Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus

A side effect of therapy with procainamide and numerous other medications is a lupus-like syndrome characterized by autoantibodies directed against denatured DNA and the (H2A-H2B)-DNA subunit of chromatin. We tested the possibility that an effect of lupus-inducing drugs on central T cell tolerance underlies these phenomena. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, resulted in prompt production of IgM antidenatured DNA antibodies in C57BL/6xDBA/2 F1 mice. Subsequently, IgG antichromatin antibodies began to appear in the serum 3 wk after the second injection and were sustained for several months. Specificity, inhibition and blocking studies demonstrated that the PAHA-induced antibodies showed remarkable specificity to the (H2A-H2B)-DNA complex. No evidence for polyclonal B cell activation could be detected based on enumeration of Ig-secreting B cells and serum Ig levels, suggesting that a clonally restricted autoimmune response was induced by intrathymic PAHA. The IgG isotype of the antichromatin antibodies indicated involvement of T cell help, and proliferative responses of splenocytes to oligonucleosomes increased up to 100-fold. As little as 5 microM PAHA led to a 10-fold T cell proliferative response to chromatin in short term organ culture of neonatal thymi. We suggest that PAHA interferes with self-tolerance mechanisms accompanying T cell maturation in the thymus, resulting in the emergence of chromatin-reactive T cells followed by humoral autoimmunity.     

Arsenic intoxication presenting with macrocytosis and peripheral neuropathy, without anemia

A case of arsenic intoxication associated with macrocytosis and neuropathy, without anemia, is presented. Evaluation of a 68-year-old man with a long history of peripheral neuropathy and persistent macrocytosis revealed exposure to an insecticide. Analysis of urine and hair revealed elevated levels of arsenic. A short course of d-penicillamine failed to promote urinary excretion of arsenic. Removal of the insecticide resulted in resolution of macrocytosis and slight improvement of neuropathy. This case emphasizes that arsenic intoxication should be considered in patients with macrocytosis with peripheral neuropathy, even in the absence of anemia.     

Threshold voltage-minimum gate length trade-off in buried channelPMOS devices for scaled supply voltage CMOS technologies

The trade-off between threshold voltage (V_th) and the minimum gate length (L_min) is discussed for optimizing the performance of buried channel PMOS transistors for low voltage/low power high-speed digital CMOS circuits. In a low supply voltage CMOS technology it is desirable to scale V_th and L_min for improved circuit performance. However, these two parameters cannot be scaled independently due to the channel punch-through effect. Statistical process/device modeling, split lot experiments, circuit simulations, and measurements are performed to optimize the PMOS transistor current drive and CMOS circuit speed. We show that trading PMOS transistor V_th for a smaller L_min results in faster circuits for low supply voltage (3.3 to 1.8 V) n⁺-polysilicon gate CMOS technology, Circuit simulation and measurements are performed in this study. Approximate empirical expressions are given for the optimum buried channel PMOS transistor V _th for minimizing CMOS circuit speed for cases involving: (1) constant capacitive load and (2) load capacitance proportional to MOS gate capacitance. The results of the numerical exercise are applied to the centering of device parameters of a 0.5 μm 3.3 V CMOS technology that (a) matches the speed of our 0.5 μm 5 V CMOS technology, and (b) achieves good performance down to 1.8 V power supply. For this process the optimum PMOS transistor V_th (absolute value) is approximately 0.85-0.90 V     

Formant labelling using pole-focused spectra

An algorithm is introduced which labels formants from the peaks of pole-focused spectra. A clustering procedure is first used to produce line segments of possible formants. These can be considered as anchor traces for the later processing. Rule-based labelling is then applied to provide final formant trace estimates. Experimental results show that the proposed algorithm offers improved formant labelling accuracy.     

On the detection of motion and the computation of optical flow

A method for the detection of motion in image sequences is presented. In this method, the intensity history at each pixel is convolved with the second derivative in time of a temporal Gaussian smoothing function. The zero crossings in a single frame of the resulting function indicate the positions of moving edges. Intensity changes in time due to illumination effects do not produce zero crossings; thus, they are not interpreted as motion by the present method. It is also shown that the spatial and temporal derivatives of this function can be used to compute the component of the optical flow that is normal to the zero-crossing contours. This computation is also insensitive to nonconvective temporal and spatial variations in the image intensity that are caused by illumination effects     

Tests of assumptions about the joint receipt of gambles in rank- and sign-dependent utility theory.

A rank- and sign-dependent utility theory is based on an operation of joint receipt of 2 independent gambles and 3 assumptions regarding the operation (R. D. Luce, 1992). The authors tested these 3 assumptions (i.e., segregation, duplex decomposition, and the additivity of certainty equivalents over joint receipt) using both judged and choice certainty equivalents (CEs). Median choice CEs provided support for both segregation and duplex decomposition but little support for additivity in gains or in losses, whereas median judged CEs also failed to support segregation. The latter failure appears to result from some Ss misunderstanding the instructions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)