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New technologies generate risks, for the evaluation of which various mechanisms have been developed; the most frequent of these mechanisms consists of advice from committees of experts to the bodies whose role is to decide whether a new technology should be implemented or not. Such committees try to measure the magnitude of the threats that accompany the introduction of a new technology in order that the policy-makers may take their decisions in the light of the reports of the experts. The legitimacy of such reports is not only found in the technical capacity of its authors, but also in the impartiality of their recommendations. On numerous occasions, nevertheless, the effective presence of this evaluation finds itself today under suspicion. There are various methods that can be employed to try to resolve this problem. Firstly by reinforcing the mechanisms on which the technocratic evaluation of the risk are based; for example, through transparency in the selection of the experts. Secondly, by means of the incorporation of democratic mechanisms in the scientific-technological policy. The exposure of the internal conditions to the dynamics of the technological change that make possible the institutionalised involvement of society in the control of risk, as well as of the mechanisms to realise it are the principal subjects of this work.
Dual- or multi-target ligands have gained increased attention in the past years due to several advantages, including more simple pharmacokinetic and phamarcodynamic properties compared to a combined application of several drugs. Furthermore multi-target ligands often possess improved efficacy. We present a new approach for the discovery of dual-target ligands using aligned pharmacophore models combined with a shape-based scoring. Starting with two sets of known active compounds for each target, a number of different pharmacophore models is generated and subjected to pairwise graph-based alignment using the Kabsch-Algorithm. Since a compound may be able to bind to different targets in different conformations, the algorithm aligns pairs of pharmacophore models sharing the same features which are not necessarily at the exactly same spatial distance. Using the aligned models, a pharmacophore search on a multi-conformation-database is performed to find compounds matching both models. The potentially “dual” ligands are scored by a shape-based comparison with the known active molecules using ShaEP.
Using this approach, we performed a prospective fragment-based virtual screening for dual 5-LO/sEH inhibitors. Both enzymes play an important role in the arachidonic acid cascade and are involved in inflammatory processes, pain, cardiovascular diseases and allergic reactions. Beside several new selective inhibitors we were able to find a compound inhibiting both enzymes in low micromolar concentrations. The results indicate that the idea of aligned pharmacophore models can be successfully employed for the discovery of dual-target ligands.
Vor Kurzem hat das koreanische Höchstgericht den lebensverkürzenden Behandlungsabbruch durch die Entnahme des Beatmungsgeräts als zulässig befunden. Dafür sollen zwei Voraussetzungen erfüllt sein; 1) der Eintritt des irreversiblen Todesprozesses, 2) der ernstliche mutmaßliche Wille des Patienten. Dabei sind auch die folgenden abweichenden Meinungen vertreten. Sie gehen davon aus, dass im betreffenden Fall der nahe Todesvorgang noch nicht eingetreten ist. Darüber hinaus darf die Selbstbestimmung des Patienten nur in der negativen Weise vollzogen und keinesfalls in positiver Weise, denn dies würde den Selbstmord bedeuten. Außerdem ist der mutmaßliche Wille der Patientin von ihrem hypothetischen zu unterscheiden. Allerdings könnte der Behandlungsabbruch unabhängig vom Willen des Patienten ohne Rekurs auf die Selbstbestimmung des Patienten genehmigt werden, wenn auf die immanenten Schranken des ärztlichen Auftrags abgestellt werden. In der Sterbehilfe steht die Unverfügbarkeit des Lebens im Gegensatz zu der Selbstbestimmung des Patienten. Dabei zeigt sich aber, dass der Schutz des Lebens angesichts der Tötung im Krieg oder in der Notwehrlage nur ein relativer ist. Genauso lässt sich das Recht des Patienten nicht als das auf das eigene Leben, sondern lediglich als das auf den natürlichen Tod verstehen. Im vorliegenden Fall kommt es in rechtlicher Hinsicht auf sog. Passive Sterbehilfe an. Wenn hier der in Kürze bevorstehende Todeseintritt und die mutmaßliche Einwilligung der Patienten nicht abzulehnen ist, soll der Behandlungsabbruch rechtfertigt werden. Allerdings darf der einseitige Behandlungsabbruch nicht bewilligt werden und zwar vor allem deshalb, weil das Selbstbestimmungsrecht des Patienten vernachlässigt werden kann.
Diffusion of e-learning as an innovation and economic aspects of e-learning support structures
(2012)
Meanwhile, many universities and educational institutions have implemented an e-learning center or some similar, often smaller institutional units in order to support the usage of new media in teaching and learning processes [1]. This paper addresses questions around the installation of such e-learning support structures at different levels of an institution and also looks at the diffusion of e-learning as an innovation in educational institutions.
In this paper I demonstrate the utility of a Values in Design (VID) perspective for the assessment, the design and development of e-democracy tools. In the first part, I give some background information on Values in Design and Value-Sensitive Design and their relevance in the context of e-democracy. In part 2, I analyze three different e-democracy tools from a VID-perspective. The paper ends with some conclusions concerning the merits of VID for e-democracy as well as some considerations concerning the dual tasks of philosophers in assessing and promoting value-sensitive technology design.
