503 research outputs found
A Review of Prosthetic Interface Stress Investigations
Over the last decade, numerous experimental and numerical analyses have been conducted to investigate the stress distribution between the residual limb and prosthetic socket of persons with lower limb amputation. The objectives of these analyses have been to improve our understanding of the residual limb/prosthetic socket system, to evaluate the influence of prosthetic design parameters and alignment variations on the interface stress distribution, and to evaluate prosthetic fit. The purpose of this paper is to summarize these experimental investigations and identify associated limitations. In addition, this paper presents an overview of various computer models used to investigate the residual limb interface, and discusses the differences and potential ramifications of the various modeling formulations. Finally, the potential and future applications of these experimental and numerical analyses in prosthetic design are presented
Young’s Modulus and Volume Porosity Relationships for Additive Manufacturing Applications
Recent advancements in additive manufacturing (or rapid prototyping) technologies allow the fabrication of end-use components with defined porous structures. For example, one area of particular interest is the potential to modify the flexibility (bending stiffness) of orthopedic implants through the use of engineered porosity (i.e., design and placement of pores) and subsequent fabrication of the implant using additive manufacturing processes. However, applications of engineered porosity require the ability to accurately predict mechanical properties from knowledge or characterization of the pore structure and the existence of robust equations characterizing the property–porosity relationships. As Young’s modulus can be altered by variations in pore shape as well as pore distribution, numerous semi-analytical and theoretical relationships have been proposed to describe the dependence of mechanical properties on porosity. However, the utility and physical meaning of many of these relationships is often unclear as most theoretical models are based on some idealized physical microstructure, and the resulting correlations often cannot be applied to real materials and practical applications. This review summarizes the evolution and development of relationships for the effective Young’s modulus of a porous material and concludes that verifiable equations yielding consistently reproducible results tied to specific pore structures do not yet exist. Further research is needed to develop and validate predictive equations for the effective Young’s modulus over a volume porosity range of 20–50 %, the range of interest over which existing equations, whether based on effective medium theories or empirical results, demonstrate the largest disparity and offers the greatest opportunity for beneficial modification of bending stiffness in orthopedic applications using currently available additive manufacturing techniques
Monitoring Early-Stage Protein Aggregation by an Aggregation-Induced Emission Fluorogen
Highly ordered protein aggregates, termed amyloid fibrils, are associated with a broad range of diseases, many of which are neurodegenerative, for example, Alzheimer\u27s and Parkinson\u27s. The transition from soluble, functional protein into insoluble amyloid fibril occurs via a complex process involving the initial generation of highly dynamic early stage aggregates or prefibrillar species. Amyloid probes, for example, thioflavin T and Congo red, have been used for decades as the gold standard for detecting amyloid fibrils in solution and tissue sections. However, these well-established dyes do not detect the presence of prefibrillar species formed during the early stages of protein aggregation. Prefibillar species have been proposed to play a key role in the cytotoxicity of amyloid fibrils and the pathogenesis of neurodegenerative diseases. Herein, we report a novel fluorescent dye (bis(triphenylphosphonium) tetraphenylethene (TPE-TPP)) with aggregation-induced emission characteristics for monitoring the aggregation process of amyloid fibrils. An increase in TPE-TPP fluorescence intensity is observed only with ordered protein aggregation, such as amyloid fibril formation, and not with stable molten globules states or amorphously aggregating species. Importantly, TPE-TPP can detect the presence of prefibrillar species formed early during fibril formation. TPE-TPP exhibits a distinctive spectral shift in the presence of prefibrillar species, indicating a unique structural feature of these intermediates. Using fluorescence polarization, which reflects the mobility of the emitting entity, the specific oligomeric pathways undertaken by various proteins during fibrillation could be discerned. Furthermore, we demonstrate the broad applicability of TPE-TPP to monitor amyloid fibril aggregation, including under diverse conditions such as at acidic pH and elevated temperature, or in the presence of amyloid inhibitors
Month-Timescale Optical Variability in the M87 Jet
A previously inconspicuous knot in the M87 jet has undergone a dramatic
outburst and now exceeds the nucleus in optical and X-ray luminosity.
