A dominant-negative transgene defines a role for p56lck in thymopoiesis

The lymphocyte-specific protein tyrosine kinase p56lck participates in T cell signaling through functional interactions with components of the T cell antigen receptor complex and the interleukin-2 receptor. Additional insight into the function of p56lck has now been obtained through the generation of transgenic animals expressing high levels of a catalytically inactive form of this kinase (p56lckR273). Mice bearing the lckR273 transgene manifested a severe defect in the production of virtually all T lymphocytes. Those exceptional CD3+ cells that escaped the effects of the lckR273 transgene were confined primarily to the T cell subset that expresses gamma/delta T cell receptors. Remarkably, construction of a dose-response curve for the effects of the lckR273 transgene revealed that developmental arrest of thymocytes occurred at a discrete stage in the normal T cell maturation pathway, corresponding to a point at which thymoblasts ordinarily begin a series of mitotic divisions that result in expansion and maturation. These results suggest that p56lck normally regulates T cell production by metering the replicative potential of immature thymoblasts.     

Neuropathologic diagnosis of Alzheimer disease: interrater reliability in the assessment of senile plaques and neurofibrillary tangles

The potential advantages of using digital techniques instead of film-based radiography have been discussed extensively for the past 10 years. A major future application of digital techniques is computer-assisted diagnosis: the use of computer techniques to assist the radiologist in the diagnostic process. One aspect of this assistance is computer-assisted detection. The detection of small lung nodule has been recognized as a clinically difficult task for many years. Most of the literature has indicated that the rate for finding lung nodules (size range from 3 mm to 15 mm) is only approximately 65%, in those cases in which the undetected nodules could be found retrospectively. In recent published research, image processing techniques, such as thresholding and morphological analysis, have been used to enhance true-positive detection. However, these methods still produce many false-positive detections. We have been investigating the use of neural networks to distinguish true-positives nodule detections among those areas of interest that are generated from a signal enhanced image. The initial results show that the trained neural networks program can increase true-positive detections and moderately reduce the number of false-positive detections. The program reported here can perform three modes of lung nodule detection: thresholding, profile matching analysis, and neural network. This program is fully automatic and has been implemented in a DEC 5000/200 (Digital Equipment Corp, Maynard, MA) workstation. The total processing time for all three methods is less than 35 seconds. In this report, key image processing techniques and neural network for the lung nodule detection are described and the results of this initial study are reported.     

Salt hydrates as absorbents in heat pump cycles

A thermodynamic analysis has shown that inorganic salt hydrates are attractive candidates for absorbents in heat pump cycles. Their computed performance efficiencies compare favorably to those of previously proposed solid and liquid absorbents, under conditions typical of domestic, solar-powered, intermittent operation. It was found that hydrate cooling cycles, with coefficients-of-performance in the range of 0.6-0.7, can significantly outperform all others considered. In space heating applications, solid-absorbent cycles were far superior to a typical liquid-absorbent cycle in both overall efficiency and per cent of thermal energy input stored. Predicted hydrate coefficients-of-performance were in the range 1.4-1.6 with 75–85 per cent effective storage.     

High-speed low-voltage modulation with a nonsymmetric Mach-Zehnderinterferometer

The authors demonstrate broadband optical modulation with a Ti:LiNbO₃ nonsymmetric interferometer at microwave frequencies up to 16 GHz. The 3-dB bandwidth of 8.7 GHz is only slightly less than the theoretical limit of 9.6 GHz for a 1-cm-long device. The device uses a 2-μm-thick gold-plated asymmetric stripline electrode, with a characteristic impedance of 40 Ω and ohmic loss of 3 dB/cm at 10 GHz. The DC switching voltage is 6.5 V, and the on/off ratio is -16 dB. Fabrication tolerances in the nonsymmetric interferometer are much less strict than for directional coupler modulators with comparable performance, making this device a better candidate for use in communications systems     

Optimal contaminant removal in fermentation and waste treatment processes

A bifunctional enzymatic catalyst system may be optimally distributed along a plug flow tubular reactor to reduce trace contamination. For the system considered in this study, there are nine possible optimal catalyst distribution policies, depending on the magnitude of the initial concentrations, the relative oxidizing power of the contaminants, and the residence time in the reactor. The effects of these system parameters on the optimal distribution policies are discussed, as is the possibility of replacing the optimal policies with suboptimal decisions. The relative errors caused by the suboptimal policies are found to be insignificant in many cases, but the approximations may not do as well if the oxidizing contaminants have relatively very different effects.     

Regional stability for a tubular reactor with axial mixing

A graphical phase-plane procedure is suggested by which regions of stability can be estimated for a tubular reactor. The technique uses a super-position of limits for primary flow and reaction effects and those arising from secondary axial dispersion. Several detailed numerical tests are reported to substantiate the conjecture.     

Geodesic Warps by Conformal Mappings

In recent years there has been considerable interest in methods for diffeomorphic warping of images, with applications in e.g. medical imaging and evolutionary biology. The original work generally cited is that of the evolutionary biologist D’Arcy Wentworth Thompson, who demonstrated warps to deform images of one species into another. However, unlike the deformations in modern methods, which are drawn from the full set of diffeomorphisms, he deliberately chose lower-dimensional sets of transformations, such as planar conformal mappings. In this paper we study warps composed of such conformal mappings. The approach is to equip the infinite dimensional manifold of conformal embeddings with a Riemannian metric, and then use the corresponding geodesic equation in order to obtain diffeomorphic warps. After deriving the geodesic equation, a numerical discretisation method is developed. Several examples of geodesic warps are then given. We also show that the equation admits totally geodesic solutions corresponding to scaling and translation, but not to affine transformations.     

CD8 inhibits signal transduction through the T cell receptor in CD4-CD8- thymocytes from T cell receptor transgenic mice reconstituted with a transgenic CD8 alpha molecule

T cell repertoire selection processes involve intracellular signaling events generated through the TCR. The CD4 and CD8 coreceptor molecules can act as positive regulators of TCR signal transduction during these developmental processes. In this report, we have used TCR transgenic mice to determine whether TCR signaling can be modulated by the CD8 coreceptor molecule. These mice express on the majority of their T cells a TCR specific for the male (H-Y) Ag presented by the H-2Db MHC class I molecule. We show that CD4-CD8-, but not CD4-CD8+, thymocytes expressing the H-Y TCR responded with high intracellular calcium fluxes to TCR/CD3 stimulation without extensive receptor cross-linking. To examine the effects of CD8 expression on intracellular signaling responses in the CD4-CD8- cells, the H-Y TCR transgenic mice were mated with transgenic mice that constitutively expressed the CD8 alpha molecule on all T cells. The expression of the CD8 alpha alpha homodimer in the CD4-CD8-thymocytes led to impaired intracellular calcium responses and less efficient protein tyrosine phosphorylation of substrates after TCR engagement. In male H-2b H-Y transgenic mice, the majority of thymocytes have been deleted with the surviving cells expressing a high density of the transgenic TCR and exhibiting either a CD4-CD8- or CD4-CD8lo phenotype. It has been postulated that these cells escaped deletion by down-regulating the CD8 molecule. In the H-Y TCR/CD8 alpha double transgenic male mice, the CD4-CD8lo cells were completely eliminated as a result of CD8 alpha expression. However, the CD4-CD8- T cells were not deleted despite normal levels of the CD8 alpha transgene expression. These results suggest that the CD4-CD8- thymocytes may not be susceptible to the same deletional mechanisms as other thymocytes expressing TCR-alpha beta.