Structure−Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents

Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model.     

Finite constants: characterizations of a new decidable set of constants

Constant propagation, the replacement of program terms which represent a unique value at run time by their values, is a classical program optimization method. In spite of being treated for years, constant propagation still has been in the unsatisfactory phase of heuristics. We enhance the known constant propagation techniques to obtain an algorithm which is optimal for programs without loops. Fundamental is the introduction of a new decidable set of constants, the finite constants. This set has two different characterizations: a denotational one, which directly specifies our iterative algorithm and an operational one, which delivers the completeness or optimality of this algorithm for programs without loops. The algorithm is implemented in a commercial compiler project.     

Modellqualität als Indikator für Softwarequalität: eine Taxonomie

Zusammenfassung  Komplexit?t, Anforderungsmanagement und Variantenvielfalt sind zentrale Herausforderungen bei der Entwicklung und Evolution heutiger softwaregesteuerter Systeme. Diesen wird zunehmend durch den Einsatz modellbasierter Entwicklungsmethoden begegnet. Dadurch wird das Modell zum zentralen Artefakt und die Erstellung und Nutzung von Modellen zu einer zentralen T?tigkeit in der Softwareentwicklung. Mit der Bedeutung der Modelle steigen auch die Ansprüche an ihre Qualit?t. Dieser Beitrag untersucht die Implikationen, die daraus entstehen, insbesondere werden sinnvolle Qualit?tsmerkmale für softwarebeschreibende Modelle identifiziert und diskutiert.     

The microscopy cell (MicCell), a versatile modular flowthrough system for cell biology, biomaterial research, and nanotechnology

We describe a novel microfluidic perfusion system for high-resolution microscopes. Its modular design allows pre-coating of the coverslip surface with reagents, biomolecules, or cells. A poly(dimethylsiloxane) (PDMS) layer is cast in a special molding station, using masters made by photolithography and dry etching of silicon or by photoresist patterning on glass or silicon. This channel system can be reused while the coverslip is exchanged between experiments. As normal fluidic connectors are used, the link to external, computer-programmable syringe pumps is standardized and various fluidic channel networks can be used in the same setup. The system can house hydrogel microvalves and microelectrodes close to the imaging area to control the influx of reaction partners. We present a range of applications, including single-molecule analysis by fluorescence correlation spectroscopy (FCS), manipulation of single molecules for nanostructuring by hydrodynamic flow fields or the action of motor proteins, generation of concentration gradients, trapping and stretching of live cells using optical fibers precisely mounted in the PDMS layer, and the integration of microelectrodes for actuation and sensing.     

Symbolic control of visual attention: The role of working memory and attentional control settings.

This study examined how 1 symbol is selected to control the allocation of attention when several symbols appear in the visual field. In Experiments 1-3, the critical target feature was color, and it was found that uninformative central arrows that matched the color of the target were selected and produced unintentional shifts of attention (i.e., involuntary, initiated slowly, producing long-lasting facilitatory effects). Experiment 4 tested whether such selection is the result of an attentional filter or of a competition bias due to a match of incoming information against integrated object representations stored in working memory. Here, the critical feature was shape and color was irrelevant, but matching color arrows were still selected. Thus, features of objects in working memory will bias the selection of symbols in the visual field, and such selected symbols are capable of producing unintentional shifts of attention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Novel Readout Electronics for Thickness Shear-Mode Liquid Sensors Compensating for Spurious Conductivity and Capacitances

In this paper, a readout circuit for a thickness shear-mode (TSM) resonator is presented which can be used for sensing applications in liquids such as viscosity sensing. The system features compensation of both spurious capacitances and conductances in parallel to the resonator. This allows measurements even in conductive liquids without the need for an elaborate sealing of the sensor. The influence of the spurious elements is determined by means of two orthogonal synchronous detectors and eliminated by active compensation using voltage-controlled amplifiers (VCAs). Furthermore, the circuit is robust against possible phase errors. The basic concept is discussed in detail, and a readout circuit is developed. A prototype is presented, and sample results are given, demonstrating the feasibility of the approach     

Hydroformylierung einfach und mehrfach ungesättigter Fettstoffe mit heterogenisierten Cobaltcarbonyl- und R

