The effect of boundary constraints on finite element modelling of the human pelvis

The use of finite element analysis (FEA) to investigate the biomechanics of anatomical systems critically relies on the specification of physiologically representative boundary conditions. The biomechanics of the pelvis has been the specific focus of a number of FEA studies previously, but it is also a key aspect in other investigations of, for example, the hip joint or new design of hip prostheses. In those studies, the pelvis has been modelled in a number of ways with a variety of boundary conditions, ranging from a model of the whole pelvic girdle including soft tissue attachments to a model of an isolated hemi-pelvis. The current study constructed a series of FEA models of the same human pelvis to investigate the sensitivity of the predicted stress distributions to the type of boundary conditions applied, in particular to represent the sacro-iliac joint and pubic symphysis. Varying the method of modelling the sacro-iliac joint did not produce significant variations in the stress distribution, however changes to the modelling of the pubic symphysis were observed to have a greater effect on the results. Over-constraint of the symphysis prevented the bending of the pelvis about the greater sciatic notch, and underestimated high stresses within the ilium. However, permitting medio-lateral translation to mimic widening of the pelvis addressed this problem. These findings underline the importance of applying the appropriate boundary conditions to FEA models, and provide guidance on suitable methods of constraining the pelvis when, for example, scan data has not captured the full pelvic girdle. The results also suggest a valid method for performing hemi-pelvic modelling of cadaveric or archaeological remains which are either damaged or incomplete

Delivery of short interfering ribonucleic acid-complexed magnetic nanoparticles in an oscillating field occurs via caveolae-mediated endocytosis

Gene delivery technologies to introduce foreign genes into highly differentiated mammalian cells have improved significantly over the last few decades. Relatively new techniques such as magnetic nanoparticle-based gene transfection technology are showing great promise in terms of its high transfection efficiency and wide-ranging research applications. We have developed a novel gene delivery technique, which uses magnetic nanoparticles moving under the influence of an oscillating magnetic array. Herein we successfully introduced short interfering RNA (siRNA) against green fluorescent protein (GFP) or actin into stably-transfected GFP-HeLa cells or wild-type HeLa and rat aortic smooth muscle cells, respectively. This gene silencing technique occurred in a dose- and cell density- dependent manner, as reflected using fluorescence intensity and adhesion assays. Furthermore, using endocytosis inhibitors, we established that these magnetic nanoparticle-nucleic acid complexes, moving across the cell surface under the influence of an oscillating magnet array, enters into the cells via the caveolae-mediated endocytic pathway

Modeling and control of anterior–posterior and medial–lateral sways in standing posture

To study essential anterior–posterior and medial–lateral sways of the stance caused by rotational movements about the ankle and hip joints, a mathematical model is developed for the 3D postural kinematics and dynamics. The model is in the form of nonlinear differential–algebraic equations corresponding to a biomechanical system with holonomic constraints. A nonlinear feedback control law is further derived for stabilizing the upright stance, whilst eliminating internal torques induced by the constraints on postural movements. Numerical simulations of the model parametrized with experimental data of human body segments illustrate the performance of postural balancing with the proposed control

Whole genome sequencing of experimental hybrids supports meiosis-like sexual recombination in Leishmania

Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete stages nor cell fusion events have been directly observed during parasite development in the vector, we have relied on a classical genetic analysis to determine if Leishmania has a true sexual cycle. Here, we used whole genome sequencing to follow the chromosomal inheritance patterns of experimental hybrids generated within and between different strains of L. major and L. infantum. We also generated and sequenced the first experimental hybrids in L. tropica. We found that in each case the parental somy and allele contributions matched the inheritance patterns expected under meiosis 97–99% of the time. The hybrids were equivalent to F1 progeny, heterozygous throughout most of the genome for the markers that were homozygous and different between the parents. Rare, non-Mendelian patterns of chromosomal inheritance were observed, including a gain or loss of somy, and loss of heterozygosity, that likely arose during meiosis or during mitotic divisions of the progeny clones in the fly or culture. While the interspecies hybrids appeared to be sterile, the intraspecies hybrids were able to produce backcross and outcross progeny. Analysis of 5 backcross and outcross progeny clones generated from an L. major F1 hybrid, as well as 17 progeny clones generated from backcrosses involving a natural hybrid of L. tropica, revealed genome wide patterns of recombination, demonstrating that classical crossing over occurs at meiosis, and allowed us to construct the first physical and genetic maps in Leishmania. Altogether, the findings provide strong evidence for meiosis-like sexual recombination in Leishmania, presenting clear opportunities for forward genetic analysis and positional cloning of important genes.</div

The FeSi phase diagram to 150 GPa

The melting curve of FeSi has been determined to 150 GPa in the laser-heated diamond anvil cell (LH-DAC) on the basis of discontinuities in the power versus temperature function. A multianvil experimental cross-check at 12 GPa using textural criteria as a proxy for melting is in good agreement with our LH-DAC results. The melting point of FeSi reaches ∼4000 K at the core mantle boundary and an extrapolated value of 4900 K at the inner-core boundary (ICB). We also present the melting curve as determined by the Lindemann melting law; this agrees well with our experimental curve to 70 GPa and then diverges to higher temperatures, reaching 6200 K at the ICB. These temperatures are substantially higher than previous LH-DAC determinations. The boundary of the ε-FeSi → CsCl-FeSi subsolidus transition has also been determined by synchrotron-based X-ray diffraction at high pressures, and the results confirm a negative Clapeyron slope for the transition. We conclude that if present, FeSi is likely to be solid within the D″ layer and is unlikely to be present within the inner core for any plausible bulk core silicon content.9 page(s

