The bldC developmental locus of Streptomyces coelicolor encodes a member of a family of small DNA-binding proteins related to the DNA-binding domains of the MerR family.

The bldC locus, required for formation of aerial hyphae in Streptomyces coelicolor, was localized by map-based cloning to the overlap between cosmids D17 and D25 of a minimal ordered library. Subcloning and sequencing showed that bldC encodes a member of a previously unrecognized family of small (58- to 78-residue) DNA-binding proteins, related to the DNA-binding domains of the MerR family of transcriptional activators. BldC family members are found in a wide range of gram-positive and gram-negative bacteria. Constructed {Delta}bldC mutants were defective in differentiation and antibiotic production. They failed to form an aerial mycelium on minimal medium and showed severe delays in aerial mycelium formation on rich medium. In addition, they failed to produce the polyketide antibiotic actinorhodin, and bldC was shown to be required for normal and sustained transcription of the pathway-specific activator gene actII-orf4. Although {Delta}bldC mutants produced the tripyrrole antibiotic undecylprodigiosin, transcripts of the pathway-specific activator gene (redD) were reduced to almost undetectable levels after 48 h in the bldC mutant, in contrast to the bldC+ parent strain in which redD transcription continued during aerial mycelium formation and sporulation. This suggests that bldC may be required for maintenance of redD transcription during differentiation. bldC is expressed from a single promoter. S1 nuclease protection assays and immunoblotting showed that bldC is constitutively expressed and that transcription of bldC does not depend on any of the other known bld genes. The bldC18 mutation that originally defined the locus causes a Y49C substitution that results in instability of the protein

DevA, a GntR-like transcriptional regulator required for development in streptomyces coelicolor

The gram-positive filamentous bacterium Streptomyces coelicolor has a complex developmental cycle with three distinct phases: growth of the substrate mycelium, development of reproductive structures called aerial hyphae, and differentiation of these aerial filaments into long chains of exospores. During a transposon mutagenesis screen, we identified a novel gene (devA) required for proper development. The devA mutant produced only rare aerial hyphae, and those that were produced developed aberrant spore chains that were much shorter than wild-type chains and had misplaced septa. devA encodes a member of the GntR superfamily, a class of transcriptional regulators that typically respond to metabolite effector molecules. devA forms an operon with the downstream gene devB, which encodes a putative hydrolase that is also required for aerial mycelium formation on R5 medium. S1 nuclease protection analysis showed that transcription from the single devA promoter was temporally associated with vegetative growth, and enhanced green fluorescent protein transcriptional fusions showed that transcription was spatially confined to the substrate hyphae in the wild type. In contrast, devAB transcript levels were dramatically upregulated in a devA mutant and the devA promoter was also active in aerial hyphae and spores in this background, suggesting that DevA might negatively regulate its own production. This suggestion was confirmed by gel mobility shift assays that showed that DevA binds its own promoter region in vitro

Characterization of Microbial Activity

The overall goal of this study is to investigate the phenomena that affect the fate and transport of radionuclides in the environment. The objective of this task, “Characterization of Microbial Activity”, is to develop a molecular biological method for the characterization of the microbial population indigenous to the Yucca Mountain Project site, with emphasis in detection and measurement of species or groups of microorganisms that could be involved in actinide and/or metal reduction, and subsurface transport. Subtasks consist of QA planning and preparation, and literature review. This task is part of a cooperative agreement between the UNLV Research Foundation and the U.S. Department of Energy (#DE-FC28-04RW12237) titled “Yucca Mountain Groundwater Characterization”

Nested partnerships and interdisciplinary science: from the National Medical Cyclotron to the research cyclotron of the National Imaging Facility

In Australia, the routine use of medical isotopes produced by a prototype cyclotron for diagnostic imaging commenced in the early 1990s. Since then, the mainly clinically focused imaging in nuclear medicine has become a broader and more interdisciplinary endeavour. As 'molecular imaging', it has become a field that supports a wide range of basic, translational and clinical research and draws in skills from many areas, including physics, chemistry, engineering, biology and medicine. Such growth has been accompanied by the emergence of scientific collaborations well beyond individual institutions. This paper provides the historical context to the former National Medical Cyclotron (NMC) facility (1992-2009) at Camperdown, Sydney and the subsequent partnerships that led to its refurbishment as the new site of the National Imaging Facility (NIF) Cyclotron, a flagship research facility enabled by the National Collaborative Research Infrastructure Strategy (NCRIS). It is now the centrepiece of a physical research infrastructure as well as a growing network of collaborations that open up access to medical isotopes for research and clinical applications across Australia to new users and applications. It is also a contemporary example of how science has moved from individual scholarly endeavour to highly networked activity. The funding model initiated through NCRIS included shared funding, funding leveraging and in-kind contributions primarily for the establishment of the large instrument and laboratory infrastructure rather than their operational costs. Here, we illustrate how partnership arrangements emerged at institutional, state and national level and how they address the task of providing open access to, and sustainable operation of, a major piece of research infrastructure that spans multiple institutions. © The Royal Society of NSW

