Keratoconus prediction using a finite element model of the cornea with local biomechanical properties

PURPOSE: The ability to predict and understand which biomechanical properties of the cornea are responsible for the stability or progression of keratoconus may be an important clinical and surgical tool for the eye-care professional. We have developed a finite element model of the cornea, that tries to predicts keratoconus-like behavior and its evolution based on material properties of the corneal tissue. METHODS: Corneal material properties were modeled using bibliographic data and corneal topography was based on literature values from a schematic eye model. Commercial software was used to simulate mechanical and surface properties when the cornea was subject to different local parameters, such as elasticity. RESULTS: The simulation has shown that, depending on the corneal initial surface shape, changes in local material properties and also different intraocular pressures values induce a localized protuberance and increase in curvature when compared to the remaining portion of the cornea. CONCLUSIONS: This technique provides a quantitative and accurate approach to the problem of understanding the biomechanical nature of keratoconus. The implemented model has shown that changes in local material properties of the cornea and intraocular pressure are intrinsically related to keratoconus pathology and its shape/curvature.

EVALUATING VIBRATIONS ON A SMALL-SCALE MODEL OF A TIMBER FOOTBRIDGE

In Brazil, the study of pedestrian-induced vibration on footbridges has been undertaken since the early 1990s, for concrete and steel footbridges. However, there are no recorded studies of this kind for timber footbridges. Brazilian code ABNT NBR 7190 (1997) gives design requirements only for static loads in the case of timber footbridges, without considering the serviceability limit state from pedestrian-induced vibrations. The aim of this work is to perform a theoretical dynamic, numerical and experimental analysis on simply-supported timber footbridges, by using a small-scale model developed from a 24 m span and 2 m width timber footbridge, with two main timber beams. Span and width were scaled down (1:4) to 6 m e 0.5 in, respectively. Among the conclusions reached herein, it is emphasized that the Euler-Bernoulli beam theory is suitable for calculating the vertical and lateral first natural frequencies in simply-supported timber footbridges; however, special attention should be given to the evaluation of lateral bending stiffness, as it leads to conservative values.

Bronchus-Associated Lymphoid Tissue (BALT) and Survival in a Vaccine Mouse Model of Tularemia

Background: Francisella tularensis causes severe pulmonary disease, and nasal vaccination could be the ideal measure to effectively prevent it. Nevertheless, the efficacy of this type of vaccine is influenced by the lack of an effective mucosal adjuvant. Methodology/Principal Findings: Mice were immunized via the nasal route with lipopolysaccharide isolated from F. tularensis and neisserial recombinant PorB as an adjuvant candidate. Then, mice were challenged via the same route with the F. tularensis attenuated live vaccine strain (LVS). Mouse survival and analysis of a number of immune parameters were conducted following intranasal challenge. Vaccination induced a systemic antibody response and 70% of mice were protected from challenge as showed by their improved survival and weight regain. Lungs from mice recovering from infection presented prominent lymphoid aggregates in peribronchial and perivascular areas, consistent with the location of bronchus-associated lymphoid tissue (BALT). BALT areas contained proliferating B and T cells, germinal centers, T cell infiltrates, dendritic cells (DCs). We also observed local production of antibody generating cells and homeostatic chemokines in BALT areas. Conclusions: These data indicate that PorB might be an optimal adjuvant candidate for improving the protective effect of F. tularensis antigens. The presence of BALT induced after intranasal challenge in vaccinated mice might play a role in regulation of local immunity and long-term protection, but more work is needed to elucidate mechanisms that lead to its formation.

Intestinal Anti-Inflammatory Activity of Baccharis dracunculifolia in the Trinitrobenzenesulphonic Acid Model of Rat Colitis

