Universal linear least squares prediction: upper and lower bounds

We consider the problem of sequential linear prediction of real-valued sequences under the square-error loss function. For this problem, a prediction algorithm has been demonstrated whose accumulated squared prediction error, for every bounded sequence, is asymptotically as small as the best fixed linear predictor for that sequence, taken from the class of all linear predictors of a given order p. The redundancy, or excess prediction error above that of the best predictor for that sequence, is upper-bounded by A/sup 2/P ln(n)/n, where n is the data length and the sequence is assumed to be bounded by some A. We provide an alternative proof of this result by connecting it with universal probability assignment. We then show that this predictor is optimal in a min-max sense, by deriving a corresponding lower bound, such that no sequential predictor can ever do better than a redundancy of A/sup 2/p ln(n)/n.     

Radiologic findings in gout

Radiological gout manifestations are detectable in the early stage, but also especially in the chronic stage of gout. Whereas in the early stage only soft tissue mutations (bursitis inflammation) and light calcium deposits are usually discernible, chronic gout leads to asymmetrical, diverse forms of osseous destruction, favouring smaller joints, but also affecting larger ones, which are caused by the intra-articular and extra-articular deposit of tophus material, corresponding to the progression and degree of severity of the illness. Radiologically-detectable changes in other organs, such as the kidneys, will be addressed. The high number of, and to some extent very characteristic, osseous mutations are compared with those mutations which are very similar to the diagnoses of other syndromes affecting the joints. Specifically, problems in differentiating diagnosis of rheumatoid arthritis, arthritis psoriatica, chondrocalcinosis, and other diseases of the joints will receive special mention. Reference is also made to the extreme diagnostic difficulties resulting from the rare but nevertheless conceivable influence of gout on the spine or sacroiliac joints. The method of magnetic resonance imaging for gout shows a characteristic signal behaviour of the tophus material. It has been determined that, through magnetic resonance tomography, interosseous tophi can be detected earlier and in a more widespread manner than with the aid of native X-ray images, such that an increase in the use of this method is to be expected.     

Carbachol can potentiate N-methyl-D-aspartate responses in the rat hippocampus by a staurosporine and thapsigargin-insensitive mechanism

Experiments were performed to investigate the mechanism underlying the potentiation of N-methyl-D-aspartate (NMDA) responses by carbachol (CCh) in the CA1 region of rat hippocampal slices. CCh (300 nM) potentiated responses to NMDA, but not to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), in a readily reversible manner. Potentiation occurred in slices treated with 200 nM tetrodotoxin and perfused with Mg(2+)-free medium. It also occurred in slices treated with either staurosporine (1 microM), which is a potent inhibitor of a variety of protein kinases including protein kinase C (PKC), or thapsigargin (10 microM), which depletes intracellular Ca2+ stores by preventing their refilling. However, CCh-induced potentiation was abolished in slices perfused with Ca(2+)-free medium. These data suggest that low concentrations of CCh can acutely potentiate NMDA responses in the hippocampus by a Ca(2+)-sensitive process that is probably independent of both the activation of PKC and the release of Ca2+ from intracellular stores. This mechanism is similar to that underlying the potentiation of NMDA responses by the metabotropic glutamate receptor (mGluR) agonist, aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD).     

Repair of DNA methylphosphotriesters through a metalloactivated cysteine nucleophile

The Escherichia coli Ada protein repairs methylphosphotriesters in DNA by direct, irreversible methyl transfer to one of its own cysteines. Upon methyl transfer, Ada acquires the ability to bind specific DNA sequences and thereby to induce genes that confer resistance to methylating agents. The amino-terminal domain of Ada, which comprises the methylphosphotriester repair and sequence-specific DNA binding elements, contains a tightly bound zinc ion. Analysis of the zinc binding site by cadmium-113 nuclear magnetic resonance and site-directed mutagenesis revealed that zinc participates in the autocatalytic activation of the active site cysteine and may also function as a conformational switch.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

Reliable computation by networks in the presence of noise

Lower bounds on the depth of Boolean networks that can compute reliably in the presence of randomly occurring failures are proved. A bound is also given on the reliability that error-tolerant networks can achieve: this bound implies a limit strictly smaller than 1/2 on the failure probability per gate that can be tolerated. The results improve upon recently published bounds of N. Pippenger (ibid., vol.IT-34, p.194-7, 1988) on the depth of error-tolerant formulas and extend the bounds to the case of reliable computation by networks