Conformal prediction for frequency-severity modeling

We present a nonparametric model-agnostic framework for building prediction intervals of insurance claims, with finite sample statistical guarantees, extending the technique of split conformal prediction to the domain of two-stage frequency-severity modeling. The effectiveness of the framework is showcased with simulated and real datasets. When the underlying severity model is a random forest, we extend the two-stage split conformal prediction procedure, showing how the out-of-bag mechanism can be leveraged to eliminate the need for a calibration set and to enable the production of prediction intervals with adaptive width

Straightforward method for the preparation of lysine-based double-chained anionic surfactants

Double-chained surfactants with potential biocompatibility have been prepared in high yields by lysine acylation with four natural saturated fatty acids (C(6) to C(12)) and with cis-undec-5-enoic acid. The surfactants were found to assemble into nanotubules in aqueous medium and, when mixed with a commercial cationic surfactant, to spontaneously form liposomes

The Nlrc4 Inflammasome Contributes to Restriction of Pulmonary Infection by Flagellated Legionella spp. that Trigger Pyroptosis

The Nlrc4 inflammasome is triggered in response to contamination of the host cell cytoplasm with bacterial flagellin, which induces pyroptosis, a form of cell death that accounts for restriction of bacterial infections. Although induction of pyroptosis has been extensively investigated in response to Salmonella typhimurium and Legionella pneumophila, little is known regarding the role of the inflammasome for restriction of non-pneumophila Legionella species. Here, we used five species of the Legionella genus to investigate the importance of the inflammasome for restriction of bacterial infection in vivo. By infecting mice deficient for inflammasome components, we demonstrated that caspase-1 and Nlrc4, but not Asc, contribute to restriction of pulmonary infection with L. micdadei, L. bozemanii, L. gratiana, and L. rubrilucens. L. longbeachae, a non-flagellated bacterium that fails to trigger pyroptosis, was not restricted by the inflammasome and induced death in the infected mice. In contrast to L. longbeachae, flagellin mutants of L. pneumophila did not induce mice death; therefore, besides bypassing the Nlrc4 inflammasome, L. longbeachae may employ additional virulence strategies to replicate in mammalian hosts. Collectively, our data indicate that the Nlrc4 inflammasome plays an important role in host protection against opportunistic pathogenic bacteria that express flagellin

Stimuli-sensitive self-assembled tubules based on lysine-derived surfactants as nanocarriers for proteins

Drug delivery vectors based on amphiphilic molecules present considerable advantages, namely versatility in physicochemical properties and sensitivity to stimuli. Amino acid-based surfactants, in particular, are rather promising amphiphiles for this purpose1 because of their enhanced biocompatibility compared to conventional surfactants. In addition to forming micelles and vesicles, they can self-organize into other complex supramolecular structures, such as fibers, twisted ribbons, helical tapes and nanotubes.2,3 Herein, we have studied a family of novel anionic double-chained lysine-based surfactants, with variable degree of chain length mismatch. Because of their peculiar structure, these compounds are able to form in water tubular structures with assorted morphologies, as evidenced by video-enhanced light microscopy (VELM), scanning electron microscopy (SEM and cryo-SEM), cryogenic transmission electron microscopy (cryo-TEM) and atomic force microscopy (AFM).3 The loading ability of the tubules towards lysozyme, under varying experimental conditions, has been investigated inter alia by differential scanning microcalorimetry, gel electrophoresis and UV/VIS spectroscopy, with the goal of assessing the efficiency of these aggregates as pH- and temperature-sensitive nanocarriers for a model biomolecule. Results on the stability of the native and loaded tubules when in contact with different fluids (serum, artificial saliva, artificial sweat, blood), and on their toxicity in human cells, are also presented and discussed.FCT is gratefully acknowledged for financial support through Ph.D. grant SFRH/BD/108629/2015. CIQUP acknowledges financial support from FEDER/COMPETE and FCT through grants UID/QUI/00081/2013, POCI-01-0145-FEDER- 006980 and NORTE-01-0145-FEDER-000028

Object oriented programming : data preparation and visualization of FEM models

In this paper two object oriented applications are described. The former is intended to generate data associated with the finite element method (FEM) and the later is a three-dimensional visualization tool named 3DMesh. Both are based on the principles of object oriented programming, namely encapsulation, inheritance and polymorphism. To support the preparation of FEM data, a language named 3DO was developed. Its syntax is similar to a subset of the C++ programming language. 3DO is based on object construction and modification by methods that require a small number of arguments. With this tool, mesh generation, definition of properties and loads and mesh refinement can be performed with limited user effort, even when the model is complex. All the generated information can be visualized with the program 3DMesh. This application is based on the OpenGL library and uses the Microsoft Foundation Classes to simplify its integration in the MS-Windows environment. 3DMesh implements an interactive navigation technique that allows the visualization of the model interior, preserving its integrity. Model attributes and the results of the FEM analysis can also be visualized

Network Formation of Catanionic Vesicles and Oppositely Charged Polyelectrolytes. Effect of Polymer Charge Density and Hydrophobic Modification

