Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.

Members of the TGF-beta superfamily appear to modulate mesenchymal differentiation, including the processes of cartilage and bone formation. Nothing is yet known about the function of the TGF-beta-related factor vgr-1, also called bone morphogenetic protein-6 (BMP-6), and only limited studies have been conducted on the most closely related factors BMP-5, osteogenic protein-1 (OP-1) or BMP-7, and OP-2. Because vgr-1 mRNA has been localized in hypertrophic cartilage, this factor may play a vital role in endochondral bone formation. We developed antibodies to vgr-1, and documented that vgr-1 protein was expressed in hypertrophic cartilage of mice. To further characterize the role of this protein in bone differentiation, we generated CHO cells that overexpressed recombinant murine vgr-1 protein. Western blot analysis documented that recombinant vgr-1 protein was secreted into the media and was proteolytically processed to yield the mature vgr-1 molecule. To assess the biological activity of recombinant vgr-1 in vivo, we introduced the vgr-1-expressing CHO cells directly into the subcutaneous tissue of athymic nude mice. CHO-vgr-1 cells produced localized tumors, and the continuous secretion of vgr-1 resulted in tumors with a strikingly different gross and histological appearance as compared to the parental CHO cells. The tumors of control CHO cells were hemorrhagic, necrotic, and friable, whereas the CHO-vgr-1 tumors were dense, firm, and fibrotic. In contrast with control CHO tumors, the nests of CHO-vgr-1 tumor cells were surrounded by extensive connective tissue, which contained large regions of cartilage and bone. Further analysis indicated that secretion of vgr-1 from the transfected CHO tumor cells induced the surrounding host mesenchymal cells to develop along the endochondral bone pathway. These findings suggest that endochondral bone formation

Application of endochronic densification law for designing vibroflotation soil improvement technique

The densification phenomenon in dry or completely drained sands is mainly due to the application of dynamic loading, like an earthquake or other kind of vibrations. This fact causes a reduction of voids volume and in a consequence the compaction of the soil. A finite element model, including the generalized endochronic densification law, formulated in cylindrical coordinates, has been developed for simulating the vibroflotation soil improvement technique the numerical model. Punctual dynamic loadings, like those occurring in vibroflotation treatment, are reproduced in the code. There are several other vibration-compacting soil improvement techniques which could be modelled like an axi-symmetric problem with this new approach, which includes absorbent boundary conditions (silent boundaries)

Numerical Simulations of the Monotonic and Cyclic Behaviour of Offshore Wind Turbine Monopile Foundations in Clayey Soils

Most of the reported centrifuge tests available in the existing literature on offshore wind turbine foundations are focused on the behaviour of monopiles in sands, but very few studies on clayey soils can be found, due to the very long saturation and consolidation periods required to properly conduct experiments in such materials. Moreover, most of the reported numerical simulations using finite element analyses have been validated with monotonic centrifuge tests only. In this research, both monotonic and cyclic performance of offshore wind turbines in clay are validated and justified. The relationship between the monopile rotation in clays and the geometry and strength of the soil has been found and quantified. A prediction of the rotation for a high number of cycles of loading, based on the one experienced by the pile during the first cycle, can be obtained using the correlation derived in the paper. For those cases in which the rotation does not reach a steady value after a high number of cycles, the cumulative rate has been found significantly larger than the prediction conducted with standard analytical methods. A new design methodology for the design of offshore monopile foundations in clay is presented

Impact of hypoglycemia on patients with type 2 diabetes mellitus and their quality of life, work productivity, and medication adherence.

BackgroundThe purpose of this study was to determine the characteristics of adults with type 2 diabetes mellitus (T2DM) that correlate with greater risk of hypoglycemia and determine the impact of hypoglycemia on health-related quality of life, work productivity, and medication adherence from a patient perspective.MethodsData from a large web-based survey were retrospectively analyzed. Adults with a diagnosis of T2DM taking antihyperglycemic agents were included in the analysis. Participants with knowledge of their hypoglycemic history were divided into three groups: those experiencing recent hypoglycemia (previous 3 months), those experiencing nonrecent hypoglycemia, and those never experiencing hypoglycemia.ResultsOf the participants with T2DM taking antihyperglycemic agents who were knowledgeable of their hypoglycemia history, 55.7% had ever experienced hypoglycemia. Of those, 52.7% had recent hypoglycemia. Compared with those who never experienced hypoglycemia, those who experienced hypoglycemia tended to: be younger; be more aware of their glycated hemoglobin (HbA1c) levels; have higher HbA1c levels; have a higher body mass index; have higher Charlson Comorbidity Index scores; be on insulin, sulfonylureas, and/or glucagon-like peptide-1 agonists; and be less adherent to their antihyperglycemic agents. Hypoglycemia interfered with social activities, caused more missed work (absenteeism), more impairment while at work (presenteeism), and decreased overall work productivity compared with patients who had never experienced hypoglycemia. Overall health-related quality of life, as determined by the Short Form-36 health questionnaire, was negatively impacted by hypoglycemia. Both Physical and Mental Summary scores were significantly lower for the recent hypoglycemia and nonrecent hypoglycemia groups compared with the never hypoglycemia group.ConclusionHypoglycemia can negatively impact many aspects of life. Greater awareness of those who are at risk for developing hypoglycemia can lead to the development of measures (eg, patient and physician education) to prevent future hypoglycemia episodes

