The Shanghai Cooperation Organization (SCO): Challenges Ahead and Potential Solutions

The SCO faces the challenges of improving cohesion, better managing relations with external parties, enlargement, variations of economic cooperation between member states, a slow pace of decision making and poor quality decision implementation. To mature and consolidate the organizations young and growing global status it needs to improve communications and relationships between all stakeholders, develop a legally binding framework, address economic and security issues, generate better leadership from its two largest partners and develop an enlargement program

The Escherichia coli RutR transcription factor binds at targets within genes as well as intergenic regions.

The Escherichia coli RutR protein is the master regulator of genes involved in pyrimidine catabolism. Here we have used chromatin immunoprecipitation in combination with DNA microarrays to measure the binding of RutR across the chromosome of exponentially growing E. coli cells. Twenty RutR-binding targets were identified and analysis of these targets generated a DNA consensus logo for RutR binding. Complementary in vitro binding assays showed high-affinity RutR binding to 16 of the 20 targets, with the four low-affinity RutR targets lacking predicted key binding determinants. Surprisingly, most of the DNA targets for RutR are located within coding segments of the genome and appear to have little or no effect on transcript levels in the conditions tested. This contrasts sharply with other E. coli transcription factors whose binding sites are primarily located in intergenic regions. We suggest that either RutR has yet undiscovered function or that evolution has been slow to eliminate non-functional DNA sites for RutR because they do not have an adverse effect on cell fitness

A Novel 3D TCAD simulation of a Thermoelectric Module configured for Thermoelectric Power Generation

This paper documents the novel design, modelling and 3D simulation of a single thermoelectric couple using the Technology Computer Aided Design (TCAD) semiconductor simulation software package by Synopsys. Preliminary simulation results are presented for thermoelectric power generation, and successfully demonstrate the basic thermoelectric effects, and how the application of a temperature gradient to a thermoelectric couple results in a small amount of electrical power being generated at a load resistor. The TCAD simulation model will enable further investigation in the future into different material structures, thermoelectric couple and module design, and the improvement in efficiency and thermoelectric module performance

DNA Sampling: a method for probing protein binding at specific loci on bacterial chromosomes

We describe a protocol, DNA sampling, for the rapid isolation of specific segments of DNA, together with bound proteins, from Escherichia coli K-12. The DNA to be sampled is generated as a discrete fragment within cells by the yeast I-SceI meganuclease, and is purified using FLAG-tagged LacI repressor and beads carrying anti-FLAG antibody. We illustrate the method by investigating the proteins bound to the colicin K gene regulatory region, either before or after induction of the colicin K gene promoter

Autoregulation of the Escherichia coli melR promoter: repression involves four molecules of MelR

The Escherichia coli MelR protein is a transcription activator that autoregulates its own promoter by repressing transcription initiation. Optimal repression requires MelR binding to a site that overlaps the melR transcription start point and to upstream sites. In this work, we have investigated the different determinants needed for optimal repression and their spatial requirements. We show that repression requires a complex involving four DNA-bound MelR molecules, and that the global CRP regulator plays little or no role

What is the clinical and ethical importance of incidental abnormalities found by knee MRI?

INTRODUCTION: Magnetic resonance imaging (MRI) is increasingly used to examine joints for research purposes. It may detect both suspected and unsuspected abnormalities. This raises both clinical and ethical issues, especially when incidental abnormalities are detected. The prevalence of incidental, potentially clinically significant abnormalities identified by MRI and their clinical significance in a population undergoing knee MRI in research studies are unknown. METHODS: We examined the prevalence of such lesions in healthy asymptomatic adults and those with symptomatic knee osteoarthritis (OA) undergoing knee MRI with limited sequences for the purpose of research. The MRI findings in 601 asymptomatic subjects and 132 with knee OA who underwent at least one limited knee MRI scan for cartilage volume measurement were examined by an MRI radiologist for the presence of potentially clinically significant abnormalities. RESULTS: These were present in 2.3% of healthy and 2.3% of OA subjects. All required further investigation to exclude non-benign disease, including four with bone marrow expansion (0.7%), requiring further investigation and management. A single potentially life-threatening lesion, a myeloma lesion, was identified in a subject with symptomatic knee OA on their second MRI scan in a longitudinal study. CONCLUSION: As musculoskeletal MRI is increasingly used clinically and for research purposes, the potential for detecting unsuspected abnormalities that require further investigation should be recognized. Incorporating a system to detect these, to characterize unexpected findings, and to facilitate appropriate medical follow-up when designing studies using this technology should be considered ethical research practice

Threat history controls flexible escape behavior in mice.