Hydroformylation of mono and multiple unsaturated fatty substances with heterogenized cobaltcarbonyl and rhodiumcarbonyl catalysts. Heterogenized cobalt and rhodiumcarbonyl catalyst systems can be used for the hydroformylation of mono and polyunsatured fatty substances in a technically simple and satisfying manner to useful chemical intermediates. The used solid tert. phosphane complex ligands have a silicate matrix and therefore they are also suitable for the cobalt catalyzed hydroformylation which is best performed at temperatures of 160–180^oC. The cobalt catalyzed reaction gives with polyunsaturated fatty substances almost only products with monofunctionalized fatty acid chains. Whereas, the rhodium catalyzed reaction gives with linolic acid compounds inhomogeneous mixtures of mono- and diformyl derivatives of these fatty substances. The heterogenized rhodium carbonyl catalyst systems therefore seem to be more suitable for the hydroformylation of monounsaturated compounds. This is also true for rhodiumcarbonylsupported aqueous phase-catalysts which give likewise mixtures of mono and diformyl derivatives in the hydroformylation of polyunsaturated fatty substances. In batch process after the complete conversion of the olefin and reduction of the CO/H₂-pressure the loss of catalyst metal from the support is negligible and in most cases below the detection limit (<1 ppm).     

The role of forest and bioenergy strategies in the global carbon cycle

Forest and bioenergy strategies offer the prospect of reduced CO₂ emissions to the atmosphere. Such strategies can affect the net flux of carbon to the atmosphere through 4 mechanisms: storage of C in the biosphere; storage of C in forest products; use of biofuels to displace fossil-fuel use; use of wood products which often displaces other products that require more fossil fuel for their production. We use the mathematical model GORCAM (Graz/Oak Ridge Carbon Accounting Model) to examine these mechanisms for 16 land-use scenarios. Over long time intervals the amount of C stored in the biosphere and in forest products reaches a steady state and continuing mitigation of C emissions depends on the extent to which fossil fuel use is displaced by the use of bioenergy and wood products. The relative effectiveness of alternative forest and bioenergy strategies and their impact on net C emissions strongly depend, for example, on the productivity of the site, its current usage, and the efficiency with which the harvest is used. When growth rates are high and harvest is used efficiently, the dominant opportunity for net reduction in C emissions is seen to be fossil-fuel displacement. At the growth rates and efficiencies of harvest utilization adopted in many of our base scenarios, the net C balance at the end of 100 years is very similar whether trees are harvested and used for energy and traditional forest products, or reforestation and forest protection strategies are implemented. The C balance on a plantation system that provides a constant output of biomass products can look different than the balance of a single parcel of land.     

A formal model for the interoperability of service clouds

Large-scale service-oriented computing is based on the idea that services from various servers are combined into one distributed application. Referring to a collection of services on one server as a ??service cloud??, the problem investigated in this paper is to define formal high-level specifications of such distributed applications and to enable the location of suitable services for them. Based on the language-independent model of Abstract State Services (AS²s), which serves as a universal integrated model for data and software as services, we extend AS²s by high-level action schemes called ??plots?? as a means to specify permitted sequences of service operations. On these grounds, we develop a model for service mediators, that is, specifications of composed services in which service slots have to be filled by actual services, and investigate matching conditions for slots of mediators and services. For a services to match a slot in a mediator, a (generalised) projection of the mediator must comply with the plot of the service. Furthermore, the service must be semantically adequate, which requires the use of a service ontology.     

(S)-Reutericyclin: Susceptibility Testing and In Vivo Effect on Murine Fecal Microbiome and Volatile Organic Compounds

We aimed to assess the in vitro antimicrobial activity and the in vivo effect on the murine fecal microbiome and volatile organic compound (VOC) profile of (S)-reutericyclin. The antimicrobial activity of (S)-reutericyclin was tested against Clostridium difficile, Listeria monocytogenes, Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Staphylococcus (S.) epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa and Propionibacterium acnes. Reutericyclin or water were gavage fed to male BALBc mice for 7 weeks. Thereafter stool samples underwent 16S based microbiome analysis and VOC analysis by gas chromatography mass spectrometry (GC-MS). (S)-reutericyclin inhibited growth of S. epidermidis only. Oral (S)-reutericyclin treatment caused a trend towards reduced alpha diversity. Beta diversity was significantly influenced by reutericyclin. Linear discriminant analysis Effect Size (LEfSe) analysis showed an increase of Streptococcus and Muribaculum as well as a decrease of butyrate producing Ruminoclostridium, Roseburia and Eubacterium in the reutericyclin group. VOC analysis revealed significant increases of pentane and heptane and decreases of 2,3-butanedione and 2-heptanone in reutericyclin animals. The antimicrobial activity of (S)-reutericyclin differs from reports of (R)-reutericyclin with inhibitory effects on a multitude of Gram-positive bacteria reported in the literature. In vivo (S)-reutericyclin treatment led to a microbiome shift towards dysbiosis and distinct alterations of the fecal VOC profile.