Flexible Support Stanchion

Figure 1 shows the assembly drawing of the Central Calorimeter Cryostat Flexible Support Stanchion. Figures 2 and 3 show the Flexible Support STanchion in detail. These Stanchions support the cryostat safely, reduce the heat load to the cryostat from the ambient by a factor of more than ten, provide a spring like action that reduce the loads created by thermal contraction of the cryostat and position the cryostate accurately. Table 1 shows all of the details of the Flexible Support system for the C.C. Cryostat

Central Calorimeter Support Cradle Jack Failure Analysis

The Central Calorimeter and its support cradle are to be supported by either hydraulic or mechanical jacks. If hydraulics are used, each support will use two hydraulically coupled jacks with two out of the four supports hydraulically coupled giving the effect of a three point support system. If mechanical jacks are used, all four points are used for support. Figure 2 shows two examples of jack placement on a 3.5 inch support plate. These two support scenarios lead to five jack failure cases to be studied. This report deals with the way in which a 0.25 inch drop (failed jack) at one support affects the stresses in the cradle. The stresses from each failure case were analyzed in two ways. First, stress factors, defined as quotients of stress intensities of the failed case with respect to the static case, were generated and then, hand calculations similar to those in Engineering Note 3740.215-EN-14 were done using the reaction forces from the failed case

The effects of cyclic and dynamic loading on the fracture resistance of nuclear piping steels. Technical report, October 1992--April 1996

This report presents the results of the material property evaluation efforts performed within Task 3 of the IPIRG-2 Program. Several related investigations were conducted. (1) Quasi-static, cyclic-load compact tension specimen experiments were conducted using parameters similar to those used in IPIRG-1 experiments on 6-inch nominal diameter through-wall-cracked pipes. These experiments were conducted on a TP304 base metal, an A106 Grade B base metal, and their respective submerged-arc welds. The results showed that when using a constant cyclic displacement increment, the compact tension experiments could predict the through-wall-cracked pipe crack initiation toughness, but a different control procedure is needed to reproduce the pipe cyclic crack growth in the compact tension tests. (2) Analyses conducted showed that for 6-inch diameter pipe, the quasi-static, monotonic J-R curve can be used in making cyclic pipe moment predictions; however, sensitivity analyses suggest that the maximum moments decrease slightly from cyclic toughness degradation as the pipe diameter increases. (3) Dynamic stress-strain and compact tension tests were conducted to expand on the existing dynamic database. Results from dynamic moment predictions suggest that the dynamic compact tension J-R and the quasi-static stress-strain curves are the appropriate material properties to use in making dynamic pipe moment predictions

Fracture toughness evaluations of TP304 stainless steel pipes

In the IPIRG-1 program, the J-R curve calculated for a 16-inch nominal diameter, Schedule 100 TP304 stainless steel (DP2-A8) surface-cracked pipe experiment (Experiment 1.3-3) was considerably lower than the quasi-static, monotonic J-R curve calculated from a C(T) specimen (A8-12a). The results from several related investigations conducted to determine the cause of the observed toughness difference are: (1) chemical analyses on sections of Pipe DP2-A8 from several surface-cracked pipe and material property specimen fracture surfaces indicate that there are two distinct heats of material within Pipe DP2-A8 that differ in chemical composition; (2) SEN(T) specimen experimental results indicate that the toughness of a surface-cracked specimen is highly dependent on the depth of the initial crack, in addition, the J-R curves from the SEN(T) specimens closely match the J-R curve from the surface-cracked pipe experiment; (3) C(T) experimental results suggest that there is a large difference in the quasi-static, monotonic toughness between the two heats of DP2-A8, as well as a toughness degradation in the lower toughness heat of material (DP2-A8II) when loaded with a dynamic, cyclic (R = {minus}0.3) loading history

Quantification of Epithelial Cell Differentiation in Mammary Glands and Carcinomas from DMBA- and MNU-Exposed Rats

Rat mammary carcinogenesis models have been used extensively to study breast cancer initiation, progression, prevention, and intervention. Nevertheless, quantitative molecular data on epithelial cell differentiation in mammary glands of untreated and carcinogen-exposed rats is limited. Here, we describe the characterization of rat mammary epithelial cells (RMECs) by multicolor flow cytometry using antibodies against cell surface proteins CD24, CD29, CD31, CD45, CD49f, CD61, Peanut Lectin, and Thy-1, intracellular proteins CK14, CK19, and FAK, along with phalloidin and Hoechst staining. We identified the luminal and basal/myoepithelial populations and actively dividing RMECs. In inbred rats susceptible to mammary carcinoma development, we quantified the changes in differentiation of the RMEC populations at 1, 2, and 4 weeks after exposure to mammary carcinogens DMBA and MNU. DMBA exposure did not alter the percentage of basal or luminal cells, but upregulated CD49f (Integrin α6) expression and increased cell cycle activity. MNU exposure resulted in a temporary disruption of the luminal/basal ratio and no CD49f upregulation. When comparing DMBA- or MNU-induced mammary carcinomas, the RMEC differentiation profiles are indistinguishable. The carcinomas compared with mammary glands from untreated rats, showed upregulation of CD29 (Integrin β1) and CD49f expression, increased FAK (focal adhesion kinase) activation especially in the CD29hi population, and decreased CD61 (Integrin β3) expression. This study provides quantitative insight into the protein expression phenotypes underlying RMEC differentiation. The results highlight distinct RMEC differentiation etiologies of DMBA and MNU exposure, while the resulting carcinomas have similar RMEC differentiation profiles. The methodology and data will enhance rat mammary carcinogenesis models in the study of the role of epithelial cell differentiation in breast cancer

