EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.     

Cytosolic and nuclear distribution of PPARgamma2 in differentiating 3T3-L1 preadipocytes

In light of the pivotal role that PPARgamma2 plays in the expression of fat specific genes (e.g., A-FABP), we have examined the hypothesis that a rise in PPARgamma2 protein is required for the expression of A-FABP, and that the acceleration of fat cell differentiation by the thiazolidinedione agent, pioglitazone (PIOG), reflects an increase in the abundance of PPARgamma2 mRNA and protein. Western analyses surprisingly revealed that undifferentiated 3T3-L1 fibroblasts contained significant levels of PPARgamma2 protein; that the amount of total cellular PPARgamma2 only increased 2-fold during differentiation; and that the levels of PPARgamma2 protein and mRNA were not increased by PIOG even though fat cell differentiation was accelerated by PIOG as revealed by a 20-fold increase in A-FABP expression. Cell fractionation studies revealed that PPARgamma2 was evenly distributed between the cytosolic and nuclear compartments in both undifferentiated and differentiating 3T3-L1 cells. Immunocytochemical studies with a PPARgamma2-specific antibody indicated that PPARgamma2 was diffusely distributed throughout the cytosol of undifferentiated 3T3-L1 cells, but as the differentiation progressed, the PPARgamma2 became focused around the developing lipid droplets. In contrast to PPARgamma2, undifferentiated 3T3-L1 cells contained no measurable quantities of RXRalpha, but once fat cell differentiation was initiated by treatment with IBMX and dexamethasone, the cellular content of RXRalpha increased several fold. The rise in RXRalpha content paralleled the induction of A-FABP, but the expression of RXRalpha was not enhanced by PIOG. Although the amount of PPARgamma2 and RXRalpha was unaffected by PIOG, gel shift assays revealed that PIOG stimulated PPARgamma2/RXRalpha binding to the adipose response element of A-FABP by 5-fold in less than 12 h. Apparently, RXRalpha rather than PPARgamma2 is the pivotal trans-factor essential for the initiation of terminal fat cell differentiation. However, the high cytsolic content of PPARgamma2 and its association with the lipid droplet of differentiating 3T3-L1 cells suggests PPARgamma2 may possess a cytosolic function in the developing fat cell.     

Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992

BACKGROUND: Little is known about the cause of inflammatory breast carcinoma (IBC), the most aggressive form of breast cancer. To the authors' knowledge, no studies have investigated whether IBC risk factors are different from those for breast carcinoma overall, and there has been only one report of IBC incidence and survival patterns. METHODS: The authors used data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for the period 1975-1992 to calculate age-adjusted incidence and survival rates for 913 white and 121 African American women with IBC involving dermal invasion of lymphatic ducts and 166,375 white and 13,674 African American women with other types of breast carcinoma (non-IBC). RESULTS: Between 1975-1977 and 1990-1992, IBC incidence doubled, increasing among whites from 0.3 to 0.7 cases per 100,000 person-years and among African Americans from 0.6 to 1.1 cases. However, rates for African Americans varied due to the small numbers of IBC cases. The twofold increase in IBC incidence was higher than that observed for non-IBC during the same period (27% for African Americans and 25% for whites). IBC patients were significantly younger at diagnosis than non-IBC patients; and among both IBC and non-IBC patients, African Americans were younger than whites. Overall survival was significantly worse for IBC patients than for non-IBC patients and for African Americans than for whites. Among whites, 3-year survival improved more for IBC patients than for non-IBC patients between 1975-1979 and 1988-1992, increasing from 32% to 42% for IBC patients (P=0.0001) and from 80% to 85% for non-IBC patients (P=0.0001). CONCLUSIONS: The disparities observed in incidence trends and age at diagnosis, particularly according to race, highlight the need for further investigation of the differences between IBC and non-IBC incidence.     

Quantitative ECT: Comparison of Recovery Coefficient and Linearity of Detector Response for Single Photon and Coincidence Detection (F-18, B+ 511 keV)

The response characteristics of two tomographic systems were compared for imaging of positron emitters: a) a SPECT system with a 3/8 in crystal and 511 keV detector shielding, equipped with a specially designed 511 keV collimator, and b) a PET V system using coincidence detection. SPECT transverse plane resolution was 19 mm FWHM and 35 mm FWTM for a radius of rotation of 16 cm. Corresponding resolution for PET was 14 mm FWHM and 28 mm FWTM. Transverse images through a phantom containing cylindrical sources of various cross sections and uniform activity were obtained for each detector. The measured count density or recovery coefficient was found to decrease with source size, the dependence being similar for both systems. The theoretical values for recovery coefficients were calculated by convolution of a Gaussian fit to the SPECT resolution (FWHM, FWTM) values with the uniform cross section of each source. This simple mathematical model confirmed that the recovery coefficient dependence on source size was primarily related to the limited resolution of the detector. Experimental measurements demonstrated that the SPECT resolution for volume sources was sufficient for quantitation, although some limitations exist with respect to source sizes smaller than the detector resolution.     

