Microscopic measurement of the linear compressibilities of two-dimensional fatty acid mesophases

The linear compressibility of two-dimensional fatty acid mesophases has determined by grazing incidence x-ray diffraction. Surface pressure vs molecular area isotherms were reconstructed from these measurements, and the linear compressibility (relative distortion along a given direction for isotropic applied stress) was determined both in the sample plane and in a plane normal to the aliphatic chain director (transverse plane). The linear compressibilities range over two orders of magnitude from 0.1 to 10 m/N and are distributed depending on their magnitude in 4 different sets which we are able to associate with different molecular mechanisms. The largest compressibilities (10m/N) are observed in the tilted phases. They are apparently independent of the chain length and could be related to the reorganization of the headgroup hydrogen-bounded network, whose role should be revalued. Intermediate compressibilities are observed in phases with quasi long-range order (directions normal to the molecular tilt in L_2 or L_2' phases, S phase), and could be related to the ordering of these phases. The lowest compressibilities are observed in the solid untilted CS phase and for 1 direction of the S and L_2'' phases. They are similar to the compressibility of crystalline polymers and correspond to the interactions between methyl groups in the crystal. Finally, negative compressibilities are observed in the transverse plane for L_2' and L_2'' phases and can be traced to subtle reorganizations upon untilting.Comment: 24 pages, 17 figure

Influence of control selection in genome-wide association studies: the example of diabetes in the Framingham Heart Study

Epidemiologic study designs represent a major challenge for genome-wide association studies. Most such studies to date have selected controls from the pool of participants without the disease of interest at the end of the study time. These choices can lead to biased estimates of exposure effects. Using data from the Framingham Heart Study (Genetic Analysis Workshop 16 Problem 2), we evaluate the impact on genetic association estimates for designs with control selection based on status at the end of a study (case exclusion (CE) sampling) to control selection based on incidence density (ID) sampling, when controls are selected from the pool of participants who are disease-free at the time a case is diagnosed. Cases are defined as those diagnosed with type 2 diabetes (T2D). We estimated odds ratios for 18 previously confirmed T2D variants using 189 cases selected by ID sampling and using 231 cases selected by CE sampling. We found none of these single-nucleotide polymorphisms to be significantly associated with T2D using either design. Because these empirical analyses were based on a small number of cases and on single-nucleotide polymorphisms with likely small effect sizes, we supplemented this work with simulated data sets of 500 cases from each strategies across a variety of allele frequencies and effect sizes. In our simulated datasets, we show ID sampling to be less biased than CE, although CE shows apparent increased power due to the upward bias of point estimates. We conclude that ID sampling is an appropriate option for genome-wide association studies

Quantifying spin Hall angles from spin pumping: Experiments and Theory

Spin Hall effects intermix spin and charge currents even in nonmagnetic materials and, therefore, ultimately may allow the use of spin transport without the need for ferromagnets. We show how spin Hall effects can be quantified by integrating permalloy/normal metal (N) bilayers into a coplanar waveguide. A dc spin current in N can be generated by spin pumping in a controllable way by ferromagnetic resonance. The transverse dc voltage detected along the permalloy/N has contributions from both the anisotropic magnetoresistance (AMR) and the spin Hall effect, which can be distinguished by their symmetries. We developed a theory that accounts for both. In this way, we determine the spin Hall angle quantitatively for Pt, Au and Mo. This approach can readily be adapted to any conducting material with even very small spin Hall angles.Comment: 4 pages, 4 figure

Efficacy of cyclosporin A in psoriasis: a summary of the United States’ experience

Since its discovery in 1972, cyclosporin A (CyA) has been widely used in the experimental treatment of multiple inflammatory diseases considered to be of immune-mediated aetiology. In dermatology, oral CyA is most effective in the treatment of psoriasis and has been used successfully for plaque-type, pustular and erythrodermic forms of the disease. While dosages ranging from 1 to 14 mg/kg/day have been used, a starting dose of 4 mg/kg/day gives a rapid response with few side-effects. Nephrotoxicity remains the greatest concern in long-term use of the drug. Although intralesional CyA has proven effective in psoriasis, topical preparations have not. It is hoped that future research will provide effective topical formulations of CyA which are efficacious without the risks inherent in systemic administration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72330/1/j.1365-2133.1990.tb02878.x.pd

Precision of readout at the hunchback gene: analyzing short transcription time traces in living fly embryos

The simultaneous expression of the hunchback gene in the numerous nuclei of the developing fly embryo gives us a unique opportunity to study how transcription is regulated in living organisms. A recently developed MS2-MCP technique for imaging nascent messenger RNA in living Drosophila embryos allows us to quantify the dynamics of the developmental transcription process. The initial measurement of the morphogens by the hunchback promoter takes place during very short cell cycles, not only giving each nucleus little time for a precise readout, but also resulting in short time traces of transcription. Additionally, the relationship between the measured signal and the promoter state depends on the molecular design of the reporting probe. We develop an analysis approach based on tailor made autocorrelation functions that overcomes the short trace problems and quantifies the dynamics of transcription initiation. Based on live imaging data, we identify signatures of bursty transcription initiation from the hunchback promoter. We show that the precision of the expression of the hunchback gene to measure its position along the anterior-posterior axis is low both at the boundary and in the anterior even at cycle 13, suggesting additional post-transcriptional averaging mechanisms to provide the precision observed in fixed embryos

Effects of agonists of peroxisome proliferator-activated receptor γ on proteoglycan degradation and matrix metalloproteinase production in rat cartilage in vitro

AbstractObjective To examine the effects of agonists of peroxisome proliferator-activated receptor (PPAR) γ on proteoglycan degradation induced by interleukin (IL)-1β or tumor necrosis factor (TNF)α in cartilage in vitro.Design Proteoglycan degradation was measured as release of radioactivity from rat cartilage explants previously labeled with 35SO2−4. Western blots were used to examine tissue levels of aggrecan neoepitopes NITEGE and VDIPEN, generated by aggrecanases and matrix metalloproteinases (MMP), respectively. Production of MMP-2, -3 and -9 by cultured rat chondrocytes was measured by zymography and by fluorimetric assay.Results IL-1β-induced proteoglycan degradation was likely due to aggrecanase, since it was associated with a strong increase of NITEGE signal. MMP-dependent VDIPEN signal increased only after further incubation with pro-MMP activator APMA. PPAR agonists 15d-PGJ2 and GI262570 (10μM) inhibited IL-1β- and TNFα-induced proteoglycan degradation measured both before and after addition of APMA. The agonists also inhibited cytokine-induced MMP production by isolated chondrocytes.Conclusion This study shows that PPARγ agonists inhibit cytokine-induced proteoglycan degradation mediated by both aggrecanase and MMP. This effect is associated with inhibition of production of MMP-3 and -9. These results support the interest for PPARγ agonists as candidate inhibitors of pathological cartilage degradation. Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved