Articular contact in a three-dimensional model of the knee

This study is aimed at the analysis of articular contact in a three-dimensional mathematical model of the human knee-joint. In particular the effect of articular contact on the passive motion characteristics is assessed in relation to experimentally obtained joint kinematics. Two basically different mathematical contact descriptions were compared for this purpose. One description was for rigid contact and one for deformable contact. The description of deformable contact is based on a simplified theory for contact of a thin elastic layer on a rigid foundation. The articular cartilage was described either as a linear elastic material or as a non-linear elastic material. The contact descriptions were introduced in a mathematical model of the knee. The locations of the ligament insertions and the geometry of the articular surfaces were obtained from a joint specimen of which experimentally determined kinematic data were available, and were used as input for the model. The ligaments were described by non-linear elastic line elements. The mechanical properties of the ligaments and the articular cartilage were derived from literature data. Parametric model evaluations showed that, relative to rigid articular contact, the incorporation of deformable contact did not alter the motion characteristics in a qualitative sense, and that the quantitative changes were small. Variation of the elasticity of the elastic layer revealed that decreasing the surface stiffness caused the ligaments to relax and, as a consequence, increased the joint laxity, particularly for axial rotation. The difference between the linear and the non-linear deformable contact in the knee model was very small for moderate loading conditions. The motion characteristics simulated with the knee model compared very well with the experiments. It is concluded that for simulation of the passive motion characteristics of the knee, the simplified description for contact of a thin linear elastic layer on a rigid foundation is a valid approach when aiming at the study of the motion characteristics for moderate loading conditions. With deformable contact in the knee model, geometric conformity between the surfaces can be modelled as opposed to rigid contact which assumed only point contact

The Angio-Fibrotic Switch of VEGF and CTGF in Proliferative Diabetic Retinopathy

BACKGROUND: In proliferative diabetic retinopathy (PDR), vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) cause blindness by neovascularization and subsequent fibrosis, but their relative contribution to both processes is unknown. We hypothesize that the balance between levels of pro-angiogenic VEGF and pro-fibrotic CTGF regulates angiogenesis, the angio-fibrotic switch, and the resulting fibrosis and scarring. METHODS/PRINCIPAL FINDINGS: VEGF and CTGF were measured by ELISA in 68 vitreous samples of patients with proliferative DR (PDR, N = 32), macular hole (N = 13) or macular pucker (N = 23) and were related to clinical data, including degree of intra-ocular neovascularization and fibrosis. In addition, clinical cases of PDR (n = 4) were studied before and after pan-retinal photocoagulation and intra-vitreal injections with bevacizumab, an antibody against VEGF. Neovascularization and fibrosis in various degrees occurred almost exclusively in PDR patients. In PDR patients, vitreous CTGF levels were significantly associated with degree of fibrosis and with VEGF levels, but not with neovascularization, whereas VEGF levels were associated only with neovascularization. The ratio of CTGF and VEGF was the strongest predictor of degree of fibrosis. As predicted by these findings, patients with PDR demonstrated a temporary increase in intra-ocular fibrosis after anti-VEGF treatment or laser treatment. CONCLUSIONS/SIGNIFICANCE: CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis in proliferative retinopathy

High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas

Contains fulltext : 80487.pdf (publisher's version ) (Open Access)BACKGROUND: The diagnosis of benign renal oncocytomas (RO) and chromophobe renal cell carcinomas (RCC) based on their morphology remains uncertain in several cases. METHODS: We have applied Affymetrix GeneChip Mapping 250 K NspI high-density oligoarrays to identify small genomic alterations, which may occur beyond the specific losses of entire chromosomes, and also Affymetrix GeneChip HG-U133 Plus2.0 oligoarrays for gene expression profiling. RESULTS: By analysing of DNA extracted from 30 chRCCs and 42 ROs, we have confirmed the high specificity of monosomies of chromosomes 1, 2, 6, 10, 13, 17 and 21 in 70-93% of the chRCCs, while ROs displayed loss of chromosome 1 and 14 in 24% and 5% of the cases, respectively. We demonstrated that chromosomal gene expression biases might correlate with chromosomal abnormalities found in chromophobe RCCs and ROs. The vast majority genes downregulated in chromophobe RCC were mapped to chromosomes 2, 6, 10, 13 and 17. However, most of the genes overexpressed in chromophobe RCCs were located to chromosomes without any copy number changes indicating a transcriptional regulation as a main event. CONCLUSION: The SNP-array analysis failed to detect recurrent small deletions, which may mark loci of genes involved in the tumor development. However, we have identified loss of chromosome 2, 10, 13, 17 and 21 as discriminating alteration between chromophobe RCCs and ROs. Therefore, detection of these chromosomal changes can be used for the accurate diagnosis in routine histology

Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D9k (CaBP-9k), that may be used to assess estrogenic activity of EDs

Measuring the Initial Mass Function of Low Mass Stars and Brown Dwarfs

I review efforts to determine the form and any lower limit to the initial mass function in the Galactic disk, using observations of low-mass stars and brown dwarfs in the field, young clusters and star forming regions. I focus on the methodologies that have been used and the uncertainties that exist due to observational limitations and to systematic uncertainties in calibrations and theoretical models. I conclude that whilst it is possible that the low-mass IMFs deduced from the field and most young clusters are similar, there are too many problems to be sure; there are examples of low-mass cluster IMFs that appear to be very discrepant and the IMFs for brown dwarfs in the field and young clusters have yet to be reconciled convincingly.Comment: From a series of lectures presented at the Evry-Schatzman school on Low-mass stars and the transition from stars to brown dwarfs, edited by C. Charbonnel, C. Reyle, M. Schultheis. To appear in the EAS Conference Series. 47p

CRB1-Associated Retinal Dystrophy Patients Have Expanded Lewis Glycoantigen-Positive T Cells

PURPOSE. Eye inflammation may occur in patients with inherited retinal dystrophies (IRDs) and is seen frequently in IRDs associated with mutations in the CRB1 gene. The purpose of this study was to determine the types of inflammatory cells involved in IRDs, by deep profiling the composition of peripheral blood mononuclear cells of patients with a CRB1-associated IRD. METHODS. This study included 33 patients with an IRD with confirmed CRB1 mutations and 32 healthy controls. A 43-parameter flow cytometry analysis was performed on peripheral blood mononuclear cells isolated from venous blood. FlowSOM and manual Boolean combination gating were used to identify and quantify immune cell subsets. RESULTS. Comparing patients with controls revealed a significant increase in patients in the abundance of circulating CD4+ T cells and CD8+ T cells that express sialyl Lewis X antigen. Furthermore, we detected a decrease in plasmacytoid dendritic cells and an IgA+CD24+CD38+ transitional B-cell subset in patients with an IRD. CONCLUSIONS. Patients with a CRB1-associated IRD show marked changes in blood leukocyte composition, affecting lymphocyte and dendritic cell populations. These results implicate inflammatory pathways in the disease manifestations of IRDs

Chandra observations of SGR 1627-41 near quiescence

We report on an observation of SGR 1627-41 made with the Chandra X-ray Observatory on 2011 June 16. Approximately three years after its outburst activity in 2008, the source's flux has been declining, as it approaches its quiescent state. For an assumed power-law spectrum, we find that the absorbed 2--10 keV flux for the source is $1.0^{+0.3}_{-0.2} \times 10^{-13} erg cm^{-2} s^{-1}$ with a photon index of $2.9 \pm 0.8$ ($N_H=1.0\times10^{23}$ cm^{-2}). This flux is approximately consistent with that measured at the same time after the source's outburst in 1998. With measurements spanning 3 years after the 2008 outburst, we analyze the long-term flux and spectral evolution of the source. The flux evolution is well described by a double exponential with decay times of 0.5 $\pm$ 0.1 and 59 $\pm$ 6 days, and a thermal cooling model fit suggests that SGR 1627-41 may have a hot core ($T_c ~ 2\times 10^8$ K). We find no clear correlation between flux and spectral hardness as found in other magnetars. We consider the quiescent X-ray luminosities of magnetars and the subset of rotation-powered pulsars with high magnetic fields ($B >~ 10^{13}$ G) in relation to their spin-inferred surface magnetic-field strength, and find a possible trend between the two quantities.Comment: 25 pages, 5 figures, 3 tables. Accepted for publication in Ap

CD34 marks angiogenic tip cells in human vascular endothelial cell cultures

The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis