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Showing papers by "Free University of Berlin published in 2008"


Journal ArticleDOI
TL;DR: The Health Action Process Approach (HAPA) as mentioned in this paper suggests a distinction between preintentional motivation processes that lead to a behavioral intention, and postintentional volition processes that leads to the actual health behavior.
Abstract: Health-compromising behaviors such as physical inactivity and poor dietary habits are difficult to change. Most social-cognitive theories assume that an individual’s intention to change is the best direct predictor of actual change. But people often do not behave in accordance with their intentions. This discrepancy between intention and behavior is due to several reasons. For example, unforeseen barriers could emerge, or people might give in to temptations. Therefore, intention needs to be supplemented by other, more proximal factors that might compromise or facilitate the translation of intentions into action. Some of these postintentional factors have been identified, such as perceived self-efficacy and strategic planning. They help to bridge the intention– behavior gap. The Health Action Process Approach (HAPA) suggests a distinction between (a) preintentional motivation processes that lead to a behavioral intention, and (b) postintentional volition processes that lead to the actual health behavior. In this article, seven studies are reported that examine the role of volitional mediators in the initiation and adherence to five health behaviors: physical exercise, breast self-examination, seat belt use, dietary behaviors, and dental flossing. The general aim is to examine the applicability of the HAPA and its universality by replicating it across different health behaviors, based on various measures, time spans, and samples from different countries. Les comportements nuisibles a la sante tels que le manque d’exercice physique et les mauvaises habitudes alimentaires sont difficiles a modifier. La plupart des theories socio-cognitives admettent que le meilleur predicteur d’un reel changement est l’intention que la personne a de changer. Mais la conduite est souvent en contradiction avec les intentions. La divergence entre intention et comportement est due a plusieurs raisons. Par exemple, des obstacles imprevus

1,789 citations


Journal ArticleDOI
TL;DR: The authors used selected proxy-based reconstructions of different climate variables, together with state-of-the-art time series of natural forcings (orbital variations, solar activity variations, large tropical volcanic eruptions, land cover and greenhouse gases), underpinned by results from GCMs and Earth System Models of Intermediate Complexity (EMICs), to establish a comprehensive explanatory framework for climate changes from the mid-Holocene (MH) to pre-industrial time.

1,539 citations


Journal ArticleDOI
15 Aug 2008-Science
TL;DR: A global survey of messenger RNA splicing events identified 94,241 splice junctions and showed that exon skipping is the most prevalent form of alternative splicing.
Abstract: The functional complexity of the human transcriptome is not yet fully elucidated. We report a high-throughput sequence of the human transcriptome from a human embryonic kidney and a B cell line. We used shotgun sequencing of transcripts to generate randomly distributed reads. Of these, 50% mapped to unique genomic locations, of which 80% corresponded to known exons. We found that 66% of the polyadenylated transcriptome mapped to known genes and 34% to nonannotated genomic regions. On the basis of known transcripts, RNA-Seq can detect 25% more genes than can microarrays. A global survey of messenger RNA splicing events identified 94,241 splice junctions (4096 of which were previously unidentified) and showed that exon skipping is the most prevalent form of alternative splicing.

1,288 citations


Journal ArticleDOI
TL;DR: An algorithm, miRDeep, is presented, which uses a probabilistic model of miRNA biogenesis to score compatibility of the position and frequency of sequenced RNA with the secondary structure of the miRNA precursor.
Abstract: The capacity of highly parallel sequencing technologies to detect small RNAs at unprecedented depth suggests their value in systematically identifying microRNAs (miRNAs). However, the identification of miRNAs from the large pool of sequenced transcripts from a single deep sequencing run remains a major challenge. Here, we present an algorithm, miRDeep, which uses a probabilistic model of miRNA biogenesis to score compatibility of the position and frequency of sequenced RNA with the secondary structure of the miRNA precursor. We demonstrate its accuracy and robustness using published Caenorhabditis elegans data and data we generated by deep sequencing human and dog RNAs. miRDeep reports altogether approximately 230 previously unannotated miRNAs, of which four novel C. elegans miRNAs are validated by northern blot analysis.

