Market-based Recommendation: Agents that Compete for Consumer Attention

The amount of attention space available for recommending suppliers to consumers on e-commerce sites is typically limited. We present a competitive distributed recommendation mechanism based on adaptive software agents for efficiently allocating the 'consumer attention space', or banners. In the example of an electronic shopping mall, the task is delegated to the individual shops, each of which evaluates the information that is available about the consumer and his or her interests (e.g. keywords, product queries, and available parts of a profile). Shops make a monetary bid in an auction where a limited amount of 'consumer attention space' for the arriving consumer is sold. Each shop is represented by a software agent that bids for each consumer. This allows shops to rapidly adapt their bidding strategy to focus on consumers interested in their offerings. For various basic and simple models for on-line consumers, shops, and profiles, we demonstrate the feasibility of our system by evolutionary simulations as in the field of agent-based computational economics (ACE). We also develop adaptive software agents that learn bidding strategies, based on neural networks and strategy exploration heuristics. Furthermore, we address the commercial and technological advantages of this distributed market-based approach. The mechanism we describe is not limited to the example of the electronic shopping mall, but can easily be extended to other domains

LITOS - A new balloon-borne instrument for fine-scale turbulence soundings in the stratosphere

We have developed a new compact balloon payload called LITOS (Leibniz-Institute Turbulence Observations in the Stratosphere) for high resolution wind turbulence soundings in the stratosphere up to 35 km altitude. The wind measurements are performed using a constant temperature anemometer (CTA) with a vertical resolution of ∼2.5 mm, i.e. 2 kHz sampling rate at 5 m/s ascent speed. Thereby, for the first time, it is possible to study the entire turbulence spectrum down to the viscous subrange in the stratosphere. Including telemetry, housekeeping, batteries and recovery unit, the payload weighs less than 5 kg and can be launched from any radiosonde station. Since autumn 2007, LITOS has been successfully launched several times from the Leibniz-Institute of Atmospheric Physics (IAP) in Kühlungsborn, Germany (54° N, 12° E). Two additional soundings were carried out in 2008 and 2009 in Kiruna, Sweden (67° N, 21° E) as part of the BEXUS program (Balloon-borne EXperiments for University Students). We describe here the basic principle of CTA measurements and prove the validity of this method in the stratosphere. A first case study allows a clear distinction between non-turbulent regions and a turbulent layer with a thickness of some tens of meters. Since our measurements cover the transition between the inertial and viscous subrange, energy dissipation rates can be calculated with high reliability

Molecular Dissection of the Essential Features of the Origin of Replication of the Second Vibrio cholerae Chromosome

ABSTRACT Vibrionaceae family members are interesting models for studying DNA replication initiation, as they contain two circular chromosomes. Chromosome II (chrII) replication is governed by two evolutionarily unique yet highly conserved elements, the origin DNA sequence oriCII and the initiator protein RctB. The minimum functional region of oriCII, oriCII-min, contains multiple elements that are bound by RctB in vitro, but little is known about the specific requirements for individual elements during oriCII initiation. We utilized undirected and site-specific mutagenesis to investigate the functionality of mutant forms of oriCII-min and assessed binding to various mutant forms by RctB. Our analyses showed that deletions, point mutations, and changes in RctB target site spacing or methylation all impaired oriCII-min-based replication. RctB displayed a reduced affinity for most of the low-efficacy origins tested, although its characteristic cooperative binding was generally maintained. Mutations that removed or altered the relative positions of origin components other than RctB binding sites (e.g., AT-rich sequence, DnaA target site) also abolished replicative capacity. Comprehensive mutagenesis and deep-sequencing-based screening (OriSeq) allowed the identification of a previously uncharacterized methylated domain in oriCII that is required for origin function. Together, our results reveal the remarkable evolutionary honing of oriCII and provide new insight into the complex interplay between RctB and oriCII

Individualized Stabilization Criteria–Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion

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Multihospital Outbreak of Clostridium difficile Infection, Cleveland, Ohio, USA

To determine whether a multihospital Clostridium difficile outbreak was associated with epidemic strains and whether use of particular fluoroquinolones was associated with increased infection rates, we cultured feces from C. difficile–infected patients. Use of fluoroquionolones with enhanced antianaerobic activity was not associated with increased infection rates

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion

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Transcriptional analysis of temporal gene expression in germinating Clostridium difficile 630 endospores.

Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth

Butyrate oxidation attenuates the butyrate-induced improvement of insulin sensitivity in myotubes

Skeletal muscle insulin resistance is a key pathophysiological process that precedes the development of type 2 diabetes. Whereas an overload of long-chain fatty acids can induce muscle insulin resistance, butyrate, a short -chain fatty acid (SCFA) produced from dietary fibre fermentation, prevents it. This preventive role of butyrate has been attributed to histone deacetylase (HDAC)-mediated transcription regulation and activation of mito-chondrial fatty-acid oxidation. Here we address the interplay between butyrate and the long-chain fatty acid palmitate and investigate how transcription, signalling and metabolism are integrated to result in the butyrate -induced skeletal muscle metabolism remodelling. Butyrate enhanced insulin sensitivity in palmitate-treated, insulin-resistant C2C12 cells, as shown by elevated insulin receptor 1 (IRS1) and pAKT protein levels and Slc2a4 (GLUT4) mRNA, which led to a higher glycolytic capacity. Long-chain fatty-acid oxidation capacity and other functional respiration parameters were not affected. Butyrate did upregulate mitochondrial proteins involved in its own oxidation, as well as concentrations of butyrylcarnitine and hydroyxybutyrylcarnitine. By knocking down the gene encoding medium-chain 3-ketoacyl-CoA thiolase (MCKAT, Acaa2), butyrate oxidation was inhibited, which amplified the effects of the SCFA on insulin sensitivity and glycolysis. This response was associated with enhanced HDAC inhibition, based on histone 3 acetylation levels. Butyrate enhances insulin sensitivity and induces glycolysis, without the requirement of upregulated long-chain fatty acid oxidation. Butyrate catabolism functions as an escape valve that attenuates HDAC inhibition. Thus, inhibition of butyrate oxidation indirectly prevents insulin resistance and stimulates glycolytic flux in myotubes treated with butyrate, most likely via an HDAC-dependent mechanism.Diabetes mellitus: pathophysiological changes and therap

Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability

Metabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These programs are not static entities but can change swiftly as a consequence of extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients with FLT3 internal tandem duplications (FLT3-ITD+) are characterized by a high expression of succinate-CoA ligases and high activity of mitochondrial electron transport chain (ETC) complex II, thereby driving high mitochondrial respiration activity linked to the Krebs cycle. While inhibition of ETC complex II enhances apoptosis in FLT3-ITD+ AML, cells also quickly adapt by importing lactate from the extracellular microenvironment. 13C3-labelled lactate metabolic flux analyses reveal that AML cells use lactate as a fuel for mitochondrial respiration. Inhibition of lactate transport by blocking Monocarboxylic Acid Transporter 1 (MCT1) strongly enhances sensitivity to ETC complex II inhibition in vitro as well as in vivo. Our study highlights a metabolic adaptability of cancer cells that can be exploited therapeutically.</p

Clostridium difficile plasmid isolation as an epidemiologic tool

A large hospital outbreak of Clostridium difficile diarrhea at the Minneapolis Veterans Administration Medical Center (MVAMC) was studied by plasmid profile typing. Plasmids were obtained from 30 (37 %) of 82 clinical isolates from MVAMC patients and 10 (67 %) of 15 non-MVAMC isolates. While bacteriophage plus bacteriocin typing and polyacrylamide gel electrophoresis (PAGE) plus bacterial agglutination typing proved more universally applicable, plasmid profiles may be useful for tracing isolated epidemic outbreaks, reinfections and relapses caused by plasmid-bearing strains.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47897/1/10096_2005_Article_BF01963112.pd