Knowledge Reuse for Customization: Metamodels in an Open Design Community for 3d Printing

Theories of knowledge reuse posit two distinct processes: reuse for replication and reuse for innovation. We identify another distinct process, reuse for customization. Reuse for customization is a process in which designers manipulate the parameters of metamodels to produce models that fulfill their personal needs. We test hypotheses about reuse for customization in Thingiverse, a community of designers that shares files for three-dimensional printing. 3D metamodels are reused more often than the 3D models they generate. The reuse of metamodels is amplified when the metamodels are created by designers with greater community experience. Metamodels make the community's design knowledge available for reuse for customization-or further extension of the metamodels, a kind of reuse for innovation

Design study for a magnetically supported reaction wheel

Results are described of a study program in which the characteristics of a magnetically supported reaction wheel are defined. Tradeoff analyses are presented for the principal components, which are then combined in several reaction wheel design concepts. A preliminary layout of the preferred configuration is presented along with calculated design and performance parameters. Recommendations are made for a prototype development program

Development of a Novel Method for Biochemical Systems Simulation: Incorporation of Stochasticity in a Deterministic Framework

Heart disease, cancer, diabetes and other complex diseases account for more than half of human mortality in the United States. Other diseases such as AIDS, asthma, Parkinson’s disease, Alzheimer’s disease and cerebrovascular ailments such as stroke not only augment this mortality but also severely deteriorate the quality of human life experience. In spite of enormous financial support and global scientific effort over an extended period of time to combat the challenges posed by these ailments, we find ourselves short of sighting a cure or vaccine. It is widely believed that a major reason for this failure is the traditional reductionist approach adopted by the scientific community in the past. In recent times, however, the systems biology based research paradigm has gained significant favor in the research community especially in the field of complex diseases. One of the critical components of such a paradigm is computational systems biology which is largely driven by mathematical modeling and simulation of biochemical systems. The most common methods for simulating a biochemical system are either: a) continuous deterministic methods or b) discrete event stochastic methods. Although highly popular, none of them are suitable for simulating multi-scale models of biological systems that are ubiquitous in systems biology based research. In this work a novel method for simulating biochemical systems based on a deterministic solution is presented with a modification that also permits the incorporation of stochastic effects. This new method, through extensive validation, has been proven to possess the efficiency of a deterministic framework combined with the accuracy of a stochastic method. The new crossover method can not only handle the concentration and spatial gradients of multi-scale modeling but it does so in a computationally efficient manner. The development of such a method will undoubtedly aid the systems biology researchers by providing them with a tool to simulate multi-scale models of complex diseases

Colistin: understanding the mechanism of action and the causes of treatment failure

The rapid rise in the prevalence of pathogenic bacteria that are resistant to front-line antibiotic drugs has necessitated a simultaneous upsurge in the use of “last-resort” antimicrobial agents. Colistin is one such antibiotic of last-resort that is increasingly used in the clinic as a salvage therapy to treat infections caused by multi-drug resistant Gram-negative microorganisms, including Pseudomonas aeruginosa and Escherichia coli. Unfortunately, despite its growing importance, colistin treatment is toxic, frequently fails, and resistance to the antibiotic is an intensifying threat. There is, therefore, a crucial requirement to augment the efficacy of colistin therapy, but efforts to do so are hampered by a lack of understanding about the drug’s mechanism of action. The work in this thesis initially uncovered a novel process by which colistin-susceptible P. aeruginosa cells survive exposure to the antibiotic, through the extracellular release of lipopolysaccharide (LPS) molecules that inactivate colistin in the external environment. In attempting to overcome this mode of drug tolerance by inhibiting LPS biosynthesis, critical insight into colistin’s bactericidal mechanism was obtained – namely, that the antibiotic kills Gram-negative bacteria by targeting LPS in the cytoplasmic membrane, not by interacting with membrane phospholipids, as previously thought. This finding in turn led to investigations about the site where colistin resistance, mediated by cationic chemical modifications to LPS, was conferred. It was shown that resistance to colistin in P. aeruginosa and E. coli, acquired through the harbouring of diverse plasmid-borne mobile colistin resistance (mcr) genes or chromosomal mutations, was in fact conferred at the cytoplasmic membrane, as opposed to the outer membrane of bacterial cells. Subsequent experiments revealed that intrinsic colistin resistance in Burkholderia cenocepacia was mediated at the outer membrane, and that strains of Enterobacter cloacae possess a unique inducible form of hetero-resistance to colistin. After characterising the mode of action of colistin and a number of potential causes of colistin treatment failure, new combination treatment strategies were designed to improve the effectiveness of colistin therapy. Using murepavadin, an inhibitor of the LPS transport system in pre-clinical development, to accumulate LPS in the cytoplasmic membrane proved to be particularly potent at amplifying the bactericidal activity of colistin in vitro against clinical isolates, in an in vivo murine lung infection model, and for overcoming colistin resistance. Furthermore, the capacity for colistin to permeabilise the outer membrane of colistin-resistant bacteria was exploited to re-sensitise Gram-negative pathogenic organisms to rifampicin, an antibiotic which normally cannot traverse the cell envelope. In summary, this work has identified how colistin works and why it often fails clinically, as well as providing urgently-needed novel solutions to enhance colistin efficacy and patient outcomes.Open Acces