1,135 citations


Journal ArticleDOI
TL;DR: It is concluded that beclin 1 deficiency disrupts neuronal autophagy, modulates APP metabolism, and promotes neurodegeneration in mice and that increasing beClin 1 levels may have therapeutic potential in AD.
Abstract: Autophagy is the principal cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Recently, autophagy has been implicated in neurodegeneration, but whether it is detrimental or protective remains unclear. Here we report that beclin 1, a protein with a key role in autophagy, was decreased in affected brain regions of patients with Alzheimer disease (AD) early in the disease process. Heterozygous deletion of beclin 1 (Becn1) in mice decreased neuronal autophagy and resulted in neurodegeneration and disruption of lysosomes. In transgenic mice that express human amyloid precursor protein (APP), a model for AD, genetic reduction of Becn1 expression increased intraneuronal amyloid beta (Abeta) accumulation, extracellular Abeta deposition, and neurodegeneration and caused microglial changes and profound neuronal ultrastructural abnormalities. Administration of a lentiviral vector expressing beclin 1 reduced both intracellular and extracellular amyloid pathology in APP transgenic mice. We conclude that beclin 1 deficiency disrupts neuronal autophagy, modulates APP metabolism, and promotes neurodegeneration in mice and that increasing beclin 1 levels may have therapeutic potential in AD.

1,057 citations


Journal ArticleDOI
TL;DR: In this article, the authors synthesize palaeoclimate records from the mid-latitude arid Asian region dominated today by the Westerlies ("arid central Asia" (ACA)) to evaluate spatial and temporal patterns of moisture changes during the Holocene.

947 citations


Journal ArticleDOI
TL;DR: In this article, the authors examined the relationship between self-efficacy, job stress, and burnout, focusing on mediation (selfefficacy → job stress → burnout) and questioned whether such a mediation would be dependent on the levels of other variables (moderated mediation).
Abstract: Teacher self-efficacy is studied as a personal resource factor that may protect from the experience of job strain and, thus, make the escalation of burnout less likely. The article examines the relationships between self-efficacy, job stress, and burnout, focusing on mediation (self-efficacy → job stress → burnout). Moreover, it questions whether such a mediation, if found, would be dependent on the levels of other variables (moderated mediation). Study I, with two samples of teachers (N= 1,203), examined this putative mechanism cross-sectionally and found such an effect, in particular for younger teachers and those with low general self-efficacy. Study II, with 458 teachers, replicated the results longitudinally over a period of one year by employing structural equation models. In a cross-lagged panel design, low self-efficacy preceded burnout. Further research should study these mechanisms by interventions that aim at strengthening teacher self-efficacy as a protective resource factor. L’auto-efficacite des enseignants est etudiee comme une ressource personnelle pouvant les proteger de l’experience de la contrainte professionnelle et rendre l’escalade dans le burnout moins probable. Cet article examine les liens entre l’auto-efficacite, le stress au travail et le burnout, en se focalisant sur la mediation (auto-efficacite→ stress au travail → burnout). En outre, il questionne la facon dont une telle mediation, si elle est averee, pourrait etre dependante du niveau des autres variables (mediation moderee). La recherche 1 comprend deux echantillons d’enseignants (N= 1,203). Elle examine ce mecanisme croise suppose et revele un tel effet, en particulier pour les enseignants les plus jeunes et ceux ayant une auto-efficacite generale basse. L’etude 2 effectuee aupres de 458 enseignants confirme ces resultats, obtenus cette fois de facon longitudinale sur une periode d’un an en employant des modeles aequation structurale. Ainsi, une auto-efficacite basse precede le burnout. Des recherches plus poussees pourraient etudier les mecanismes par lesquels des interventions renforcent ou non l’auto-efficacite des enseignants comme source de protection.