Diagnostic and Monitoring CERN Accelerator Controls Infrastructure : The DIAMON Project First Deployment in Operation

The CERN accelerator controls infrastructure spans over several machines and several thousands of devices are used to collect and transmit piece of control data. Each of these remote devices might fail and therefore prevent correct operation. A complete diagnostic and monitoring infrastructure has been developed in order to provide Operation crews with complete and easy to use graphical interface presenting the state of the controls system. Simple agents running in each surveyed item periodically report monitoring information to a central server. Graphical JAVA clients in the operation centers subscribe to this monitoring data and display a view of the current state of the machines. Mouse actions from these clients allows for diagnostic commands to be sent to the agent to get additional details or to repair a faulty situation. This presentation will describe the overall architecture of DIAMON, present the different agents running in the controls system and a few views of the graphical clients. The outcome of the first months in operation of the DIAMON tools will also be presented. Finally, the future plans will be exposed

Characterization of microbial populations in the subsurface

This task is part of a cooperative agreement between the UNLV Research Foundation and the U.S. Department of Energy (#DE-FC28-04RW12237) titled “Yucca Mountain Groundwater Characterization”. The work was conducted in the Harry Reid Center for Environmental Studies, Microbiology Division of the University of Nevada, Las Vegas from October 1, 2004 to September 30, 2006. The overall goal of this research was to investigate the phenomena that affect the fate and transport of radionuclides in the environment. The purpose of this task (ORD-RF-01), “Characterization of Microbial Activity”, was to develop a molecular biological method for the characterization of the microbial population indigenous to the Yucca Mountain Project site, with emphasis in detection and measurement of species or groups of microorganisms that could be involved in actinide and/or metal reduction, and subsurface transport. To quantify and characterize the microbial populations, including microorganisms that may be viable but are not currently physiologically active, a molecular biological approach was utilized to amplify and detect microbial DNA present in the subsurface. This approach, termed polymerase chain reaction (PCR), results in the amplification of DNA sequences that are unique to the groups of microorganisms of interest. Quantitative PCR (QPCR) assays were developed and used for the measurement of subsurface microbial populations. The protocols were evaluated in laboratory tests involving representative microbial species and genera, and tested by assaying available subsurface samples previously collected from the Yucca Mountain Project site. Other subtasks included Quality Assurance (QA) planning and preparation, and a literature review. This work was subject to the Nevada System of Higher Education (NSHE) QA Program requirements

Paper Session I-B - An Evaluation of Electronic Nose for Space Program Applications

The ability to monitor air contaminants in the Shuttle and the International Space Station is important to ensure the health and safety of astronauts. Three specific space applications have been identified that would benefit from a chemical monitor: organic contaminants in crew cabins, propellant contaminants in the airlock, and pre-combustion fire detection. NASA has assessed several commercial and developing electronic noses (e-noses) for these applications. A preliminary series of tests identified those e-noses that exhibited sufficient sensitivity to the vapors of interest. These e-noses were further tested to assess their ability to identify vapors, and in-house software has been developed to enhance identification. This paper describes the tests, the classification ability of selected e-noses, and the software improvements made to meet the requirements for these space program applications

Turbulent mixing and the formation of an intermediate nepheloid layer above the Siberian continental shelf break

Intermediate nepheloid layers (INLs) form important pathways for the cross-slope transport and vertical export of particulate matter, including carbon. While intermediate maxima in particle settling fluxes have been reported in the Eurasian Basin of the Arctic Ocean, direct observations of turbid INLs above the continental slope are still lacking. In this study, we provide the first direct evidence of an INL, coinciding with enhanced mid-water turbulent dissipation rates, over the Laptev Sea continental slope in summer 2018. Current velocity data show a period of enhanced downslope flow with depressed isopcynals, suggesting that the enhanced turbulent dissipation is probably the consequence of the presence of an unsteady lee wave. Similar events occur mostly during ice free periods, suggesting an increasing frequency of episodic cross-slope particle transport in the future. The discovery of the INL and the episodic generation mechanism provide new insights into particle transport dynamics in this rapidly changing environment

Predictors of individual response to placebo or tadalafil 5mg among men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: An integrated clinical data mining analysis

Background: A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown. Methods: This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface. Findings: International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ∼50%for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group Conclusions: This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of tadalalfil 5mg once daily in the treatment of LUTS-BPH in the majority of patients and the importance of evaluating individual patient need in selecting the most appropriate treatment. Copyright