1,446 research outputs found

    Biomineralization mediated by anaerobic methane-consuming cell consortia

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    Insect adhesion on rough surfaces: analysis of adhesive contact of smooth and hairy pads on transparent microstructured substrates.

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    Insect climbing footpads are able to adhere to rough surfaces, but the details of this capability are still unclear. To overcome experimental limitations of randomly rough, opaque surfaces, we fabricated transparent test substrates containing square arrays of 1.4 µm diameter pillars, with variable height (0.5 and 1.4 µm) and spacing (from 3 to 22 µm). Smooth pads of cockroaches (Nauphoeta cinerea) made partial contact (limited to the tops of the structures) for the two densest arrays of tall pillars, but full contact (touching the substrate in between pillars) for larger spacings. The transition from partial to full contact was accompanied by a sharp increase in shear forces. Tests on hairy pads of dock beetles (Gastrophysa viridula) showed that setae adhered between pillars for larger spacings, but pads were equally unable to make full contact on the densest arrays. The beetles' shear forces similarly decreased for denser arrays, but also for short pillars and with a more gradual transition. These observations can be explained by simple contact models derived for soft uniform materials (smooth pads) or thin flat plates (hairy-pad spatulae). Our results show that microstructured substrates are powerful tools to reveal adaptations of natural adhesives for rough surfaces

    Real-time non-invasive measurement and monitoring of wheel-rail contact using ultrasonic reflectometry

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    Rail stress levels are vital to the lifespan of rail tracks, and are responsible for the safe operation and ride comfort of train services. In particular, wheel–rail contact stress is a dominating factor affecting wear, cracking, fatigue and failure of both wheel and rail. The wheel–rail interaction problem has long been investigated, yet detailed contact information on real cases remains obscure due to the interface complexity, including the varying wheel and rail profiles and lack of effective stress characterisation methods. Ultrasound image study, as an excellent non-destructive evaluation (NDE) method, is widely used in railway systems for defect detection, stress determination and rail profile checking. Specifically, ultrasonic reflectometry has proved successful in making static machine-element contact measurements. This article introduces a novel measuring method for both short-term and long-term dynamic wheel–rail contact monitoring purposes based on ultrasonic reflectometry. The method is investigated in detail, including the study of ultrasound propagation pathways in the rail, and the optimum placement of ultrasonic elements as well as actuator–receiver combinations. The proposed monitoring technique is expected to characterise and monitor the contact behaviour of operating high-speed rail system in real-time

    Design, synthesis and biological characterization of novel inhibitors of CD38

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    Human CD38 is a novel multi-functional protein that acts not only as an antigen for B-lymphocyte activation, but also as an enzyme catalyzing the synthesis of a Ca 2+ messenger molecule, cyclic ADP-ribose, from NAD +. It is well established that this novel Ca 2+ signaling enzyme is responsible for regulating a wide range of physiological functions. Based on the crystal structure of the CD38/NAD + complex, we synthesized a series of simplified N-substituted nicotinamide derivatives (Compound1-14). A number of these compounds exhibited moderate inhibition of the NAD + utilizing activity of CD38, with Compound4 showing the highest potency. The crystal structure of CD38/Compound4 complex and computer simulation of Compound7 docking to CD38 show a significant role of the nicotinamide moiety and the distal aromatic group of the compounds for substrate recognition by the active site of CD38. Biologically, we showed that both Compounds4 and 7 effectively relaxed the agonist-induced contraction of muscle preparations from rats and guinea pigs. This study is a rational design of inhibitors for CD38 that exhibit important physiological effects, and can serve as a model for future drug development. © 2011 The Royal Society of Chemistry.postprin

    An evaluation of ultrasonic arrays for the static and dynamic measurement of wheel rail contact pressure and area

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    The interfacial contact conditions between a railway vehicle wheel and the rail are paramount to the lifespan, safety and smooth operation of any rail network. The wheel/rail interface contact pressure and area conditions have been estimated, calculated and simulated by industry and academia for many years, but a method of accurately measuring dynamic contact conditions has yet to be realised. Methods using pressure sensitive films and controlled air flow have been employed, but both are limited. Ultrasonic reflectometry is the term given to active ultrasonics in which an ultrasonic transducer is mounted on the outer surface of a component and a sound wave is generated. This ultrasonic wave packet propagates through the host medium and reflects off the contacting interface of interest. The reflected waveform is then detected and contact area and interfacial stiffness information can be extracted from the signal using the quasi-static spring model. Stiffness can be related to contact pressure by performing a simple calibration procedure. Previous contact pressure measurement work has relied on using a focusing transducer and a 2-dimensional scanning arrangement which results in a high resolution image of the wheel/rail contact, but is limited to static loading of a specimen cut from a wheel and rail. The work described in this paper has assessed the feasibility of measuring a dynamic wheel/rail contact patch using an array of 64 ultrasonic elements mounted in the rail. Each element is individually pulsed in sequence to build up a linear cross sectional pressure profile measurement of the interface. These cross-sectional, line measurements are then processed and collated resulting in a 2-dimensional contact pressure profile. Measurements have been taken at different speeds and loads

    Understanding the nature of "superhard graphite"

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    Numerous experiments showed that on cold compression graphite transforms into a new superhard and transparent allotrope. Several structures with different topologies have been proposed for this phase. While experimental data are consistent with these models, the only way to solve this puzzle is to find which structure is kinetically easiest to form. Using state-of-the-art molecular-dynamics transition path sampling simulations, we investigate kinetic pathways of the pressure-induced transformation of graphite to various superhard candidate structures. Unlike hitherto applied methods for elucidating nature of superhard graphite, transition path sampling realistically models nucleation events necessary for physically meaningful transformation kinetics. We demonstrate that nucleation mechanism and kinetics lead to MM-carbon as the final product. WW-carbon, initially competitor to MM-carbon, is ruled out by phase growth. Bct-C4_4 structure is not expected to be produced by cold compression due to less probable nucleation and higher barrier of formation

    The skeletal phenotype of chondroadherin deficient mice

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    Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth

    Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

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    Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

    Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria

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    Accuracy of protein synthesis is enabled by the selection of amino acids for tRNA charging by aminoacyl-tRNA synthetases (ARSs), and further enhanced by the proofreading functions of some of these enzymes for eliminating tRNAs mischarged with noncognate amino acids. Mouse models of editing-defective cytoplasmic alanyl-tRNA synthetase (AlaRS) have previously demonstrated the importance of proofreading for cytoplasmic protein synthesis, with embryonic lethal and progressive neurodegeneration phenotypes. Mammalian mitochondria import their own set of nuclear-encoded ARSs for translating critical polypeptides of the oxidative phosphorylation system, but the importance of editing by the mitochondrial ARSs for mitochondrial proteostasis has not been known. We demonstrate here that the human mitochondrial AlaRS is capable of editing mischarged tRNAs in vitro, and that loss of the proofreading activity causes embryonic lethality in mice. These results indicate that tRNA proofreading is essential in mammalian mitochondria, and cannot be overcome by other quality control mechanisms
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