926 citations


Journal ArticleDOI
TL;DR: The physics behind the drug nanocrystals and changes of their physical properties are discussed, and the special physical effects of nanocry crystals explained which are utilized in each market product.
Abstract: Nanotechnology will affect our lives tremendously over the next decade in very different fields, including medicine and pharmacy Transfer of materials into the nanodimension changes their physical properties which were used in pharmaceutics to develop a new innovative formulation principle for poorly soluble drugs: the drug nanocrystals The drug nanocrystals do not belong to the future; the first products are already on the market The industrially relevant production technologies, pearl milling and high pressure homogenization, are reviewed The physics behind the drug nanocrystals and changes of their physical properties are discussed The marketed products are presented and the special physical effects ofnanocrystals explained which are utilized in each market product Examples of products in the development pipelines (clinical phases) are presented and the benefits for in vivo administration of drug nanocrystals are summarized in an overview

818 citations


Journal ArticleDOI
TL;DR: This paper discusses a selection of promising and interesting research areas in the design of protocols and systems for wireless industrial communications that have either emerged as hot topics in the industrial communications community in the last few years, or which could be worthwhile research Topics in the next few years.
Abstract: In this paper we discuss a selection of promising and interesting research areas in the design of protocols and systems for wireless industrial communications. We have selected topics that have either emerged as hot topics in the industrial communications community in the last few years (like wireless sensor networks), or which could be worthwhile research topics in the next few years (for example cooperative diversity techniques for error control, cognitive radio/opportunistic spectrum access for mitigation of external interferences).

696 citations


Journal ArticleDOI
TL;DR: This Review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.
Abstract: The investigation of biological processes by chemical methods, commonly referred to as chemical biology, often requires chemical access to biologically relevant macromolecules such as peptides and proteins. Building upon solid-phase peptide synthesis, investigations have focused on the development of chemoselective ligation and modification strategies to link synthetic peptides or other functional units to larger synthetic and biologically relevant macromolecules. This Review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.

676 citations


Journal ArticleDOI
TL;DR: This work presents OpenMS, a software framework for rapid application development in mass spectrometry designed to be portable, easy-to-use and robust while offering a rich functionality ranging from basic data structures to sophisticated algorithms for data analysis.
Abstract: Mass spectrometry is an essential analytical technique for high-throughput analysis in proteomics and metabolomics. The development of new separation techniques, precise mass analyzers and experimental protocols is a very active field of research. This leads to more complex experimental setups yielding ever increasing amounts of data. Consequently, analysis of the data is currently often the bottleneck for experimental studies. Although software tools for many data analysis tasks are available today, they are often hard to combine with each other or not flexible enough to allow for rapid prototyping of a new analysis workflow. We present OpenMS, a software framework for rapid application development in mass spectrometry. OpenMS has been designed to be portable, easy-to-use and robust while offering a rich functionality ranging from basic data structures to sophisticated algorithms for data analysis. This has already been demonstrated in several studies. OpenMS is available under the Lesser GNU Public License (LGPL) from the project website at http://www.openms.de .

Journal ArticleDOI
01 Aug 2008
TL;DR: In this article, a discrete treatment of adapted framed curves, parallel transport, and holonomy is presented for a discrete geometric model of thin flexible rods with arbitrary cross section and undeformed configuration.
Abstract: We present a discrete treatment of adapted framed curves, parallel transport, and holonomy, thus establishing the language for a discrete geometric model of thin flexible rods with arbitrary cross section and undeformed configuration. Our approach differs from existing simulation techniques in the graphics and mechanics literature both in the kinematic description---we represent the material frame by its angular deviation from the natural Bishop frame---as well as in the dynamical treatment---we treat the centerline as dynamic and the material frame as quasistatic. Additionally, we describe a manifold projection method for coupling rods to rigid-bodies and simultaneously enforcing rod inextensibility. The use of quasistatics and constraints provides an efficient treatment for stiff twisting and stretching modes; at the same time, we retain the dynamic bending of the centerline and accurately reproduce the coupling between bending and twisting modes. We validate the discrete rod model via quantitative buckling, stability, and coupled-mode experiments, and via qualitative knot-tying comparisons.

Journal ArticleDOI
10 Jul 2008-Neuron
TL;DR: It is demonstrated that Arc/Arg3.1 is translationally induced within 5 min of mGluR activation, and this response is essential for mGLUR-dependent LTD, and a model in which eEF2K-eEF2 and FMRP coordinately control the dynamic translation of Arc/ Arg3.

