Kranc: a Mathematica application to generate numerical codes for tensorial evolution equations

We present a suite of Mathematica-based computer-algebra packages, termed "Kranc", which comprise a toolbox to convert (tensorial) systems of partial differential evolution equations to parallelized C or Fortran code. Kranc can be used as a "rapid prototyping" system for physicists or mathematicians handling very complicated systems of partial differential equations, but through integration into the Cactus computational toolkit we can also produce efficient parallelized production codes. Our work is motivated by the field of numerical relativity, where Kranc is used as a research tool by the authors. In this paper we describe the design and implementation of both the Mathematica packages and the resulting code, we discuss some example applications, and provide results on the performance of an example numerical code for the Einstein equations.Comment: 24 pages, 1 figure. Corresponds to journal versio

Fretting Corrosion Behavior of Additive Manufactured and Cryogenic-Machined Ti6Al4V for Biomedical Applications

Metal ion release, caused by synergistic effect of wear and corrosion, is one of the major concerns related to the prostheses lifetime. In this work, samples of additive manufactured Ti6Al4V are machined under dry cutting and cryogenic cooling conditions and their performances in terms of corrosion and fretting corrosion response are investigated. A wet and temperature-controlled apparatus equipped with an electro-chemical cell is designed and set-up in order to evaluate the fretting corrosion effect acting at the interfaces. The obtained results show that the cryogenic machining improves the corrosion and fretting corrosion behavior of the investigated additive manufactured Ti6Al4V

Unoccupied states in Cu and Zn octaethyl-porphyrin and phthalocyanine

Copper and zinc phthalocyanines and porphyrins are used in organic light emitting diodes and dye-sensitized solar cells. Using near edge x-ray absorption fine structure (NEXAFS) spectroscopy at the Cu 2p and Zn 2p edges, the unoccupied valence states at the Cu and Zn atoms are probed and decomposed into 3d and 4s contributions with the help of density functional calculations. A comparison with the N 1s edge provides the 2p states of the N atoms surrounding the metal, and a comparison with inverse photoemission provides a combined density of states.This work was supported by the NSF (Award Nos. CHE-1026245 and DMR-0537588 (SRC)) and by the DOE (Contract Nos. DE-FG02-01ER45917 (end station) and DE-AC03-76SF00098 (ALS)). J.M.G.L. and A.R. acknowledge financial support from Spanish MEC (FIS2007-65702-C02-01), ACI-Promociona (ACI2009-1036), Grupos Consolidados UPV/EHU del Gobierno Vasco (IT-319-07), the European Union through the FP7 e-I3 ETSF (Contract No. 211956), and THEMA (Contract No. 228539) projects.Peer Reviewe

The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease.

Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal microbiome of dogs with defined disease phenotypes

Inoculation of the Leishmania infantum HSP70-II null mutant induces long-term protection against L. amazonensis infection in BALB/c mice

Leishmania amazonensis parasites are etiological agents of cutaneous leishmaniasis in the New World. BALB/c mice are highly susceptible to L. amazonensis challenge due to their inability to mount parasite-dependent IFN-γ-mediated responses. Here, we analyzed the capacity of a single administration of the LiΔHSP70-II genetically-modified attenuated L. infantum line in preventing cutaneous leishmaniasis in mice challenged with L. amazonensis virulent parasites. In previous studies, this live attenuated vaccine has demonstrated to induce long-protection against murine leishmaniasis due to Old World Leishmania species. Vaccinated mice showed a reduction in the disease evolution due to L. amazonensis challenge, namely reduction in cutaneous lesions and parasite burdens. In contrast to control animals, after the challenge, protected mice showed anti-Leishmania IgG2a circulating antibodies accompanied to the induction of Leishmania-driven specific IFN-γ systemic response. An analysis performed in the lymph node draining the site of infection revealed an increase of the parasite-specific IFN-ϒ production by CD4+ and CD8+ T cells and a decrease in the secretion of IL-10 against leishmanial antigens. Since the immunity caused by the inoculation of this live vaccine generates protection against different forms of murine leishmaniasis, we postulate LiΔHSP70-II as a candidate for the development of human vaccines.This research was funded by grants from Ministerio de Ciencia e Innovación FISPI11/00095 and FISPI14/00366 (FEDER FUNDING) to M.S. and RYC-2016-19463 and RTI2018-343 to S.I. J.M.R. and M.S. are funded by the Fondo de Investigaciones Sanitarias (ISCIII-RETICRD16/0027/008-FEDER). E.H.G. is supported by a FPI grant from the Spanish Ministerio de Ciencia e Innovación. Institutional grants from the Fundación Ramón Areces and Banco de Santander to the CBMSO are also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine functionalized gold nanoparticles

