Treatment of Neuroblastoma with an Engineered “Obligate” Anaerobic Salmonella typhimurium Strain YB1

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The two PPX-GppA homologues from Mycobacterium tuberculosis have distinct biochemical activities

Inorganic polyphosphate (poly-P), guanosine pentaphosphate (pppGpp) and guanosine tetraphosphate (ppGpp) are ubiquitous in bacteria. These molecules play a variety of important physiological roles associated with stress resistance, persistence, and virulence. In the bacterial pathogen Mycobacterium tuberculosis, the identities of the proteins responsible for the metabolism of polyphosphate and (p)ppGpp remain to be fully established. M. tuberculosis encodes two PPX-GppA homologues, Rv0496 (MTB-PPX1) and Rv1026, which share significant sequence similarity with bacterial exopolyphosphatase (PPX) and guanosine pentaphosphate 5′-phosphohydrolase (GPP) proteins. Here we delineate the respective biochemical activities of the Rv0496 and Rv1026 proteins and benchmark these against the activities of the PPX and GPP proteins from Escherichia coli. We demonstrate that Rv0496 functions as an exopolyphosphatase, showing a distinct preference for relatively short-chain poly-P substrates. In contrast, Rv1026 has no detectable exopolyphosphatase activities. Analogous to the E. coli PPX and GPP enzymes, the exopolyphosphatase activities of Rv0496 are inhibited by pppGpp and, to a lesser extent, by ppGpp alarmones, which are produced during the bacterial stringent response. However, neither Rv0496 nor Rv1026 have the ability to hydrolyze pppGpp to ppGpp; a reaction catalyzed by E. coli PPX and GPP. Both the Rv0496 and Rv1026 proteins have modest ATPase and to a lesser extent ADPase activities. pppGpp alarmones inhibit the ATPase activities of Rv1026 and, to a lesser extent, the ATPase activities of Rv0496. We conclude that PPX-GppA family proteins may not possess all the catalytic activities implied by their name and may play distinct biochemical roles involved in polyphosphate and (p)ppGpp metabolic pathways. © 2012 2012 Choi et al.published_or_final_versio

Genetically modified "obligate" anaerobic Salmonella typhimurium as a therapeutic strategy for neuroblastoma

published_or_final_versio

Mathematical modelling of container transfers for a fleet of autonomous straddle carriers

The main contribution of this paper is a mathematical model describing performance metrics for coordinating multiple mobile robots in a seaport container terminal. The scenario described here requires dealing with many difficult practical challenges such as the presence of multiple levels of container stacking and sequencing, variable container orientations, and vehicular dynamics that require finite acceleration and deceleration times. Furthermore, in contrast to the automatically guided vehicle planning problem in a manufacturing environment, the container carriers described here are free ranging. Although, the port structure imposes a set of "virtual" roadways along which the vehicles are allowed to travel, path planning is essential in preventing contention and collisions. A performance metric which minimises total yard-vehicle usage, while producing robust traffic plans by encouraging both early starting and finishing of jobs is presented for different vehicle fleet sizes and job allocation scenarios. ©2010 IEEE

Urban spatial patterns in a monocentric city with car-owning and no-car-owning residents

The existing monocentric city models mostly assume that residents are completely rational when making residential location and mode choice, and their direct utilities only depend on the consumption of two normal goods, a housing service and a composite non-housing good. This paper develops a new model by explicitly integrating the preference for solo-driving into car owners' direct utility functions. It is found that, an upward sloping rent-distance relationship exists nearby the Central Business District (CBD) when all residents are car owners, which is significantly different from the conclusion reported in literature. Considering the impact of car owners' preference for solo-driving, we differentiate two possible urban spatial patterns in a monocentric city with car-owning and no-car-owning residents. Numerical results show that an increase of car ownership does not always lead to an expansion in the city size

EMAAS: An extensible grid-based Rich Internet Application for microarray data analysis and management