Journal ArticleDOI
01 Jul 2008
TL;DR: This work applies the first exact solution for functional modules in PPI networks by computing optimal-scoring subnetworks based on integer-linear programming and its connection to the well-known prize-collecting Steiner tree problem from Operations Research.
Abstract: Motivation: With the exponential growth of expression and protein–protein interaction (PPI) data, the frontier of research in systems biology shifts more and more to the integrated analysis of these large datasets. Of particular interest is the identification of functional modules in PPI networks, sharing common cellular function beyond the scope of classical pathways, by means of detecting differentially expressed regions in PPI networks. This requires on the one hand an adequate scoring of the nodes in the network to be identified and on the other hand the availability of an effective algorithm to find the maximally scoring network regions. Various heuristic approaches have been proposed in the literature. Results: Here we present the first exact solution for this problem, which is based on integer-linear programming and its connection to the well-known prize-collecting Steiner tree problem from Operations Research. Despite the NP-hardness of the underlying combinatorial problem, our method typically computes provably optimal subnetworks in large PPI networks in a few minutes. An essential ingredient of our approach is a scoring function defined on network nodes. We propose a new additive score with two desirable properties: (i) it is scalable by a statistically interpretable parameter and (ii) it allows a smooth integration of data from various sources. We apply our method to a well-established lymphoma microarray dataset in combination with associated survival data and the large interaction network of HPRD to identify functional modules by computing optimal-scoring subnetworks. In particular, we find a functional interaction module associated with proliferation over-expressed in the aggressive ABC subtype as well as modules derived from non-malignant by-stander cells. Availability: Our software is available freely for non-commercial purposes at http://www.planet-lisa.net. Contact: tobias.mueller@biozentrum.uni-wuerzburg.de

Book
05 Jun 2008
TL;DR: Fischer-Lichte as discussed by the authors traces the emergence of performance as an art event in its own right, and sets performance art on an equal footing with the traditional art object, heralding a new aesthetics.
Abstract: In this book, Erika Fischer-Lichte traces the emergence of performance as 'an art event' in its own right. In setting performance art on an equal footing with the traditional art object, she heralds a new aesthetics. The peculiar mode of experience that a performance provokes – blurring distinctions between artist and audience, body and mind, art and life – is here framed as the breeding ground for a new way of understanding performing arts, and through them even wider social and cultural processes. With an introduction by Marvin Carlson, this translation of the original Asthetik des Performativen addresses key issues in performance art, experimental theatre and cultural performances to lay the ground for a new appreciation of the artistic event.

Journal ArticleDOI
TL;DR: In this article, the importance of focusing more attention on climate policies and programs of state (prefectural, provincial), regional, metropolitan, and local levels of government is discussed.
Abstract: This article introduces this special issue that deals with subnational (and, in the case of the European Union, sub-supranational) global climate change politics. While recognizing the limitations that face local governments, the article discusses the importance of focusing more attention on climate policies and programs of state (prefectural, provincial), regional, metropolitan, and local levels of government, where implementation of national climate change policies and programs must occur. Four cases are examined in detail: California within the United States, Germany within the European Union, prefectures and some municipalities (Tokyo and Kyoto) within Japan, and provinces and prefectures within China. The reasons why local governments sometimes choose to act as agenda setters are considered, the ways local governments can influence national government policies are discussed, the role of international networks in diffusing policy ideas among local governments is introduced, and the obstacles to affect...

Journal ArticleDOI
TL;DR: An efficient interface specification as a set of C++ classes is derived that separates the applications from the grid data structures and thus, user implementations become independent of the underlying grid implementation.
Abstract: In a companion paper (Bastian et al. 2007, this issue) we introduced an abstract definition of a parallel and adaptive hierarchical grid for scientific computing. Based on this definition we derive an efficient interface specification as a set of C++ classes. This interface separates the applications from the grid data structures. Thus, user implementations become independent of the underlying grid implementation. Modern C++ template techniques are used to provide an interface implementation without big performance losses. The implementation is realized as part of the software environment DUNE (http://dune-project.org/). Numerical tests demonstrate the flexibility and the efficiency of our approach.

Journal ArticleDOI
TL;DR: Dynamics-based networks, also called Markov State Models, can be interpreted and adaptively improved using statistical concepts, such as the mean first passage time, reactive flux and sampling error analysis, which makes transition networks powerful tools for understanding large-scale conformational changes.