Baccharis dracunculifolia DC (Asteraceae) is a Brazilian medicinal plant popularly used for its antiulcer and anti-inflammatory properties. This plant is the main botanical source of Brazilian green propolis, a natural product incorporated into food and beverages to improve health. The present study aimed to investigate the chemical profile and intestinal anti-inflammatory activity of B. dracunculifolia extract on experimental ulcerative colitis induced by trinitrobenzenosulfonic acid (TNBS). Colonic damage was evaluated macroscopically and biochemically through its evaluation of glutathione content and its myeloperoxidase (MPO) and alkaline phosphatase activities. Additional in vitro experiments were performed in order to test the antioxidant activity by inhibition of induced lipid peroxidation in the rat brain membrane. Phytochemical analysis was performed by HPLC using authentic standards. The administration of plant extract (5 and 50 mgkg(-1)) significantly attenuated the colonic damage induced by TNBS as evidenced both macroscopically and biochemically. This beneficial effect can be associated with an improvement in the colonic oxidative status, since plant extract prevented glutathione depletion, inhibited lipid peroxidation and reduced MPO activity. Caffeic acid, p-coumaric acid, aromadendrin-4-O-methyl ether, 3-prenyl-p-coumaric acid, 3,5-diprenyl-p-coumaric acid and baccharin were detected in the plant extract.

Human Dental Pulp Cells: A New Source of Cell Therapy in a Mouse Model of Compressive Spinal Cord Injury

Strategies aimed at improving spinal cord regeneration after trauma are still challenging neurologists and neuroscientists throughout the world. Many cell-based therapies have been tested, with limited success in terms of functional outcome. In this study, we investigated the effects of human dental pulp cells (HDPCs) in a mouse model of compressive spinal cord injury (SCI). These cells present some advantages, such as the ease of the extraction process, and expression of trophic factors and embryonic markers from both ecto-mesenchymal and mesenchymal components. Young adult female C57/BL6 mice were subjected to laminectomy at T9 and compression of the spinal cord with a vascular clip for 1 min. The cells were transplanted 7 days or 28 days after the lesion, in order to compare the recovery when treatment is applied in a subacute or chronic phase. We performed quantitative analyses of white-matter preservation, trophic-factor expression and quantification, and ultrastructural and functional analysis. Our results for the HDPC-transplanted animals showed better white-matter preservation than the DMEM groups, higher levels of trophic-factor expression in the tissue, better tissue organization, and the presence of many axons being myelinated by either Schwann cells or oligodendrocytes, in addition to the presence of some healthy-appearing intact neurons with synapse contacts on their cell bodies. We also demonstrated that HDPCs were able to express some glial markers such as GFAP and S-100. The functional analysis also showed locomotor improvement in these animals. Based on these findings, we propose that HDPCs may be feasible candidates for therapeutic intervention after SCI and central nervous system disorders in humans.

Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

Background: The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods: Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) similar to 250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting). Results: Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics vs. nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 +/- 37, 431.3 +/- 36, 316.2 +/- 5, 363.8 +/- 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 +/- 25.21, 73.40 +/- 53.30, 148.4 +/- 93 in RD-SHR, STZ-SHR-and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 +/- 0.9, 2.12 +/- 0.9, 7.38 +/- 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups vs. SHR. Conclusions: Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

Mechanism and model of the oscillatory electro-oxidation of methanol

A mechanism for the kinetic instabilities observed in the galvanostatic electro-oxidation of methanol is suggested and a model developed. The model is investigated using stoichiometric network analysis as well as concepts from algebraic geometry (polynomial rings and ideal theory) revealing the occurrence of a Hopf and a saddle-node bifurcation. These analytical solutions are confirmed by numerical integration of the system of differential equations. (C) 2010 American Institute of Physics

Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice

The role of exercise training (ET) on cardiac renin-angiotensin system (RAS) was investigated in 3-5 month-old mice lacking alpha(2A-) and alpha(2C-)adrenoceptors (alpha(2A)/alpha(2C)ARKO) that present heart failure (HF) and wild type control (WT). ET consisted of 8-week running sessions of 60 min, 5 days/week. In addition, exercise tolerance, cardiac structural and function analysis were made. At 3 months, fractional shortening and exercise tolerance were similar between groups. At 5 months, alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction and fibrosis associated with increased cardiac angiotensin (Ang) II levels (2.9-fold) and increased local angiotensin-converting enzyme activity (ACE 18%). ET decreased alpha(2A)/alpha(2C)ARKO cardiac Ang II levels and ACE activity to age-matched untrained WT mice levels while increased ACE2 expression and prevented exercise intolerance and ventricular dysfunction with little impact on cardiac remodeling. Altogether, these data provide evidence that reduced cardiac RAS explains, at least in part, the beneficial effects of ET on cardiac function in a genetic model of HF.

