217 research outputs found

    Function Based Design-by-Analogy: A Functional Vector Approach to Analogical Search

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    Design-by-analogy is a powerful approach to augment traditional concept generation methods by expanding the set of generated ideas using similarity relationships from solutions to analogous problems. While the concept of design-by-analogy has been known for some time, few actual methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting functional analogies from data sources has been developed to provide this capability, here based on a functional basis rather than form or conflict descriptions. Building on past research, we utilize a functional vector space model (VSM) to quantify analogous similarity of an idea's functionality. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We also develop document parsing algorithms to reduce text descriptions of the data sources down to the key functions, for use in the functional similarity analysis and functional vector space modeling. To do this, we apply Zipf's law on word count order reduction to reduce the words within the documents down to the applicable functionally critical terms, thus providing a mapping process for function based search. The reduction of a document into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. As a verification of the approach, two original design problem case studies illustrate the distance range of analogical solutions that can be extracted. This range extends from very near-field, literal solutions to far-field cross-domain analogies.National Science Foundation (U.S.) (Grant CMMI-0855326)National Science Foundation (U.S.) (Grant CMMI-0855510)National Science Foundation (U.S.) (Grant CMMI-0855293)SUTD-MIT International Design Centre (IDC

    Design-by-analogy: experimental evaluation of a functional analogy search methodology for concept generation improvement

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    Design-by-analogy is a growing field of study and practice, due to its power to augment and extend traditional concept generation methods by expanding the set of generated ideas using similarity relationships from solutions to analogous problems. This paper presents the results of experimentally testing a new method for extracting functional analogies from general data sources, such as patent databases, to assist designers in systematically seeking and identifying analogies. In summary, the approach produces significantly improved results on the novelty of solutions generated and no significant change in the total quantity of solutions generated. Computationally, this design-by-analogy facilitation methodology uses a novel functional vector space representation to quantify the functional similarity between represented design problems and, in this case, patent descriptions of products. The mapping of the patents into the functional analogous words enables the generation of functionally relevant novel ideas that can be customized in various ways. Overall, this approach provides functionally relevant novel sources of design-by-analogy inspiration to designers and design teams.SUTD-MIT International Design Centre (IDC)National Science Foundation (U.S.) (Grant Numbers CMMI-0855326, CMMI-0855510, and CMMI-08552930

    Facilitating Design-by-Analogy: Development of a Complete Functional Vocabulary and Functional Vector Approach to Analogical Search

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    Design-by-analogy is an effective approach to innovative concept generation, but can be elusive at times due to the fact that few methods and tools exist to assist designers in systematically seeking and identifying analogies from general data sources, databases, or repositories, such as patent databases. A new method for extracting analogies from data sources has been developed to provide this capability. Building on past research, we utilize a functional vector space model to quantify analogous similarity between a design problem and the data source of potential analogies. We quantitatively evaluate the functional similarity between represented design problems and, in this case, patent descriptions of products. We develop a complete functional vocabulary to map the patent database to applicable functionally critical terms, using document parsing algorithms to reduce text descriptions of the data sources down to the key functions, and applying Zipf’s law on word count order reduction to reduce the words within the documents. The reduction of a document (in this case a patent) into functional analogous words enables the matching to novel ideas that are functionally similar, which can be customized in various ways. This approach thereby provides relevant sources of design-by-analogy inspiration. Although our implementation of the technique focuses on functional descriptions of patents and the mapping of these functions to those of the design problem, resulting in a set of analogies, we believe that this technique is applicable to other analogy data sources as well. As a verification of the approach, an original design problem for an automated window washer illustrates the distance range of analogical solutions that can be extracted, extending from very near-field, literal solutions to far-field cross-domain analogies. Finally, a comparison with a current patent search tool is performed to draw a contrast to the status quo and evaluate the effectiveness of this work.National Science Foundation (U.S.) (grant number CMMI-0855510)National Science Foundation (U.S.) (grant number CMMI-0855326)National Science Foundation (U.S.) (grant number CMMI-0855293)SUTD-MIT International Design Centre (IDC