Monitoring of M87 with the Hubble Space Telescope and Chandra X-ray Observatory
during 2002-2003, has found month-timescale optical variability in both the
nucleus and HST-1, a knot in the jet 0.82'' from the nucleus. We discuss the
behavior of the variability timescales as well as spectral energy distribution
of both components. In the nucleus, we see nearly energy-independent
variability behavior. Knot HST-1, however, displays weak energy dependence in
both X-ray and optical bands, but with nearly comparable rise/decay timescales
at 220 nm and 0.5 keV. The flaring region of HST-1 appears stationary over
eight months of monitoring. We consider various emission models to explain the
variability of both components. The flares we see are similar to those seen in
blazars, albeit on longer timescales, and so could, if viewed at smaller
angles, explain the extreme variability properties of those objects.Comment: 4 pages, 3 figures, ApJ Lett., in pres
Proteostasis and the Regulation of Intra- and Extracellular Protein Aggregation by ATP-Independent Molecular Chaperones: Lens α-Crystallins and Milk Caseins
Conspectus: Molecular chaperone proteins perform a diversity of roles inside and outside the cell. One of the most important is the stabilization of misfolding proteins to prevent their aggregation, a process that is potentially detrimental to cell viability. Diseases such as Alzheimer\u27s, Parkinson\u27s, and cataract are characterized by the accumulation of protein aggregates. In vivo, many proteins are metastable and therefore under mild destabilizing conditions have an inherent tendency to misfold, aggregate, and hence lose functionality. As a result, protein levels are tightly regulated inside and outside the cell. Protein homeostasis, or proteostasis, describes the network of biological pathways that ensures the proteome remains folded and functional. Proteostasis is a major factor in maintaining cell, tissue, and organismal viability.
We have extensively investigated the structure and function of intra- and extracellular molecular chaperones that operate in an ATP-independent manner to stabilize proteins and prevent their misfolding and subsequent aggregation into amorphous particles or highly ordered amyloid fibrils. These types of chaperones are therefore crucial in maintaining proteostasis under normal and stress (e.g., elevated temperature) conditions. Despite their lack of sequence similarity, they exhibit many common features, i.e., extensive structural disorder, dynamism, malleability, heterogeneity, oligomerization, and similar mechanisms of chaperone action. In this Account, we concentrate on the chaperone roles of α-crystallins and caseins, the predominant proteins in the eye lens and milk, respectively. Intracellularly, the principal ATP-independent chaperones are the small heat-shock proteins (sHsps). In vivo, sHsps are the first line of defense in preventing intracellular protein aggregation. The lens proteins αA- and αB-crystallin are sHsps. They play a crucial role in maintaining solubility of the crystallins (including themselves) with age and hence in lens proteostasis and, ultimately, lens transparency. As there is little metabolic activity and no protein turnover in the lens, crystallins are very long lived proteins. Lens proteostasis is therefore very different to that in normal, metabolically active cells. Crystallins undergo extensive post-translational modification (PTM), including deamidation, racemization, phosphorylation, and truncation, which can alter their stability. Despite this, the lens remains transparent for tens of years, implying that lens proteostasis is intimately integrated with crystallin PTMs. Many PTMs do not significantly alter crystallin stability, solubility, and functionality, which thereby facilitates lens transparency. In the long term, however, extensive accumulation of crystallin PTMs leads to large-scale crystallin aggregation, lens opacification, and cataract formation. Extracellularly, various ATP-independent molecular chaperones exist that exhibit sHsp-like structural and functional features. For example, caseins, the major milk proteins, exhibit chaperone ability by inhibiting the amorphous and amyloid fibrillar aggregation of a diversity of destabilized proteins. Caseins maintain proteostasis within milk by preventing deleterious casein amyloid fibril formation via incorporation of thousands of individual caseins into an amorphous structure known as the casein micelle. Hundreds of nanoclusters of calcium phosphate are sequestered within each casein micelle through interactions with short, highly phosphorylated casein sequences. This results in a stable biofluid that contains a high concentration of potentially amyloidogenic caseins and concentrations of calcium and phosphate that can be far in excess of the solubility of calcium phosphate. Casein micelle formation therefore performs vital roles in neonatal nutrition and calcium homeostasis in the mammary gland
Evidence that vulture restaurants increase the local abundance of mammalian carnivores in South Africa
Vulture restaurants are used worldwide as a conservation tool to provide threatened vultures with a source of supplementary carrion free from anthropogenic contaminants such as poisons and veterinary drugs. While the impacts of supplementary feeding sites on ecosystem and scavenging community dynamics have been investigated in Europe, no information is currently available for southern Africa. This study presents evidence that providing supplementary carrion for vultures stimulated an increase in local abundance of two species of mammalian carnivores, the brown hyaena (Hyaena brunnea) and the black-backed jackal (Canis mesomelas). These findings require that the wider impacts of providing supplementary carrion for conserving threatened species are fully investigated
Extending long-range phasing and haplotype library imputation algorithms to large and heterogeneous datasets
A multi-part strategy for introgression of exotic germplasm into elite plant breeding programs using genomic selection
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