Gold nanoparticles (AuNPs), which have been widely used for the delivery of photosensitizers for photodynamic therapy (PDT) of cancer, can be dispersed in aqueous solutions, improving the delivery of the hydrophobic photosensitizer into the body. Furthermore, the large surface of AuNPs can be functionalized with a variety of ligands, including proteins, nucleic acids and carbohydrates, that allow selective targeting to cancer tissue. In this study, gold nanoparticles were functionalized with a mixed monolayer of a zinc phthalocyanine and a lactose derivative. For the first time, a carbohydrate was used with a dual purpose, as the stabilizing agent of the gold nanoparticles in aqueous solutions and as the targeting agent for breast cancer cells. The functionalization of the phthalocyanine-AuNPs with lactose led to the production of water-dispersible nanoparticles that are able to generate singlet oxygen and effect cell death upon irradiation. The targeting ability of lactose of the lactose-phthalocyanine functionalized AuNPs was studied in vitro towards the galectin-1 receptor on the surface of breast cancer cells. The targeting studies showed the exciting potential of lactose as a specific targeting agent for galactose-binding receptors overexpressed on breast cancer cells

SHP-1 Regulates Antigen Cross-Presentation and Is Exploited by Leishmania to Evade Immunity.

Intracellular pathogens have evolved strategies to evade detection by cytotoxic CD8+ T lymphocytes (CTLs). Here, we ask whether Leishmania parasites trigger the SHP-1-FcRγ chain inhibitory axis to dampen antigen cross-presentation in dendritic cells expressing the C-type lectin receptor Mincle. We find increased cross-priming of CTLs in Leishmania-infected mice deficient for Mincle or with a selective loss of SHP-1 in CD11c+ cells. The latter also shows improved cross-presentation of cell-associated viral antigens. CTL activation in vitro reveals increased MHC class I-peptide complex expression in Mincle- or SHP-1-deficient CD11c+ cells. Neuraminidase treatment also boosts cross-presentation, suggesting that Leishmania triggers SHP-1-associated sialic-acid-binding receptors. Mechanistically, enhanced antigen processing correlates with reduced endosomal acidification in the absence of SHP-1. Finally, we demonstrate that SHP-1 inhibition improves CD11c+ cell-based vaccination against the parasite. Thus, SHP-1-mediated impairment of cross-presentation can be exploited by pathogens to evade CTLs, and SHP-1 inhibition improves CTL responses during vaccination.Work in the S.I. laboratory is funded by the Spanish Ministerio de Ciencia e Innovación (MICINN), Agencia Estatal de Investigación, and Fondo Europeo de Desarrollo Regional (RTI2018-094484-B-I00 and RYC-2016-19463). S.C.K. is a recipient of a FPU fellowship (FPU16/03142) from the Spanish Ministry of Education, Culture and Sports. M.M.-L. is a recipient of an EMBO Long-Term Fellowship (EMBO LTF 463-2019).S

Evidence of major dry mergers at M* > 2 x 10^11 Msun from curvature in early-type galaxy scaling relations?