Tunable Microstrip Filters for Modern Wireless Communications

Microwave filters are essential components for a large variety of modern communication systems. Filters engage in many recreating roles in RF and microwave applications. Forthcoming technologies like wireless communications are racing with RF and microwave filters in performance, physical and cost parameters. Developing technologies in materials and fabrications are defining new paths in filter designs. Tunable filters that are able to cover a number of different frequency bands are always on demand by the progressing communications technology. In this paper, Electromagnetic Band Gap (EBG) structure is studied and the novel configurations of periodic filters on dielectric materials that dynamically change their electromagnetic properties under a DC voltage bias are obtained and analysed. A tunable filter is designed using a dielectric material which produces tuning in the filter frequency. The research is carried on a single resonance element and experimented for tunability variations. S-parameter responses are obtained and analysed for the developed model through simulations. The filter with EBG structure showed tunability replacing the Liquid Crystal (LC) dielectric material is presented

Hybrid Clustering with Application to Web Pages

This project explains the process of clustering web pages. With the immense increase in the number of web pages available on the internet, it has become difficult to search for web pages. The clustering of web pages will improve the presentation of web pages to the user and saves the time spent on searching web pages. Various clustering techniques have been proposed by various research scientists to cluster the web pages, but all the techniques suggested have some drawbacks. Since there is lot of scope for further improvement in the field of clustering, the system proposed in this report takes the clustering of web pages a step ahead. The proposed system use the queries from the user and get the results from search engine, then processes the results and provides the final result clusters to users

Supersonic Corner Flows in Rectangular Channels

Rectangular channel geometries are widely encountered in supersonic flows, such as in wind tunnels and in aircraft inlets. Shock-boundary-layer interactions in these flows are known to exhibit significant three-dimensionality, due to the presence of sidewalls and associated corner boundary layers. The main effect is on the local separation of these corner regions, which then affects the wider flow field. Successful prediction of the overall flow therefore relies on the corner separation to be determined accurately. This, in turn, requires knowledge of the flow momentum distribution within the corner boundary layers. However, numerical methods struggle to reliably compute these flows and there is not much experimental data on supersonic corner boundary layers for comparison. This thesis addresses the outstanding gap in knowledge by performing validation-quality experiments on the corner regions of a Mach 2.5 channel flow, with a unit Reynolds number of approximately 40 million per metre. The experiments are conducted in the rectangular test section of a supersonic wind tunnel at the University of Cambridge. An analysis of the wind tunnel experiments, alongside computational data provided by the US Air Force Research Laboratory, reveals that the corner boundary layers are strongly influenced by the geometry of the two-dimensional nozzles used to produce the supersonic flow. The dominant effect is related to bulk vertical velocities within the sidewall boundary layers, induced by vertical pressure gradients in the nozzle. For some very particular geometries, a second influence may be associated with a region of separated flow immediately ahead of the nozzle, which generates vortices within the sidewall boundary layer. Through these mechanisms, the nozzle geometry is seen to strongly influence both the thickness and the structure of the corner boundary layers. High-quality experimental data in the corner regions are used to validate relevant numerical methods. Simple linear eddy-viscosity type turbulence models are found to compute these flows particularly poorly, with a 7% discrepancy in streamwise velocity. This is largely due to the fact that they do not capture known, stress-induced, corner vortices. However, the quadratic constitutive relation improves prediction of the corner boundary-layer structure, reducing experimental-computational differences by as much as half. This improvement is associated with vorticity generation in these corner regions, albeit with slightly different properties to the physical vortices. This production of vorticity depends only on the presence of a quadratic term in the eddy-viscosity model and not on which particular quadratic term is used. A more general form of the quadratic constitutive relation with one additional term is proposed, which appears to exhibit substantial improvements in the prediction of turbulent stress anisotropies. The nozzle geometry effects are exploited to produce two otherwise-identical experimental setups with distinctly different momentum distributions in the corner boundary layers. A full-span wedge introduces an oblique shock with flow deflection angle, 8 degrees, which impinges on the floor boundary layer. The two setups exhibit quite dissimilar separation behaviour, not only in the corner regions but also on the tunnel's centre span, with a difference in central separation length of as much as 35%. The observed behaviour is consistent with expectations based on local flow momentum affecting corner separation size, and on the displacement effect of this corner separation influencing the wider flow.This material is based upon work supported by the US Air Force Office of Scientific Research under award FA9550–16–1–0430

Large Deviation Local Limit Theorems for Ratio Statistics

Let {T„, n \u3e 1} be an arbitrary sequence of non-lattice random variables and {Sn, n \u3e 1} be another sequence of positive non-lattice random variables. Let the two sequences be independent. Let Ø1n and Ø2n be the moment genereating functions of {Tn, n \u3e 1} and { Sn,n \u3e 1} respectively. Let {an} be a sequence of real numbers such that an —»• oo