A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion

Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.     

Armenian cochineal (Porphyrophora hamelii) and purpurin‐rich madder in ancient polychromy

Samples removed from funeral figurines, dated the third to the second century BC (Hellenistic period) and found in Macedonia, Greece, are investigated using high‐performance liquid chromatography. Two results are reported that provide new insights into ancient polychromy. Firstly, high‐performance liquid chromatography results, in combination with historical information, indicate that insect species of cochineal, most probably Porphyrophora hamelii Brandt, was used in Hellenistic objects. Secondly, madder detected in the archaeological samples contains high amounts of purpurin (alizarin is either not detected or detected in trace). This relative composition, which is recorded using the hydrochloric acid method for dyestuff extraction, is consistent with that prepared from wild madder (Rubia peregrina L.), which is a common plant in the Mediterranean region.     

Fatigue crack growth simulation in adhesively bonded composite joints

A numerical model has been developed for simulating fatigue crack growth (debonding) in adhesively bonded composite joints subjected to mode‐I, mode‐II, and mixed‐mode I + II loading conditions. The model employs a cohesive zone model described by a modified bilinear traction‐separation law. Fatigue damage in the composite adherends is not considered in the model. To account for crack divergence and reduce sensitivity of numerical results on mesh density, a crack front detection algorithm based on the effective element's length was employed. The model is implemented as a user‐defined subroutine (UMAT) in the commercial FE code LS‐DYNA. The model's input parameters, in the form of a modified Paris law, and the validation data were obtained from experimental tests conducted by the authors. It was found that the model is able to successfully simulate crack growth in the regime of the experimental data.     

A novel MINLP-based representation of the original complex model for predicting gasoline emissions

The Environmental Protection Agency (EPA) introduced Reformulated Gasoline (RFG) requirements as a measure to reduce emissions from gasoline-powered vehicles in certain geographic areas. As part of this effort, the EPA developed empirical models for predicting emissions as a function of gasoline properties and established statutory baseline emissions from a representative set of gasolines. All reformulated gasoline requires certification via this model, known as the Complex Model, and all refiners and importers calculate emissions performance reductions from the statutory baseline gasoline. The current representation of the Complex Model is extremely difficult to implement within refinery operations models or to use in combination with models for designer gasoline. RFG and boutique fuels are key driving forces in the North American refining industry.The RFG models introduce increasingly complex constraints with the major limitation that they are implicitly defined through a series of complicated disjunctions assembled by the EPA in the form of spreadsheets. This implicit and cumbersome representation of the emissions predictive models renders rigorous optimization and sensitivity analysis very difficult to address directly. In this paper, we discuss how the federal government requirements for reformulated gasoline can be restated as a set of mixed-integer nonlinear programming (MINLP) constraints with the aid of disjunctive programming techniques. We illustrate the use of this model with two simple example fuel blending problems.     

GLU♮ embedded in C++: a marriage between multidimensional and object‐oriented programming

The embedding of a small but expressive language of multidimensional functional programming in a well known and widely used language of object‐oriented programming leads to the combination of two radically different programming models. In this paper, we formally define the syntax and semantics of GLU^?, which can be thought of as the multidimensional core of Lucid and GLU, and we describe its implementation as a language embedded in C++. With the aid of a few examples, we argue that the marriage of the two programming models is not only compatible and natural, but also that it produces a new and interesting hybrid language. Copyright © 2004 John Wiley & Sons, Ltd.     

Non-functional variants of yeast mitochondrial ATP synthase subunit 8 that assemble into the complex

Myocardial and pulmonary beta-adrenoceptors can be imaged with 2-(S)-(-)-(9H-carbazol-4-yl-oxy)-3-[1-(fluoromethyl)ethyl]amino-2- propanol (S-1'-[18F]fluorocarazolol, I). Quantification of unmodified fluorocarazolol in plasma is necessary for analysis of PET images in terms of receptor densities. We have determined I and its radioactive metabolites in rat, sheep and human plasma, using (1) solid-phase extraction (C18) followed by reversed-phase HPLC and (2) direct injection of untreated plasma samples on an internal-surface reversed-phase (ISRP) column. The two methods were in good agreement. Unmodified I decreased from over 99% initially to less than 5%, 5-10% and 20% at 60 min post-injection in rats, sheep and human volunteers, respectively. Protein binding in sheep and human plasma was determined by ultrafiltration. The fraction of total plasma radioactivity bound to protein and the fraction representing unmodified radioligand were linearly correlated, suggesting that fluorocarazolol was more than 70% protein-bound, whereas its metabolites showed negligible protein binding. Direct injection of plasma on an ISRP column seems a convenient method for quantification of lipophilic radioligands such as fluorocarazolol.     

The TSIMMIS Approach to Mediation: Data Models and Languages

TSIMMIS—The Stanford-IBM Manager of Multiple InformationSources—is a system for integrating information. It offers a datamodel and a common query language that are designed to support thecombining of information from many different sources. It also offerstools for generating automatically the components that are needed tobuild systems for integrating information. In this paper we shalldiscuss the principal architectural features and their rationale.