1,255 research outputs found

    Holistic engineering design : a combined synchronous and asynchronous approach

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    To aid the creation and through-life support of large, complex engineering products, organizations are placing a greater emphasis on constructing complete and accurate records of design activities. Current documentary approaches are not sufficient to capture activities and decisions in their entirety and can lead to organizations revisiting and in some cases reworking design decisions in order to understand previous design episodes. Design activities are undertaken in a variety of modes; many of which are dichotomous, and thus each require separate documentary mechanisms to capture information in an efficient manner. It is possible to identify the modes of learning and transaction to describe whether an activity is aimed at increasing a level of understanding or whether it involves manipulating information to achieve a tangible task. The dichotomy of interest in this paper is that of synchronous and asynchronous working, where engineers may work alternately as part of a group or as individuals and where different forms of record are necessary to adequately capture the processes and rationale employed in each mode. This paper introduces complimentary approaches to achieving richer representations of design activities performed synchronously and asynchronously, and through the undertaking of a design based case study, highlights the benefit of each approach. The resulting records serve to provide a more complete depiction of activities undertaken, and provide positive direction for future co-development of the approaches

    Ethyl Orthocarbonate [Orthocarbonic acid, tetrahethyl ester]

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    A solution of sodium ethoxide is prepared under nitrogen from 70 g. (3.04 g. atoms) of sodium and 2 l. of absolute ethanol (Note 1) in a 3-l. three-necked flask which is equipped with mechanical stirrer, efficient reflux condenser, dropping funnel, and a thermometer which dips below the level of the liquid in the flask. Chloropicrin (100 g., 0.61 mole) (Note 2) is placed in the dropping funnel, and the stirred solution is heated to 58–60° with a water bath. The chloropicrin is added at a rate of 30–35 drops per minute until the reaction becomes self-sustaining (about 20 minutes), at which point the water bath is removed and the balance of the chloropicrin is added at a rate sufficient to maintain the temperature at 58–60° (Note 3). When the addition, which requires nearly 2 hours, is complete, the stirrer is stopped and the mixture is allowed to stand overnight

    Using computational fluid dynamics (CFD) to design and characterize a microfluidic bioreactor for rapid release of culture-derived platelets

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    Platelet transfusions are entirely dependent on human volunteer donors, and these methods are limited by platelet storage at room temperature, a 5-day platelet shelf life, and differences in donor/recipient immunology. Much progress has been made in generating large numbers of culture-derived megakaryocytes (Mks, the precursor cells to platelets). However, much remains unknown about what initiates and regulates platelet formation, so stimulating a high percentage of Mks to undergo terminal maturation and platelet release in vitro remains a major challenge. Methods of in vitro platelet production have typically yielded less than 10 platelets/Mk, compared to \u3e1,000 in vivo. In vivo, platelets are formed when bone marrow Mks extend long, cytoplasmic projections, called proplatelets (proPLTs), into the sinusoid where shear forces accelerate proPLT elongation and release platelets into circulation. Recent studies have demonstrated the utility of shear forces to enhance platelet release from cultured Mks in vitro. We are exploring the production of platelet-like particles (PLPs) within a microfluidic bioreactor that utilizes shear forces on Mks to generate proPLTs and PLPs. Microfluidic devices have emerged as a valuable tool for cell culture studies. Advantages include low input cell requirements, the ability to screen multiple conditions in parallel, compatibility with time-lapse imaging, and tight control of microenvironment conditions. In addition, device fabrication is straightforward and inexpensive using soft photolithography. In this study, we performed a computational fluid dynamics (CFD) analysis of several published platelet microbioreactor systems, and used the results to develop a new bioreactor system. Through CFD simulations and microfluidic device fabrication, a design – test – build methodology was used to develop a dual-flow microfluidic bioreactor system with uniform shear stress at levels similar to those found in the bone marrow niche. Experimental studies were conducted to validate the simulations in terms of streamline profiles and flow patterns with and without cell capture. Furthermore, the design of the bioreactor allows for a wide physiological shear rate range, and fits within the stage of a fluorescent microscope housed in an incubator that allows for real-time analysis of proPLT formation and PLP release. The videos and images captured within our system show that the new bioreactor not only promotes the prototypical proPLT formation process with beadson-a-string morphology, but also supports rapid release of individual PLPs – which has been observed in vivo, but not previously reported for platelet bioreactors. In addition, we demonstrate that step increases in the shear forces within the microbioreactor system can be used to enhance proPLT and PLP formation. Bioreactor-derived PLPs exhibit functional activity, as evidenced by CD41a and CD42b surface marker expression, CD62P translocation from granules to the surface in response to thrombin agonist activation, and morphological/ cytoskeletal changes upon binding to fibrinogen – before and after activation. The system can be further scaled, for example, through parallelization of reactors

    A Graphic Method For Depicting Horizontal Direction Data On Vertical Outcrop Photographs

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    Outcrop photographs which show two-dimensional representations of three-dimensionally dipping surfaces (e.g., bedding planes, cross-bed foresets) are commonly utilized in the description of sedimentary strata. In many instances, accurate depiction of the dip direction of such features is paramount for understanding their interpretation, and for visualizing the true form of three-dimensional bodies (e.g., conceptualizing the form of an architectural element in a cliff-face, preserved as a vertical slice that has been cut oblique to paleocurrent direction). However, as an outcrop photograph often presents information on a vertical plane and directional data refers to a horizontal plane, the accurate co-depiction of both sets of information may be challenging. There is presently no universal method for illustrating such measurements on outcrop photographs: techniques in common usage are often imprecise, and the lack of uniformity hinders comparison between different images. Here we present a method for accurately depicting horizontal direction data on vertical outcrop photographs which permits instant visualization of dip relative to the illustrated outcrop geometry. The method is simple to apply, does not compromise primary data, and is unobtrusive to other visual information within images; thus having utility across a broad spectrum of geological investigations

    Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning

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    Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct cell identities in the ventral neural tube through a Gli-mediated (Gli1-3) transcriptional network. Identifying Gli targets in a systematic fashion is central to the understanding of the action of Shh. We examined this issue in differentiating neural progenitors in mouse. An epitope-tagged Gli-activator protein was used to directly isolate cis-regulatory sequences by chromatin immunoprecipitation (ChIP). ChIP products were then used to screen custom genomic tiling arrays of putative Hedgehog (Hh) targets predicted from transcriptional profiling studies, surveying 50-150 kb of non-transcribed sequence for each candidate. In addition to identifying expected Gli-target sites, the data predicted a number of unreported direct targets of Shh action. Transgenic analysis of binding regions in Nkx2.2, Nkx2.1 (Titf1) and Rab34 established these as direct Hh targets. These data also facilitated the generation of an algorithm that improved in silico predictions of Hh target genes. Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process

    997-90 Right (RV) and Left Ventricular (LV) Geometry and Myocyte Contractile Processes with Dilated Cardiomyopathy (DCM): Disparity Between Myocyte Growth and β-Adrenergic Responsiveness

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    The progression of DCM has been assumed to be a homogenous process for both the RV and LV. However, this assumption has never been tested. Accordingly, we measured myocyte contractile performance (velocity of shortening, VELSHORT; percent shortening, PERSHORT) at baseline (BASE) and after β-adrenergic receptor stimulation (βAR, 25 nM isoproterenol) of isolated myocytes taken from the RV and LV of 5 pigs with pacing induced DCM (240 bpm, 3 weeks) and 5 control pigs (CON). RV and LV mass/body weight (MASS) and myocyte length and cross-sectional area (CSA) were also determined.CON-RVCON-LVDCM-RVDCM-LVVELSHORT-BASE (μm/s)90±5+50±148±2*,+32±1*VELSHORT-βAR (μm/s)206±8+150±5123±8*111±9*PERSHORT-BASE (%)5.8±0.2+4.6±0.13.1±0.1*,+2.2±0.1*PERSHORT-βAR (%)11.5±0.3+10.2±0.359±0.3*5.2±0.4*Length (μm)150±2+137±1179±2*,+173±2*CSA (μm2)176±4+362±8232±4*,+292±5*Mass (gm/kg)0.8±0.1+2.8±0.11.6±0.1*,+2.9±0.2+p<0.05 vs LV*p<005 vS CONIn controls, RV myocytes were longer and had a smaller CSA, but enhanced contractile performance at baseline and with β-adrenergic stimulation. With DCM, no LV hypertrophy occurred. In contrast, RV chamber and cellular hypertrophy occurred and was associated with a persistent increase of RV myocyte baseline contractile function.SummaryThis study demonstrated, for the first time, that differences in RV and LV myocyte function and β-adrenergic responsiveness exist in normal and DCM states. More importantly, a disparity in RV and LV myocyte growth with DCM occurred. Thus, in this model of DCM, RV and LV growth and changes in contractile performance are not a homogenous process, and suggest that inherent differences exist in the response of RV and LV myocytes to stress

    Optoelectronic analysis of multijunction wire array solar cells

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    Wire arrays have demonstrated promising photovoltaic performance as single junction solar cells and are well suited to defect mitigation in heteroepitaxy. These attributes can combine in tandem wire array solar cells, potentially leading to high efficiencies. Here, we demonstrate initial growths of GaAs on Si_(0.9)Ge_(0.1) structures and investigate III-V on Si_(1-x)Ge_x device design with an analytical model and optoelectronic simulations. We consider Si_(0.1)Ge_(0.9) wires coated with a GaAs_(0.9)P_(0.1) shell in three different geometries: conformal, hemispherical, and spherical. The analytical model indicates that efficiencies approaching 34% are achievable with high quality materials. Full field electromagnetic simulations serve to elucidate the optical loss mechanisms and demonstrate light guiding into the wire core. Simulated current-voltage curves under solar illumination reveal the impact of a varying GaAs_(0.9)P_(0.1) minority carrier lifetime. Finally, defective regions at the hetero-interface are shown to have a negligible effect on device performance if highly doped so as to serve as a back surface field. Overall, the growths and the model demonstrate the feasibility of the proposed geometries and can be used to guide tandem wire array solar cell designs

    Evolution of alluvial mudrock forced by early land plants.

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    Mudrocks are a primary archive of Earth's history from the Archean eon to recent times, and their source-to-sink production and deposition play a central role in long-term ocean chemistry and climate regulation. Using original and published stratigraphic data from all 704 of Earth's known alluvial formations from the Archean eon (3.5 billion years ago) to the Carboniferous period (0.3 billion years ago), we prove contentions of an upsurge in the proportion of mud retained on land coeval with vegetation evolution. We constrain the onset of the upsurge to the Ordovician-Silurian and show that alluvium deposited after land plant evolution contains a proportion of mudrock that is, on average, 1.4 orders of magnitude greater than the proportion contained in alluvium from the preceding 90% of Earth's history. We attribute this shift to the ways in which vegetation revolutionized mud production and sediment flux from continental interiors
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