The reconstruction of social meaning in the space of flows

Artikkeli on alunperin julkaistu teoksessa: The informational city (1989) / Manuel Castells

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity.

A simple, robust and rapid approach to detect carbapenemases in Gram-negative isolates by MALDI-TOF mass spectrometry: validation with triple quadripole tandem mass spectrometry, microarray and PCR.

Carbapenemases should be accurately and rapidly detected, given their possible epidemiological spread and their impact on treatment options. Here, we developed a simple, easy and rapid matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based assay to detect carbapenemases and compared this innovative test with four other diagnostic approaches on 47 clinical isolates. Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount of antibiotic present in the supernatant after 1 h of incubation and both MALDI-TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103 microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of Aeromonas were not detected because their chromosomal carbapenemase is not targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based approach that uses a stable 10-μg disk of ertapenem was highly efficient in detecting carbapenemase, with a sensitivity higher than that of PCR and microarray.

The influence of drinking pattern, at individual and aggregate levels, on alcohol-related negative consequences.

AIM: To determine the extent drinking patterns (at the individual and country level) are associated with alcohol-related consequences over and above the total alcohol the person consumes. METHODS: Hierarchical linear models were estimated based on general population surveys conducted in 18 countries participating in the GENACIS project. RESULTS: In general, the positive association between drinking pattern scores and alcohol-related consequences was found at both the individual and country levels, independent of volume of drinking. In addition, a significant interaction effect indicated that the more detrimental the country's drinking pattern, the less steep the association between the volume of drinking and its consequences. CONCLUSION: Drinking patterns have an independent impact on consequences over and above the relationship between volume and consequences.

Free-breathing 3D steady-state free precession coronary MR angiography with radial k-space sampling: comparison with cartesian k-space sampling and cartesian gradient-echo coronary MR angiography--pilot study.

The authors compared radial steady-state free precession (SSFP) coronary magnetic resonance (MR) angiography, cartesian k-space sampling SSFP coronary MR angiography, and gradient-echo coronary MR angiography in 16 healthy adults and four pilot study patients. Standard gradient-echo MR imaging with a T2 preparatory pulse and cartesian k-space sampling was the reference technique. Image quality was compared by using subjective motion artifact level and objective contrast-to-noise ratio and vessel sharpness. Radial SSFP, compared with cartesian SSFP and gradient-echo MR angiography, resulted in reduced motion artifacts and superior vessel sharpness. Cartesian SSFP resulted in increased motion artifacts (P <.05). Contrast-to-noise ratio with radial SSFP was lower than that with cartesian SSFP and similar to that with the reference technique. Radial SSFP coronary MR angiography appears preferable because of improved definition of vessel borders.

Approximation and support theorem for a wave equation in two space dimensions

We prove a characterization of the support of the law of the solution for a stochastic wave equation with two-dimensional space variable, driven by a noise white in time and correlated in space. The result is a consequence of an approximation theorem, in the convergence of probability, for equations obtained by smoothing the random noise. For some particular classes of coefficients, approximation in the Lp-norm for p¿1 is also proved.

Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography-negative chemical ionization-mass spectrometry.

Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. A gas chromatography-mass spectrometry (GC-MS)-negative chemical ionization method is presented which allows measuring very low levels of midazolam (MID), 1-OH midazolam (1OHMID) and 4-OH midazolam (4OHMID), in plasma, after derivatization with the reagent N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide. The standard curves were linear over a working range of 20 pg/ml to 5 ng/ml for the three compounds, with the mean coefficients of correlation of the calibration curves (n = 6) being 0.999 for MID and 1OHMID, and 1.0 for 4OHMID. The mean recoveries measured at 100 pg/ml, 500 pg/ml, and 2 ng/ml, ranged from 76 to 87% for MID, from 76 to 99% for 1OHMID, from 68 to 84% for 4OHMID, and from 82 to 109% for N-ethyloxazepam (internal standard). Intra- (n = 7) and inter-day (n = 8) coefficients of variation determined at three concentrations ranged from 1 to 8% for MID, from 2 to 13% for 1OHMID and from 1 to 14% for 4OHMID. The percent theoretical concentrations (accuracy) were within +/-8% for MID and 1OHMID, within +/-9% for 4OHMID at 500 pg/ml and 2 ng/ml, and within +/-28% for 4OHMID at 100 pg/ml. The limits of quantitation were found to be 10 pg/ml for the three compounds. This method can be used for phenotyping cytochrome P4503A in humans following the administration of a very low oral dose of midazolam (75 microg), without central nervous system side-effects.