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.     

A Systematic Review and Meta-Analysis of Pharmacogenetic Studies in Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is an important global public health problem due to its high prevalence and morbidity. Although the treatment of nephrology patients has changed considerably, ineffectiveness and side effects of medications represent a major issue. In an effort to elucidate the contribution of genetic variants located in several genes in the response to treatment of patients with CKD, we performed a systematic review and meta-analysis of all available pharmacogenetics studies. The association between genotype distribution and response to medication was examined using the dominant, recessive, and additive inheritance models. Subgroup analysis based on ethnicity was also performed. In total, 29 studies were included in the meta-analysis, which examined the association of 11 genes (16 polymorphisms) with the response to treatment regarding CKD. Among the 29 studies, 18 studies included patients with renal transplantation, 8 involved patients with nephrotic syndrome, and 3 studies included patients with lupus nephritis. The present meta-analysis provides strong evidence for the contribution of variants harbored in the ABCB1, IL-10, ITPA, MIF, and TNF genes that creates some genetic predisposition that reduces effectiveness or is associated with adverse events of medications used in CKD.     

An EWMA signed ranks control chart with reliable run length performances

During the design phase of a control chart, the determination of its exact run length properties plays a vital role for its optimal operation. Markov chain or integral equation methods have been extensively applied in the design phase of conventional control charts. However, for distribution-free schemes, due to the discrete nature of the statistics being used (such as the sign or the Wilcoxon signed rank statistics, for instance), it is impossible to accurately compute their run length properties. In this work, a modified distribution-free phase II exponentially weighted moving average (EWMA)-type chart based on the Wilcoxon signed rank statistic is considered and its exact run length properties are discussed. A continuous transformation of the Wilcoxon signed rank statistic, combined with the classical Markov chain method, is used for the determination of the average run length in the in- and out-of control cases. Moreover, its exact performance is derived without any knowledge of the distribution of sample observations. Finally, an illustrative example is provided showing the practical implementation of our proposed chart.     

The potential of WHR/batch and cullet preheating for energy efficiency in the EU ETS glass industry and the related energy incentives

The European Emissions Trading Scheme (EU ETS) covers approximately 45% of European greenhouse gases (GHGs), 11,000 stationary installations as well as aircraft operators. The EU ETS particularly affects the energy-intensive industries while it imposes a significant risk of “carbon leakage,” i.e., the risk of EU industry departing to countries with weaker restraints on GHG emissions. The EU glass industry, being capital intensive and also requiring long investment cycles, is the world’s largest glass producer with a market share close to one third of global production. Therefore, it is of significant importance to view the position of the EU ETS glass industry in terms of energy conservation possibilities. The present paper utilizes a vertical approach to provide information on both ETS market evolution and specific technical information to support technological innovation to the glass industry. EU ETS glass industry is analyzed regarding the balance between allocated European Union emission allowances (EUAs), verified CO₂ emissions, and potential shortfall in allowances so as to determine the situation of glass industries and the extent of urge for energy-saving activities towards the strengthening of their position within the requirements of the EU ETS phase III. The replication potential of waste heat recovery (WHR) through batch preheating is specifically addressed since it is considered a promising technology according to the latest Best Available Techniques (BAT) reference document for the glass industry under Directive IED 2010/75/EU. A case study for a container glass furnace based on simulation results is presented investigating the impact of different operating and design configurations on specific energy consumption and CO₂ emissions.     

Graphite Oxide and Aromatic Amines: Size Matters

Experimental and theoretical studies are performed in order to illuminate, for first time, the intercalation mechanism of polycyclic aromatic molecules into graphite oxide. Two representative molecules of this family, aniline and naphthalene amine are investigated. After intercalation, aniline molecules prefer to covalently connect to the graphene oxide matrix via chemical grafting, while napthalene amine molecules bind with the graphene oxide surface through π–π interactions. The presence of intercalated aromatic molecules between the graphene oxide layers is demonstrated by X‐ray diffraction, while the type of interaction between graphene oxide and polycyclic organic molecules is elucidated by X‐ray photoelectron spectroscopy. Combined quantum mechanical and molecular mechanical calculations describe the intercalation mechanism and the aniline grafting, rationalizing the experimental data. The present work opens new perspectives for the interaction of various aromatic molecules with graphite oxide and the so‐called “intercalation chemistry”.     

Cyclooxygenase Inhibition Alters Proliferative,Migratory, and Invasive Properties of Human Glioblastoma Cells In Vitro

Prostaglandin E₂ (PGE₂) is known to increase glioblastoma (GBM) cell proliferation and migration while cyclooxygenase (COX) inhibition decreases proliferation and migration. The present study investigated the effects of COX inhibitors and PGE₂ receptor antagonists on GBM cell biology. Cells were grown with inhibitors and dose response, viable cell counting, flow cytometry, cell migration, gene expression, Western blotting, and gelatin zymography studies were performed. The stimulatory effects of PGE₂ and the inhibitory effects of ibuprofen (IBP) were confirmed in GBM cells. The EP2 and EP4 receptors were identified as important mediators of the actions of PGE₂ in GBM cells. The concomitant inhibition of EP2 and EP4 caused a significant decrease in cell migration which was not reverted by exogenous PGE₂. In T98G cells exogenous PGE₂ increased latent MMP2 gelatinolytic activity. The inhibition of COX1 or COX2 caused significant alterations in MMP2 expression and gelatinolytic activity in GBM cells. These findings provide further evidence for the importance of PGE₂ signalling through the EP2 and the EP4 receptor in the control of GBM cell biology. They also support the hypothesis that a relationship exists between COX1 and MMP2 in GBM cells which merits further investigation as a novel therapeutic target for drug development.     

Impact of Functionalized Polystyrenes as the Electron Injection Layer on Gold and Aluminum Surfaces: A Combined Theoretical and Experimental Study

At metal/organic interfaces, the insertion of an organic monolayer can significantly modify the surface properties of the substrate, especially in terms of charge injection across the interface. Herein, we study the formation of an insulating monolayer of morpholine or amine-functionalized polystyrene on Al(111) and Au(111) surfaces and its impact on surface work-function and charge injection. First-principles calculations based on Density Functional Theory have been carried out and point to a significant decrease in the work-function of modified metal surfaces; this is in very good agreement with ultraviolet photoemission spectroscopy measurements performed on the Au(111) surface. In addition, a bilayer cathode, consisting of a thin film of high-work-function metal, such as Al and Au, and a layer of amine-functionalized polystyrene, was also fabricated and tested in organic light-emitting diodes. Such bilayer structures exhibit substantially enhanced efficiency when compared with controls without the functionalized polymers. Our combined theoretical and experimental investigation gives insight into how a thin layer of a commodity polymer can be used to transform rather high-work-function metals into high-performance cathodes to provide efficient electron injection.     

Quantifying the water–energy nexus in Greece

In this paper we provide an assessment of the water–energy nexus for Greece. More specifically, the amount of freshwater consumed per unit of energy produced is determined: for both conventional (lignite, diesel and fuel oil-fired) and advanced (combined operation of gas turbine) thermal power plants in the electricity generation sector; for extraction and refining activities in the primary energy production sector; and for the production of biodiesel that is used as a blend in the ultimately delivered automotive diesel fuel. In addition, the amount of electricity consumed for the purposes of water supply and sewerage is presented. In view of the expected effects of climate change in the Mediterranean region, the results of this study highlight the need for authorities to prepare a national strategy that will ensure climate resilience in both energy and water sectors of the country.