E-democracy as the frame of networked public discourse : information, consensus and complexity
(2012)
The quest for democracy and the political reflection about its future are to be understood nowadays in the horizon of the networked information revolution. Hence, it seems difficult to speak of democracy without speaking of e-democracy, the key issue of which is the re-configuration of models of information production and concentration of attention, which are to be investigated both from a political and an epistemological standpoint. In this perspective, our paper aims at analyzing the multi-agent dimension of networked public discourse, by envisaging two competing models of structuring this discourse (those of dialogue and of claim) and by suggesting to endorse the epistemic idea of complementarity as a guidance principle for elaborating a form of partnership between traditional and electronic media.
Einleitung: Lokoregionäre Rezidivtumore der Kopf-Hals-Region können häufig nicht mehr kurativ operativ oder radiotherapeutisch behandelt werden, so dass neue Therapiekonzepte erforderlich sind. Es konnte gezeigt werden, dass statische Magnetfelder (SMF) Tumorwachstum und -angiogenese signifikant beeinflussen und zu einem intratumoralen Ödem führen. Das Ziel der vorliegenden Studie war die Evaluation des Effektes von SMF auf die Permeabilität von Tumorblutgefäßen und die therapeutische Nutzbarkeit in Kombination mit einer konventionellen Chemotherapie.
Methoden: Zellen eines syngenen amelanotischen Melanoms wurden in transparente Rückenhautkammern bei Goldhamstern implantiert. Unter SMF-Exposition von 587 mT wurde fluoreszenzmikroskopisch die Extravasation von rhodaminmarkiertem Albumin zur Errechnung der Gefäßpermeabilität gemessen und intratumorale Leukozyten-Endothelzell-Interaktionen quantifiziert. Für die anschließende Therapiestudie wurden die antitumoralen Effekte einer Kombinationstherapie von Paclitaxel und SMF-Exposition verglichen mit drei Kontrollgruppen (Glucose, Paclitaxel allein, SMF allein; je n=6).
Ergebnisse: SMF führen zu einer signifikanten Erhöhung der Tumorblutgefäßpermeabilität bei unveränderten Leukozyten-Endothelzell-Interaktionen. Die Kombinationstherapie von SMF und Paclitaxel ist – bezogen auf Tumorwachstum und Angiogenese – Monotherapien überlegen.
Schlussfolgerung: Eine SMF-induzierte Steigerung der Gefäßpermeabilität kann die Blut-Tumor-Schranke beeinflussen und somit die Effektivität einer Chemotherapie mit kleinmolekularen Substanzen wie Paclitaxel deutlich steigern. Bei Verwendung von Kopfspulen erscheint eine derartige adjuvante Kombinationstherapie für lokoregionäre Karzinomrezidive der Kopf-Hals-Region besonders geeignet.
The aim of this contribution is to introduce and outline a third theory of rights. Concentrating on claim-rights, it proposes to approach this aim via the concept of a directed duty. This approach is justified by the widely shared presupposition that an entity has a right if and only if a duty is owed to this entity. Unlike some prominent other proposals, this contribution does not contrast directed duties with undirected ones. It contrasts two ways a duty can be related to an entity. On the one hand, a duty can be owed to an entity. In this case it is directed to this entity. On the other hand, a duty can concern an entity. There is no reason to presuppose that they exclude each other, on the contrary. Theories of rights have to reconstruct the difference between these two ways a duty can be related to an entity. After having introduced the starting point for a theory of rights in that way, the two classic theories of rights will be rejected, the will theory and the interest theory. The main focus lies on the shortcomings of the different versions of the interest theory. This criticism helps to formulate the conditions a convincing theory of rights has to meet. In the last part, the status theory of rights will be outlined.
The diagram-based method to prove correctness of program transformations consists of computing
complete set of (forking and commuting) diagrams, acting on sequences of standard reductions
and program transformations. In many cases, the only missing step for proving correctness of a
program transformation is to show the termination of the rearrangement of the sequences. Therefore
we encode complete sets of diagrams as term rewriting systems and use an automated tool
to show termination, which provides a further step in the automation of the inductive step in
correctness proofs.
Dworkin`s political theory is characterized by the interpretative integrity of morality, law, and politics, the so-called “hedgehog’s approach”. The interpretative integrity approach functions on multiple levels. Firstly, philosophical foundations of his theory of justice are linked to his conception of just liberal society and state. Secondly, from the perspective of political morality, interpretative concepts of law and morality are internally connected, in addition to interpretative concepts of equality, liberty, and democracy. Thirdly, from the perspective of philosophical foundations, individual ethics, personal morality and political morality are mutually connected. The aforementioned ethical and moral foundations are also related – in a wider sense of philosophical foundations - with his gnoseological conception regarding value concepts in law, politics and morality, and with his episthemological conception regarding an objective truth in the field of values, in a sense that the value concepts are interpretative and can be objectively true when articulated in accordance with methodological rules and standards of a »reflexive equilibrium« and an interpretative integrity, and in accordance with the so-called internal scepticism in the context of value pluralism.
The term “ethics” in a “narrower” sense refers to individual ethics, the study of how to live well, while the “ethics” in a “broader” sense refers to personal morality, the study of how we must treat other people. The term “morality” however, is used primarily to denote a political morality, the issue of how a sovereign power should treat its citizens.
Philosophical foundations of Dworkin`s political theory of justice, his conception of two cardinal values of humanity, his concievement of individual ethics, personal morality and political morality will be in the focus of consideration.