Intracellular mechanisms of specific beta-adrenoceptor antagonists involved in improved cardiac function and survival in a genetic model of heart failure

beta-blockers, as class, improve cardiac function and survival in heart failure (HF). However, the molecular mechanisms underlying these beneficial effects remain elusive. In the present study, metoprolol and carvedilol were used in doses that display comparable heart rate reduction to assess their beneficial effects in a genetic model of sympathetic hyperactivity-induced HF (alpha(2A)/alpha(2C)-ARKO mice). Five month-old HF mice were randomly assigned to receive either saline, metoprolol or carvedilol for 8 weeks and age-matched wild-type mice (WT) were used as controls. HF mice displayed baseline tachycardia, systolic dysfunction evaluated by echocardiography, 50% mortality rate, increased cardiac myocyte width (50%) and ventricular fibrosis (3-fold) compared with WT. All these responses were significantly improved by both treatments. Cardiomyocytes from HF mice showed reduced peak [Ca(2+)](i) transient (13%) using confocal microscopy imaging. Interestingly, while metoprolol improved [Ca(2+)](i) transient, carvedilol had no effect on peak [Ca(2+)](i) transient but also increased [Ca(2+)] transient decay dynamics. We then examined the influence of carvedilol in cardiac oxidative stress as an alternative target to explain its beneficial effects. Indeed, HF mice showed 10-fold decrease in cardiac reduced/oxidized glutathione ratio compared with WT, which was significantly improved only by carvedilol treatment. Taken together, we provide direct evidence that the beneficial effects of metoprolol were mainly associated with improved cardiac Ca(2+) transients and the net balance of cardiac Ca(2+) handling proteins while carvedilol preferentially improved cardiac redox state. (C) 2008 Elsevier Inc. All rights reserved.

The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice

Sympathetic hyperactivity (SH) and renin angiotensin system (RAS) activation are commonly associated with heart failure (HF), even though the relative contribution of these factors to the cardiac derangement is less understood. The role of SH on RAS components and its consequences for the HF were investigated in mice lacking alpha(2A) and alpha(2C) adrenoceptor knockout (alpha(2A)/alpha(2C) ARKO) that present SH with evidence of HF by 7 mo of age. Cardiac and systemic RAS components and plasma norepinephrine (PN) levels were evaluated in male adult mice at 3 and 7 mo of age. In addition, cardiac morphometric analysis, collagen content, exercise tolerance, and hemodynamic assessments were made. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF, while displaying elevated PN, activation of local and systemic RAS components, and increased cardiomyocyte width (16%) compared with wild-type mice (WT). In contrast, at 7 mo, alpha(2A)/alpha(2C)ARKO mice presented clear signs of HF accompanied only by cardiac activation of angiotensinogen and ANG II levels and increased collagen content (twofold). Consistent with this local activation of RAS, 8 wk of ANG II AT(1) receptor blocker treatment restored cardiac structure and function comparable to the WT. Collectively, these data provide direct evidence that cardiac RAS activation plays a major role underlying the structural and functional abnormalities associated with a genetic SH-induced HF in mice.

A transient three-dimensional heat transfer model of the human body

The objective of this work is to develop an improved model of the human thermal system. The features included are important to solve real problems: 3D heat conduction, the use of elliptical cylinders to adequately approximate body geometry, the careful representation of tissues and important organs, and the flexibility of the computational implementation. Focus is on the passive system, which is composed by 15 cylindrical elements and it includes heat transfer between large arteries and veins. The results of thermal neutrality and transient simulations are in excellent agreement with experimental data, indicating that the model represents adequately the behavior of the human thermal system. (C) 2009 Elsevier Ltd. All rights reserved.

Modeling, control and experimental validation of a novel actuator based on shape memory alloys

The paper presents the development of a mechanical actuator using a shape memory alloy with a cooling system based on the thermoelectric effect (Seebeck-Peltier effect). Such a method has the advantage of reduced weight and requires a simpler control strategy as compared to other forced cooling systems. A complete mathematical model of the actuator was derived, and an experimental prototype was implemented. Several experiments are used to validate the model and to identify all parameters. A robust and nonlinear controller, based on sliding-mode theory, was derived and implemented. Experiments were used to evaluate the actuator closed-loop performance, stability, and robustness properties. The results showed that the proposed cooling system and controller are able to improve the dynamic response of the actuator. (C) 2009 Elsevier Ltd. All rights reserved.