For early-type galaxies, the correlations between stellar mass and size, velocity dispersion, surface brightness, color, axis ratio and color-gradient all indicate that two mass scales, M* = 3 x 10^10 Msun and M* = 2 x 10^11 Msun, are special. The smaller scale could mark the transition between wet and dry mergers, or it could be related to the interplay between SN and AGN feedback, although quantitative measures of this transition may be affected by morphological contamination. At the more massive scale, mean axis ratios and color gradients are maximal, and above it, the colors are redder, the sizes larger and the velocity dispersions smaller than expected based on the scaling at lower M*. In contrast, the color-sigma relation, and indeed, most scaling relations with sigma, are not curved: they are well-described by a single power law, or in some cases, are almost completely flat. When major dry mergers change masses, sizes, axis ratios and color gradients, they are expected to change the colors or velocity dispersions much less. Therefore, the fact that scaling relations at sigma > 150 km/s show no features, whereas the size-M*, b/a-M*, color-M* and color gradient-M* relations do, suggests that M* = 2 x 10^11 Msun is the scale above which major dry mergers dominate the assembly histories of early-type galaxies.Comment: 5 pages, 3 figures. Accepted for publication in MNRA

On the mechanical behaviour of PEEK and HA cranial implants under impact loading

The human head can be subjected to numerous impact loadings such as those produced by a fall or during sport activities. These accidents can result in skull fracture and in some complex cases, part of the skull may need to be replaced by a biomedical implant. Even when the skull is not damaged, such accidents can result in brain swelling treated by decompressive craniectomy. Usually, after recovery, the part of the skull that has been removed is replaced by a prosthesis. In such situations, a computational tool able to analyse the choice of prosthesis material depending on the patient's specific activity has the potential to be extremely useful for clinicians. The work proposed here focusses on the development and use of a numerical model for the analysis of cranial implants under impact conditions. In particular, two main biomaterials commonly employed for this kind of prosthesis are polyether-ether-ketone (PEEK) and macroporous hydroxyapatite (HA). In order to study the suitability of these implants, a finite element head model comprising scalp, skull, cerebral falx, cerebrospinal fluid and brain tissues, with a cranial implant replacing part of the skull has been developed from magnetic resonance imaging data. The human tissues and these two biocompatible materials have been independently studied and their constitutive models are provided here. A computational model of the human head under impact loading is then implemented and validated, and a numerical comparison of the mechanical impact response of PEEK and HA implants is presented. This comparison was carried out in terms of the effectiveness of both implants in ensuring structural integrity and preventing traumatic brain injury.The researchers of the University Carlos III are indebted to the Ministerio de Economía y Competitividad de España (Project DPI2014-57989-P) and Vicerrectorado de Política Científica UC3M (Project 2013-00219-002) for the financial support. A.J. acknowledges funding from the European Union's Seventh Framework Programme (FP7 2007–2013) ERC Grant Agreement No. 306587. MRI data were provided by the Human Connectome Project, WUMinn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Center for Systems Neuroscience at Washington University. Finally, we would like to thank Dr. S Barhli and Prof. J Marrow for valuable assistance with the X-ray tomography; the machine used was bought from EPSRC Grant EP/M02833X/1 “University of Oxford: experimental equipment upgrade”. Open Access funded by European Research Counci

How Large Can We Build a Cyclic Assembly? Impact of Ring Size on Chelate Cooperativity in Noncovalent Macrocyclizations

This is the peer-reviewed version of the following article: Angewandte Chemie International 56, 49 (2017): 15649-15653, which has been published in final form at https://doi.org/10.1002/anie.201709563. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-Archiving.Self-assembled systems rely on intramolecular cooperative effects to control their growth and regulate their shape, thus yielding discrete, well-defined structures. However, as the size of the system increases, cooperative effects tend to dissipate. We analyze here this situation by studying a set of oligomers of different lengths capped with guanosine and cytidine nucleosides, which associate in cyclic tetramers by complementary Watson–Crick H-bonding interactions. As the monomer length increases, and thus the number of C(sp)–C(sp 2 ) σ-bonds in the π-conjugated skeleton, the macrocycle stability decreases due to a notable reduction in effective molarity (EM), which has a clear entropic origin. We determined the relationship between EM or ΔS and the number of σ-bonds, which allowed us to predict the maximum monomer lengths at which cyclic species would still assemble quantitatively, or whether the cyclic species would not able to compete at all with linear oligomers over the whole concentration rangeFunding from the European Union (ERC-Starting Grant 279548) and MINECO (CTQ2014-57729-P) is gratefully acknowledge