The conjoint measurement problem

Call number: LD2668 .R4 1966 J7

A Relationship Between Constraint and the Critical Crack Tip Opening Angle

Of the various approaches used to model and predict fracture, the Crack Tip Opening Angle (CTOA) fracture criterion has been successfully used for a wide range of two-dimensional thin-sheet and thin plate applications. As thicker structure is considered, modeling the full three-dimensional fracture process will become essential. This paper investigates relationships between the local CTOA evaluated along a three-dimensional crack front and the corresponding local constraint. Previously reported tunneling crack front shapes were measured during fracture by pausing each test and fatigue cycling the specimens to mark the crack surface. Finite element analyses were run to model the tunneling shape during fracture, with the analysis loading conditions duplicating those tests. The results show an inverse relationship between the critical fracture value and constraint which is valid both before maximum load and after maximum load

Influence of Mixed Mode I-Mode II Loading on Fatigue Delamination Growth Characteristics of a Graphite Epoxy Tape Laminate

Mixed mode I-mode II interlaminar tests were conducted on IM7/8552 tape laminates using the mixed-mode bending test. Three mixed mode ratios, G(sub II)/G(sub T) = 0.2, 0.5, and 0.8, were considered. Tests were performed at all three mixed-mode ratios under quasi-static and cyclic loading conditions, where the former static tests were used to determine initial loading levels for the latter fatigue tests. Fatigue tests at each mixed-mode ratio were performed at four loading levels, Gmax, equal to 0.5G(sub c), 0.4G(sub c), 0.3G(sub c), and 0.2G(sub c), where G(sub c) is the interlaminar fracture toughness of the corresponding mixed-mode ratio at which a test was performed. All fatigue tests were performed using constant-amplitude load control and delamination growth was automatically documented using compliance solutions obtained from the corresponding quasi-static tests. Static fracture toughness data yielded a mixed-mode delamination criterion that exhibited monotonic increase in Gc with mixed-mode ratio, G(sub II)/G(sub T). Fatigue delamination onset parameters varied monotonically with G(sub II)/G(sub T), which was expected based on the fracture toughness data. Analysis of non-normalized data yielded a monotonic change in Paris law exponent with mode ratio. This was not the case when normalized data were analyzed. Fatigue data normalized by the static R-curve were most affected in specimens tested at G(sub II)/G(sub T)=0.2 (this process has little influence on the other data). In this case, the normalized data yielded a higher delamination growth rate compared to the raw data for a given loading level. Overall, fiber bridging appeared to be the dominant mechanism, affecting delamination growth rates in specimens tested at different load levels and differing mixed-mode ratios

Performance of Two Boron-Modified S-816 Alloys in a Turbojet Engine Operated at 1650 F

S-816+B and modified S-816+B cast cobalt-base alloys were evaluated as turbine-bucket materials at 16500 F. Stress-rupture and tensile data obtained from these alloys had indicated satisfactory strength for engine operation at 1650 F. Although both alloys exhibited a limited ductility in room-temperature laboratory impact tests, there was a significant increase in impact resistance in the 1650 F tests. Bucket failures began after 10 hours of engine testing and continued at various intervals during the 107.5-hour test. Bucket lives were short relative to the predicted lives based on stress-rupture considerations (280 hr for S-816+B and 1750 hr for modified S-816+B). No significant difference was apparent in the performance of the two alloy groups. The primary cause of bucket failures in both alloys was mechanical fatigue. Impact damage occurred as a direct result of bucket tip fatigue failures and was a secondary cause of bucket failures. The impact of small pieces of fractured bucket tips on surrounding buckets caused a relatively large amount of impact damage to buckets of both alloys. The amount of impact damage from induced fractures at the bucket midspan, which provided relatively large failed fragments, was no greater than that which occurred as a result of tip failures

Dissecting the psoriasis transcriptome: inflammatory- and cytokine-driven gene expression in lesions from 163 patients

