8,340 research outputs found

    Design for product-embedded disassembly pathways

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    This paper presents a computational method for designing an assembly with multiple built-in disassembly pathways, each of which can be activated to retrieve certain components. It is motivated by the global sales of consumer products whose optimal end-of-life options vary geographically due to local recycling/reuse infrastructures and regulatory requirements. Given the sets of components to be retrieved at each location, the method simultaneously determines the spatial configurations of components and locator features, such that each set of desired components is retrieved via a domino-like self-disassembly" process triggered by the removal of a fastener. A multi-objective generic algorithm is utilized to search for Pareto-optimal designs in terms of the realization of the desired disassembly pathways, the satisfaction of distance specifications among components, the minimization of disassembly cost at each location, and the efficient use of on-component locator features. A case study demonstrates the feasibility of the method.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87258/4/Saitou77.pd

    Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

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    Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

    Synthetic Supramolecular Systems in Life-like Materials and Protocell Models

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    One of the biggest challenges in modern chemistry is the preparation of synthetic materials with life-like behavior for the assembly of artificial cells. In recent years, numerous artificial systems that mimic cellular components and functions have been developed. Supramolecular chemistry plays a key role in such cell mimics given that non-covalent interactions control the shape and function of many biomolecules, such as DNA base pairing, protein structure, ligand-receptor binding, and lipid membrane packing. However, the complexity of living cells constitutes a major challenge for their bottom-up assembly from pure synthetic materials. Inspired by the building blocks of nature, a wide range of supramolecular systems have been developed to reproduce cellular functions such as cell-cell communication, signaling cascades, and dynamic cytoskeleton assemblies. This review surveys a selection of key advances in synthetic derivatives of biomolecules with supramolecular organization and life-like behavior by addressing their non-covalent foundation and integration as increasingly complex protocell modelsThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI; SAF2017-89890-R), Xunta de Galicia (ED431C 2017/25, 2016-AD031, and ED431G/09), ISCIII (RD16/0008/003), and the European Commission (EC; European Regional Development Fund). I.I. thanks the EC and AEI for MSCA-IF (2018-843332) and JdC (FJCI-2017-31795) fellowships, respectively. J.M. received a Ramón y Cajal grant (RYC-2013-13784), an ERC-Stg grant (DYNAP-677786), and a Young Investigator Grant from the Human Frontier Science Program (RGY0066/2017)S

    Exploring communication and collective behaviour between spatially organised inorganic protocell communities

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    A living system profoundly relies on mass, information and energy interactions through cell-cell and cell-environment networks. As a step towards understanding such interactions, it is beneficial to design and create bottom-up artificial living systems from non-living components, with a specific focus on synergistic interactivity between artificial cells (protocells) and their local environment. Although there are several routes for fabricating protocellular systems, we recognise key challenges associated with a) developing protocellular models with high levels of organisational tunability, b) achieving cell-environment bilateral communication, and c) realising autonomous self-assembly and regulation of protocell systems. The aim of this thesis is thus to review some matrix-based and matrix-free methods of inorganic protocell (colloidosome) 3D-spatial organisation, as judicious system designs capable of cell-cell and cell-environment communication, collective behaviours, and dynamic self-assembly, in close relation with local environments.The first experimental chapter details assembly of colloidosomes within hydrogel or coacervate-based matrices. A droplet microfluidic technique is employed as a novel method for encapsulating segregated colloidosome colonies within alginate hydrogel microspheres. The technique exploits high tunability for customisable size, ratio, microscale geometry, and 3D-patterning parameters. Benefiting from the versatility associated with such matrix-based systems, the second experimental chapter develops 3D-organised colloidosomes for collective signalling and emergent behaviours. Notably, spatially segregated colonies show proximity-mediated chemical communication with increased kinetics compared to analogous homogenous arrangements. This proximity-enhanced colloidosome signalling is exploited, alongside segregated ionic/covalent crosslinking transitions in the environment, to obtain simultaneous structural degradation and resilience of hydrogel hemispheres as a programmable mechanism for protocell ejection. Colloidosomes are also employed as simple signalling hotspots within coacervate-matrix systems. The final experimental chapter aims to re-imagine colloidosome organisation into a matrix-free system, capable of dynamic self-assembly and self-sorting via electrostatically-active membrane appendages. Alginate-coated and chitosan-coated colloidosomes are either co-assembled or self-sorted, in response to varied pH environments. Again, these systems are highly coordinated with their environment and as such, can be spatially pattered according to temporal pH changes through endogenous enzyme catalysis. Furthermore, a spatiotemporal effect on the rate of colloidosome communication in the presence of a hostile guest molecule is demonstrated. <br/

