SV40 T antigen directed by a powerful erythroid enhancer-promoter produced sarcomas and pancreatic tumors but not erythroid-specific tumors in transgenic mice

We have expressed the simian virus 40 (SV40) large T antigen oncogene in erythroid tissues of mice to test its ability to immortilize erythroid cells. A transgene construct was built in which the SV40 large T antigen structural gene was linked to erythroid-specific enhancer and promoter sequences. The enhancer employed was the human beta-globin family microlocus control region, and the promoter sequences were derived from the human beta-globin promoter. Transgenic mice were generated and they expressed T antigen in the bone marrow and spleen cells. Yet, no hematopoietic neoplasia arose in these mice. Instead, after a lag period of 2-6 months, the mice developed soft tissue sarcomas and pancreatic islet-cell tumors that expressed high levels of T antigen.     

Apoptosis in the early human placental bed and its discrimination from necrosis using the in-situ DNA ligation technique

Extensive areas of necrosis are present in the early human placental bed. Our aim was to determine whether apoptosis is also a feature. A method was therefore required to differentiate unequivocally necrosis and apoptosis. Initially, terminal deoxynucleotide transferase-mediated dUTP nick-end labelling was used to visualize apoptotic cells. However, non-specific labelling, probably due to free DNA released by necrotic cells, was excessive; thus, in-situ DNA ligation was employed. In this technique, two DNA fragments with single-base 3' overhangs and blunt-ends were labelled with a fluorochrome and then ligated to the DNA breaks on the sections. Immunolabelling for cytokeratin or leukocyte common antigen was performed to determine the phenotype of apoptotic cells identified by the in-situ DNA ligation technique. A proportion of the dying cells was confirmed to be trophoblasts. No co-localization with leukocyte common antigen was found in this region, suggesting that maternal macrophages and natural killer cells (CD56+) were not dying by apoptosis in significant numbers. In conclusion, in-situ DNA ligation in association with immunocytochemistry can readily distinguish apoptosis from necrosis in the placental bed. The results suggest that a proportion of invading trophoblast cells are eliminated by apoptosis in early pregnancy.     

Difference in the expression of Fas/Fas-ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD

Acute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lymphocytes, very little information is available concerning the mechanism of lethality. In this study, we investigated both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent HLA-matched related allogeneic BMT (n = 16) and normal donors (n = 10), and several distinct features were observed. First, the reconstitutions of CD3+ and CD56+ cells were different between the aGVHD+ and aGVHD- group. In particular, the percentage of CD3-CD56+ cells was significantly decreased in patients with aGVHD (P < 0.01). Second, the expansion of CD8+ (P = 0.01) and CD8+ CD28- T cells (P = 0.03) was a characteristic finding in patients with aGVHD. Finally, we found that the percentages of Fas+CD8+, Fas+HLA-DR+ and FasL+ CD8+ cells were significantly increased. Fas antigen was highly coexpressed on most of the lymphocyte subsets, especially on CD8+ cells (P < 0.01), and also, significantly higher coexpression of FasL on CD8+ cells was found in patients with aGVHD (P < 0.01). In summary, an increase in the percentage of CD8+ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible role for the Fas/FasL pathway in the effector phase of aGVHD.     

Application of empirical mode decomposition (EMD) for automated identification of congestive heart failure using heart rate signals

