Overexpression of HER2 modulates bcl-2, bcl-XL, and tamoxifen-induced apoptosis in human MCF-7 breast cancer cells

Overexpression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. Here we investigated the effects of HER2 on expression of apoptotic pathways and modulation of tamoxifen-induced apoptosis in ER-positive MCF-7 breast cancer cells. We report that HER2 overexpression in MCF-7 cells is accompanied by up-regulation of antiapoptotic Bcl-2 and Bcl-XL proteins and suppression of tamoxifen-induced apoptosis. In addition, human tumor cell lines that are both ER positive and overexpress HER2 also express enhanced levels of Bcl-2 compared to cells that are either ER positive or overexpress HER2 alone. Our findings suggest that possible deregulation of antiapoptotic Bcl-2 and Bcl-XL may be associated with the enhanced survival of HER2-overexpressing and ER-positive breast cancer cells treated with antiestrogens.     

A two-stage MMSE multiuser decision feedback detector using successive/parallel interference cancellation

In this paper, we present a novel two-stage minimum-mean-squared-error (MMSE) multiuser decision feedback detector (DFD) for code division multiple access systems working in the frequency-selective multipath fading environment. The first stage of the proposed cascaded structure is the noise-predictive successive DFD (NP-S-DFD), in which the active users are detected successively using the conventional bell labs layered space-time (BLAST) ordering criterion. The second stage includes an adaptive successive/parallel DFD (SP-DFD), which uses the tentative decisions obtained at the first stage for multiuser interference cancellation and data detection. Therefore, the proposed two-stage DFD may be called noise-predictive successive SP-DFD (NP-S-SP-DFD). Simulation results are presented to demonstrate the substantial improvement in the bit error rate performance of NP-S-SP-DFD over the conventional single-stage and cascaded DFDs. It may be inferred that the proposed DFD provides additional performance gain, when the order in which the users are detected is optimized according to the BLAST ordering based on MMSE criterion.     

Binary rewriting and call interception for efficient runtime protection against buffer overflows

Buffer overflow vulnerabilities are one of the most commonly and widely exploited security vulnerabilities in programs. Most existing solutions for avoiding buffer overflows are either inadequate, inefficient or incompatible with existing code. In this paper, we present a novel approach for transparent and efficient runtime protection against buffer overflows. The approach is implemented by two tools: Type Information Extractor and Depositor (TIED) and LibsafePlus. TIED is first used on a binary executable or shared library file to extract type information from the debugging information inserted in the file by the compiler and reinsert it in the file as a data structure available at runtime. LibsafePlus is a shared library that is preloaded when the program is run. LibsafePlus intercepts unsafe C library calls such as strcpy and uses the type information made available by TIED at runtime to determine whether it would be ‘safe’ to carry out the operation. With our simple design we are able to protect most applications with a performance overhead of less than 10%. Copyright © 2006 John Wiley & Sons, Ltd.     

A study of the impact of instability on relative permeability and capillary pressure

Because of the rapid changes in saturation which take place in the immediate vicinity of a displacement front, it is not possible to estimate relative permeabilities over the entire saturation range of interest when using the external-drive method. It is demonstrated in this study that this limitation can be removed, if data from an unstabilized and/ or unstable displacement are used. Furthermore, it is shown that use of such data is permissible, provided: (a) saturation profiles and pressure gradients in both phases can be measured directly; (b) the external-drive theory is modified to account for the existence of capillary pressure gradients; and (c) the analysis is carried out from a Lagrangian rather than a Eulerian point of view.A comparison of relative permeabilities obtained by using the Lagrangian method with those obtained using the conventional (without capillary pressure term) and the modified (with the capillary pressure term) Eulerian methods was undertaken to demonstrate the effect of the neglect of the capillary pressure term on relative permeabilities. Also investigated in this study was the impact of instability on the relative permeability and capillary pressure curves for unstable displacements and the effect of instability on the saturation profiles, fractional flow curves and the residual oil saturation. In addition, the effect of instability on the residual oil saturation was studied.     

Deceleration of a porous rotating disk in a viscous fluid

The flow due to a rotating disk decelerating with an angular velocity inversely proportional to time with either surface suction (or injection) which again varies with time is investigated. The unsteady Navier-Stokes equations are transformed to non-linear ordinary differential equations using similarity transformations. The resulting equations are solved numerically using a globally convergent homotopy method. The flow depends on two non-dimensional parameters, namely an unsteadiness parameter $\text{S}$ and a suction (or injection) parameter $\text{A}$. Some interesting numerical results are presented graphically and discussed.     