Interactive Simulation of Rigid Body Dynamics in Computer Graphics

Interactive rigid body simulation is an important part of many modern computer tools, which no authoring tool nor game engine can do without. Such high‐performance computer tools open up new possibilities for changing how designers, engineers, modelers and animators work with their design problems. This paper is a self contained state‐of‐the‐art report on the physics, the models, the numerical methods and the algorithms used in interactive rigid body simulation all of which have evolved and matured over the past 20 years. Furthermore, the paper communicates the mathematical and theoretical details in a pedagogical manner. This paper is not only a stake in the sand on what has been done, it also seeks to give the reader deeper insights to help guide their future research.     

Water sorption kinetics in poly(aryl ether ether ketone)

The kinetics of diffusion of water from different activity vapors and liquid phase have been investigated in glassy amorphous poly(aryl ether ether ketcne) (PEEK) films at the temperature of 60°C and in glassy semicrystalline PEEK sheets at different temperatures, respectively. In the case of the amorphous PEEK films (250 μm thick) the data at low activity levels were interpreted by means of a purely Fickian mechanism. At higher activity levels the material has shown the presence of a relaxation process; in this case the data have been interpreted using a model proposed by Berens and Hopfenberg. Equilibrium sorption isotherm is also reported. Liquid water sorption in semicrystalline (30%) PEEK sheets (2 mm thick) has been determined to follow the classical Fickian mechanism. The water uptake values obtained for both amorphous and semicrystalline PEEK, confirm the good moisture and liquid water resistance of this kind of high performance thermoplastic polymer.     

Analysis of the effects of the polymerization route of ethylene‐propylene‐diene rubbers (EPDM) on the properties of polypropylene‐EPDM blends

A comparative study of two ethylene‐propylene‐diene rubbers (EPDM) polymerized by both conventional (Ziegler–Natta catalysts) and new techniques (metallocene catalysts) is presented. For this purpose, thermoplastic elastomers based on isotactic polypropylene (iPP) and EPDM blends at different percentages were prepared and their properties examined. In particular, the processing behavior and mechanical properties are reported. So, the flow properties analyzed by torque value, melt index, and rheological study reveal that the blends containing EPDM synthesized by metallocene catalyst present a smaller viscosity, thus offering better processing behavior. On the other hand, the mechanical properties show that metallocene EPDM rubbers give rise to more elastic materials with a higher deformation at break and resilience as well as a lower compression set. Moreover, the effectiveness of these innovative EPDM rubbers as impact modifiers for PP is demonstrated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 25–37, 2002     

Guessing Tangents in Normal Flows

Given a flow field parallel to isophote normals, a normal flow field, we seek a unobservable tangential field as the minimum of a general energy functional of the total field. We generalize existing methods to any linear, differential operator order on the combined field while keeping the projection onto the isophote normal constant. We discuss invariant flow fields, present a novel iterative solution based on Euler-Lagrange equations, prove continuous convergence, and give synthetic examples for common energy functionals. Possible uses are: estimating physical flow in image sequences, estimating human growth processes, and co-warping textures in animation sequences.     

Evaluation of Nd:YAG-pumped Raman shifter as a broad-spectrum light source

We have examined the utility of a gas-filled, Nd:YAG-laser-pumped Raman shifter as a possible broad-spectrum light source. Six to nine new output frequencies with pulse energies above 1 μJ are produced when a pure-hydrogen or pure-methane Raman shifter is pumped with 40 mJ of secondharmonic, 20 mJ of third-harmonic, or 11 mJ of fourth-harmonic pump pulse energy. Optimum output occurs at pressures of approximately 10 atm for the pure-gas experiments. We also report the output frequencies and pulse energies of a mixed hydrogen-methane Raman shifter pumped by 20 mJ of the third harmonic of the laser for various proportions of the two gases at pressures up to nearly 20 atm. Depending on composition and pressure, over a dozen new output lines with pulse energies over 1 μJ can be produced. We discuss the nonlinear processes involved, the optimum operating conditions, and the suitability of the source for our application of groundwater monitoring.