Anmerkungen zum Entwurf der "Verwaltungsgrundsätze-Verfahren" vom 18. Oktober 2004

Nachdem der BFH durch seine Entscheidung vom 17. Oktober 20011 festgestellt hat, dass es über die allgemeinen Regelungen hinsichtlich der handels- und steuerrechtlichen Buchführungspflichten keine hinausgehenden besonderen Dokumentationspflichten für Verrechnungspreise gibt, hat der Gesetzgeber hierauf mit dem Steuervergünstigungsabbaugesetz reagiert und eine entsprechende Verpflichtung im § 90 Abs. 3 AO geschaffen. Die Umsetzung dieser Dokumentationspflichten erfolgte im Rahmen der so genannten Gewinnabgrenzungsaufzeichnungsverordnung, die im Schrifttum auf ein geteiltes Echo gestoßen ist. Ergänzt wird dieser Regelungsbereich nunmehr um den unter dem Datum vom 28. Oktober 2004 veröffentlichten ?Entwurf der ?Grundsätze für die Prüfung der Einkunftsabgrenzung zwischen international verbundenen Unternehmen und zwischen anderen nahe stehenden Personen mit grenzüberschreitenden Geschäftsbeziehungen im Bezug auf Berichtigungen, Ermittlungs- und Mitwirkungspflichten sowie Verständigungs- und EUSchiedsverfahren (Verwaltungsgrundsätze-Verfahren)??. Die Autoren haben mit Datum vom 15. November 2004 gegenüber dem BMF hierzu die folgende Stellungnahme abgegeben. Unser Anliegen war es dabei, die Forderung der Finanzverwaltung einer kritischen Würdigung zu unterziehen und dabei insbesondere auf mögliche Schwierigkeiten im Rahmen der Umsetzung in den Unternehmen hinzuweisen. --

Anmerkungen zum Entwurf der Gewinnabgrenzungsaufzeichnungsverordnung GAufzV vom 11. August 2003 (BR-Drucks. 583/03)

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Aktuelle steuerliche Neuregelungen und deren Auswirkungen auf unternehmerische Entscheidungen: Unter besonderer Berücksichtigung des Steuervergünstigungsabbaugesetzes vom 11. April 2003

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Is TEA an inhibitor for human Aquaporin-1?

Excessive water uptake through aquaporins can be life threatening, and disregulation of water permeability causes many diseases. Therefore, reversible aquaporin inhibitors are highly desired. In this paper, we identified the binding site for tetraethylammonium (TEA) of the membrane water channel aquaporin-1 by a combined molecular docking and molecular dynamics simulation approach. The binding site identified from docking studies was independently confirmed with an unbiased molecular dynamics simulation of an aquaporin tetramer embedded in a lipid membrane, surrounded by a 100-mM tetraethylammonium solution in water. A third independent assessment of the binding site was obtained by umbrella sampling simulations. These simulations, in addition, revealed a binding affinity of more than 17 kJ/mol, corresponding to an IC50 value of << 3 mM. Finally, we observed in our simulations a 50% reduction of the water flux in the presence of TEA, in agreement with water permeability measurements on aquaporin expressed in oocytes. These results confirm TEA as a putative lead for an aquaporin-1 inhibitor

Detection of Functional Modes in Protein Dynamics

Proteins frequently accomplish their biological function by collective atomic motions. Yet the identification of collective motions related to a specific protein function from, e.g., a molecular dynamics trajectory is often non-trivial. Here, we propose a novel technique termed “functional mode analysis” that aims to detect the collective motion that is directly related to a particular protein function. Based on an ensemble of structures, together with an arbitrary “functional quantity” that quantifies the functional state of the protein, the technique detects the collective motion that is maximally correlated to the functional quantity. The functional quantity could, e.g., correspond to a geometric, electrostatic, or chemical observable, or any other variable that is relevant to the function of the protein. In addition, the motion that displays the largest likelihood to induce a substantial change in the functional quantity is estimated from the given protein ensemble. Two different correlation measures are applied: first, the Pearson correlation coefficient that measures linear correlation only; and second, the mutual information that can assess any kind of interdependence. Detecting the maximally correlated motion allows one to derive a model for the functional state in terms of a single collective coordinate. The new approach is illustrated using a number of biomolecules, including a polyalanine-helix, T4 lysozyme, Trp-cage, and leucine-binding protein

Crystal Structure of a Yeast Aquaporin at 1.15 Å Reveals a Novel Gating Mechanism

Atomic-resolution X-ray crystallography, functional analyses, and molecular dynamics simulations suggest a novel mechanism for the regulation of water flux through the yeast Aqy1 water channel

SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage

SARS coronavirus (SCoV) nonstructural protein (nsp) 1, a potent inhibitor of host gene expression, possesses a unique mode of action: it binds to 40S ribosomes to inactivate their translation functions and induces host mRNA degradation. Our previous study demonstrated that nsp1 induces RNA modification near the 5′-end of a reporter mRNA having a short 5′ untranslated region and RNA cleavage in the encephalomyocarditis virus internal ribosome entry site (IRES) region of a dicistronic RNA template, but not in those IRES elements from hepatitis C or cricket paralysis viruses. By using primarily cell-free, in vitro translation systems, the present study revealed that the nsp1 induced endonucleolytic RNA cleavage mainly near the 5′ untranslated region of capped mRNA templates. Experiments using dicistronic mRNAs carrying different IRESes showed that nsp1 induced endonucleolytic RNA cleavage within the ribosome loading region of type I and type II picornavirus IRES elements, but not that of classical swine fever virus IRES, which is characterized as a hepatitis C virus-like IRES. The nsp1-induced RNA cleavage of template mRNAs exhibited no apparent preference for a specific nucleotide sequence at the RNA cleavage sites. Remarkably, SCoV mRNAs, which have a 5′ cap structure and 3′ poly A tail like those of typical host mRNAs, were not susceptible to nsp1-mediated RNA cleavage and importantly, the presence of the 5′-end leader sequence protected the SCoV mRNAs from nsp1-induced endonucleolytic RNA cleavage. The escape of viral mRNAs from nsp1-induced RNA cleavage may be an important strategy by which the virus circumvents the action of nsp1 leading to the efficient accumulation of viral mRNAs and viral proteins during infection

Rechtshandbuch E-Business-Rechtliche Rahmenbedingungen für Geschäfte im Internet

Die immer stärkere Verbreitung und kommerzielle Nutzung des Internets führen zu einer Vielzahl von neuen Problemen für die Rechtspraxis. Im Rechtshandbuch E-Business behandeln die Autoren in 38 Beiträgen die wesentlichen Rahmenbedingungen für den Handel im Internet. Die Beiträge sind in drei Gruppen untergliedert. Nach einer Einführung in die technischen und wirtschaftlichen Grundlagen folgt eine Darstellung der rechtlichen Grundlagen, wie etwa der Vertragsabschluss im Internet, das Urheberrecht, der Datenschutz, das Kartellrecht und das Arbeitsrecht. Der dritte Teil behandelt spezielle Geschäftsfelder im Online-Bereich, wie namentlich Providerverträge, Web-Hosting, Versteigerungen im Internet sowie Wertpapierhandel und Finanzdienstleistungen

A framework for black-box SLO tuning of multi-tenant applications in Kubernetes

Resource management concepts of container orchestration platforms such as Kubernetes can be used to achieve multi-tenancy with quality of service differentiation between tenants. However, to support cost-effective enforcement of Service Level Objectives (SLOs) about response time or throughput, an automated resource optimization approach is needed for mapping custom SLOs of different tenants to cost-efficient resource allocation policies. We propose a versatile tool for cost-effective SLO tuning, named k8-resource-optimizer, that relies on black-box performance tuning algorithms. We illustrate and validate the tool for optimizing different resource configuration properties of a simple job processing application. Our experiments showed that k8-resource-optimizer can find near-optimal configurations for different multi-tenant deployment settings and different types of resource parameters. However an open research challenge is that, when the number of parameters increases, the total tuning cost may also increase beyond what is acceptable for contemporary cloud-native applications. We shortly discuss three possible complementary solutions to tackle this challenge.status: Published onlin

Vector redesign and in‐droplet cell‐growth improves enrichment and recovery in live Escherichia coli

Abstract: Directed evolution (DE) is a widely used method for improving the function of biomolecules via multiple rounds of mutation and selection. Microfluidic droplets have emerged as an important means to screen the large libraries needed for DE, but this approach was so far partially limited by the need to lyse cells, recover DNA, and retransform into cells for the next round, necessitating the use of a high‐copy number plasmid or oversampling. The recently developed live cell recovery avoids some of these limitations by directly regrowing selected cells after sorting. However, repeated sorting cycles used to further enrich the most active variants ultimately resulted in unfavourable recovery of empty plasmid vector‐containing cells over those expressing the protein of interest. In this study, we found that engineering of the original expression vector solved the problem of false positives (i.e. plasmids lacking an insert) cells containing empty vectors. Five approaches to measure activity of cell‐displayed enzymes in microdroplets were compared. By comparing various cell treatment methods prior to droplet sorting two things were found. Substrate encapsulation from the start, that is prior to expression of enzyme, showed no disadvantage to post‐induction substrate addition by pico‐injection with respect to recovery of true positive variants. Furthermore in‐droplet cell growth prior to induction of enzyme production improves the total amount of cells retrieved (recovery) and proportion of true positive variants (enrichment) after droplet sorting