A fracture mechanics model to study indentation cutting

Many cutting processes, such as chopping, slicing, and carving, consist in 2 different stages: an initial stage of indentation, in which the cutting tool is pushed into the material under the action of an external force, and a second stage, where the target material undergoes a progressive separation. This second stage is characterised by the formation of a fracture surface followed by the cut propagation due to the increasing external force, until eventually a steady state might occur. The purpose of this paper is to analyse the cutting process by means of some concepts of fracture mechanics and discuss the occurrence of the steady state. A simple model is used to obtain an analytic expression of the stress intensity factor at the tip of the cut and investigate the evolution of the fracture process. It is found that the cut propagation depends on the wedge sharpness. The analytic results are compared with finite element analyses, where the effect of tip blunting due to plasticity is taken into account. The influence of the cutting tool geometry is also discussed

on the fracture processes of cutting

Abstract: The process of cutting is treated as a fracture mechanical process. For an elliptic rigid wedge pressed into an elastic material, fracture may occur as an autonomous process if the tip of the wedge is sufficiently blunt or is affected by the geometry of the wedge if the tip is sharp. The conditions leading to the former or the latter case is obtained as a relation between the wedge tip radius, the fracture toughness and the modulus of elasticity. These limits and the intermediate states are discussed. The implications of the drastic changes of the mechanical state of the near tip region when the wedge edge is sharp are also discussed

relation between ribosomal rna genes and the dna satellites of phaseolus coccineus

The main band DNA of Phaseolus coccineus has a buoyant density of 1.692 g/ml. In roots, shoots, integuments and suspensors there is a DNA satellite with a buoyant density of 1.700 g/ml. The satellite of the roots, shoots and integuments represents approximately 28.2 %, 29.4 % and 34.7 % respectively of the total DNA. In suspensors, where polyteny occurs, besides the 1.700 g/ml satellite there is a second one at 1.696 g/ml. They represent about 32.9 % and 13.1 % of the total DNA. H3-25S and H3-18S ribosomal RNA of Phaseolus coccineus were hybridized separately with DNA of shoots from CsCl gradient fractions. In both hybridizations the peak of labelling coincides with the position of the DNA satellite with a buoyant density of 1.700 g/ml. Thus the genes for 25S and 18S are mainly located in this DNA component. Hybridization experiments at saturation inputs of H3-25S ribosomal RNA with DNA of shoots, integuments, roots and suspensors give saturation values of 0.72 %, 0.64 %, 0.51 % and 0.42 % respectively. The lower saturation value in the suspensors may indicate an underreplication of ribosomal genes in this tissue. This is partly cancelled out by the amplification in another DNA: that of the second satellite at 1.696 g/ml which does not seem to be part of the ribosomal DNA

RNA editing of the GLI1 transcription factor modulates the output of Hedgehog signaling

The Hedgehog (HH) signaling pathway has important roles in tumorigenesis and in embryonal patterning. The Gliomaassociated oncogene 1 (GLI1) is a key molecule in HH signaling, acting as a transcriptional effector and, moreover, is considered to be a potential therapeutic target for several types of cancer. To extend our previous focus on the implications of alternative splicing for HH signal transduction, we now report on an additional post-transcriptional mechanism with an impact on GLI1 activity, namely RNA editing. The GLI1 mRNA is highly edited at nucleotide 2179 by adenosine deamination in normal cerebellum, but the extent of this modification is reduced in cell lines from the cerebellar tumor medulloblastoma. Additionally, basal cell carcinoma tumor samples exhibit decreased GLI1 editing compared with normal skin. Interestingly, knocking down of either ADAR1 or ADAR2 reduces RNA editing of GLI1. This adenosine to inosine substitution leads to a change from Arginine to Glycine at position 701 that influences not only GLI1 transcriptional activity, but also GLI1-dependent cellular proliferation. Specifically, the edited GLI1, GLI1-701G, has a higher capacity to activate most of the transcriptional targets tested and is less susceptible to inhibition by the negative regulator of HH signaling suppressor of fused. However, the Dyrk1a kinase, implicated in cellular proliferation, is more effective in increasing the transcriptional activity of the non-edited GLI1. Finally, introduction of GLI1-701G into medulloblastoma cells confers a smaller increase in cellular growth relative to GLI1. In conclusion, our findings indicate that RNA editing of GLI1 is a regulatory mechanism that modulates the output of the HH signaling pathway. Copyright © 2013 Landes Bioscience

Sebum lipids influence macrophage polarization and activation

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Structural characterization of an all-aminosugar-containing capsular polysaccharide from Colwellia psychrerythraea 34H

