Extracting biomedical information from large metabolomic datasets by multivariate data analysis is of considerable complexity. Common challenges include among others screening for differentially produced metabolites, estimation of fold changes, and sample classification. Prior to these analysis steps, it is important to minimize contributions from unwanted biases and experimental variance. This is the goal of data preprocessing. In this work, different data normalization methods were compared systematically employing two different datasets generated by means of nuclear magnetic resonance (NMR) spectroscopy. To this end, two different types of normalization methods were used, one aiming to remove unwanted sample-to-sample variation while the other adjusts the variance of the different metabolites by variable scaling and variance stabilization methods. The impact of all methods tested on sample classification was evaluated on urinary NMR fingerprints obtained from healthy volunteers and patients suffering from autosomal polycystic kidney disease (ADPKD). Performance in terms of screening for differentially produced metabolites was investigated on a dataset following a Latin-square design, where varied amounts of 8 different metabolites were spiked into a human urine matrix while keeping the total spike-in amount constant. In addition, specific tests were conducted to systematically investigate the influence of the different preprocessing methods on the structure of the analyzed data. In conclusion, preprocessing methods originally developed for DNA microarray analysis, in particular, Quantile and Cubic-Spline Normalization, performed best in reducing bias, accurately detecting fold changes, and classifying samples.
Both neonatal humans and mice are exquisitely susceptible to severe HSV infection. We have now documented a profound defect in the ability of neonatal C57BL/6 mice to produce anti-HSV ADCC antibody. This ability is acquired over the first 2 to 4 wk of life. Reconstitution of neonatal mice by i.p. injection of peritoneal cells from adult nonimmune syngeneic mice both affords dose-dependent protection against lethal HSV infection and reconstitutes the antibody-production defect. By cell-separation techniques (adherence, nylon wool column purification, B cell panning) and cell ablation techniques (silica treatment, irradiation, anti-T cell, anti-Ia, anti-Lyt-1.2 and anti-Lyt-2.2 monoclonal antibodies plus complement treatment) the subpopulations involved in the antibody production reconstitution of neonatal mice by adult cells were identified. These include both an Ia+, radioresistant, adherent, silica-sensitive macrophage population and a nylon wool column-purified, radiosensitive, anti-T, anti-Lyt-1.2-sensitive helper T cell population. The latter cell may be substituted for by concanavalin A-stimulated lymphokine-containing spleen cell supernatants or human recombinant IL 2. In addition to reconstitution of ADCC antibody production, the same cell populations, or cells plus lymphokine-containing supernatants or IL 2, protected the newborn mice from lethal HSV infection. Further characterization of this system and of soluble replacement factors has implications for therapy or immunoprophylaxis of human neonates with, or at risk of, HSV infection. 相似文献
Ovarian steroids and growth factors are intragonadal modulators which augment a key endpoint of follicle-stimulating hormone (FSH) action in granulosa cells: the induction of aromatase activity. Studies of these paracrine hormones that enhance FSH-stimulated estrogen biosynthesis by cultured rat granulosa cells, have led to the development of a sensitive and specific
bioassay for FSH. This newly developed granulosa cell aromatase bioassay (GAB) allows for the measurement of bioactive FSH levels in serum and urine of humans and animals with various physiological and pathological conditions. These studies have demonstrated that the GAB assay is useful in detecting possible changes in the molecular forms of FSH. The adaptation of this method for urine samples allows for the measurement of bio-FSH levels in situations where venipuncture is not practical or in species for which specific radioimmunoassays are not available. 相似文献
Summary C-band polymorphisms of chromosome 1 can be quantified by Ce bands visualized using oblique epi-illumination. In this paper the polymorphic region of chromosome 9, including variants such as 9qh+, inversions, and translocations, was analyzed in a total of 1860 chromosomes from 20 individuals and 8 fetuses. In this sample we found between zero and five Ce bands on 9q and between zero and four Ce bands on 9p with a maximum of five Ce bands per chromosome. On the basis of these observations at least 19 different polymorphic patterns can be expected theoretically, 15 of which were observed in our sample. Among these, five polymorphic Ce-band classes were distinguishable by the method presented. Considering both homologues, 52=25 quantitatively discernible chromosome 9 pairs may exist. 相似文献
