Characterization of RarA, a Novel AraC Family Multidrug Resistance Regulator in Klebsiella pneumoniae

Transcriptional regulators, such as SoxS, RamA, MarA, and Rob, which upregulate the AcrAB efflux pump, have been shown to be associated with multidrug resistance in clinically relevant Gram-negative bacteria. In addition to the multidrug resistance phenotype, these regulators have also been shown to play a role in the cellular metabolism and possibly the virulence potential of microbial cells. As such, the increased expression of these proteins is likely to cause pleiotropic phenotypes. Klebsiella pneumoniae is a major nosocomial pathogen which can express the SoxS, MarA, Rob, and RamA proteins, and the accompanying paper shows that the increased transcription of ramA is associated with tigecycline resistance (M. Veleba and T. Schneiders, Antimicrob. Agents Chemother. 56:4466-4467, 2012). Bioinformatic analyses of the available Klebsiella genome sequences show that an additional AraC-type regulator is encoded chromosomally. In this work, we characterize this novel AraC-type regulator, hereby called RarA (Regulator of antibiotic resistance A), which is encoded in K. pneumoniae, Enterobacter sp. 638, Serratia proteamaculans 568, and Enterobacter cloacae. We show that the overexpression of rarA results in a multidrug resistance phenotype which requires a functional AcrAB efflux pump but is independent of the other AraC regulators. Quantitative real-time PCR experiments show that rarA (MGH 78578 KPN_02968) and its neighboring efflux pump operon oqxAB (KPN_02969_02970) are consistently upregulated in clinical isolates collected from various geographical locations (Chile, Turkey, and Germany). Our results suggest that rarA overexpression upregulates the oqxAB efflux pump. Additionally, it appears that oqxR, encoding a GntR-type regulator adjacent to the oqxAB operon, is able to downregulate the expression of the oqxAB efflux pump, where OqxR complementation resulted in reductions to olaquindox MICs.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 EURODIAB centres during 1989-2008

Objectives: To investigate seasonal variation in month of diagnosis in children with type 1 diabetes registered in EURODIAB centres during 1989-2008.
Methods: 23 population-based registers recorded date of diagnosis in new cases of clinically diagnosed type 1 diabetes in children aged under 15 years. Completeness of ascertainment was assessed through capture-recapture methodology and was high in most centres. A general test for seasonal variation (11df) and Edward's test for sinusoidal (sine wave) variation (2df) were employed. Time series methods were also used to investigate if meteorological data were predictive of monthly counts after taking account of seasonality and long term trends.
Results: Significant seasonal variation was apparent in all but two small centres, with an excess of cases apparent in the winter quarter. Significant sinusoidal pattern was also evident in all but two small centres with peaks in December (14 centres), January (5 centres) or February (2 centres). Relative amplitude varied from ±11% to ±39% (median ±18%). There was no relationship across the centres between relative amplitude and incidence level. However there was evidence of significant deviation from the sinusoidal pattern in the majority of centres. Pooling results over centres, there was significant seasonal variation in each age-group at diagnosis, but with significantly less variation in those aged under 5 years. Boys showed marginally greater seasonal variation than girls. There were no differences in seasonal pattern between four sub-periods of the 20 year period. In most centres monthly counts of cases were not associated with deviations from normal monthly average temperature or sunshine hours; short term meteorological variations do not explain numbers of cases diagnosed.
Conclusions: Seasonality with a winter excess is apparent in all age-groups and both sexes, but girls and the under 5s show less marked variation. The seasonal pattern changed little in the 20 year period.

The Making of Modern Turkish Architecture

This is the introductory essay of ARCAM’s (Architectuurcentrum Amsterdam) “Turkey Today: Contemporary Turkish Architecture in Turkey and the Netherlands” Exhibit, which took place in September-November 2004 in Amsterdam, The Netherlands. The author also consulted the curators.

ARCAM Sergisi:Modern Turkiyeyi Anlamak

This is an interview with the author about the "Turkey Today: Contemporary Turkish Architecture in Turkey and the Netherlands” Exhibition in Amsterdam, The Netherlands. The author consulted the curators and wrote the introductory essay of the exhibition.

An Integrated Sensing System for Monitoring the Corrosion Activity in Concrete Blocks Exposed at Hangzhou Bay Bridge

This paper discusses the importance of integrated sensing systems comprising techniques that give different types of data from a structure exposed to the marine environment so that its service life could reliably be predicted. For this purpose, a novel sensor combination was designed and installed in concrete panels which were exposed to Hangzhou Bay Bridge in China. The integrated sensor probe was used to monitor the cover concrete as well as the reinforcement. The sensor probes were connected to a monitoring station, which enabled access and control of the data remotely from Belfast, UK. The initial data obtained from the monitoring station gives interesting information on the early age properties of concrete and distinct variations in these properties with different types of concrete. This paper also reports the variation in electrical properties of different concrete samples and environmental data in response to the marine exposure condition at Hangzhou bay bridge.

A downlink power control scheme for interference avoidance in femtocells

Femtocells being small low powered base stations provide sufficient increase in system capacity along with better indoor coverage. However, the dense deployment of femtocells face the main challenge of co channel interference with macrocell users. In this paper, this interference problem is addressed by proposing a novel downlink power control algorithm for femtocells. The proposed algorithm gradually reduces the downlink transmit power of femtocells when they are informed about a nearby macrocell user under interference. This information is given to the femtocells by the macrocell base station through a unidirectional downlink broadcast channel. Simulation results show that the algorithm causes the macrocell to accommodate large number of femtocells within its area, whereas at the same time protecting the macrocell users from any harmful interference.

Protracted Peace processes: Policy (Un)learning and the Cyprus Debacle

The article examines why a comprehensive settlement to resolve the Cyprus problem has yet to be reached despite the existence of a positive incentive structure and the proactive involvement of regional and international organizations, including the European Union and the United Nations. To address this question, evidence from critical turning points in foreign policy decision-making in Turkey, Greece and the two communities in Cyprus is drawn on. The role of hegemonic political discourses is emphasized, and it is argued that the latter have prevented an accurate evaluation of incentives that could have set the stage for a constructive settlement. However, despite the political debacle in the Cypriot negotiations, success stories have emerged, such as the reactivation of the Committee for Missing Persons (CMP), a defunct body for almost 25 years, to become the most successful bi-communal project following Cyprus’s EU accession. Contradictory evidence in the Cypriot peace process is evaluated and policy lessons to be learned from the CMP ‘success story’ are identified.