Journal ArticleDOI
TL;DR: In this article, the authors argue that the market logic of modernisation and competition for innovation combined with the market potential of global environmental needs serve as important driving forces behind eco-innovation.

Journal ArticleDOI
TL;DR: The definitions in this article serve as the basis for an implementation of an abstract grid interface as C++ classes in the framework (Bastian et al. 2008, this issue).
Abstract: We give a mathematically rigorous definition of a grid for algorithms solving partial differential equations. Unlike previous approaches (Benger 2005, PhD thesis; Berti 2000, PhD thesis), our grids have a hierarchical structure. This makes them suitable for geometric multigrid algorithms and hierarchical local grid refinement. The description is also general enough to include geometrically non-conforming grids. The definitions in this article serve as the basis for an implementation of an abstract grid interface as C++ classes in the framework (Bastian et al. 2008, this issue).

Journal ArticleDOI
TL;DR: CSD and PID are described in patients with malignant middle cerebral artery infarction detected by subdural electrocorticography (ECoG) and found to cause secondary neuronal damage and infarct expansion.
Abstract: Summary of Clinical Data Clinical data of the 16 patients (5 male and 11 femalepatients) are summarized in Table 1. Mean age was52.6 years ( 9.7). The left hemisphere was affected in6 and the right in 10 patients. Nine patients had ad-ditional infarction of either the ACA or the posteriorcerebral artery territory. Preoperative Glasgow ComaScale (full range, 3–15) was 10.3 ( 2.9), mean ex-tended Glasgow Outcome Scale (range, 1 [dead] to 8[full recovery to premorbid level]) after 6 months was2.9 ( 1.2). Mean time between stroke onset and op-eration was 34.1 ( 27.5) hours; mean time betweenstroke onset and start of monitoring was 39.8 ( 27.3)hours. Summary of Electrocorticographic Data ECoG data are summarized in Table 2. In the firstpatient, ECoG monitoring yielded continuous techni-cal artifacts; therefore, this patient was excluded fromECoG analysis. Monitoring was initiated soon aftersurgery and return of a patient to the intensive careunit. Aggregate duration of monitoring (all patients)was 1,638.1 hours; mean duration of monitoring perpatient was 109.2 hours ( 37.1). All patients re-mained sedated and ventilated throughout the mea-surement. In three patients, ECoG remained flatthroughout monitoring, and in two of these patients,no SPCs were observed. Seizure activity did not occurin any patient.In total, 127 episodes of CSD were detected in 8patients. In every CSD, a stereotyped SPC spreadingbetween adjacent channels was accompanied by a tran-sient depression of the ECoG activity, which recoveredover time (see Fig 1D). Because each channel displayedthe potential difference between its two active elec-trodes, the spread of the SPC from one electrode to thenext was seen from the phase reversal between twoneighboring channels sharing a common electrode (seeFig 1D, upper traces). In 8 patients, a total of 42 PIDswere observed. All PIDs were characterized by spreadof SPCs between neighboring channels, in the absenceof any pre-event background ECoG activity. Accord-ingly, such SPCs were not accompanied by a depres-sion of ECoG activity. PID therefore represents spread-ing depolarization in otherwise electrically silent tissue.In 4 patients, a total of 65 SPCs did not show clearspread of depolarizations. We kept analysis conservativeand did not include such simultaneous depolarizationsin the further analysis because the criteria for spreadingdepolarizations based on existing experimental andclinical studies specify spread of a depolarization as aprerequisite to score it as CSD or PID.Time delay between onset of monitoring and theDohmen et al: CSD and PID in Human Stroke

Journal ArticleDOI
TL;DR: It is demonstrated how the ATPases' C termini function to facilitate substrate entry by identifying the sites in the archaeal 20S where PAN's C-terminal residues bind and determining the structures of the gate in its closed and open forms.