    One-carbon metabolism in cancer

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    Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

    Respiratory plasticity in response to changes in oxygen supply and demand

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    Aerobic organisms maintain O2 homeostasis by responding to changes in O2 supply and demand in both short and long time domains. In this review, we introduce several specific examples of respiratory plasticity induced by chronic changes in O2 supply (environmental hypoxia or hyperoxia) and demand (exercise-induced and temperature-induced changes in aerobic metabolism). These studies reveal that plasticity occurs throughout the respiratory system, including modifications to the gas exchanger, respiratory pigments, respiratory muscles, and the neural control systems responsible for ventilating the gas exchanger. While some of these responses appear appropriate (e.g., increases in lung surface area, blood O2 capacity, and pulmonary ventilation in hypoxia), other responses are potentially harmful (e.g., increased muscle fatigability). Thus, it may be difficult to predict whole-animal performance based on the plasticity of a single system. Moreover, plastic responses may differ quantitatively and qualitatively at different developmental stages. Much of the current research in this field is focused on identifying the cellular and molecular mechanisms underlying respiratory plasticity. These studies suggest that a few key molecules, such as hypoxia inducible factor (HIF) and erythropoietin, may be involved in the expression of diverse forms of plasticity within and across species. Studying the various ways in which animals respond to respiratory challenges will enable a better understanding of the integrative response to chronic changes in O2 supply and deman

    The Art of Research: A Divergent/Convergent Framework and Opportunities for Science-Based Approaches

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    Applying science to the current art of producing engineering and research knowledge has proven difficult, in large part because of its seeming complexity. We posit that the microscopic processes underlying research are not so complex, but instead are iterative and interacting cycles of divergent (generation of ideas) and convergent (testing and selecting of ideas) thinking processes. This reductionist framework coherently organizes a wide range of previously disparate microscopic mechanisms which inhibit these processes. We give examples of such inhibitory mechanisms and discuss how deeper scientific understanding of these mechanisms might lead to dis-inhibitory interventions for individuals, networks and institutional levels

    Tunable anisotropy in inverse opals and emerging optical properties

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    Using self-assembly, nanoscale materials can be fabricated from the bottom up. Opals and inverse opals are examples of self-assembled nanomaterials made from crystallizing colloidal particles. As self-assembly requires a high level of control, it is challenging to use building blocks with anisotropic geometry to form complex opals, which limits the realizable structures. Typically, spherical colloids are employed as building blocks, leading to symmetric, isotropic superstructures. However, a significantly richer palette of directionally dependent properties are expected if less symmetric, anisotropic structures can be created, especially originating from the assembly of regular, spherical particles. Here we show a simple method to introduce anisotropy into inverse opals by subjecting them to a post-assembly thermal treatment that results in directional shrinkage of the silica matrix caused by condensation of partially hydrated sol-gel silica structures. In this way, we can tailor the shape of the pores, and the anisotropy of the final inverse opal preserves the order and uniformity of the self-assembled structure, while completely avoiding the need to synthesize complex oval-shaped particles and crystallize them into such target geometries. Detailed X-ray photoelectron spectroscopy (XPS) and infrared (IR) spectroscopy studies clearly identify increasing degrees of sol-gel condensation in confinement as a mechanism for the structure change. A computer simulation of structure changes resulting from the condensation-induced shrinkage further confirmed this mechanism. As an example of property changes induced by the introduction of anisotropy, we characterized the optical spectra of the anisotropic inverse opals and found that the optical properties can be controlled in a precise way using calcination temperature

