Methyltransferase Contingencies in the Pathway of Everninomicin D Antibiotics and Analogues

Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A₁, C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A₁- and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A₁-ring phenol and H-ring C-4’ hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates.     

The Determinants of Debt and (Private) Equity Financing: The Case of Young, Innovative SMEs from Germany

Financial theory creates a puzzle. Some authors argue that high-risk entrepreneurs choose debt contracts instead of equity contracts since risky but high returns are of relatively more value for a loan-financed firm. Conversely, authors who focus explicitly on start-up finance predict that entrepreneurs are the more likely to seek equity-like venture capital contracts, the more risky their projects are. Our paper is an initial step towards resolving this puzzle empirically. We present microeconometric evidence on the determinants of debt and equity financing in young and innovative SMEs. We pay special attention to the role of risk for the choice of the method of financing. Since risk is not directly observable we use different indicators for financial and project risk. It turns out that our data generally confirms the hypothesis that the probability that a young high-tech firm receives equity financing is an increasing function of the financial risk. With regard to the intrinsic project risk, our results are less conclusive, as some of our indicators of a risky project are found to have a negative effect on the likelihood to be financed by private equity.     

Multibody simulation tool for the calculation of lashing loads on RoRo ships

Approximately 80% of the international transport of goods is carried on by means of ships. A large portion of the transport capacity is represented by Roll-on-Roll-off (RoRo) ships. Especially in Europe this is a relevant potential for the RoRo segment. Consequently, the design and construction of RoRo ships plays an increasing role for German shipyards and their suppliers. In order to make the loading and unloading procedure of trailer economically more competitive, ship owners would like to improve the lashing of trailers on the ship. On the basis of a multibody system formalism, a software tool has been developed which allows for an optimization of the loading of trailers on RoRo ships. Commemorative Contribution.     

Dynamic Complexity Theory Revisited

Dynamic complexity investigates the required effort to maintain knowledge about a property of a structure under changing operations. This article introduces a refined notion of dynamic problems which takes the initial structure into account. It develops the basic structural complexity notions accordingly. It also shows that the dynamic version of the LOGCFL-complete problem D₂LREACH(acyclic) can be maintained with first-order updates.     

Multiple object semilinear motion planning

We present a method based on extended linear real quantifier elimination for multiple object semilinear motion planning, i.e. finding collision-free trajectories for several robots in a time dependent environment. For practical applicability the method is limited to polygonal objects and linear trajectories. It can, however, deal with situations involving even non-convex objects.     

Pulmonary function after one-lung ventilation in newborns: the basis for neonatal thoracoscopy

BACKGROUND: To maintain good exposure during major video-assisted thoracic surgery it is necessary to deflate completely the ipsilateral lung. However, little is known about the effects of one-lung ventilation (OLV) on pulmonary function in newborn patients. METHODS: Ten neonatal domestic pigs with a mean age of 6+/-0.6 days were intubated and ventilated in pressure-controlled mode (inspired oxygen fraction=1.0). One-lung ventilation was maintained for 120 minutes. Serial measurements of hemodynamics and gas exchange were done before, during, and until 90 minutes after OLV. Pulmonary function testing was performed before and after OLV for each lung separately. RESULTS: With the inspired oxygen fraction set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar-arterial oxygen tension gradient increased slightly from the baseline value of 2.6% +/-0.3% to 3.8%+/-0.3% during OLV (mean+/-standard error of the mean; p=0.02), and from 358+/-28 to 407+/-18 mm Hg (not significant), respectively. Both values returned to baseline during the subsequent ventilation of both lungs. Static compliance and resistance of the ventilated lung did not change. Compliance of the collapsed lung decreased after reexpansion from 0.42+/-0.07 to 0.29+/-0.06 mL x cm H2O(-1) x kg(-1), p=0.008). Resistance remained unchanged (0.22+/-0.02 versus 0.25+/-0.05 cm H2O x L(-1) x s(-1); not significant). CONCLUSIONS: There were only minor effects on pulmonary function during and after OLV in the neonatal piglet. Alterations in gas exchange during OLV were minimal. Prolonged collapse of the lung with subsequent reexpansion was associated with a slight decrease in compliance, indicating some mild lung injury.     

Keine Mautdaten für Ermittlungsverfahren

Das Autobahnmautgesetz zeichnet sich durch eine strenge Zweckbindung für die Mautdaten aus. Diese dürfen ausschlie?lich für die Zwecke des Mautgesetzes erhoben und verarbeitet werden. Diese Vorgabe hat das LG Magdeburg in einem Beschluss richtungsweisend auch für die Verbindungsdaten der GSM-Kommunikation best?tigt.     

Fractal measures for meromorphic functions of finite order

We prove several essential fractal properties, such as positivity, finiteness or local infinity, of Hausdorff and packing measures of radial Julia sets for large subclasses of entire and meromorphic functions considered in our previous work: çGeometric thermodynamical formalism and real analyticity for meromorphic functions of finite order'. Most of the results proven are shown to be optimal.