Regional Climate Trends and Scenarios for the U.S. National Climate Assessment Part 4. Climate of the U.S. Great Plains

This document is one of series of regional climate descriptions designed to provide input that can be used in the development of the National Climate Assessment (NCA). As part of a sustained assessment approach, it is intended that these documents will be updated as new and well-vetted model results are available and as new climate scenario needs become clear. It is also hoped that these documents (and associated data and resources) are of direct benefit to decision makers and communities seeking to use this information in developing adaptation plans. There are nine reports in this series, one each for eight regions defined by the NCA, and one for the contiguous U.S. The eight NCA regions are the Northeast, Southeast, Midwest, Great Plains, Northwest, Southwest, Alaska, and Hawai‘i/Pacific Islands. These documents include a description of the observed historical climate conditions for each region and a set of climate scenarios as plausible futures – these components are described in more detail below. While the datasets and simulations in these regional climate documents are not, by themselves, new, (they have been previously published in various sources), these documents represent a more complete and targeted synthesis of historical and plausible future climate conditions around the specific regions of the NCA. There are two components of these descriptions. One component is a description of the historical climate conditions in the region. The other component is a description of the climate conditions associated with two future pathways of greenhouse gas emissions

Depleted uranium is not toxic to rat brain endothelial (RBE4) cells

Abstract: Studies on Gulf War veterans with depleted uranium (DU) fragments embedded in their soft tissues have led to suggestions of possible DU-induced neurotoxicity. We investigated DU uptake into cultured rat brain endothelial cells (RBE4). Following the determination that DU readily enters RBE4 cells, cytotoxic effects were analyzed using assays for cell volume increase, heat shock protein 90 (Hsp90) expression, 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) reduction, and lactate dehydrogenase (LDH) activity. The results of these studies show that uptake of the U 3 O 8 uranyl chloride form of DU into RBE4 cells is efficient, but there are little or no resulting cytotoxic effects on these cells as detected by common biomarkers. Thus, the present experimental paradigm is rather reassuring and provides no indication for overt cytotoxicity in endothelial cells exposed to DU. Index Entries: Depleted uranium (DU); heavey metal toxicity; blood-brain barrier; endothelium. Article: INTRODUCTION Depleted uranium (DU) is a component of military munitions and is therefore the subject of important toxicity studies. Specifically, the possibility of DU neurotoxicity is under investigation. DU is a dense heavy metal used without reserve in many military applications. Chemically similar to natural uranium, but depleted of much of the radioactivity of the 235 U and 234 U isotopes, DU is a low-specific-activity metal that has several advantages for use as weapons material. Neurotoxicity could potentially arise from the chemical or radioactive properties of DU, and the level of neurotoxicity is as yet undetermined (1-3). Gulf War veterans with DU fragments embedded in their soft tissues were studied and the results suggested that there might be DU-associated effects on behavior and cognition (1-4). Rats embedded with DU fragments accumulated uranium in a range of tissues, with early levels highest in the kidney and a gradual increase in bone accumulation. Brain tissues were found to have far lower levels, with the hippocampus showing high levels among the brain regions following physiologically relevant exposures and cerebellum accumulating the highest levels upon extremely high exposure levels For a blood-borne contaminant to cause neurotoxicity, it must first cross the blood-brain barrier (BBB). This barrier protects the central nervous system (CNS) from toxicants in the blood, and its ability to protect against metal neurotoxicity was reviewed by Zheng et al. (7). The capillaries of the brain are lined with endothelial cells acting as the first line of defense in the BBB. The high degree of tightness of the junctions that link the endothelial cells virtually prevents any paracellular passage from occurring in physiological conditions. In addition, several transport proteins can increase the brain-to-blood efflux of various compounds (e.g., Pglycoproteins or multidrug resistance proteins [MDR] of the ATP-binding cassette [ABC]) (7). The molecula

Reversal of cell, circuit and seizure phenotypes in a mouse model of DNM1epileptic encephalopathy

Dynamin-1 is a large GTPase with an obligatory role in synaptic vesicle endocytosis at mammalian nerve terminals. Heterozygous missense mutations in the dynamin-1 gene (DNM1) cause a novel form of epileptic encephalopathy, with pathogenic mutations clustering within regions required for its essential GTPase activity. We reveal the most prevalent pathogenic DNM1 mutation, R237W, disrupts dynamin-1 enzyme activity and endocytosis when overexpressed in central neurons. To determine how this mutation impacted cell, circuit and behavioural function, we generated a mouse carrying the R237W mutation. Neurons from heterozygous mice display dysfunctional endocytosis, in addition to altered excitatory neurotransmission and seizure-like phenotypes. Importantly, these phenotypes are corrected at the cell, circuit and in vivo level by the drug, BMS-204352, which accelerates endocytosis. Here, we demonstrate a credible link between dysfunctional endocytosis and epileptic encephalopathy, and importantly reveal that synaptic vesicle recycling may be a viable therapeutic target for monogenic intractable epilepsies.<br/