RATIONALE:Accurate knowledge of the cellular composition of the heart is essential to fully understand the changes that occur during pathogenesis and to devise strategies for tissue engineering and ...regeneration.
OBJECTIVE:To examine the relative frequency of cardiac endothelial cells, hematopoietic-derived cells, and fibroblasts in the mouse and human heart.
METHODS AND RESULTS:Using a combination of genetic tools and cellular markers, we examined the occurrence of the most prominent cell types in the adult mouse heart. Immunohistochemistry revealed that endothelial cells constitute >60%, hematopoietic-derived cells 5% to 10%, and fibroblasts <20% of the nonmyocytes in the heart. A refined cell isolation protocol and an improved flow cytometry approach provided an independent means of determining the relative abundance of nonmyocytes. High-dimensional analysis and unsupervised clustering of cell populations confirmed that endothelial cells are the most abundant cell population. Interestingly, fibroblast numbers are smaller than previously estimated, and 2 commonly assigned fibroblast markers, Sca-1 and CD90, under-represent fibroblast numbers. We also describe an alternative fibroblast surface marker that more accurately identifies the resident cardiac fibroblast population.
CONCLUSIONS:This new perspective on the abundance of different cell types in the heart demonstrates that fibroblasts comprise a relatively minor population. By contrast, endothelial cells constitute the majority of noncardiomyocytes and are likely to play a greater role in physiological function and response to injury than previously appreciated.
A combined theoretical/experimental approach accurately quantifying post-necking hardening phenomena in ductile sheet materials that initially exhibit diffuse necking in tension is presented. The ...method is based on the minimization of the discrepancy between the internal and the external work in the necking zone during a quasi-static tensile test. The main focus of this paper is on the experimental validation of the method using an independent material test. For this purpose, the uniaxial tube expansion test is used to obtain uniaxial strain hardening behavior beyond the point of maximum uniform strain in a tensile test. The proposed method is used to identify the post-necking hardening behavior of a cold rolled interstitial-free steel sheet. It is demonstrated that commonly adopted phenomenological hardening laws cannot accurately describe all hardening stages. An alternative phenomenological hardening model is presented which enables to disentangle pre- and post-necking hardening behavior. Additionally, the influence of the yield surface on the identified post-necking hardening behavior is scrutinized. The results of the proposed method are compared with the hydraulic bulge test. Unlike the hydraulic bulge test, the proposed method predicts a decreased hardening rate in the post-necking regime which might be associated with probing stage IV hardening. While inconclusive, the discrepancy with the hydraulic bulge test suggests differential work hardening at large plastic strains.
A novel cruciform specimen design is proposed, which is a composite of existing specimens. The typical shortcomings of many existing designs are that the strains achievable in the test-section before ...failure are very limited and the stresses in the test-section cannot be easily determined from experimental measurements, or without the use of an inverse finite element analysis. The proposed specimen overcomes both of these difficulties. The proposed geometry features slotted arms; very tight corner radii; a test-section of reduced thickness; and a sharp transition between the arms and the test-section. This new geometry is investigated numerically, at first. It is shown that the stress and strain distributions in the test-section are very uniform, with the exception of a thin outer boundary-layer. This implies that the strains can be measured anywhere in the test-section (except at the boundary-layer) without significant impact on the results. Subsequently, a virtual biaxial experiment is described. Two materials (steel 1018 and aluminum Al-2090-T3) are considered, each with an appropriate material model (Hill 1948 and Yld2004-3D, respectively). In both cases, the proposed specimen identifies the material model very accurately, using only the load cell readings and strains measured within the test-section. Finally, the proposed specimen is used in biaxial experiments to identify an appropriate material model for the dual-phase steel DP 590. It is shown that the Yld2004-3D model captures the material behavior up to almost 10 % strain; however the coefficients of this model should evolve with plastic deformation, for best fitting performance. During the course of the experimental study, the uniformity of the strain fields is assessed using the Digital Image Correlation method.
Tension and compression experiments on magnesium rolled sheets and extruded products of AZ31 (Mg + 3%Al + 1%Zn) and ZE10 (Mg + 1%Zn + 0.3%Ce based misc metal) were performed at room temperature. The ...tests were conducted along the longitudinal and the transverse direction to quantify the in-plane anisotropy. Samples built from adhesively-bonded layers of sheets were used for in-plane as well as through-thickness compression testing. It was verified that this simple testing method leads to identical results as using comb-like dies and equi-biaxial bulge testing, respectively. In the case of uniaxial loading, the longitudinal and transverse strain components were measured using independent extensometers.
R
-values were calculated from these signals. The mechanical responses were correlated to the microstructure and the texture. The recorded differences between tensile and compressive response reveal the strength differential effect of the materials. The distortional character of the plastic behaviour is evidenced through their responses to equi-biaxial tensile loading. Significant differences in the compressive responses of the two alloys were identified by comparing the respective hardening rates.