Electrocardiogram is widely used to diagnose the congestive heart failure (CHF). It is the primary noninvasive diagnostic tool that can guide in the management and follow-up of patients with CHF. Heart rate variability (HRV) signals which are nonlinear in nature possess the hidden signatures of various cardiac diseases. Therefore, this paper proposes a nonlinear methodology, empirical mode decomposition (EMD), for an automated identification and classification of normal and CHF using HRV signals. In this work, HRV signals are subjected to EMD to obtain intrinsic mode functions (IMFs). From these IMFs, thirteen nonlinear features such as approximate entropy \( (E_{\text{ap}}^{x} ) \), sample entropy \( (E_{\text{s}}^{x} ) \), Tsallis entropy \( (E_{\text{ts}}^{x} ) \), fuzzy entropy \( (E_{\text{f}}^{x} ) \), Kolmogorov Sinai entropy \( (E_{\text{ks}}^{x} ) \), modified multiscale entropy \( (E_{{{\text{mms}}_{y} }}^{x} ) \), permutation entropy \( (E_{\text{p}}^{x} ) \), Renyi entropy \( (E_{\text{r}}^{x} ) \), Shannon entropy \( (E_{\text{sh}}^{x} ) \), wavelet entropy \( (E_{\text{w}}^{x} ) \), signal activity \( (S_{\text{a}}^{x} ) \), Hjorth mobility \( (H_{\text{m}}^{x} ) \), and Hjorth complexity \( (H_{\text{c}}^{x} ) \) are extracted. Then, different ranking methods are used to rank these extracted features, and later, probabilistic neural network and support vector machine are used for differentiating the highly ranked nonlinear features into normal and CHF classes. We have obtained an accuracy, sensitivity, and specificity of 97.64, 97.01, and 98.24 %, respectively, in identifying the CHF. The proposed automated technique is able to identify the person having CHF alarming (alerting) the clinicians to respond quickly with proper treatment action. Thus, this method may act as a valuable tool for increasing the survival rate of many cardiac patients.

     

Integration of Derivative Control on SIPIC in Motor Speed Control

The proportional–integral–derivative (PID) controller is the most commonly used controller in control application due to its simplicity. However, the control output may exceed the plant input limit which eventually deteriorates the system performance. This is known as a windup phenomenon, which causes large overshoot, long settling time and instability in the control system. Various anti‐windup methods have been introduced to overcome the windup phenomenon such as the Steady‐State Integral Proportional‐Integral Controller (SIPIC). Due to the coupling of the proportional, integral and derivative tuning gains, it is difficult to tune for non‐overshoot and short settling time to coexist in a PID. With decoupling, a greater range of tuning gains can be applied to control the rising slope without disturbing the damping state. Currently, SIPIC with decoupling effect has only been studied for the proportional and integral tuning gains. This paper presents the effect of integrating derivative control on SIPIC in motor speed control. SIPIC+D shows better speed control on a direct current motor under no‐load and loading conditions compared with other existing anti‐windup added with derivative control.     

Effect of process conditions on the weld‐line strength and microstructure of microcellular injection molded parts

This study was aimed at understanding how the process conditions affect the weld‐line strength and microstructure of injection molded microcellular parts. A design of experiments (DOE) was performed and polycarbonate tensile test specimens were produced for tensile tests and microscopic analysis. Injection molding trials were performed by systematically adjusting four process parameters (i.e., melt temperature, shot size, supercritical fluid (SCF) level, and injection speed). For comparison, conventional solid specimens were also produced. The tensile strength was measured at the weld line and away from the weld line. The weld‐line strength of injecton molded microcellular parts was lower than that of its solid counterparts. It increased with increasing shot size, melt temperature, and injection speed, and was weakly dependent on the supercritical fluid level. The microstructure of the molded specimens at various cross sections were examined using scanning electron microscope (SEM) and a light microscope to study the variation of cell size and density with different process conditions.     

Study of injection molded microcellular polyamide‐6 nanocomposites

This study aims to explore the processing benefits and property improvements of combining nanocomposites with microcellular injection molding. The microcellular nanocomposite processing was performed on an injection‐molding machine equipped with a commercially available supercritical fluid (SCF) system. The molded samples produced based on the Design of Experiments (DOE) matrices were subjected to tensile testing, impact testing, Dynamic Mechanical Analysis (DMA), and Scanning Electron Microscope (SEM) analyses. Molding conditions and nano‐clays have been found to have profound effects on the cell structures and mechanical properties of polyamide‐6 (PA‐6) base resin and nanocomposite samples. The results show that microcellular nanocomposite samples exhibit smaller cell size and uniform cell distribution as well as higher tensile strength compared to the corresponding base PA‐6 microcellular samples. Among the molding parameters studied, shot size has the most significant effect on cell size, cell density, and tensile strength. Fractographic study reveals evidence of different modes of failure and different regions of fractured structure depending on the molding conditions. Polym. Eng. Sci. 44:673–686, 2004. © 2004 Society of Plastics Engineers.