<p>Abstract</p> <p>Background</p> <p>Microarray experimentation requires the application of complex analysis methods as well as the use of non-trivial computer technologies to manage the resultant large data sets. This, together with the proliferation of tools and techniques for microarray data analysis, makes it very challenging for a laboratory scientist to keep up-to-date with the latest developments in this field. Our aim was to develop a distributed e-support system for microarray data analysis and management.</p> <p>Results</p> <p>EMAAS (Extensible MicroArray Analysis System) is a multi-user rich internet application (RIA) providing simple, robust access to up-to-date resources for microarray data storage and analysis, combined with integrated tools to optimise real time user support and training. The system leverages the power of distributed computing to perform microarray analyses, and provides seamless access to resources located at various remote facilities. The EMAAS framework allows users to import microarray data from several sources to an underlying database, to pre-process, quality assess and analyse the data, to perform functional analyses, and to track data analysis steps, all through a single easy to use web portal. This interface offers distance support to users both in the form of video tutorials and via live screen feeds using the web conferencing tool EVO. A number of analysis packages, including R-Bioconductor and Affymetrix Power Tools have been integrated on the server side and are available programmatically through the Postgres-PLR library or on grid compute clusters. Integrated distributed resources include the functional annotation tool DAVID, GeneCards and the microarray data repositories GEO, CELSIUS and MiMiR. EMAAS currently supports analysis of Affymetrix 3' and Exon expression arrays, and the system is extensible to cater for other microarray and transcriptomic platforms.</p> <p>Conclusion</p> <p>EMAAS enables users to track and perform microarray data management and analysis tasks through a single easy-to-use web application. The system architecture is flexible and scalable to allow new array types, analysis algorithms and tools to be added with relative ease and to cope with large increases in data volume.</p

Erectile dysfunction as a possible important side effect of metformin: A case report

Metformin-induced sexual dysfunction is rare in patients with diabetes mellitus. Herein, we present the case of a 57-year-old man newly diagnosed with type 2 diabetes mellitus who developed erectile dysfunction following treatment with metformin 500 mg BD. Prior to taking metformin, he had well-controlled hypertension, hyperlipidaemia and normal sexual function. Two weeks after beginning metformin therapy, he was diagnosed with erectile dysfunction after experiencing persistent difficulty achieving an erection. After discontinuation of metformin, his sexual function returned to normal. To determine whether sexual dysfunction is caused by metformin, we rechallenged the patient with metformin 500 mg BD. After 15 days, he became impotent again, confirming that metformin was the most likely cause of his sexual problem. Metformin was stopped, and his sexual function returned to normal after 3 weeks. The adverse reaction is ‘probable’ according to the World Health Organization–Uppsala Monitoring Centre

On Semiclassical Limits of String States

We explore the relation between classical and quantum states in both open and closed (super)strings discussing the relevance of coherent states as a semiclassical approximation. For the closed string sector a gauge-fixing of the residual world-sheet rigid translation symmetry of the light-cone gauge is needed for the construction to be possible. The circular target-space loop example is worked out explicitly.Comment: 12 page

Spirulina (Arthrospira) industry in Inner Mongolia of China: current status and prospects

This paper outlines an investigation on current situation of Spirulina (Arthrospira) industry in Inner Mongolia, an internal region of China with temperate continental climate. More than 20 Spirulina plants have been established in Inner Mongolia since 2001, most of which are located at Wulan Town in the Ordos Plateau. By the end of 2009, the total annual production of Spirulina in the Ordos Plateau surpassed 700 t (dw), which account for ca. 80% of the total productivity of Inner Mongolia, and ca. 20% of China. Besides abundant solar radiation and enough freshwater favorable for Spirulina production, the three technical strategies contribute to the prosperity and success of Spirulina industry in the region: (1) reducing the cost or investment by overall advantages of rich local natural resources with low cost for Spirulina production, such as alkaline lakes, coal, electricity, and sandy land; (2) controlling the culture temperature and to avoid contamination by building plastic greenhouses on raceway ponds, (3) reducing investment by simplifying the construction of the ponds and the greenhouses. As the result, the growth period of Spirulina has been prolonged from about 120 to about 165 days, the cost of Spirulina has decreased by 25–30%, and the quality of products has been enhanced substantially. Inner Mongolia is expected to become the largest base for Spirulina production not only in China, but also in the world in the near future