Journal ArticleDOI
19 Sep 2008-Science
TL;DR: In this article, the authors used femtosecond time and angle-resolved photoelectron spectroscopy (trARPES) to optically pump and probe TbTe3, an excellent model system with which to study microscopic cooperative effects.
Abstract: Obtaining insight into microscopic cooperative effects is a fascinating topic in condensed matter research because, through self-coordination and collectivity, they can lead to instabilities with macroscopic impacts like phase transitions. We used femtosecond time- and angle-resolved photoelectron spectroscopy (trARPES) to optically pump and probe TbTe3, an excellent model system with which to study these effects. We drove a transient charge density wave melting, excited collective vibrations in TbTe3, and observed them through their time-, frequency-, and momentum-dependent influence on the electronic structure. We were able to identify the role of the observed collective vibration in the transition and to document the transition in real time. The information that we demonstrate as being accessible with trARPES will greatly enhance the understanding of all materials exhibiting collective phenomena.

Journal ArticleDOI
TL;DR: NPCs from neonatal mouse brains are isolated and infected with viral vectors expressing Oct4, Sox2, Klf4, and c‐Myc, suggesting that in vitro reprogramming is a universal process and that the combination of factors necessary for reprograming is dependent on cellular context.
Abstract: Expression of the transcription factors Oct4, Sox2, Klf4, and c-Myc in mesodermal and endodermal derivatives, including fibroblasts, lymphocytes, liver, stomach, and beta cells, generates induced pluripotent stem (iPS) cells. It remains unknown, however, whether cell types of the ectodermal lineage are equally amenable to reprogramming into iPS cells by the same combination of factors. To test this, we have isolated genetically marked neural progenitor cells (NPCs) from neonatal mouse brains and infected them with viral vectors expressing Oct4, Sox2, Klf4, and c-Myc. Infected NPCs gave rise to iPS cells that expressed markers of embryonic stem cells, showed demethylation of pluripotency genes, formed teratomas, and contributed to viable chimeras. In contrast to other somatic cell types, NPCs expressed high levels of endogenous Sox2 and thus did not require viral Sox2 expression for reprogramming into iPS cells. Our data show that in addition to mesoderm- and endoderm-derived cell types, neural progenitor cells of the ectodermal lineage can be reprogrammed into iPS cells, suggesting that in vitro reprogramming is a universal process. These results also imply that the combination of factors necessary for reprogramming is dependent on cellular context. Disclosure of potential conflicts of interest is found at the end of this article.

Journal ArticleDOI
TL;DR: The design and content of SeqAn are described, which comprises implementations of existing, practical state-of-the-art algorithmic components to provide a sound basis for algorithm testing and development and greatly simplifies the rapid development of new bioinformatics tools.
Abstract: Background The use of novel algorithmic techniques is pivotal to many important problems in life science. For example the sequencing of the human genome [1] would not have been possible without advanced assembly algorithms. However, owing to the high speed of technological progress and the urgent need for bioinformatics tools, there is a widening gap between state-of-the-art algorithmic techniques and the actual algorithmic components of tools that are in widespread use.

Journal ArticleDOI
TL;DR: In this paper, a basic nine-step reaction cycle involving eight steps of alternating deprotonation and oxidation of the Mn-complex prior to O-O bond formation and dioxygen release is discussed.

Proceedings ArticleDOI
10 Dec 2008
TL;DR: This course outlines its mathematical foundations, describes recent methods for parameterizing meshes over various domains, discusses emerging tools like global parameterization and inter-surface mapping, and demonstrates a variety of parameterization applications.
Abstract: Mesh parameterization is a powerful geometry processing tool with numerous computer graphics applications, from texture mapping to animation transfer. This course outlines its mathematical foundations, describes recent methods for parameterizing meshes over various domains, discusses emerging tools like global parameterization and inter-surface mapping, and demonstrates a variety of parameterization applications.

Proceedings ArticleDOI
21 Apr 2008
TL;DR: This workshop summary will outline the technical context in which Linked Data is situated, describe developments in the past year through initiatives such as the Linking Open Data community project, and look ahead to the workshop itself.
Abstract: The Web is increasingly understood as a global information space consisting not just of linked documents, but also of Linked Data. More than just a vision, the resulting Web of Data has been brought into being by the maturing of the Semantic Web technology stack, and by the publication of an increasing number of datasets according to the principles of Linked Data.The Linked Data on the Web (LDOW2008) workshop brings together researchers and practitioners working on all aspects of Linked Data. The workshop provides a forum to present the state of the art in the field and to discuss ongoing and future research challenges. In this workshop summary we will outline the technical context in which Linked Data is situated, describe developments in the past year through initiatives such as the Linking Open Data community project, and look ahead to the workshop itself.

