A method for evaluating the selectivity of electrodes implanted fornerve simulation

The scale of stimulating electrodes possible for use in functional electrical stimulation to restore motor and sensory function is rapidly approaching that of individual neurons. Although the electrodes may approach the dimensions of single nerve cells, it is unclear if the region of excitation elicited by each electrode will be correspondingly small. Previous techniques for evaluating this have either been tedious or have lacked the resolution necessary. This paper describes a method that uses the refractory interaction of the compound action potentials elicited by a stimulus pulse pair, along with high-resolution recording of those potentials, to achieve measurements of the selectivity of stimulation down to the scale of a few axon diameters. The feasibility of this technique is demonstrated in sciatic nerves of frogs (Rana Catesbiana) acutely implanted with a sapphire electrode array.     

Multi-agent cooperation for particle accelerator control

Quite exhaustive theoretical studies exist in DAI, but it seems that there is not enough feedback from practice. In this paper we present practical investigations for applying and justifying the theoretical DAI results in a real industrial controls environment, and, conversely, we discuss the theoretical aspects of practical findings in these applied investigations made for accelerator control and operation. The results presented here are partly based on the research carried out at CERN during the ESPRIT-II Project ARCHON™. A generalized hypothesis is introduced, based on a unified view of control, monitoring, diagnosis, maintenance and repair tasks leading to a general method of cooperation for expert systems by exchanging hypotheses and leads to a mapping of different tasks in accelerator control to cooperating agents. This has been tested for task and result-sharing cooperation scenarios and we also report on studies carried out in relation to accelerator timings and their diagnosis as well as the transformation of these systems into a multi-agent community. Generalized hypotheses also allow us to treat the repetitive diagnosis-recovery cycle as a task-sharing cooperation. Problems with such a loop or even recursive calls between the different agents are discussed.     

Delayed development of symptomatic improvement by (--)-deprenyl in Parkinson's disease

Twenty de novo patients with Parkinson's disease (Hoehn-Yahr stages I, II, III) were studied in a double blind trial after introducing (--)-deprenyl monotherapy. The parkinsonian symptoms were assessed by a novel graded clinical rating scale, by UPDRS and by the North Western self-rating scale. A significant change was observed in motor behaviour and daily activity (UPDRS) after 3 weeks of treatment with (--)-deprenyl at 10 mg/day. The total scores using UPDRS and the North Western ratings were changed significantly after 4 weeks. The greatest changes observed were in walking and in hypokinesia. Rigidity was not modified by (--)-deprenyl.     

Evidence that C1q binds specifically to CH2-like immunoglobulin gamma motifs present in the autoantigen calreticulin and interferes with complement activation

Calreticulin (CRT) is located predominantly in the endoplasmic reticulum (ER) of cells, where it functions as a quality control controller of protein folding. However, CRT is also a prevalent autoantigen in patients with systemic lupus erythematosus (SLE), where its release from the cell may arise as a results of dysfunctional apoptosis and inefficient removal of ER vesicles, which are an abundant source of CRT and other autoantigens. Indicative of this is the presence of autoantibodies against CRT in the sera of 40-60% of all SLE patients. Once released into the circulation, CRT might bind directly to C1q and we have suggested that this association may result in a defect in C1q-mediated clearance of antigen-antibody complexes. It has been previously shown that CRT under physiological salt conditions binds to the globular head of C1q. It is known that the globular head region of C1q binds to the CH2 domain in the Fc portion of immunoglobulin gamma (IgG). The N-terminal half of CRT contains a number of short regions of 7-10 amino acids that show sequence similarity to the putative C1q binding region in the CH2 domain of IgG. By use of a series of 92 overlapping CRT synthetic peptides, a number of C1q binding sites on the CRT molecule have been identified, including several containing a CH2-like motif similar to the ExKxKx C1q binding motif found in the CH2 domain of IgG. A number of these peptides were shown to inhibit binding of C1q to IgG and reduce binding of native CRT to C1q. Moreover, several of the peptides were capable of inhibiting the classical pathway of complement activation. These studies have identified specific binding sites on the CRT molecule for C1q and lend support to the hypothesis that interaction of CRT with C1q may interfere with the ability of C1q to associate with immune complexes in autoimmune-related disorders.     

A rail-to-rail ping-pong op-amp

A rail-to-rail ping-pong op-amp achieves offset cancellation and 1/f noise reduction without folding of the input spectrum. The clocking scheme minimizes the clock feedthrough and the residual offset due to charge injection. With a clock frequency of 100 kHz, the residual offset is less than 100 μV, and the input referred noise is about 225 nV/Hz ^1/2. The rail-to-rail distortion at 1 kHz is lower than -71 dB. The total silicon area is 610×420 μm², and the circuit dissipates 1.5 mW from a single 5 V supply     

Monogenic determinants of familial Alzheimer''s disease: presenilin-1 mutations

The authors describe a new simple noniterative, yet efficient method to estimate the risk ratio in studies using case-parental control design. The new method is compared with two other noniterative methods, Khoury's method and Flanders and Khoury's method, and with a maximum likelihood-based method of Schaid and Sommer. The authors found that the variance of the new estimation method is usually smaller than that of Khoury's method or Flanders and Khoury's method and that it is slightly larger than that of the maximum likelihood-based method of Schaid and Sommer. Despite the slightly large variance of the new estimator compared with that of the maximum likelihood-based method, the simplicity of the new estimator and its variance makes the new method appealing. When genotypic information for only one parent is available, the authors also describe a method to estimate the risk ratio without assuming Hardy-Weinberg equilibrium or random mating. A simple formula for the variance of the estimator is given.     