Macrosegregation of Impurities in Directionally Solidified Silicon

Directional solidification of molten metallurgical-grade Si was carried out in a vertical Bridgman furnace. The effects of changing the mold velocity from 5 to 110 mu m seconds(-1) on the macrosegregation of impurities during solidification were investigated. The macrostructures of the cylindrical Si ingots obtained in the experiments consist mostly of columnar grains parallel to the ingot axis. Because neither cells nor dendrites can be observed on ingot samples, the absence of precipitated particles and the fulfillment of the constitutional supercooling criterion suggest a planar solid-liquid interface for mold velocities a parts per thousand currency sign10 mu m seconds(-1). Concentration profiles of several impurities were measured along the ingots, showing that their bottom and middle are purer than the metallurgical Si from which they solidified. At the ingot top, however, impurities accumulated, indicating the typical normal macrosegregation. When the mold velocity decreases, the macrosegregation and ingot purity increase, changing abruptly for a velocity variation from 20 to 10 mu m seconds(-1). A mathematical model of solute transport during solidification shows that, for mold velocities a parts per thousand yen20 mu m seconds(-1), macrosegregation is caused mainly by diffusion in a stagnant liquid layer assumed at the solid-liquid interface, whereas for lower velocities, macrosegregation increases as a result of more intense convective solute transport.

Animated solid model of the lung constructed from unsynchronized MR sequential images

This work discusses a 4D lung reconstruction method from unsynchronized MR sequential images. The lung, differently from the heart, does not have its own muscles, turning impossible to see its real movements. The visualization of the lung in motion is an actual topic of research in medicine. CT (Computerized Tomography) can obtain spatio-temporal images of the heart by synchronizing with electrocardiographic waves. The FOV of the heart is small when compared to the lung`s FOV. The lung`s movement is not periodic and is susceptible to variations in the degree of respiration. Compared to CT, MR (Magnetic Resonance) imaging involves longer acquisition times and it is not possible to obtain instantaneous 3D images of the lung. For each slice, only one temporal sequence of 2D images can be obtained. However, methods using MR are preferable because they do not involve radiation. In this paper, based on unsynchronized MR images of the lung an animated B-Repsolid model of the lung is created. The 3D animation represents the lung`s motion associated to one selected sequence of MR images. The proposed method can be divided in two parts. First, the lung`s silhouettes moving in time are extracted by detecting the presence of a respiratory pattern on 2D spatio-temporal MR images. This approach enables us to determine the lung`s silhouette for every frame, even on frames with obscure edges. The sequence of extracted lung`s silhouettes are unsynchronized sagittal and coronal silhouettes. Using our algorithm it is possible to reconstruct a 3D lung starting from a silhouette of any type (coronal or sagittal) selected from any instant in time. A wire-frame model of the lung is created by composing coronal and sagittal planar silhouettes representing cross-sections. The silhouette composition is severely underconstrained. Many wire-frame models can be created from the observed sequences of silhouettes in time. Finally, a B-Rep solid model is created using a meshing algorithm. Using the B-Rep solid model the volume in time for the right and left lungs were calculated. It was possible to recognize several characteristics of the 3D real right and left lungs in the shaded model. (C) 2007 Elsevier Ltd. All rights reserved.

Deciphering the weathering processes using environmental mineralogy and geochemistry: Towards an integrated model of laterite and podzol genesis in the Upper Amazon Basin

This article reports major results from collaborative research between France and Brazil on soil and water systems, carried out in the Upper Amazon Basin. It reveals the weathering processes acting in the partly inundated, low elevation plateaus of the Basin, mostly covered by evergreen forest. Our findings are based on geochemical data and mineral spectroscopy that probe the crystal chemistry of Fe and Al in mineral phases (mainly kaolinite, Al- and Fe-(hydr)oxides) of tropical soils (laterites). These techniques reveal crystal alterations in mineral populations of different ages and changes of metal speciation associated with mineral or organic phases. These results provide an integrated model of soil formation and changes (from laterites to podzols) in distinct hydrological compartments of the Amazon landscapes and under altered water regimes. (C) 2010 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.