Dialysis,cardiovascular disease,and the future

Atherosclerosis, particularly coronary atherosclerosis, is accelerated in renal failure, as originally postulated by Belding Scribner. But in contrast to previous opinion, myocardial infarction from coronary heart disease is not the single major cause of cardiac death in dialyzed patients, the most common causes being sudden death and cardiac failure. Apart from coronary heart disease, the following cardiomyopathic features are prevalent and explain a large part of the excess cardiac risk: cardiomyocyte dropout, left ventricular hypertrophy, cardiac interstitial fibrosis, microangiopathy with arteriolar thickening, and capillary deficit as well as reduced ischemia tolerance. Recently, cardiovascular risk factors related to abnormal mineral metabolism, particularly phosphate and vitamin D, have gained unanticipated importance. Controlled evidence has become available concerning intervention with ACE inhibitors, angiotensin receptor blockers, β‐blockers, and statins in dialyzed patients. It is imperative that apart from the “classical” cardiovascular risk factors that do not exhaustively explain the excessive cardiovascular risk in dialyzed patients, novel pathomechanisms are considered and investigated; potential examples include depression, sleep abnormalities, etc. The above arguments do not negate the fact that today's modalities of renal replacement therapy are poor substitutes for the normal kidney's function so that as a result alternative strategies, e.g., daily dialysis, may also dramatically improve cardiovascular risk.     

Integrated satellite-HAP systems

Thus far, high-altitude platform (HAP)-based systems have been mainly conceived as an alternative to satellites for complementing the terrestrial network. This article aims to show that HAP should no longer be seen as a competitor technology by investors of satellites, but as a key element for an efficient hybrid terrestrial-satellite communication system. Two integrated HAP-satellite scenarios are presented, in which the HAP is used to overcome some of the shortcomings of satellite-based communications. Moreover, it is shown that the integration of HAPs with satellite systems can be used to provide more efficient fleet-management and traffic-control services and more powerful data-relay systems.     

EPC 2000 – State of play nearly two years on

The European Patent Convention as revised in 2000 (EPC 2000) [1] entered into force on 13 December 2007. While the revision changed rather little in terms of substantive patent law, it did change procedural practice compared to the EPC in force before, drafted in 1973. This article looks at some key features of the European patent grant and post-grant procedures that either have changed fundamentally or have been newly introduced, and their effect on patent document collections.     

Role of VEGF-A and Its Receptors in Sporadic and MEN2-Associated Pheochromocytoma

Pheochromocytoma (PHEO), a rare catecholamine producing tumor arising from the chromaffin cells, may occurs sporadically (76%–80%) or as part of inherited syndromes (20%–24%). Angiogenesis is a fundamental step in tumor proliferation and vascular endothelial growth factor (VEGF-A) is the most well-characterized angiogenic factor. The role of angiogenic markers in PHEO is not fully understood; investigations were therefore made to evaluate the expression of VEGF-A and its receptors in PHEO and correlate to clinical parameters. Twenty-nine samples of PHEO were evaluated for VEGF-A, VEGF receptor-1 (VEGFR-1) VEGFR-2 expression and microvessel density (MVD) by immunohistochemistry. Clinical data were reviewed in medical records. The mean age of patients was 38 ± 14 years, and 69% were woman. VEGF-A, VEGFR-1 and VEGFR-2 staining were detected in nearly all PHEO samples. No significant correlation was observed between VEGF-A, VEGFR-1, VEGFR-2 expression or MVD and age at diagnosis, tumor size or sporadic and hereditary PHEO. However, the levels of expression of these molecules were significantly higher in malignant PHEO samples (p = 0.027, p = 0.003 and p = 0.026, respectively).VEGF-A and its receptors were shown to be up-regulated in malignant PHEO, suggesting that these molecules might be considered as therapeutic targets for unresectable or metastatic tumors.     

Binding to Large Enzyme Pockets: Small‐Molecule Inhibitors of Trypanothione Reductase

The causative agents of the parasitic disease human African trypanosomiasis belong to the family of trypanosomatids. These parasitic protozoa exhibit a unique thiol redox metabolism that is based on the flavoenzyme trypanothione reductase (TR). TR was identified as a potential drug target and features a large active site that allows a multitude of possible ligand orientations, which renders rational structure‐based inhibitor design highly challenging. Herein we describe the synthesis, binding properties, and kinetic analysis of a new series of small‐molecule inhibitors of TR. The conjunction of biological activities, mutation studies, and virtual ligand docking simulations led to the prediction of a binding mode that was confirmed by crystal structure analysis. The crystal structures revealed that the ligands bind to the hydrophobic wall of the so‐called “mepacrine binding site”. The binding conformation and potency of the inhibitors varied for TR from Trypanosoma brucei and T. cruzi.     

Sources and transport of selected organic micropollutants in urban groundwater underlying the city of Halle (Saale), Germany

In this study, we used isotopic (delta18O, delta2H, delta34S-SO4) and chemical tracers (boron) to assess the sources and transport processes of the micropollutants carbamazepine, galaxolide, and bisphenol A in groundwater underlying the city of Halle (Saale), Germany. Their ubiquitous presence in urban groundwater results from a combination of local river water infiltration, sewer exfiltration, and urban stormwater recharge. Attenuation during transport with infiltrating river water increased from carbamazepine (0-60%) to galaxolide (60-80%) in accordance with their increasing sorption affinity and decreasing recalcitrance against biodegradation. Distinctly higher attenuation during transport was found for carbamazepine (85-100%) and galaxolide (95-100%) if micropollutants originated from sewer exfiltration. Most likely, this is related to higher contents of organic matter and higher transit times of the respective flow paths. Although attenuation undoubtedly also affects the transport of bisphenol A, quantification is limited due to additional contributions from the urban stormwater recharge. As a consequence, micropollutant loads in groundwater indicate that groundwater discharge may dominate the export of bisphenol A from urban areas.     

Melt Electrospinning Writing of Highly Ordered Large Volume Scaffold Architectures

The additive manufacturing of highly ordered, micrometer‐scale scaffolds is at the forefront of tissue engineering and regenerative medicine research. The fabrication of scaffolds for the regeneration of larger tissue volumes, in particular, remains a major challenge. A technology at the convergence of additive manufacturing and electrospinning–melt electrospinning writing (MEW)–is also limited in thickness/volume due to the accumulation of excess charge from the deposited material repelling and hence, distorting scaffold architectures. The underlying physical principles are studied that constrain MEW of thick, large volume scaffolds. Through computational modeling, numerical values variable working distances are established respectively, which maintain the electrostatic force at a constant level during the printing process. Based on the computational simulations, three voltage profiles are applied to determine the maximum height (exceeding 7 mm) of a highly ordered large volume scaffold. These thick MEW scaffolds have fully interconnected pores and allow cells to migrate and proliferate. To the best of the authors knowledge, this is the first study to report that z‐axis adjustment and increasing the voltage during the MEW process allows for the fabrication of high‐volume scaffolds with uniform morphologies and fiber diameters.     

Cycle slipping in serial receivers for offset binary modulations

A theoretical evaluation is presented of the mean time to first slip for some closed-loop synchronizer schemes to be used in a coherent serial receiver for offset binary modulations. Various modulation formats belonging to this class are considered, and the mean time to first slip is computed for each modulation type for different values of loop bandwidth and signal-to-noise ratio. Theoretical results are confirmed by extensive computer simulations