Colwellia psychrerythraea strain 34H, a Gram-negative bacterium isolated from Arctic marine sediments, is considered a model to study the adaptation to cold environments. Recently, we demonstrated that C. psychrerythraea 34H produces two different extracellular polysaccharides, a capsular polysaccharide and a medium released polysaccharide, which confer cryoprotection to the bacterium. In this study, we report the structure of an additional capsular polysaccharide produced by Colwellia grown at a different temperature. The structure was determined using chemical methods, and one- and two-dimensional NMR spectroscopy. The results showed a trisaccharide repeating unit made up of only amino-sugar residues: N-acetyl-galactosamine, 2,4-diacetamido-2,4,6-trideoxy-glucose (bacillosamine), and 2-acetamido-2-deoxyglucuronic acid with the following structure: →4)-β-d-GlcpNAcA-(1 →3)-β-d-QuipNAc4NAc-(1 →3)-β-d-GalpNAc-(1 →. The 3D model, generated in accordance with 1H,1H-NOE NMR correlations and consisting of ten repeating units, shows a helical structure. In contrast with the other extracellular polysaccharides produced from Colwellia at 4 °C, this molecule displays only a low ice recrystallization inhibition activity

Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages

Genomic insertion of a heterologous acetyltransferase generates a new lipopolysaccharide antigenic structure in brucella abortus and brucella melitensis

Brucellosis is a bacterial zoonosis of worldwide distribution caused by bacteria of the genus Brucella. In Brucella abortus and Brucella melitensis, the major species infecting domestic ruminants, the smooth lipopolysaccharide (S-LPS) is a virulence factor. This S-LPS carries a N-formyl-perosamine homopolymer O-polysaccharide that is the major antigen in serodiagnostic tests and is required for virulence. We report that the Brucella O-PS can be structurally and antigenically modified using wbdR, the acetyl-transferase gene involved in N-acetyl-perosamine synthesis in Escherichia coli O157:H7. Brucella constructs carrying plasmidic wbdR expressed a modified O-polysaccharide but were unstable, a problem circumvented by inserting wbdR into a neutral site of chromosome II. As compared to wild-type bacteria, both kinds of wbdR constructs expressed shorter O-polysaccharides and NMR analyses showed that they contained both N-formyl and N-acetyl-perosamine. Moreover, deletion of the Brucella formyltransferase gene wbkC in wbdR constructs generated bacteria producing only N-acetyl-perosamine homopolymers, proving that wbdR can replace for wbkC. Absorption experiments with immune sera revealed that the wbdR constructs triggered antibodies to new immunogenic epitope(s) and the use of monoclonal antibodies proved that B. abortus and B. melitensis wbdR constructs respectively lacked the A or M epitopes, and the absence of the C epitope in both backgrounds. The wbdR constructs showed resistance to polycations similar to that of the wild-type strains but displayed increased sensitivity to normal serum similar to that of a per R mutant. In mice, the wbdR constructs produced chronic infections and triggered antibody responses that can be differentiated from those evoked by the wild-type strain in S-LPS ELISAs. These results open the possibilities of developing brucellosis vaccines that are both antigenically tagged and lack the diagnostic epitopes of virulent field strains, thereby solving the diagnostic interference created by current vaccines against Brucella

Evaluation of 68Ga-labeled peptide tracer for detection of gelatinase expression after myocardial infarction in rat

BACKGROUND: Matrix metalloproteinases 2 and 9 (MMP-2/9) play a role in extracellular matrix remodeling after an ischemic myocardial injury. We evaluated 68Ga-DOTA-peptide targeting MMP-2/9 for the detection of gelatinase expression after myocardial infarction (MI) in rat.METHODS: Rats were injected with 43 ± 7.7 MBq of 68Ga-DOTA-peptide targeting MMP-2/9 at 7 days (n = 7) or 4 weeks (n = 8) after permanent coronary ligation or sham operation (n = 5 at both time points) followed by positron emission tomography (PET). The left ventricle was cut in frozen sections for autoradiography and immunohistochemistry 30 minutes after tracer injection.RESULTS: Immunohistochemical staining showed MMP-2 and MMP-9 expressing cells, CD31-positive endothelial cells, and CD68-positive macrophages in the infarcted myocardium. Autoradiography showed increased tracer uptake in the infarcted area both at 7 days and 4 weeks after MI (MI-to-remote area ratio 2.5 ± 0.46 and 3.1 ± 1.0, respectively). Tracer uptake in damaged tissue correlated with the amount of CD68-positive macrophages at 7 days after MI, and CD31-positive endothelial cells at 7 days and 4 weeks after MI. The tracer was rapidly metabolized, radioactivity in the blood exceeded that of the myocardium, and tracer accumulation in the heart was not detectable by in vivo PET.CONCLUSIONS: 68Ga-DOTA-peptide targeting MMP-2/9 accumulates in the damaged rat myocardium after an ischemic injury, but tracer instability and slow clearance in vivo make it unsuitable for further evaluation.</p