Das Problem der verantworteten Therapieentscheidung in der Neonatologie

Definition of the problem: Physicians and nurses who work in neonatology—as in intensive care at all—are often forced to decide whether to stop or to continue with the treatment of a severely ill patient. The literature provides several decision making instruments, which are meant to help and to rationalize such decisions. Method and conclusion: Two of these instruments (“Schema zur ethischen Urteilsbildung nach dem Muster der aristotelischen Ethik”, Honnefelder 1994; “Nimwegener Methode für ethische Fallbesprechung”, Gordijn 1998) were tested by retrospectively examining two cases of our NICU. Results of our study show that the use of a decision making instrument is basically helpful. But the above mentioned instruments showed also shortcomings when used in the framework of neonatology. Therefore we developed the “Kölner Arbeitsbogen zur ethischen Entscheidungsfindung in der Neonatologie”, which is adapted to the specific needs of neonatology.     

Towards Pseudonymous e-Commerce

The lack of privacy is one of the main reasons that limits trust in e-commerce. Current e-commerce practice enforces a customer to disclose her identity to the e-shop and the use of credit cards makes it straightforward for an e-shop to know the real identity of its customers. Although there are some payment systems based on untraceable tokens, they are not as widely used as credit cards. Furthermore, even without buying anything, a customer is already disclosing some information about who or where she may be by just connecting to the e-shop's web server and leaving behind an IP-address. In this paper, we present novel components that enable secure pseudonymous e-commerce. On the one hand, these components allow a customer to browse through an e-shop, select goods, and pay the goods with her credit card such that neither the e-shop operator nor the credit card issuer nor an eavesdropper is able to get any information about the customer's identity. On the other hand, it is guaranteed that none of the involved parties is able to act dishonestly during the credit card payment. Such a system could greatly enhance trust in e-commerce since it overcomes the customers' privacy concerns.     

Life Cycle of Smart Contracts in Blockchain Ecosystems

This paper discusses the life cycle of decentralized smart contracts, i.e. digital and executable representations of rights and obligations in a multi-party environment. The life cycle relies on blockchain technology, i.e. a distributed digital ledger, to ensure proper implementation and integrity of the smart contracts. The life cycle consists of four subsequent phases: Creation, freezing, execution, and finalization. For each phase actors and technological services are identified and explained in detail. With the life cycle at hand, risks and limitations of smart contracts and the underlying blockchain technology are briefly discussed.     

E as in Enigma: The Mysterious Role of the Voltage-Dependent Anion Channel Glutamate E73

The voltage-dependent anion channel (VDAC) is the main passageway for ions and metabolites over the outer mitochondrial membrane. It was associated with many physiological processes, including apoptosis and modulation of intracellular Ca²⁺ signaling. The protein is formed by a barrel of 19 beta-sheets with an N-terminal helix lining the inner pore. Despite its large diameter, the channel can change its selectivity for ions and metabolites based on its open state to regulate transport into and out of mitochondria. VDAC was shown to be regulated by a variety of cellular factors and molecular partners including proteins, lipids and ions. Although the physiological importance of many of these modulatory effects are well described, the binding sites for molecular partners are still largely unknown. The highly symmetrical and sleek structure of the channel makes predictions of functional moieties difficult. However, one residue repeatedly sticks out when reviewing VDAC literature. A glutamate at position 73 (E73) located on the outside of the channel facing the hydrophobic membrane environment was repeatedly proposed to be involved in channel regulation on multiple levels. Here, we review the distinct hypothesized roles of E73 and summarize the open questions around this mysterious residue.     

Synthesis and Anticancer Evaluation of New Indole-Based Tyrphostin Derivatives and Their (p-Cymene)dichloridoruthenium(II) Complexes

New N-alkylindole-substituted 2-(pyrid-3-yl)-acrylonitriles with putative kinase inhibitory activity and their (p-cymene)Ru(II) piano-stool complexes were prepared and tested for their antiproliferative efficacy in various cancer models. Some of the indole-based derivatives inhibited tumor cell proliferation at (sub-)micromolar concentrations with IC₅₀ values below those of the clinically relevant multikinase inhibitors gefitinib and sorafenib, which served as positive controls. A focus was set on the investigation of drug mechanisms in HCT-116 p53-knockout colon cancer cells in order to evaluate the dependence of the test compounds on p53. Colony formation assays as well as experiments with tumor spheroids confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic caspase-3/7 activity and ROS formation, as well as anti-angiogenic properties. Docking calculations with EGFR and VEGFR-2 identified the two 3-aryl-2-(pyrid-3-yl)acrylonitrile derivatives 2a and 2b as potential kinase inhibitors with a preferential activity against the VEGFR-2 tyrosine kinase. Forthcoming studies will further unveil the underlying mode of action of the promising new derivatives as well as their suitability as an urgently needed novel approach in cancer treatment.     

Zur Frage der Elastizität,der Beanspruchung und der Festigkeit warmbetriebener Rohrleitungen

Zusammenfassung Die Entwicklung der Dampfkraftanlagen zu immer h?heren Temperaturen, Drücken und Leistungen zwingt den Rohrleitungsbauer, sich noch eingehender als bisher mit den Fragen der Elastizit?t, der Beanspruchung und der Festigkeit der Rohrleitung zu besch?ftigen. Zu einigen der wesentlichen Fragen werden im folgenden rechnerische und experimentelle Beitr?ge mitgeteilt. VDI