Gas Phase Ion Chemistry to Determine Isoaspartate in a Peptide Backbone.

Proof of concept evidence is presented for a new method for the determination of isoaspartate, an important post-translational modification. Chemical derivatization is performed using common reagents for the modification of carboxylic acids and shown to yield suitable diagnostic information with regard to isomerization at the aspartate residue. The diagnostic gas phase chemistry is probed by collision-induced dissociation mass spectrometry, on the timescale of the MS experiment and semi-quantitative calibration of the percentage of isoaspartate in a peptide sample is demonstrated. Graphical Abstract ᅟ.

Cocaine effects on immunocompetent cells: an observation of in vitro cocaine exposure.

This study investigated in vitro effects of cocaine on the function of T and B lymphocytes, natural killer cells and macrophages in a mouse model. In mature C57BL/6J mice (60-90 day-old), splenocytes were cultured with cocaine at different concentrations ranging from 4 to 64 microg/ml for 24 h. The exposure to cocaine in vitro was found to affect (1) T cell function, with reduced responses to stimulation of Con-A, PHA and Interleukin 2, and decreased production of gamma-IFN; (2) B cell function, with reduced response to LPS; (3) natural killer cell function, with attenuated killing capacity; (4) monocyte-macrophage function, with decreased ability to inhibit the growth of tumor cells. The results of the study indicated a direct cocaine effect on four major immune competent cells, and the generally suppressive effects of in vitro cocaine exposure may be related to its in vivo action on the immune system.

Interactive effects of cocaine and gender on thymocytes: a study of in vivo repeated cocaine exposure.

This study used a mouse model including both sexes to assess the impact of repeat cocaine exposure on the differentiation and function of T cell in thymus. Cocaine hydrochloride in 0.9% saline, 5 mg or 40 mg/kg, was administrated by i.p. injection to C57BL/6 mice for 10 days. Thymocytes were obtained 24 h after the 10th injection. Repeat in vivo cocaine exposure inhibited the proliferation of T lymphocytes in response to Con-A and Con-A plus anti-CD28. The proliferation induced by IL-2 in the Con-A stimulated T blasts was attenuated in cocaine treated mice. These effects were seen at a lower cocaine dose in female mice. The total number of thymocytes was reduced. Although the percentage of mature thymocytes (CD4+ CD8- and CD4- CD8+ cells) was not altered, the absolute cell numbers were attenuated. Both percentage and absolute cell number of immature thymocytes (CD4+ CD8+) decreased and the pre-mature (CD4- CD8-) cells increased. CD28 and CD25 expression were attenuated in Con-A stimulated thymocytes of mice treated with cocaine at 40 mg/kg. Interleukin 2 production was not significantly altered, however, gamma-IFN production was decreased by cocaine exposure at 40 mg/kg. In conclusion, cocaine exerts inhibitory effects on the function of mature thymocytes, and on the differentiation of thymocytes. A gender difference in response to cocaine was noted in that female mice were more sensitive to lower dose of cocaine exposure.

[Rehabilitation of young craniopharyngioma patients]. / Rehabilitation jugendlicher Kraniopharyngeom-Patienten.

The course of rehabilitation in 11 young patients with craniopharyngeoma was investigated. With intelligence well-preserved, neuropsychological diagnosis revealed impairments in rate and persistence in virtually all patients; behaviour disorders were present in 8 of the 11 patients, with efforts to distinguish psychoorganic from psychoreactive causality however not always successful. The neuropsychological deficits and behavioural deviations mentioned, rather than complications of a medical nature (1 of 11), resulted in only 2 patients having been able to maintain their premorbid educational/vocational status. The rehabilitative outcomes obtained in patients with clear-cut indications of diencephalic lesion (among them variations in vigilance, polyphagia, adipsia) had been unsatisfactory, whereas, in the other behaviourally disordered patients, successful outcomes were achieved by a therapeutic approach tailored to the specific needs of the individual condition.

A Test of the Gaussian-ness of a Data Set Using Clustering.

The properties of the ``magnifying glass'' method of clustering are discussed. These properties, which include unbiased and consistent estimation of the mean for Gaussian distributions and biased and inconsistent estimation of the mean for non-Gaussian distributions, lead to the development of a technique for testing data to determine whether or not it is Gaussian. An example of a non-Gaussian distribution is given to show the sensitivity of the proposed Gaussian test.

The 2-NN Rule for More Accurate NN Risk Estimation.

By proper design of a nearest-neighbor (NN) rule, it is possible to reduce effects of sample size in NN risk estimation. The 2-NN rule for the two-class problem eliminates the first-order effects of sample size. Since its asymptotic value is exactly half that of the 1-NN rule, it is possible to substitute the 2-NN rule for the 1-NN rule with a resultant increase in accuracy. For further stabilization of the risk estimate with respect to sample size, 2-NN polarization is suggested. Examples are included. The 2-NN approach is extended to M-class and 2k-NN.

An optimal global nearest neighbor metric.

A quadratic metric dAO (X, Y) =[(X - Y)T AO(X - Y)]¿ is proposed which minimizes the mean-squared error between the nearest neighbor asymptotic risk and the finite sample risk. Under linearity assumptions, a heuristic argument is given which indicates that this metric produces lower mean-squared error than the Euclidean metric. A nonparametric estimate of Ao is developed. If samples appear to come from a Gaussian mixture, an alternative, parametrically directed distance measure is suggested for nearness decisions within a limited region of space. Examples of some two-class Gaussian mixture distributions are included.

Classification error for a very large number of classes.

Classification error is analyzed for a situation where the number of possible classes may be on the order of a hundred or more. The error associated with classifying to a single class is shown to depend mainly on average nearest-neighbor distance between class means, noise level, and effective dimensionality of the class mean distribution and not much on other aspects of the distribution, noise correlation, or number of classes. Since single class error is large, separation of classes into groups is also explored. Group classification error has the same properties as single class error but the size of the error is moderated by the Bayes overlap between groups. Standard curves are provided to predict single class and group error. Also discussed are the effect of pattern blurring on classification error and the nearest-neighbor distance statistics throughout a distribution.

Estimation of the parameters of a gaussian mixture using the method of moments.

Given a general n-dimensional bimodal Gaussian mixture, this paper shows how unknown parameters may be found by the method of moments. Three cases are considered-equal modal probabilities, known but not necessarily equal probabilities, and all parameters unknown. The solution involves sample moments no higher than fourth order. For Gaussian mixtures where the number of modes is unknown, fourth-order moments can be used to count them, provided all modes have the same covariance matrix, and their multiplicity is not greater than data dimensionality. Examples of mode-counting and the determination of bimodal parameters are included.