Dielectric behaviour of glasses and glass ceramics in the system BaO-PbO-TiO2-B2O3-SiO2

Glasses with varying molar ratios of PbO/BaO in the system BaO-PbO-TiO₂-B₂O₃-SiO₂ were prepared keeping (BaO + PbO)/TiO₂ ratio equal to one. The glasses were ceramized by two-stage heat treatment. X-ray diffraction indicates that PbTiO₃ crystallizes in lead-rich glasses while BaTiO₃ precipitates in barium-rich compositions. Solid solution (Ba, Pb)TiO₃ does not seem to crystallize over the entire range of compositions. Simultaneous presence of PbO and BaO in the initial glass composition reduces the yield of ferroelectric phase. Dielectric properties have been interpreted in terms of microstructural features.     

Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions

BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated. METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle. The sample was checked immediately by a cytopathologist for adequacy. RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient. The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively. The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients). One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis. One had inflammatory cells and the patient was found to have Crohn's disease on histology. The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated. There were no complications of FNAC and patients complained of minimal discomfort. There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months. CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.     

Geometrical and sequence characteristics of alpha-helices in globular proteins

Understanding the sequence-structure relationships in globular proteins is important for reliable protein structure prediction and de novo design. Using a database of 1131 alpha-helices with nonidentical sequences from 205 nonhomologous globular protein chains, we have analyzed structural and sequence characteristics of alpha-helices. We find that geometries of more than 99% of all the alpha-helices can be simply characterised as being linear, curved, or kinked. Only a small number of alpha-helices ( approximately 4%) show sharp localized bends in their middle regions, and thus are classified as kinked. Approximately three-fourths (approximately 73%) of the alpha-helices in globular proteins show varying degrees of smooth curvature, with a mean radius of curvature of 65 +/- 33 A; longer helices are less curved. Computation of helix accessibility to the solvent indicates that nearly two-thirds of the helices ( approximately 66%) are largely buried in the protein core, and the length and geometry of the helices are not correlated with their location in the protein globule. However, the amino acid compositions and propensities of individual amino acids to occur in alpha-helices vary with their location in the protein globule, their geometries, and their lengths. In particular, Gln, Glu, Lys, and Arg are found more often in helices near the surface of globular proteins. Interestingly, kinks often seem to occur in regions where amino acids with low helix propensities (e.g., beta-branched and aromatic residues) cluster together, in addition to those associated with the occurrence of proline residues. Hence the propensities of individual amino acids to occur in a given secondary structure depend not only on conformation but also on its length, geometry, and location in the protein globule.     

Establishment of human parotid pleomorphic adenoma cells in culture: morphological and biochemical characterization

This study reports the establishment of alpha-amylase-producing human parotid pleomorphic adenoma cell lines (2HP and 2HP1) which have been maintained in culture for over 1 yr. The procedures required preparation of cellular clumps from tumor tissue and plating them on plasma clot or precoated dishes. During the initial phase of growth they required modified MCDB-153 medium without serum. When cells showed signs of degeneration they were changed to MCDB-153 medium containing first 2% and then 10% heat inactivated fetal bovine serum. Although cells grew well in MCDB-153 containing 10% serum, the epithelial cell morphology was not distinct. Therefore, the growth and morphology of cells grown in MCDB-10% serum were compared with those in RPMI growth medium containing 10% fetal bovine serum and F12 containing 10% agammaglobulin newborn bovine serum. Although the growth of cells was a little slower in F12 medium than those in MCDB and RPMI, the epithelial cell morphology was maintained better than in other growth media. The cells of 2HP and 2HP1 produce low levels of alpha-amylase and relatively high levels of alpha-amylase mRNAs of 1176 and 702 bp and contain neurofilament-160, a neuronal-specific marker. The cells of 2HP1 are tumorigenic when tested in athymic mice, but the cells of 2HP are not. The establishment of amylase-producing human parotid adenoma cell lines of different characteristics in culture provides a new opportunity to study the mechanisms of differentiation and transformation, and regulation of alpha-amylase in these cells.