Abstract Background Psoriasis lesions are characterized by large-scale shifts in gene expression. Mechanisms that underlie differentially expressed genes (DEGs), however, are not completely understood. We analyzed existing datasets to evaluate genome-wide expression in lesions from 163 psoriasis patients. Our aims were to identify mechanisms that drive differential expression and to characterize heterogeneity among lesions in this large sample. Results We identified 1233 psoriasis-increased DEGs and 977 psoriasis-decreased DEGs. Increased DEGs were attributed to keratinocyte activity (56%) and infiltration of lesions by T-cells (14%) and macrophages (11%). Decreased DEGs, in contrast, were associated with adipose tissue (63%), epidermis (14%) and dermis (4%). KC/epidermis DEGs were enriched for genes induced by IL-1, IL-17A and IL-20 family cytokines, and were also disproportionately associated with AP-1 binding sites. Among all patients, 50% exhibited a heightened inflammatory signature, with increased expression of genes expressed by T-cells, monocytes and dendritic cells. 66% of patients displayed an IFN-γ-strong signature, with increased expression of genes induced by IFN-γ in addition to several other cytokines (e.g., IL-1, IL-17A and TNF). We show that such differences in gene expression can be used to differentiate between etanercept responders and non-responders. Conclusions Psoriasis DEGs are partly explained by shifts in the cellular composition of psoriasis lesions. Epidermal DEGs, however, may be driven by the activity of AP-1 and cellular responses to IL-1, IL-17A and IL-20 family cytokines. Among patients, we uncovered a range of inflammatory- and cytokine-associated gene expression patterns. Such patterns may provide biomarkers for predicting individual responses to biologic therapy.http://deepblue.lib.umich.edu/bitstream/2027.42/112670/1/12864_2012_Article_5257.pd

Investigations To Characterize Multi-Junction Solar Cells In The Stratosphere Using Low-Cost Balloon And Communication Technologies

The use of current balloon, control and communication technologies to test multi-junction solar sell in the stratosphere to achieve near AMO conditions have been investigated. The design criteria for the technologies are that they be reliable, low cost and readily available. Progress is reported on a program to design, launch, fly and retrieve payloads dedicated to testing multi-junction solar cells

Developing a suspension transfection platform to produce adeno- associated viruses

Through the delivery of recombinant adeno-associated virus (rAAV) vectors, gene therapy has the potential to cure and/or treat many genetic disorders. Currently, most rAAV vector production processes employ triple transfection in an adherent production vessel, which has limited scalability that results in a low batch yield. Improving process yield is critical for enabling the treatment of large disease indications and lowering manufacturing costs. One way to increase rAAV vector production is to employ suspension cell culture, which would allow for a larger process scale. In this work, through optimization of transfection and process parameters, we demonstrate a significant productivity improvement over our previously established suspension transfection process. We took a Quality-by-Design (QbD) approach to explore the transfection and process parameters utilizing multi-factor Design of Experiments (DoEs). The DoE model established in the Ambr250 accurately predicted upstream productivity in the scaled up 2 L and 50 L bioreactor systems. With a clinically relevant product, this process has demonstrated the potential to yield \u3e1e14 GC/L. By increasing single-batch productivity by \u3e10-fold from a comparable adherent process, this process significantly decreases the timeline for gene therapy treatments

Psoriasis drug development and GWAS interpretation through in silico analysis of transcription factor binding sites

