169 research outputs found
Design problem exploration
The problem generation space is a critical stage in the design process that reflects the outcome of a solution. However, limited research has been conducted on problem space within design education to aid in the creative process. Within the problem generation space, there are multiple alternative views to reframe a problem statement which ultimately impact the solution. More novel problem statements have reflected an increase in unique concepts. By providing a toolset for students to diversify their problems, new perspectives of the problem are taken into the idea generation space. Research has identified heuristics that frame a problem, which have found to be helpful.
Two studies are provided to understand the relationship between heuristics and reframed statements. Study 1 analyzed students’ reframed statements without the aid of heuristics. Sixteen strategies were observed in this classroom study. In Study 2, a digital tool with twelve identified strategies were used to provide a randomized selection for implementation. Design and engineer students were used in a classroom study; each completed three strategies to compare the outcomes. The goal of Study 2 was to identify whether the students implemented the strategies and how they used each within their statements. A complementary aim was to understand how much diversity was created among the new problems after strategy use. The research reported in this paper uncovers certain strategies that performed superior in various conditions amongst other strategies within the problem generation space
RfaH Suppresses Small RNA MicA Inhibition of fimB Expression in Escherichia coli K-12
The phase variation (reversible on-off switching) of the type 1 fimbrial adhesin of Escherichia coli involves a DNA inversion catalyzed by FimB (switching in either direction) or FimE (on-to-off switching). Here, we demonstrate that RfaH activates expression of a FimB-LacZ protein fusion while having a modest inhibitory effect on a comparable fimB-lacZ operon construct and on a FimE-LacZ protein fusion, indicating that RfaH selectively controls fimB expression at the posttranscriptional level. Further work demonstrates that loss of RfaH enables small RNA (sRNA) MicA inhibition of fimB expression even in the absence of exogenous inducing stress. This effect is explained by induction of σE , and hence MicA, in the absence of RfaH. Additional work con- firms that the procaine-dependent induction of micA requires OmpR, as reported previously (A. Coornaert et al., Mol. Microbiol. 76:467–479, 2010, doi:10.1111/j.1365-2958.2010.07115.x), but also demonstrates that RfaH inhibition of fimB transcription is enhanced by procaine independently of OmpR. While the effect of procaine on fimB transcription is shown to be independent of RcsB, it was found to require SlyA, another known regulator of fimB transcription. These results demonstrate a complex role for RfaH as a regulator of fimB expression
Net-Shape HIP Powder Metallurgy Components for Rocket Engines
True net shape consolidation of powder metal (PM) by hot isostatic pressing (HIP) provides opportunities for many cost, performance and life benefits over conventional fabrication processes for large rocket engine structures. Various forms of selectively net-shape PM have been around for thirty years or so. However, it is only recently that major applications have been pursued for rocket engine hardware fabricated in the United States. The method employs sacrificial metallic tooling (HIP capsule and shaped inserts), which is removed from the part after HIP consolidation of the powder, by selective acid dissolution. Full exploitation of net-shape PM requires innovative approaches in both component design and materials and processing details. The benefits include: uniform and homogeneous microstructure with no porosity, irrespective of component shape and size; elimination of welds and the associated quality and life limitations; removal of traditional producibility constraints on design freedom, such as forgeability and machinability, and scale-up to very large, monolithic parts, limited only by the size of existing HIP furnaces. Net-shape PM HIP also enables fabrication of complex configurations providing additional, unique functionalities. The progress made in these areas will be described. Then critical aspects of the technology that still require significant further development and maturation will be discussed from the perspective of an engine systems builder and end-user of the technology
O-Antigen Delays Lipopolysaccharide Recognition and Impairs Antibacterial Host Defense in Murine Intestinal Epithelial Cells
Although Toll-like receptor (TLR) 4 signals from the cell surface of myeloid cells, it is restricted to an intracellular compartment and requires ligand internalization in intestinal epithelial cells (IECs). Yet, the functional consequence of cell-type specific receptor localization and uptake-dependent lipopolysaccharide (LPS) recognition is unknown. Here, we demonstrate a strikingly delayed activation of IECs but not macrophages by wildtype Salmonella enterica subsp. enterica sv. (S.) Typhimurium as compared to isogenic O-antigen deficient mutants. Delayed epithelial activation is associated with impaired LPS internalization and retarded TLR4-mediated immune recognition. The O-antigen-mediated evasion from early epithelial innate immune activation significantly enhances intraepithelial bacterial survival in vitro and in vivo following oral challenge. These data identify O-antigen expression as an innate immune evasion mechanism during apical intestinal epithelial invasion and illustrate the importance of early innate immune recognition for efficient host defense against invading Salmonella
Selection of Salmonella enterica Serovar Typhi Genes Involved during Interaction with Human Macrophages by Screening of a Transposon Mutant Library
The human-adapted Salmonella enterica serovar Typhi (S. Typhi) causes a systemic infection known as typhoid fever. This disease relies on the ability of the bacterium to survive within macrophages. In order to identify genes involved during interaction with macrophages, a pool of approximately 105 transposon mutants of S. Typhi was subjected to three serial passages of 24 hours through human macrophages. Mutants recovered from infected macrophages (output) were compared to the initial pool (input) and those significantly underrepresented resulted in the identification of 130 genes encoding for cell membrane components, fimbriae, flagella, regulatory processes, pathogenesis, and many genes of unknown function. Defined deletions in 28 genes or gene clusters were created and mutants were evaluated in competitive and individual infection assays for uptake and intracellular survival during interaction with human macrophages. Overall, 26 mutants had defects in the competitive assay and 14 mutants had defects in the individual assay. Twelve mutants had defects in both assays, including acrA, exbDB, flhCD, fliC, gppA, mlc, pgtE, typA, waaQGP, SPI-4, STY1867-68, and STY2346. The complementation of several mutants by expression of plasmid-borne wild-type genes or gene clusters reversed defects, confirming that the phenotypic impairments within macrophages were gene-specific. In this study, 35 novel phenotypes of either uptake or intracellular survival in macrophages were associated with Salmonella genes. Moreover, these results reveal several genes encoding molecular mechanisms not previously known to be involved in systemic infection by human-adapted typhoidal Salmonella that will need to be elucidated
Moving to the Edge: An ACM CTO Roundtable on Network Virtualization
The general IT community is just beginning to digest how the advent of virtual machines and cloud computing is changing their world. These new technologies promise to make applications more portable and increase the opportunity for more flexibility and efficiency in both on-premises and outsourced support infrastructures. However, virtualization can break long-standing linkages between applications and their supporting physical devices. Before data-center managers can take advantage of these new opportunities, they must have a better understanding of service infrastructure requirements and their linkages to applications.</jats:p
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