Primary carcinoma of the ureteral stump: a case report and a review of the literature

A case is reported of primary carcinoma of the ureteral stump with metastases following nephrectomy for benign disease. The occurrence of disseminated tumor at the time of diagnosis is uncommon, having been reported in only 3 previous cases. The autopsy findings are discussed and the literature is reviewed.     

Increase of gangliosides in atherosclerotic human aortas

Preparations of human thoracic aortas containing intima and media were obtained post-mortem, and gangliosides were isolated by standard techniques. The quantity of ganglioside sialic acid, as assayed by gas liquid chromatography, was lowest in normal aortas (33±9 nmoles N-acetyl neuraminic acid/g wet tissue) and progressively increased in aortas containing predominantly fatty streaks (54±1 nmoles N-acetyl neuraminic acid/g wet tissue), raised yellow plaques (88±23 nmoles N-acetyl neuraminic acid/g wet tissue), and ulcerated lesions (270±44 nmoles N-acetyl neuraminic acid/h wet tissues). Both thin layer chromatography of the gangliosides and gas liquid chromatography of the constituent sugars demonstrated the presence of a ganglioside with properties similar to a monosialyl lactosyl ceramide (GM₃) as the major ganglioside. A ganglioside with similar chemical characteristics was isolated from plasma and low density lipoproteins.     

Rule fitness and pathology in learning classifier systems

It has long been known that in some relatively simple reinforcement learning tasks traditional strength-based classifier systems will adapt poorly and show poor generalisation. In contrast, the more recent accuracy-based XCS, appears both to adapt and generalise well. In this work, we attribute the difference to what we call strong over general and fit over general rules. We begin by developing a taxonomy of rule types and considering the conditions under which they may occur. In order to do so an extreme simplification of the classifier system is made, which forces us toward qualitative rather than quantitative analysis. We begin with the basics, considering definitions for correct and incorrect actions, and then correct, incorrect, and overgeneral rules for both strength and accuracy-based fitness. The concept of strong overgeneral rules, which we claim are the Achilles' heel of strength-based classifier systems, are then analysed. It is shown that strong overgenerals depend on what we call biases in the reward function (or, in sequential tasks, the value function). We distinguish between strong and fit overgeneral rules, and show that although strong overgenerals are fit in a strength-based system called SB-XCS, they are not in XCS. Next we show how to design fit overgeneral rules for XCS (but not SB-XCS), by introducing biases in the variance of the reward function, and thus that each system has its own weakness. Finally, we give some consideration to the prevalence of reward and variance function bias, and note that non-trivial sequential tasks have highly biased value functions.     

Partitioning of persistent organic pollutants in grey seal (Halichoerus grypus) mother-pup pairs

Phocid seals have lipid rich milk, which is known to serve as a transfer medium through which persistent organic pollutants (POPs) move from mother to offspring during lactation. However, knowledge on this generational transfer of different POPs and the partitioning of these compounds in maternal and offspring tissues over the course of the lactation are limited. In this study we examined the qualitative and quantitative partitioning of a range of chlorinated POPs in maternal blubber, blood and milk as well as in pup blubber, collected early in the lactation period and late in the lactation period. In the lactating female, the high-chlorinated and hydrophobic compounds were passed less efficiently into the milk than the low-chlorinated compounds and more water-soluble compounds. Significantly, lower maternal blood concentrations than in maternal blubber biopsies suggest a stratification of POP concentrations in the blubber column of lactating female and lower concentrations in the metabolic active inner layers. Over the course of lactation, there was a significant increase in maternal blood and milk concentrations of POPs as opposed to no change in maternal blubber biopsy concentrations. This was most apparent for the hydrophobic and high-chlorinated compounds. The most likely explanation for this is that the metabolic active inner blubber layer, from which the milk lipids are derived from, is in steady state with the circulatory system, while the outer layers are more static and only slowly respond to changes in concentrations elsewhere in the body. The concentrations of the high-chlorinated and hydrophobic compounds were substantially lower in pup blubber than in maternal blubber. This probably relates the combined effect of these compounds stratification in maternal blubber and their slow transfer into the milk. The present study shows that the more hydrophobic and high-chlorinated compounds come to steady state less quickly in the different tissues than the more water-soluble and low-chlorinated compounds in the lactating female and her offspring. This has implications for which matrices to choose when sampling for assessing the toxicological risk of POPs in seals.