BackgroundPsoriasis is a cytokine‐mediated skin disease that can be treated effectively with immunosuppressive biologic agents. These medications, however, are not equally effective in all patients and are poorly suited for treating mild psoriasis. To develop more targeted therapies, interfering with transcription factor (TF) activity is a promising strategy.MethodsMeta‐analysis was used to identify differentially expressed genes (DEGs) in the lesional skin from psoriasis patients (n = 237). We compiled a dictionary of 2935 binding sites representing empirically‐determined binding affinities of TFs and unconventional DNA‐binding proteins (uDBPs). This dictionary was screened to identify “psoriasis response elements” (PREs) overrepresented in sequences upstream of psoriasis DEGs.ResultsPREs are recognized by IRF1, ISGF3, NF‐kappaB and multiple TFs with helix‐turn‐helix (homeo) or other all‐alpha‐helical (high‐mobility group) DNA‐binding domains. We identified a limited set of DEGs that encode proteins interacting with PRE motifs, including TFs (GATA3, EHF, FOXM1, SOX5) and uDBPs (AVEN, RBM8A, GPAM, WISP2). PREs were prominent within enhancer regions near cytokine‐encoding DEGs (IL17A, IL19 and IL1B), suggesting that PREs might be incorporated into complex decoy oligonucleotides (cdODNs). To illustrate this idea, we designed a cdODN to concomitantly target psoriasis‐activated TFs (i.e., FOXM1, ISGF3, IRF1 and NF‐kappaB). Finally, we screened psoriasis‐associated SNPs to identify risk alleles that disrupt or engender PRE motifs. This identified possible sites of allele‐specific TF/uDBP binding and showed that PREs are disproportionately disrupted by psoriasis risk alleles.ConclusionsWe identified new TF/uDBP candidates and developed an approach that (i) connects transcriptome informatics to cdODN drug development and (ii) enhances our ability to interpret GWAS findings. Disruption of PRE motifs by psoriasis risk alleles may contribute to disease susceptibility.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/1/ctm2s4016901500545-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/2/ctm2s4016901500545-sup-0018.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/3/ctm2s4016901500545-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/4/ctm2s4016901500545.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155494/5/ctm2s4016901500545-sup-0009.pd

Redshifts and Velocity Dispersions of Galaxy Clusters in the Horologium-Reticulum Supercluster

We present 118 new optical redshifts for galaxies in 12 clusters in the Horologium-Reticulum supercluster (HRS) of galaxies. For 76 galaxies, the data were obtained with the Dual Beam Spectrograph on the 2.3m telescope of the Australian National University at Siding Spring Observatory. After combining 42 previously unpublished redshifts with our new sample, we determine mean redshifts and velocity dispersions for 13 clusters, in which previous observational data were sparse. In six of the 13 clusters, the newly determined mean redshifts differ by more than 750 km/s from the published values. In the case of three clusters, A3047, A3109, and A3120, the redshift data indicate the presence of multiple components along the line of sight. The new cluster redshifts, when combined with other reliable mean redshifts for clusters in the HRS, are found to be distinctly bi-modal. Furthermore, the two redshift components are consistent with the bi-modal redshift distribution found for the inter-cluster galaxies in the HRS by Fleenor et al. (2005).Comment: 13 pages, 3 figures, Accepted to A

Indentation Plastometry of Welds

This investigation concerns the application of the profilometry-based indentation plastometry (PIP) methodology to obtain stress–strain relationships for material in the vicinity of fusion welds. These are produced by The Welding Institute (TWI), using submerged arc welding to join pairs of thick steel plates. The width of the welds varies from about 5 mm at the bottom to about 40–50 mm at the top. For one weld, the properties of parent and weld metal are similar, while for the other, the weld metal is significantly harder than the parent. Both weldments are shown to be approximately isotropic in terms of mechanical response, while there is a small degree of anisotropy in the parent metal (with the through-thickness direction being slightly softer than the in-plane directions). The PIP procedure has a high sensitivity for detecting such anisotropy. It is also shown that there is excellent agreement between stress–strain curves obtained using PIP and via conventional uniaxial testing (tensile and compressive). Finally, the PIP methodology is used to explore properties in the transition regime between weld and parent, with a lateral resolution of the order of 1–2 mm. This reveals variations on a scale that would be very difficult to examine using conventional testing