Meshfree numerical schemes applied to seepage problems through earth dams

Modelling seepage along with the mechanical responses of deformable Earth Dams under transient conditions is a challenging task, since both coupling between different phases, and computation of free-surface variables are involved. In the present work, we take on the meshfree numerical schemes to establish a framework for solving coupled, transient problems for unconfined seepage through Earth Dams. The equations of Biot are formulated in displacement (or u − w formulation) assuming an elastic solid skeleton. Shape functions based on the principle of Maximum Entropy are implemented for the meshfree framework. The free surface location and its evolution in time, is obtained by interpolation of pore water pressures through the domain. Applications to benchmark problems are compared with available results in the literature. The preliminary simulations for steady flow conditions show promising results

Effect of Class F Fly Ash on Fine Sand Compaction through Soil Stabilization

This paper presents the results of an experimental investigation carried out to evaluate the effect of fly ash (FA) on fine sand compaction and its suitability as a material for embankments. The literature review demonstrates the lack of research on stabilization of sandy material using FA. The study is concerned with the role of FA content in stabilized soil physical characteristics. The main aim of this paper is to determine the optimum quantity of FA content for stabilization of this type of soil. This is achieved through particle size distribution and compaction (standard proctor) tests. The sand was stabilized with three proportions of FA (5%, 10% and 15%) and constant cement content of 3% was used as an activator. For better comparison, the sand was also stabilized by 3% cement only so that the effect of FA could be observed more clearly. The results were in line with the literature for other types of soil, i.e. as the % of FA increases, reduction in maximum dry density and higher optimum moisture content were observed

Dynamic consolidation problems in saturated soils solved through u-w formulation in a LME meshfree framework

A meshfree numerical model, based on the principle of Local Maximum Entropy (LME), including a B-bar algorithm to avoid instabilities, is applied to solve axisymmetric consolidation problems in elastic saturated soils. This numerical scheme has been previously validated for purely elastic problems without water (mono phase), as well as for steady seepage in elastic porous media. Hereinafter, an implementation of the novel numerical method in the axisymmetric configuration is proposed, and the model is validated for well known theoretical problems of consolidation in saturated soils, under both static and dynamic conditions with available analytical solutions. The solutions obtained with the new methodology are compared with a finite element commercial software for a set of examples. After validated, solutions for dynamic radial consolidation and sinks, which have not been found elsewhere in the literature, are presented as a novelty. This new numerical approach is demonstrated to be feasible for this kind of problems in porous media, particularly for high frequency, dynamic problems, for which very few results have been found in the literature in spite of their high practical importance

Experimental evaluation of kaolin stabilised with class F fly ash

This study aims to investigate the effectiveness of fly ash (FA) in stabilising a kaolin soil through laboratory tests. Kaolin is an example of moderate plasticity clays that require stabilisation methods for construction purposes. The influence of FA on the improvement of kaolin is studied by varying its dosages in the mixtures (0%, 10% to 20%) as well as the cement content, used as an activator in different percentages (5 and 7%). The influence of the dry unit weight and the curing time of the soil mixture is also analysed through unconfined compressive strength and indirect tensile strength tests. The experimental results show that the strength increases linearly with both FA and cement contents. Moreover, higher initial dry unit weights also yield higher final strengths. To further assess the improvement, the application of the porosity over the volumetric cement content ratio, as the main variable, succeeded in attaining a relationship with the strength and the stiffness of the studied soil. Results for the combined effect of the porosity and the volumetric cement on the secant modulus were also determined. Furthermore, a unique relationship was obtained combining porosity, volumetric cement and FA content