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Garching bei München, Germany

Zeiler E.,TU Munich | Braun N.,TU Munich | Bottcher T.,EXIST Transfer of Research | Bottcher T.,Harvard University | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2011

The Clp proteolytic machinery has important functions in many bacteria such as L. monocytogenes. Some organisms encode for two uncharacterized ClpP isoforms. Vibralactone was used to study the activity and assembly of ClpP1 and ClpP2 subunits in a hetero-oligomeric complex. Electron microscopic images reveal that the tetradecameric assembly is made up of two stacked homoheptameric ClpP1 and ClpP2 rings. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


News Article
Site: http://phys.org/technology-news/

Beyond search, this technology also assists authors in researching and even in writing texts by automatically providing background information and suggesting links to relevant web sites. Living in the age of business smartphones and enterprise chatrooms, most information in companies is not distributed via spoken words but rather through e-mails, databases, and internal news portals. "According to a survey by the market analyst Gartner, a mere quarter of all companies are using automatic methods to analyze their textual information. By 2021, Gartner predicts 65 per cent will do so. This is because the amount of data inside companies is continuously growing and hence, it becomes more and more costly to have it structured and to search it successfully," says Johannes Hoffart, a researcher at the Max Planck Institute for Informatics and founder of Ambiverse. His team developed a novel text analysis technology for analyzing huge amounts of text where massive computing power and artificial intelligence (AI) are continuously "thinking along" in the background. "For analyzing texts, we rely on extremely large knowledge graphs which are built upon freely available sources such as Wikipedia or large media portals on the web. These graphs can be augmented with domain- or company-specific knowledge, such as product catalogs or customer correspondences," says Hoffart. By applying complex algorithms, these texts are screened further and analyzed with linguistic tools. "Our software then assigns companies and areas of business to their corresponding categories, which allows us to gather valuable insights on how well one's own products are positioned in the market in comparison to those of the competitors," he explains. Particularly challenging hereby is the fact that product or company names are anything but unique and tend to have completely different meanings in different contexts, making them highly ambiguous. "Our technology helps to map words and phrases to their correct objects of the real-world, that way resolving ambiguities automatically," explains the computer scientist. "Paris" for example stands for the city of light and the French capital, but also for a figure from Greek mythology or a millionfold-mentioned party girl with German ancestors - always depending on context. "Efficiently searching huge text collections is only possible if the different meanings of a name or a concept are correctly resolved," says Hoffart. The smart search engine developed by his team continuously learns and improves over time, and also automatically associates new text entries to matching categories. "These algorithms are hence attractive for companies that analyze online media or social networks to measure the degree of brand awareness for a product or the success of a marketing campaign," says Hoffart further. At Cebit, Ambiverse will further present a smart authoring platform that assists authors in researching and writing texts. Users who enter texts are automatically provided with background information, for example company-internal guidelines and manuals or web links. "Relevant concepts are linked automatically and links for further research are show", says the computer scientist. Visitors to the Ambiverse Cebit booth (hall 6, booth 28) will also have the opportunity to compete with their novel AI technology by playing a question-answering game. Ambiverse is funded by the German Federal Ministry for Economic Affairs through an EXIST Transfer of Research grant. Ambiverse, a spin-off company from the Max Planck Institute for Informatics in Saarbruecken, will be presenting this novel technology during Cebit 2016 in Hannover from 14 to 18 March at Saarland's research booth. Explore further: Researcher develops computational text analysis method made possible regardless of language or domain


Geiger S.R.,Ludwig Maximilians University of Munich | Geiger S.R.,Lawrence Berkeley National Laboratory | Bottcher T.,EXIST Transfer of Research | Sieber S.A.,TU Munich | Cramer P.,Ludwig Maximilians University of Munich
Angewandte Chemie - International Edition | Year: 2011

A "breathing" protein: The first structure of the virulence regulator and heat shock protein ClpP from Staphylococcus aureus reveals a previously unobserved compressed state of the ClpP barrel. A conformational switch in the active center "handle region" results in closure of the active sites and opening of equatorial pores. These results confirm proposed modes of processive substrate degradation and product release for the ClpP protease family. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Lorenz-Baath K.,EXIST Transfer of Research | Korotkov V.S.,EXIST Transfer of Research | LiersevonGostomski C.,Radiochemie Munich RCM | Sieber S.A.,TU Munich
ChemMedChem | Year: 2012

Bacterial infections of skin and soft tissue represent a major health threat, especially if they are caused by multidrug-resistant strains such as MRSA. Novel treatment options for topical application are urgently needed, and even if new drug candidates are identified, their properties must match the specific physical requirements of the skin in order to penetrate and reach the site of bacterial infection. β-Lactones have been shown to eliminate bacterial virulence, but knowledge about their potential in topical treatments had thus far been lacking. Herein we present the synthesis and in-depth investigations of skin permeation and skin distribution of a radioactive 14C-labeled tool compound that was formulated with various basic ointments and applied to pig skin samples. Our results show that skin penetration depends highly on the nature of the formulation base. Vaseline is the most efficient ointment and is best suited for effecting maximal drug delivery within and through the stratum corneum, an important entrance barrier, and meets the required quantities for eliciting anti-virulence effects. We are confident that the nature of these new β-lactone virulence inhibitors confers applicability and potency for topical treatment, and will translate into a new formulation of this highly potent drug candidate for the treatment of skin and soft tissue infections. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Weinandy F.,EXIST Transfer of Research | Lorenz-Baath K.,EXIST Transfer of Research | Korotkov V.S.,EXIST Transfer of Research | Bottcher T.,EXIST Transfer of Research | And 4 more authors.
ChemMedChem | Year: 2014

Skin infections caused by Staphylococcus aureus are a major clinical concern, especially if they are caused by multi-resistant strains. In these cases, a spread into deeper soft tissues or the bloodstream results in life-threatening conditions that are difficult to treat by conventional antibiotics. Previous in vitro experiments with a small β-lactone-based molecule demonstrated that antibiotic-sensitive and -resistant S. aureus strains are effectively disarmed in their virulence and corresponding pathogenicity. In this work, in vivo mouse studies show that this methodology is effective for the treatment of skin abscesses in mice. A single dose of the β-lactone significantly decreased abscess size even when applied 6 h post-infection. Although the molecule requires pharmacological optimization (improved stability, for example), this study emphasizes the potential value of antivirulence therapies. Gets under the skin: Subcutaneous administration of S. aureus into mice resulted in the rapid development of severe skin abscesses. These abscesses were significantly decreased in size by a single-dose treatment with β-lactone U1, showing that targeting bacterial virulence is a promising strategy to combat bacterial infections. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

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