    Definition of smolder experiments for Spacelab

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    The feasibility of conducting experiments in space on smoldering combustion was studied to conceptually design specific smoldering experiments to be conducted in the Shuttle/Spacelab System. Design information for identified experiment critical components is provided. The analytical and experimental basis for conducting research on smoldering phenomena in space was established. Physical descriptions of the various competing processes pertaining to smoldering combustion were identified. The need for space research was defined based on limitations of existing knowledge and limitations of ground-based reduced-gravity experimental facilities

    Investment in Sustainable Development: A UK Perspective on the Business and Academic Challenges

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    There are many legislative, stakeholder and supply chain pressures on business to be more ‘sustainable’. Universities have recognised the need for graduate knowledge and understanding of sustainable development issues. Many businesses and universities have responded and introduced Sustainable Development models into their operations with much of the current effort directed at climate change. However, as the current worldwide financial crisis slowly improves, the expectations upon how businesses operate and behave are changing. It will require improved transparency and relationships with all stakeholders, which is the essence of sustainable development. The challenges and opportunities for both business and universities are to understand the requirements of sustainable development and the transformation that is required. They should ensure that knowledge is embedded within the culture of the organisation and wider society in order to achieve a sustainable future

    Circular Composites

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    Composites are increasingly used to optimize the performance of applications as their properties can be tuned to achieve the desired functionality. The sustainability advantages during the use phase are not yet matched by lower impacts in the lifecycle of composite materials and products. In a circular economy this is problematic. This book will serve as a guide to designers who want to contribute with innovative and effective solutions. Circular recovery strategies, ranging from reuse to restructuring and recycling, are connected to the design process and concrete design approaches. By providing clear design guidelines and illustrative examples in a structured way the information is readily accessible and applicable to designers

    Disassembly Planning and Costing Through Petri Net Approach

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    In the current consumer oriented environment, many new products appear in the market almost on a daily basis. Lured by advertisements and tempted by new product features, customers are constantly purchasing newer products. Acquiring newer products for often leads to throwing out older ones, but it is a totally different story for manufacturers. They need to consider the best way to reuse a product both for economic purposes and for environmental protection. Considerations for them often include: how to minimize total disassembly cost, how to achieve the lowest total disassembly time at each processing step, and how to sort valuable parts from hazardous parts as early as possible during the disassembly procedure. In this paper, we use a Disassembly Petri-Net (DPN) to generate the Disassembly Process Plan (DPP). This plan is a sequence of disassembly tasks from the initial stage of the whole product to the final stage where each part is separated from the other parts. This disassembly plan is very valuable for product recycling or remanufacturing. Prior to having the DPN, we apply an algorithm to generate a Disassembly Precedence Matrix (DPM) helped by the construction steps involved in SolidWorks™, a solid model software used to create the part in the first place. From the DPN, we find all feasible paths and generate the corresponding costs of disassembly based upon tool changes, changes in direction of the movement and individual part characteristics (e.g. hazardous components and recycle component). Cost data was extracted from previously published studies by Boothroyd et al. to obtain the handling time and disassembly time. Afterwards, we developed the optimal or near-optimal DPP for the best time and cost based disassembly options. In summary, this paper presents a systematic method to disassemble a part into its individual components and provides a cost figure for doing so. This is in contrast with many studies reported in the literature in that they concentrate either on a measure of disassembly complexity, or even if cost is presumably the driving force, their costs are arbitrary costs based on pre-selected values for such things as tool change penalty, disassembly direction change penalty or penalty for delaying removal of hazardous materials. In this paper, we are using disassembly times based on experimental work and/or industrial experience. Given the correct labor rate, our cost evaluation indeed yields a realistic cost value

    Supercritical Water Gasification: Practical Design Strategies and Operational Challenges for Lab-Scale, Continuous Flow Reactors

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    Optimizing an industrial-scale supercritical water gasification process requires detailed knowledge of chemical reaction pathways, rates, and product yields. Laboratory-scale reactors are employed to develop this knowledge base. The rationale behind designs and component selection of continuous flow, laboratory-scale supercritical water gasification reactors is analyzed. Some design challenges have standard solutions, such as pressurization and preheating, but issues with solid precipitation and feedstock pretreatment still present open questions. Strategies for reactant mixing must be evaluated on a system-by-system basis, depending on feedstock and experimental goals, as mixing can affect product yields, char formation, and reaction pathways. In-situ Raman spectroscopic monitoring of reaction chemistry promises to further fundamental knowledge of gasification and decrease experimentation time. High-temperature, high-pressure spectroscopy in supercritical water conditions is performed, however, long-term operation flow cell operation is challenging. Comparison of Raman spectra for decomposition of formic acid in the supercritical region and cold section of the reactor demonstrates the difficulty in performing quantitative spectroscopy in the hot zone. Future designs and optimization of SCWG reactors should consider well-established solutions for pressurization, heating, and process monitoring, and effective strategies for mixing and solids handling for long-term reactor operation and data collection
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