The plasmid content and toxicity of nine different strains ofMicrocystis aeruginosa have been analyzed. The two toxic strains of the HUB Culture Collection were found to carry each two plasmids, pMA1 and pMA2, of 2.9 kb and 8.5 kb, respectively. In strains PCC 7813 and PCC 7820, also toxic, two different plasmids of 2.6 kb and 16 kb were detected. Hybridization experiments showed that there exists no sequence homology between the pMA plasmids and the plasmids found in the PCC strains; but the pMA plasmids hybridized to chromosomal DNA of the toxic strains PCC 7820, PCC 7813, HUB 063, and the nontoxic strain HUB 5-3. In nontoxic strains no or at most one plasmid of unstable occurrence could be detected. Only one of the toxic strains investigated, SAG 14.85 (NRC-1), contained no plasmid. 相似文献
The15N abundance of plants usually closely reflects the15N abundance of their major immediate N source(s); plant-available soil N in the case of non-N2-fixing plants and atmospheric N2 in the case of N2 fixing plants. The15N abundance values of these sources are usually sufficiently different from each other that a significant and systematic difference in the15N abundance between the two kinds of plants can be detected. This difference provides the basis for the natural15N abundance method of estimating the relative contribution of atmospheric N2 to N2-fixing plants growing in natural and agricultural settings. The natural15N abundance method has certain advantages over more conventional methods, particularly in natural ecosystems, since disturbance of the system is not required and the measurements may be made on samples dried in the field. This method has been tested mainly with legumes in agricultural settings. The tests have demonstrated the validity of this method of arriving at semi-quantitative estimates of biological N2-fixation in these settings. More limited tests and applications have been made for legumes in natural ecosystems. An understanding of the limits and utility of this method in these systems is beginning to emerge. Examples of systematic measurements of differences in15N abundance between non-legume N2-fixing systems and neighbouring non-fixing systems are more unusual. In principle, application of the method to estimate N2-fixation by nodulated non-legumes, using the natural15N abundance method, is as feasible as estimating N2-fixation by legumes. Most of the studies involving N2-fixing non-legumes are with this type of system (e.g., Ceanothus, Chamabatia, Eleagnus, Alnus, Myrica, and so forth). Resuls of these studies are described. Applicability for associative N2-fixation is an empirical question, the answer to which probably depends upon the degree to which fixed N goes predominantly to the plant rather than to the soil N pool. The natural15N abundance method is probably not well suited to assessing the contribution of N2-fixation by free-living microorganisms in their natural habitat, particularly soil microorganisms.This work was supported in part by subcontracts under grants from the US National Science Foundation (DEB79-21971 and BSR821618) 相似文献
The social environment affects both behavioral and physiological responses to separation from the mother. Less information
is available on the impact of the social environment on the response to separation in peer-reared infant monkeys. This study
reports the responses of peer-reared pigtail macaque infants to repeated separations, and the impact of social versus isolation
housing during the separation. The responses of two pairs of monkeys were studied during four three-day separations. One of
each pair was housed in isolation during the separation, and the other was with another pair of peers, with whom they had
been living for one month prior to the separation. The isolation-housed peer responded to the separation with behavioral agitation,
but no depression. The socially-housed peer's behavior did not differ from baseline during the separation. During successive
reunions, all the separated monkeys, regardless of housing condition, exhibited declining levels of behaviors related to maintaining
proximity to their attachment figure. Although the number of subjects is small, the results suggest that the presence of social
support, in the form of a familiar peer, can ameliorate the response to separation, and that with repeated separations the
responses of the monkeys changes significantly. 相似文献