In nonequimolar solutions of a cationic and an anionic surfactant, vesicles bearing a net charge can be spontaneously formed and apparently exist as thermodynamically stable aggregates. These vesicles can associate strongly with polymers in solution by means of hydrophobic and/or electrostatic interactions. In the current work, we have investigated the rheological and microstructural properties of mixtures of cationic polyelectrolytes and net anionic sodium dodecyl sulfate/didodecyldimethylammonium bromide vesicles. The polyelectrolytes consist of two cationic cellulose derivatives with different charge densities; the lowest charge density polymer contains also hydrophobic grafts, with the number of charges equal to the number of grafts. For both systems, polymer−vesicle association leads to a major increase in viscosity and to gel-like behavior, but the viscosity effects are more pronounced for the less charged, hydrophobically modified polymer. Evaluation of the frequency dependence of the storage and loss moduli for the two systems shows further differences in behavior: while the more long-lived cross-links occur for the more highly charged hydrophilic polymer, the number of cross-links is higher for the hydrophobically modified polymer. Microstructure studies by cryogenic transmission electron microscopy indicate that the two polymers affect the vesicle stability in different ways. With the hydrophobically modified polymer, the aggregates remain largely in the form of globular vesicles and faceted vesicles (polygon-shaped vesicles with largely planar regions). For the hydrophilic polycation, on the other hand, the surfactant aggregate structure is more extensively modified: first, the vesicles change from a globular to a faceted shape; second, there is opening of the bilayers leading to holey vesicles and ultimately to considerable vesicle disruption leading to planar bilayer, disklike aggregates. The faceted shape is tentatively attributed to a crystallization of the surfactant film in the vesicles. It is inferred that a hydrophobically modified polyion with relatively low charge density can better stabilize vesicles due to formation of molecularly mixed aggregates, while a hydrophilic polyion with relatively high charge density associates so strongly to the surfactant films, due to strong electrostatic interactions, that the vesicles are more perturbed and even disrupted

Influence of stoichiometry and structure on the optical properties of AlNxOy films

The AlNxOy system offers the possibility to obtain a wide range of responses, by tailoring the properties between Al, AlN and Al2O3, opening a significant number of possible applications. The aim of this work is to correlate the optical properties of AlNxOy thin films with their composition and structural features, taking as reference the binary systems AlNx and AlOy. In the AlNx system, the increase of the nitrogen content induced a wide variation in the optical properties, ranging from the typical profile of a polycrystalline Al-type film towards nearly constant reflectance values as low as 5%, as well as a smooth increase in samples transparency as the ratio N/Al approached unit. In the case of the AlOy system, the reflectance also decreased as the oxygen content increased, however the transition to transparent films (Al2O3-like) was more abrupt. The ternary system AlNxOy, revealed optical responses that ranged from a typical profile of a polycrystalline Al-type film, towards low and constant reflectance values in a wide range of x and y coefficients, ending up as semi-transparent when Al2O3-like films were formed. The unusual low optical reflectance of some films reveals some potential applications in solar power systems and sensors.This research is sponsored by FEDER funds through the program COMPETE-Programa Operacional Factores de Competitividade, by national funds through FCT,, under the projects PTDC/CTMNAN/ 112574/2009 and PEST-C-FIS/UI607/2011–2012, and Programa Pessoa 2010/2011—Cooperação Portugal/França, Proc. no 441.00, Project ‘COLOURCLUSTER’. J Borges also acknowledges FCT financial support under PhD grant no SFRH/BD/47118/200

Building on surface-active ionic liquids for the rescuing of the antimalarial drug chloroquine

Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug. The most potent ionic liquid was the laurate salt of chloroquine, which presented IC50 values of 4 and 110 nM against a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum, respectively, corresponding to an 11-and 6-fold increase in potency as compared to the reference chloroquine bisphosphate salt against the same strains. This unprecedented report opens new perspectives in both the fields of malaria chemotherapy and of surface-active ionic liquids derived from active pharmaceutical ingredients.publishersversionpublishe

Spontaneous vesicle formation in catanionic mixtures of amino acid-based surfactants: Chain length symmetry effects

The use of amino acids for the synthesis of novel surfactants with vesicle-forming properties potentially enhances the biocompatibility levels needed for a viable alternative to conventional lipid vesicles. In this work, the formation and characterization of catanionic vesicles by newly synthesized lysine- and serine-derived surfactants have been investigated by means of phase behavior mapping and PFG-NMR diffusometry and cryo-TEM methods. The lysine-derived surfactants are double-chained anionic molecules bearing a pseudogemini configuration, whereas the serine-derived amphiphile is cationic and single-chained. Vesicles form in the cationic-rich side for narrow mixing ratios of the two amphiphiles. Two pairs of systems were studied: one symmetric with equal chain lengths, 2C(12)/C(12), and the other highly asymmetric with 2C(8)/C(16) chains, where the serine-based surfactant has the longest chain. Different mechanisms of the vesicle-to-micelle transition were found, depending on symmetry: the 2C12/C12 system entails limited micellar growth and intermediate phase separation, whereas the 2C(8)/C(16) system shows a continuous transition involving large wormlike micelles. The results are interpreted on the basis of currently available models for the micelle-vesicle transitions and the stabilization of catanionic vesicles (energy of curvature vs mixing entropy)

DNA conformational dynamics in the presence of catanionic mixtures

DNA conformational behavior in the presence of non-stoichiometric mixtures of two oppositely charged surfactants, cetyltrimethylammonium bromide and sodium octyl sulfate, was directly visualized in an aqueous solution with the use of a fluorescence microscopy technique. It was found that in the presence of cationic-rich catanionic mixtures, DNA molecules exhibit a conformational transition from elongated coil to compact globule states. Moreover, if the catanionic mixtures form positively charged vesicles, DNA is adsorbed onto the surface of the vesicles in a collapsed globular form. When anionic-rich catanionic mixtures are present in the solution, no change in the DNA conformational behavior was detected. Cryogenic transmission electron microscopy, as well as measurements of translational diffusion coefficients of individual DNA chains, supported our optical microscopy observations.http://www.sciencedirect.com/science/article/B6T36-3WRB313-V/1/07d45ede3443f93c49fe5d72c57fdfa