    Clarifying hierarchical age–period–cohort models: A rejoinder to Bell and Jones

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    Previously, Reither et al. (2015) demonstrated that hierarchical age–period–cohort (HAPC) models perform well when basic assumptions are satisfied. To contest this finding, Bell and Jones (2015) invent a data generating process (DGP) that borrows age, period and cohort effects from different equations in Reither et al. (2015). When HAPC models applied to data simulated from this DGP fail to recover the patterning of APC effects, B&J reiterate their view that these models provide “misleading evidence dressed up as science.” Despite such strong words, B&J show no curiosity about their own simulated data—and therefore once again misapply HAPC models to data that violate important assumptions. In this response, we illustrate how a careful analyst could have used simple descriptive plots and model selection statistics to verify that (a) period effects are not present in these data, and (b) age and cohort effects are conflated. By accounting for the characteristics of B&J's artificial data structure, we successfully recover the “true” DGP through an appropriately specified model. We conclude that B&Js main contribution to science is to remind analysts that APC models will fail in the presence of exact algebraic effects (i.e., effects with no random/stochastic components), and when collinear temporal dimensions are included without taking special care in the modeling process. The expanded list of coauthors on this commentary represents an emerging consensus among APC scholars that B&J's essential strategy—testing HAPC models with data simulated from contrived DGPs that violate important assumptions—is not a productive way to advance the discussion about innovative APC methods in epidemiology and the social sciences

    The Effect of High Glucocorticoid Administration and Food Restriction on Rodent Skeletal Muscle Mitochondrial Function and Protein Metabolism

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    Glucocorticoids levels are high in catabolic conditions but it is unclear how much of the catabolic effects are due to negative energy balance versus glucocorticoids and whether there are distinct effects on metabolism and functions of specific muscle proteins.We determined whether 14 days of high dose methylprednisolone (MPred, 4 mg/kg/d) Vs food restriction (FR, food intake matched to MPred) in rats had different effects on muscle mitochondrial function and protein fractional synthesis rates (FSR). Lower weight loss (15%) occurred in FR than in MPred (30%) rats, while a 15% increase occurred saline-treated Controls. The per cent muscle loss was significantly greater for MPred than FR. Mitochondrial protein FSR in MPred rats was lower in soleus (51 and 43%, respectively) and plantaris (25 and 55%) than in FR, while similar decline in protein FSR of the mixed, sarcoplasmic, and myosin heavy chain occurred. Mitochondrial enzymatic activity and ATP production were unchanged in soleus while in plantaris cytochrome c oxidase activity was lower in FR than Control, and ATP production rate with pyruvate + malate in MPred plantaris was 28% lower in MPred. Branched-chain amino acid catabolic enzyme activities were higher in both FR and MPred rats indicating enhanced amino acid oxidation capacity.MPred and FR had little impact on mitochondrial function but reduction in muscle protein synthesis occurred in MPred that could be explained on the basis of reduced food intake. A greater decline in proteolysis may explain lesser muscle loss in FR than in MPred rats

    Overexpression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survival.

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    BACKGROUND: Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical squamous cell carcinoma (SCC) and is associated with adverse clinical outcome. We previously showed that OSMR overexpression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases migration and invasion in vitro. We hypothesised that a major contribution to this phenotype would come from epithelial-mesenchymal transition (EMT). METHODS: We performed a comprehensive integrated study, involving in vitro cell line studies, in vivo animal models and numerous clinical samples from a variety of anatomical sites. RESULTS: In independent sets of cervical, head/neck and lung SCC tissues, OSMR expression levels correlated with multiple EMT-associated phenotypic markers and transcription factors. OSM treatment of OSMR overexpressing cervical SCC cells produced consistent EMT changes and increased tumour sphere formation in suspension culture. In a mouse model, OSMR overexpressing SCC cells treated with OSM showed significant increases in lung colonisation. The biological effects of exogenous OSM were mirrored by highly significant adverse overall survival in cervical SCCs with OSMR overexpression (N=251). CONCLUSIONS: OSM:OSMR interactions are able to induce EMT, increased cancer stem cell-like properties and enhanced lung colonisation in SCC cells. These changes are likely to contribute to the highly significant adverse outcome associated with OSMR overexpression in cervical SCCs.This work was supported by Cancer Research UK (Programme Grant A13080).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group
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