489 research outputs found

    Experimental evidence of shock mitigation in a Hertzian tapered chain

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    We present an experimental study of the mechanical impulse propagation through a horizontal alignment of elastic spheres of progressively decreasing diameter ϕn\phi_n, namely a tapered chain. Experimentally, the diameters of spheres which interact via the Hertz potential are selected to keep as close as possible to an exponential decrease, ϕn+1=(1q)ϕn\phi_{n+1}=(1-q)\phi_n, where the experimental tapering factor is either q15.60q_1\simeq5.60~% or q28.27q_2\simeq8.27~%. In agreement with recent numerical results, an impulse initiated in a monodisperse chain (a chain of identical beads) propagates without shape changes, and progressively transfer its energy and momentum to a propagating tail when it further travels in a tapered chain. As a result, the front pulse of this wave decreases in amplitude and accelerates. Both effects are satisfactorily described by the hard spheres approximation, and basically, the shock mitigation is due to partial transmissions, from one bead to the next, of momentum and energy of the front pulse. In addition when small dissipation is included, a better agreement with experiments is found. A close analysis of the loading part of the experimental pulses demonstrates that the front wave adopts itself a self similar solution as it propagates in the tapered chain. Finally, our results corroborate the capability of these chains to thermalize propagating impulses and thereby act as shock absorbing devices.Comment: ReVTeX, 7 pages with 6 eps, accepted for Phys. Rev. E (Related papers on http://www.supmeca.fr/perso/jobs/

    Tailoring phase stability and electrical conductivity of Sr0.02La0.98Nb1–xTaxO4 for intermediate temperature fuel cell proton conducting electrolytes

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    Sr0.02La0.98Nb1–-xTaxO4 (SLNT, with x=0.1, 0.2, and 0.4) proton conducting oxides were synthesized by solid state reaction for application as electrolyte in solid oxide fuel cells operating below 600 °C. Dense pellets were obtained after sintering at 1600 °C for 5 h achieving a larger average grain size with increasing the tantalum content. Dilatometric measurements were used to obtain the SLNT expansion coefficient as a function of tantalum content (x), and it was found that the phase transition temperature increased with increasing the tantalum content, being T=561, 634, and 802 °C for x=0.1, 0.2, and 0.4, respectively. The electrical conductivity of SLNT was measured by electrochemical impedance spectroscopy as a function of temperature and tantalum concentration under wet (pH2O of about 0.03 atm) Ar atmosphere. At each temperature, the conductivity decreased with increasing the tantalum content, at 600 °C being 2.68×10−4, 3.14×10−5, and 5.41×10−6 Scm−1 for the x=0.1, 0.2, and 0.4 compositions, respectively. SLNT with x=0.2 shows a good compromise between proton conductivity and the requirement of avoiding detrimental phase transitions for application as a thin-film electrolyte below 600 °C

    The metabolic features of tumor-associated macrophages : opportunities for immunotherapy?

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    Funding: This work was supported by the Ministry of Education, Science, and Technological Development of the Republic of Serbia.Besides transformed cells, the tumors are composed of various cell types that contribute to undesirable tumor progression. Tumor-associated macrophages (TAMs) are the most abundant innate immune cells in the tumor microenvironment (TME). Within the TME, TAMs exhibit high plasticity and undergo specific functional metabolic alterations according to the availability of tumor tissue oxygen and nutrients, thus further contributing to tumorigenesis and cancer progression. Here, we review the main functional TAM metabolic patterns influenced by TME, including glycolysis, amino acid, and fatty acid metabolism. Moreover, this review discusses antitumor immunotherapies that affect TAM functionality by inducing cell repolarizing and metabolic profiles towards an antitumoral phenotype. Also, new macrophage-based cell therapeutic technologies recently developed using chimeric antigen receptor bioengineering are exposed, which may overcome all solid tumor physical barriers impeding the current adoptive cell therapies and contribute to developing novel cancer immunotherapies.Publisher PDFPeer reviewe

    Mesenchymal stem cell properties of dental pulp cells from deciduous teeth

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    In the present study we have isolated and identified mesenchymal stem cells (MSCs) from the exfoliated deciduous teeth dental pulp (DP-MSCs), as plastic-adherent, spindle-shaped cells with a high proliferative potential. Immunophenotype analyses revealed that DP-MSCs were positive for mesenchymal cell markers (CD90, CD44, CD105, STRO-1, vimentin and α-SMA), and negative for hematopoietic stem cell markers (CD11b, CD33, CD34, CD45, CD235a). DPMSCs were also capable of differentiating into adipogenic, chondrogenic, myogenic and osteogenic lineages, fulfilling the functional criterion for their characterization. These results demonstrate that DP-MSCs offer a valuable, readily accessible source to obtain and store adult stem cells for future use

    STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression

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    <p>Abstract</p> <p>Background</p> <p>Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the <it>STK39 </it>locus were recently associated with hypertension by genome-wide association in an Amish population; <it>in vitro </it>data from transient transfection experiments using reporter constructs suggested that altered <it>STK39 </it>expression might mediate the effect. However, other large studies have not implicated <it>STK39 </it>in hypertension. We determined whether reported SNPs influenced <it>STK39 </it>expression <it>in vivo</it>, or were associated with BP in a large British Caucasian cohort.</p> <p>Methods</p> <p>1372 members of 247 Caucasian families ascertained through a hypertensive proband were genotyped for reported risk variants in <it>STK39 </it>(rs6749447, rs3754777, rs35929607) using Sequenom technology. MERLIN software was used for family-based association testing. <it>Cis</it>-acting influences on expression were assessed <it>in vivo </it>using allelic expression ratios in cDNA from peripheral blood cells in 35 South African individuals heterozygous for a transcribed SNP in <it>STK39 </it>(rs1061471) and quantified by mass spectrometry (Sequenom).</p> <p>Results</p> <p>No significant association was seen between the SNPs tested and systolic or diastolic BP in clinic or ambulatory measurements (all p > 0.05). The tested SNPs were all associated with allelic expression differences in peripheral blood cells (p < 0.05), with the most significant association for the intronic SNP rs6749447 (P = 9.9 × 10<sup>-4</sup>). In individuals who were heterozygous for this SNP, on average the G allele showed 13% overexpression compared to the T allele.</p> <p>Conclusions</p> <p><it>STK39 </it>expression is modified by polymorphisms acting in <it>cis </it>and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with BP in a British Caucasian cohort.</p

    Mesenchymal stem cells isolated from human periodontal ligament

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    Mesenchymal stem cells (MSCs) were isolated from human periodontal ligament (hPDL-MSCs) and characterized by their morphology, clonogenic efficiency, proliferation and differentiation capabilities. hPDL-MSCs, derived from normal impacted third molars, possessed all of the properties of MSC, including clonogenic ability, high proliferation rate and multi-lineage (osteogenic, chondrogenic, adipogenic, myogenic) differentiation potential. Moreover, hPDL-MSCs expressed a typical MSC epitope profile, being positive for mesenchymal cell markers (CD44H, CD90, CD105, CD73, CD29, Stro-1, fibronectin, vimentin, alpha-SMA), and negative for hematopoietic stem cell markers (CD34, CD11b, CD45, Glycophorin-CD235a). Additionally, hPDL-MSCs, as primitive and highly multipotent cells, showed high expression of embryonic markers (Nanog, Sox2, SSEA4). The data obtained provided yet further proof that cells with mesenchymal properties can be obtained from periodontal ligament tissue. Although these cells should be further investigated to determine their clinical significance, hPDL-MSCs are believed to provide a renewable and promising cell source for new therapeutic strategies in the treatment of periodontal defects

    Interpreting changes in measles genotype: the contribution of chance, migration and vaccine coverage

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    <p>Abstract</p> <p>Background</p> <p>In some populations, complete shifts in the genotype of the strain of measles circulating in the population have been observed, with given genotypes being replaced by new genotypes. Studies have postulated that such shifts may be attributable to differences between the fitness of the new and the old genotypes.</p> <p>Methods</p> <p>We developed a stochastic model of the transmission dynamics of measles, simulating the effects of different levels of migration, vaccination coverage and importation of new genotypes on patterns in the persistence and replacement of indigenous genotypes.</p> <p>Results</p> <p>The analyses illustrate that complete replacement in the genotype of the strain circulating in populations may occur because of chance. This occurred in >50% of model simulations, for levels of vaccination coverage and numbers of imported cases per year which are compatible with those observed in several Western European populations (>80% and >3 per million per year respectively) and for the given assumptions in the model.</p> <p>Conclusion</p> <p>The interpretation of genotypic data, which are increasingly being collected in surveillance programmes, needs to take account of the underlying vaccination coverage and the level of the importation rate of measles cases into the population.</p

    Identification of Heterozygous Single- and Multi-exon Deletions in IL7R by Whole Exome Sequencing

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    PURPOSE: We aimed to achieve a retrospective molecular diagnosis by applying state-of-the-art genomic sequencing methods to past patients with T-B+NK+ severe combined immunodeficiency (SCID). We included identification of copy number variations (CNVs) by whole exome sequencing (WES) using the CNV calling method ExomeDepth to detect gene alterations for which routine Sanger sequencing analysis is not suitable, such as large heterozygous deletions. METHODS: Of a total of 12 undiagnosed patients with T-B+NK+ SCID, we analyzed eight probands by WES, using GATK to detect single nucleotide variants (SNVs) and small insertions and deletions (INDELs) and ExomeDepth to detect CNVs. RESULTS: We found heterozygous single- or multi-exon deletions in IL7R, a known disease gene for autosomal recessive T-B+NK+ SCID, in four families (seven patients). In three families (five patients), these deletions coexisted with a heterozygous splice site or nonsense mutation elsewhere in the same gene, consistent with compound heterozygosity. In our cohort, about a quarter of T-B+NK+ SCID patients (26%) had such compound heterozygous IL7R deletions. CONCLUSIONS: We show that heterozygous IL7R exon deletions are common in T-B+NK+ SCID and are detectable by WES. They should be considered if Sanger sequencing fails to detect homozygous or compound heterozygous IL7R SNVs or INDELs
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