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

Two suppression subtracted cDNA libraries have been constructed, one containing cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived cell line relative to the malignant mammary cell line, MCF-7, and the other containing cDNAs present at a higher level in the MCF-7 cells relative to the benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128 different cDNAs from the benign and malignant libraries, respectively. Using reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective libraries were differentially expressed by more than 15-fold. Amongst these were oestrogen-responsive cDNAs and expressed sequence tags. One such oestrogen-responsive expressed sequence tag, M41, is transcribed from a gene located on chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains oestrogen response elements, one of which is associated with alu repeats. M41 mRNA is expressed at a statistically significantly higher level in human breast cancer specimens than in normal human breast and benign lesions. In carcinomas, its up-regulation is associated with the development of the malignant cell

Myoepithelial cells: good fences make good neighbors

The mammary gland consists of an extensively branched ductal network contained within a distinctive basement membrane and encompassed by a stromal compartment. During lactation, production of milk depends on the action of the two epithelial cell types that make up the ductal network: luminal cells, which secrete the milk components into the ductal lumen; and myoepithelial cells, which contract to aid in the ejection of milk. There is increasing evidence that the myoepithelial cells also play a key role in the organizational development of the mammary gland, and that the loss and/or change of myoepithelial cell function is a key step in the development of breast cancer. In this review we briefly address the characteristics of breast myoepithelial cells from human breast and mouse mammary gland, how they function in normal mammary gland development, and their recently appreciated role in tumor suppression

Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells

INTRODUCTION: Notch signaling has been implicated in the regulation of cell-fate decisions such as self-renewal of adult stem cells and differentiation of progenitor cells along a particular lineage. Moreover, depending on the cellular and developmental context, the Notch pathway acts as a regulator of cell survival and cell proliferation. Abnormal expression of Notch receptors has been found in different types of epithelial metaplastic lesions and neoplastic lesions, suggesting that Notch may act as a proto-oncogene. The vertebrate Notch1 and Notch4 homologs are involved in normal development of the mammary gland, and mutated forms of these genes are associated with development of mouse mammary tumors. METHODS: In order to determine the role of Notch signaling in mammary cell-fate determination, we have utilized a newly described in vitro system in which mammary stem/progenitor cells can be cultured in suspension as nonadherent 'mammospheres'. Notch signaling was activated using exogenous ligands, or was inhibited using previously characterized Notch signaling antagonists. RESULTS: Utilizing this system, we demonstrate that Notch signaling can act on mammary stem cells to promote self-renewal and on early progenitor cells to promote their proliferation, as demonstrated by a 10-fold increase in secondary mammosphere formation upon addition of a Notch-activating DSL peptide. In addition to acting on stem cells, Notch signaling is also able to act on multipotent progenitor cells, facilitating myoepithelial lineage-specific commitment and proliferation. Stimulation of this pathway also promotes branching morphogenesis in three-dimensional Matrigel cultures. These effects are completely inhibited by a Notch4 blocking antibody or a gamma secretase inhibitor that blocks Notch processing. In contrast to the effects of Notch signaling on mammary stem/progenitor cells, modulation of this pathway has no discernable effect on fully committed, differentiated, mammary epithelial cells. CONCLUSION: These studies suggest that Notch signaling plays a critical role in normal human mammary development by acting on both stem cells and progenitor cells, affecting self-renewal and lineage-specific differentiation. Based on these findings we propose that abnormal Notch signaling may contribute to mammary carcinogenesis by deregulating the self-renewal of normal mammary stem cells

S100A7 (psoriasin) expression is associated with aggressive features and alteration of Jab1 in ductal carcinoma in situ of the breast

INTRODUCTION: The S100A7 (psoriasin) gene is highly expressed in ductal carcinoma in situ (DCIS) of the breast and can be downregulated in invasive carcinoma. Persistent S100A7 expression in invasive carcinoma is associated with a worse prognosis, and this effect may be mediated in part through interaction with the multifunctional cell signaling protein Jab1. METHODS: In order to investigate the relationship between S100A7 and progression from DCIS to invasive carcinoma, we studied S100A7 expression in 136 patients with DCIS (including 46 patients with associated invasive carcinoma) by immunohistochemistry. RESULTS: S100A7 expression was present in 63 out of 136 (46%) of DCIS lesions and was associated with estrogen receptor negative status (P = 0.0002), higher nuclear grade (P < 0.0001), necrosis (P < 0.0001) and inflammation (P < 0.0001). S100A7 status was no different between DCIS with and DCIS without an invasive component, but higher levels of S100A7 were present in DCIS associated with invasive carcinoma (P < 0.004). Analysis of a subset of cases showed that S100A7 expression was also associated with an increase in nuclear Jab1 (n = 43; P = 0.0019) and reduced p27(kip1 )(n = 47; P = 0.0168). In cases of DCIS associated with invasive carcinoma, there was also a significant reduction in S100A7 between in situ and invasive components (n = 46; P < 0.0001). In pure DCIS cases treated by local excision, there was no difference in frequency of S100A7 expression between patients with recurrence of DCIS (n = 9) and those without (n = 36). CONCLUSION: The findings reported here suggest that, although S100A7 may not be a marker for recurrence of DCIS, it is associated with poor prognostic markers in DCIS and may influence progression of breast carcinoma through its interaction with and influence on Jab1