transversely to the stretching direction. However, it is extremely difficult to obtain 100% parallel “normal” orientation. On the contrary, either type of orientation or a mixture of them can be easily developed for the higher molecular weight PDEB sample (M_w=102900).