In many instances, external sensory-evoked neuronal activity is used by the brain to select the most appropriate behavioral response. Predator-avoidance behaviors such as freezing and escape1,2 are of particular interest since these stimulus-evoked responses are behavioral manifestations of a decision-making process that is fundamental to survival.3,4 Over the lifespan of an individual, however, the threat value of agents in the environment is believed to undergo constant revision,5 and in some cases, repeated avoidance of certain stimuli may no longer be an optimal behavioral strategy.6 To begin to study this type of adaptive control of decision-making, we devised an experimental paradigm to probe the properties of threat escape in the laboratory mouse Mus musculus. First, we found that while robust escape to visual looming stimuli can be observed after 2 days of social isolation, mice can also rapidly learn that such stimuli are non-threatening. This learned suppression of escape (LSE) is extremely robust and can persist for weeks and is not a generalized adaptation, since flight responses to novel live prey and auditory threat stimuli in the same environmental context were maintained. We also show that LSE cannot be explained by trial number or a simple form of stimulus desensitization since it is dependent on threat-escape history. We propose that the action selection process mediating escape behavior is constantly updated by recent threat history and that LSE can be used as a robust model system to understand the neurophysiological mechanisms underlying experience-dependent decision-making

A Novel 3D TCAD simulation of a Thermoelectric Module configured for Thermoelectric Power Generation

This paper documents the novel design, modelling and 3D simulation of a single thermoelectric couple using the Technology Computer Aided Design (TCAD) semiconductor simulation software package by Synopsys. Preliminary simulation results are presented for thermoelectric power generation, and successfully demonstrate the basic thermoelectric effects, and how the application of a temperature gradient to a thermoelectric couple results in a small amount of electrical power being generated at a load resistor. The TCAD simulation model will enable further investigation in the future into different material structures, thermoelectric couple and module design, and the improvement in efficiency and thermoelectric module performance

Transcription factor distribution in Escherichia coli: studies with FNR protein

Using chromatin immunoprecipitation (ChIP) and high-density microarrays, we have measured the distribution of the global transcription regulator protein, FNR, across the entire Escherichia coli chromosome in exponentially growing cells. Sixty-three binding targets, each located at the 5′ end of a gene, were identified. Some targets are adjacent to poorly transcribed genes where FNR has little impact on transcription. In stationary phase, the distribution of FNR was largely unchanged. Control experiments showed that, like FNR, the distribution of the nucleoid-associated protein, IHF, is little altered when cells enter stationary phase, whilst RNA polymerase undergoes a complete redistribution

Accepting higher morbidity in exchange for sacrificing fewer animals in studies developing novel infection-control strategies.

Preventing bacterial infections from becoming the leading cause of death by the year 2050 requires the development of novel, infection-control strategies, building heavily on biomaterials science, including nanotechnology. Pre-clinical (animal) studies are indispensable for this development. Often, animal infection outcomes bear little relation to human clinical outcome. Here, we review conclusions from pathogen-inoculum dose-finding pilot studies for evaluation of novel infection-control strategies in murine models. Pathogen-inoculum doses are generally preferred that produce the largest differences in quantitative infection outcome parameters between a control and an experimental group, without death or termination of animals due to having reached an inhumane end-point during the study. However, animal death may represent a better end-point for evaluation than large differences in outcome parameters or number of days over which infection persists. The clinical relevance of lower pre-clinical outcomes, such as bioluminescence, colony forming units (CFUs) retrieved or more rapid clearance of infection is unknown, as most animals cure infection without intervention, depending on pathogen-species and pathogen-inoculum dose administered. In human clinical practice, patients suffering from infection present to hospital emergency wards, frequently in life-threatening conditions. Animal infection-models should therefore use prevention of death and recurrence of infection as primary efficacy targets to be addressed by novel strategies. To compensate for increased animal morbidity and mortality, animal experiments should solely be conducted for pre-clinical proof of principle and safety. With the advent of sophisticated in vitro models, we advocate limiting use of animal models when exploring pathogenesis or infection mechanisms