Reduced CD40L expression on ex vivo activated CD4+T-lymphocytes from patients with excellent renal allograft function measured with a rapid whole blood flow cytometry procedure

Background: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+ CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction. Materials and Methods: Whole blood from recipients of renal allografts was stimulated with PMA and ion-omycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls. Results: The median percentage +/-SEM of CD4+/ CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation ( groups 2a and 3a) revealed a higher percentage of CD4+ CD40L+ cells than patients showing a gradual increase over time ( groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b. Conclusion: After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+ CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy. Copyright (C) 2004 S. Karger AG, Basel

Non-invasive monitoring of renal transplant recipients: Urinary excretion of soluble adhesion molecules and of the complement-split product C4d

Background: The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Methods: Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: group 1: acute steroid-sensitive rejection (ASSR, n=14), group 2: acute steroid-resistant rejection (ASRR, n=12), group 3: chronic allograft dysfunction (CAD, n=20) and group 4: stable graft function (SGF, n=29). Results: All patients with rejection episodes (groups 1-3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p<0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p<0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p<0.05). Conclusion: The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment. Copyright (C) 2003 S. Karger AG, Basel

A new and flexible method for constructing designs for computer experiments

We develop a new method for constructing "good" designs for computer experiments. The method derives its power from its basic structure that builds large designs using small designs. We specialize the method for the construction of orthogonal Latin hypercubes and obtain many results along the way. In terms of run sizes, the existence problem of orthogonal Latin hypercubes is completely solved. We also present an explicit result showing how large orthogonal Latin hypercubes can be constructed using small orthogonal Latin hypercubes. Another appealing feature of our method is that it can easily be adapted to construct other designs; we examine how to make use of the method to construct nearly orthogonal and cascading Latin hypercubes.Comment: Published in at http://dx.doi.org/10.1214/09-AOS757 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

A terrestrial search for dark contents of the vacuum, such as dark energy, using atom interferometry

We describe the theory and first experimental work on our concept for searching on earth for the presence of dark content of the vacuum (DCV) using atom interferometry. Specifically, we have in mind any DCV that has not yet been detected on a laboratory scale, but might manifest itself as dark energy on the cosmological scale. The experimental method uses two atom interferometers to cancel the effect of earth's gravity and diverse noise sources. It depends upon two assumptions: first, that the DCV possesses some space inhomogeneity in density, and second that it exerts a sufficiently strong non-gravitational force on matter. The motion of the apparatus through the DCV should then lead to an irregular variation in the detected matter-wave phase shift. We discuss the nature of this signal and note the problem of distinguishing it from instrumental noise. We also discuss the relation of our experiment to what might be learned by studying the noise in gravitational wave detectors such as LIGO.The paper concludes with a projection that a future search of this nature might be carried out using an atom interferometer in an orbiting satellite. The apparatus is now being constructed

The Gravitational Horizon for a Universe with Phantom Energy

The Universe has a gravitational horizon, coincident with the Hubble sphere, that plays an important role in how we interpret the cosmological data. Recently, however, its significance as a true horizon has been called into question, even for cosmologies with an equation-of-state w = p/rho > -1, where p and rho are the total pressure and energy density, respectively. The claim behind this argument is that its radius R_h does not constitute a limit to our observability when the Universe contains phantom energy, i.e., when w < -1, as if somehow that mitigates the relevance of R_h to the observations when w > -1. In this paper, we reaffirm the role of R_h as the limit to how far we can see sources in the cosmos, regardless of the Universe's equation of state, and point out that claims to the contrary are simply based on an improper interpretation of the null geodesics.Comment: 9 pages, 1 figure. Slight revisions in refereed version. Accepted for publication in JCAP. arXiv admin note: text overlap with arXiv:1112.477

Designing fractional factorial split-plot experiments with few whole-plot factors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73673/1/j.1467-9876.2003.05029.x.pd

Effect of high glucose concentration on the synthesis of monocyte chemoattractant protein-1 in human peritoneal mesothelial cells: Involvement of protein kinase C

Human peritoneal mesothelial cells (HMC) contribute to the activation and control of inflammatory processes in the peritoneum by their potential to produce various inflammatory mediators. The present study was designed to assess the effect of glucose, the osmotic active compound in most commercially available peritoneal dialysis fluids, on the synthesis of the C-C chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured HMC. The MCP-1 concentration in the cell supernatants was determined by enzyme-linked immunosorbent assay and the MCP-1 mRNA expression was examined using Northern blot analysis. Incubation of HMC with glucose (30-120 mM) resulted in a time- and concentration-dependent increase in MCP-1 protein secretion and mRNA expression. After 24 h the MCP-1 synthesis was increased from 2.8 +/- 0.46 to 4.2 +/- 0.32 ng/10(5) cells (n = 5, p 2001 S. Karger AG. Basel

Gibbons-Hawking Effect in the Sonic de Sitter Space-Time of an Expanding Bose-Einstein-Condensed Gas

We propose an experimental scheme to observe the Gibbons-Hawking effect in the acoustic analog of a 1+1-dimensional de Sitter universe, produced in an expanding, cigar-shaped Bose-Einstein condensate. It is shown that a two-level system created at the center of the trap, an atomic quantum dot interacting with phonons, observes a thermal Bose distribution at the de Sitter temperature.Comment: 4 pages, 2 figures, RevTex4; as publishe

Experimental Designs for Binary Data in Switching Measurements on Superconducting Josephson Junctions

We study the optimal design of switching measurements of small Josephson junction circuits which operate in the macroscopic quantum tunnelling regime. Starting from the D-optimality criterion we derive the optimal design for the estimation of the unknown parameters of the underlying Gumbel type distribution. As a practical method for the measurements, we propose a sequential design that combines heuristic search for initial estimates and maximum likelihood estimation. The presented design has immediate applications in the area of superconducting electronics implying faster data acquisition. The presented experimental results confirm the usefulness of the method. KEY WORDS: optimal design, D-optimality, logistic regression, complementary log-log link, quantum physics, escape measurement

The most storage economical Runge-Kutta methods for the solution of large systems of coupled first-order differential equations

AbstractIt is shown how the attainable minimum for the memory requirements of Runge-Kutta methods can be realised for methods of the third order. These economisable third order methods belong to a one parameter sub-family from which two particular members with low error bound are selected