The large strain flow curve is an essential input for the calibration of a myriad of plasticity models required for accurately simulating sheet metal forming processes and the mechanical performance ...of formed components. Studies on large strain flow curve identification can be divided in three main categories. The first class of experiments generate statically determinate stress states which unambiguously correlate analytically to the external load and measured strains, hence enable a direct measurement of the large strain flow curve. The second category relies on the intermittently measured flow stress using pre-strained samples to construct the large strain flow curve. The third category consists of methods that minimize the discrepancy between the experimentally acquired and the numerically computed measurand to inversely identify a chosen hardening law representing the large strain flow curve. The paper presents an overview of the state-of-the-art methods to acquire the large strain flow curve of sheet metal. A selected number of methods are reviewed and recent developments are discussed in detail. Finally, an objective assessment of the selected methods is pursued by applying them to a DP600 steel sheet.
Ultrahigh energy neutrinos are interesting messenger particles since, if detected, they can transmit exclusive information about ultrahigh energy processes in the Universe. These particles, with ...energies above 10 super(16)eV , interact very rarely. Therefore, detectors that instrument several gigatons of matter are needed to discover them. The ARA detector is currently being constructed at the South Pole. It is designed to use the Askaryan effect, the emission of radio waves from neutrino-induced cascades in the South Pole ice, to detect neutrino interactions at very high energies. With antennas distributed among 37 widely separated stations in the ice, such interactions can be observed in a volume of several hundred cubic kilometers. Currently three deep ARA stations are deployed in the ice, of which two have been taking data since the beginning of 2013. In this article, the ARA detector "as built" and calibrations are described. Data reduction methods used to distinguish the rare radio signals from overwhelming backgrounds of thermal and anthropogenic origin are presented. Using data from only two stations over a short exposure time of 10 months, a neutrino flux limit of 1.5x10 super(-6)GeV/cm super(2)/s/sr is calculated for a particle energy of 10 super(18)eV , which offers promise for the full ARA detector.
The anisotropic plastic deformation behavior of extruded 5000 series aluminum alloy tubes, A5154-H112, of 76 mm outer diameter and 3.9 mm wall thickness is investigated, using a servo-controlled ...tension-internal pressure testing machine. This machine is capable of applying arbitrary stress or strain paths to a tubular specimen using an electrical, closed-loop control system. Detailed measurements were made of the initial yield locus, contours of plastic work for different levels of work-hardening, and the directions of the incremental plastic strain vectors for both linear and combined stress paths. It is found that the measured work contours constructed in the principal stress space are similar in shape, and that the directions of the incremental plastic strain vectors remain almost constant at constant stress ratios. The work-hardening behavior predicted using Hosford's or the Yld2000-2d yield functions under the assumption of isotropic hardening agrees closely with the observations for both linear and combined stress paths. The material is thus found to work-harden almost isotropically. Both yield functions are effective phenomenological plasticity models for predicting the anisotropic plastic deformation behavior of the material.
Plastic deformation of the commercial magnesium sheet alloy AZ31 under monotonic loadings was investigated by means of mechanical tests and numerical simulations. In addition to the commonly used ...uniaxial test two complementary mechanical tests were performed: a biaxial test using cruciform specimens and a hydraulic bulge test. Both tests lead to consistent results and provided evidence for the differential strain hardening character of the considered material. A polycrystalline aggregate was generated from the measured texture data. Simulations using the visco-plastic self-consistent (VPSC) scheme indicated the primary role of pyramidal slip in equibiaxial tension. Contours of equal plastic work have been generated using a methodology based on probing the aggregate in the space of principal strains. The contours were compared with the respective tests. Hardening parameters were fitted in order to capture the initial yield and evolution of iso-work contours. The limitations of the numerical framework’s predictive capability as well as the directions for parameter identification of phenomenological yield surfaces were formulated.
Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. Although fibrosis accompanies many cardiac pathologies and is generally ...deleterious, the role of fibroblasts in maintaining the basal ECM network and in fibrosis in vivo is poorly understood. We genetically ablated fibroblasts in mice to evaluate the impact on homeostasis of adult ECM and cardiac function after injury. Fibroblast-ablated mice demonstrated a substantive reduction in cardiac fibroblasts, but fibrillar collagen and the ECM proteome were not overtly altered when evaluated by quantitative mass spectrometry and N-terminomics. However, the distribution and quantity of collagen VI, microfibrillar collagen that forms an open network with the basement membrane, was reduced. In fibroblast-ablated mice, cardiac function was better preserved following angiotensin II/phenylephrine (AngII/PE)-induced fibrosis and myocardial infarction (MI). Analysis of cardiomyocyte function demonstrated altered sarcomere shortening and slowed calcium decline in both uninjured and AngII/PE-infused fibroblast-ablated mice. After MI, the residual resident fibroblasts responded to injury, albeit with reduced proliferation and numbers immediately after injury. These results indicate that the adult mouse heart tolerates a significant degree of fibroblast loss with a potentially beneficial impact on cardiac function after injury. The cardioprotective effect of controlled fibroblast reduction may have therapeutic value in heart disease.