The Antibacterial Drug Candidate SBC3 is a Potent Inhibitor of Bacterial Thioredoxin Reductase

Antibiotic resistance is a growing problem for public health and associated with increasing economic costs and mortality rates. Silver and silver-related compounds have been used for centuries due to their antimicrobial properties. In this work, we show that 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate/NHC*-Ag-OAc (SBC3) is a reversible, high affinity inhibitor of E. coli thioredoxin reductase (TrxR; K_i=10.8±1.2 nM). Minimal inhibition concentration (MIC) tests with different E. coli and P. aeruginosa strains demonstrated that SBC3 can efficiently inhibit bacterial cell growth, especially in combination with established antibiotics like gentamicin. Our results show that SBC3 is a promising antibiotic drug candidate targeting bacterial TrxR.     

Exploring design trade-offs for achieving social inclusion in multi-tiered design problems

ABSTRACT

The digital age of the future is ‘not out there to be discovered’, but it needs to be ‘designed’. The design challenge has to address questions about how we want to live, work, and learn (as individuals and as communities) and what we value and appreciate, e.g.: reflecting on quality of life and creating inclusive societies. An overriding design trade-off for the digital age is whether new developments will increase the digital divide or will create more inclusive societies. Sustaining inclusive societies means allowing people of all ages and all abilities to exploit information technologies for personally meaningful activities. Meta-design fosters the design of socio-technical environments that end-user developers can modify and evolve at use time to improve their quality of life and favour their inclusion in the society. This paper describes three case studies in the domain of assistive technologies in which end users themselves cannot act as end-user developers, but someone else (e.g.: a caregiver or a clinician) must accept this role requiring multi-tiered architectures. The design trade-offs and requirements for meta-design identified in the context of the case studies and other researchers’ projects are described to inform the development of future socio-technical environments focused on social inclusion.     

Semi‐Markovian modelling and performance analysis of variable rate traffic in ATM networks

Semi‐Markovian processes (SMP) serve as a versatile means to model various traffic types generated by sources or superposed from links in ATM networks. An efficient discrete time analysis method is proposed for SMP/G/1 queueing systems to evaluate ATM switches with non‐renewal input. Some basic results are derived for the autocorrelation function of semi‐Markovian processes and for the effect of state space reduction on autocorrelation, which show how to represent correlated traffic with given characteristic by an adequate SMP model of limited size. This revised version was published online in June 2006 with corrections to the Cover Date.     

Synthesis of Aminopyridazines from Aminocyclopropenylium Salts and Diazomethyl Compounds [1]

Amino-substituted cyclopropenylium salts ( 11a,b ) react with diazomethyl compounds ( 12a-i ) in dichloromethane or acetonitrile in the presence of a base (ethyldiisopropylamine, 1,5-diazabicyclo[4.3.0] non-5-ene) to form 4-aminopyridazines ( 13a-i ) specifically. The reaction is interpreted in terms of an initial electrophilic diazoalkane substitution to give diazomethylcyclopropenes ( 11 + 12 → 14 ) which undergo a [1.5]-cyclisation to form the betaines 16 which, in turn, isomerise with opening of the bridging bond to give the aminopyridazines 13 . In a similar manner, the tris[amino] cyclopropenylium salts 8a,b and 10a-c are converted to the 3,4,5-tris[amino]-pyridazines ( 21a-k ) by treatment with diazomethyl compounds ( 12a, c-f ).     

In-situ-Messung der Stickoxidkonzentration in turbulenten Diffusionsflammen

Zusammenfassung Die laserspektroskopischen Me?methoden laserinduzierte Fluoreszenz und spontane Ramanspektroskopie werden eingesetzt zur Messung der Konzentrationen von Stickoxid, Hydroxyl sowie der chemischen Hauptkomponenten und der Temperatur. Betrachtet wird die thermische Umsetzung von Wasserstoff mit Luftsauerstoff. Es wird die experimentelle Vorgehensweise und Problematik dargestellt. Ebenso wird der Weg der Modellierung und Berechnung turbulenter Verbrennungsvorg?nge am konkreten Beispiel skizziert. Die Annahme chemischen Gleichgewichts stellt sich als ungenügend in der Berechnung der Stickoxid- und Hydroxylkonzentrationen heraus. Eine deutlich bessere Vorhersage wird durch Einführen einer Reaktionsfortschrittsvariablen für das chemische Modell erreicht.