Journal ArticleDOI
TL;DR: The logic and sequence of molecular events underlying the motile-to-adhesive "lifestyle" switch in E. coli are revealed and a fine-tuned checkpoint system that "unlocks" curli expression only after down-regulation of flagellar gene expression is produced.
Abstract: Depending on environmental conditions, bacteria can exhibit very different “lifestyles.” They can occur in a motile single-cellular or planktonic state or as sedentary cells that use adhesive fimbriae to cluster together and form biofilms on surfaces (O’Toole et al. 2000; Hall-Stoodley et al. 2004). With Escherichia coli grown in complex medium, these states can be observed successively, with cells transiently becoming highly motile during the post-exponential growth phase (Adler and Templeton 1967; Amsler et al. 1993; Zhao et al. 2007) followed by the induction of adhesive curli fimbriae during entry into stationary phase (Olsen et al. 1989). Motility and adhesion can also be expected to be mutually exclusive—being sticky seems counterproductive for swimming around, whereas adhesion and settling down might require reduced activity of the force-generating flagellar “propellers.” A convenient way to realize such an inverse coordination would be to endow the flagellar/motility control system with at least one component that plays an inhibitory role in the adhesion control system and vice versa. In E. coli, both motility and curli-mediated adhesion are under the control of regulatory feedforward cascades, each with a master regulator at the top, which acts as a massive environmental signal integrator. For flagellar expression and motility, this master regulator is the FlhDC complex (FlhD4C2, with the flhDC operon being defined as the flagellar class 1 operon) (Liu and Matsumura 1994; Wang et al. 2006). FlhDC activates the expression of class 2 operons, which encode the inner part of the flagellum (i.e., the hook basal body that also acts as a secretion system for the outer components) as well as the flagellar σ subunit of RNA polymerase (RNAP), FliA (σ28 or σF), and its anti-σ factor, FlgM. Upon secretion of FlgM, which occurs as soon as the basal body secretion system is functional, FliA is released to activate class 3 operons that encode the outer subunits of the flagellum, additional proteins required for flagellar function and chemotaxis, as well as a number of proteins of still unknown function (Chilcott and Hughes 2000; Karlinsey et al. 2000; Aldrigde et al. 2006). Adhesive curli fimbriae, on the other hand, are expressed during entry into stationary phase (in cells that grow below 30°C). Curli fimbriae are involved in both cell–cell aggregation and surface adhesion (Barnhart and Chapman 2006). The curli control cascade is a module within the general stress response, for which the σS (RpoS) σ subunit of RNAP acts as the master regulator (Hengge-Aronis 2000). In parallel, σS-containing RNAP (EσS) activates the expression of MlrA (a MerR-like regulator) and YdaM (a GGDEF protein, see below), which, together with EσS again, are essential to activate transcription of the csgD gene. The CsgD protein (also called AgfD in Salmonella) is an essential activator for the curli structural gene operon (csgBAC), and cooperates with the vegetative RNAP at the csgB promoter (Romling et al. 2000; Brown et al. 2001; Gerstel et al. 2003; Weber et al. 2006). Another key player in the control of motility and curli expression—i.e., in bacterial “lifestyle” switching—is the signaling molecule bis-(3′–5′)-cyclic-diguanosine monophosphate (c-di-GMP) (for recent reviews, see Romling et al. 2005; Jenal and Malone 2006; Ryan et al. 2006; Tamayo et al. 2007). Overproduction of certain diguanylate cyclases (DGC; characterized by GGDEF domains) interferes with motility and strongly activates the expression of curli fimbriae and the biofilm matrix component cellulose in enteric bacteria, whereas overproduction of certain c-di-GMP-degrading phosphodiesterases (PDE; carrying EAL domains) produces the opposite phenotype. In recent mutational and biochemical analyses, specific DGCs and PDEs have been assigned antagonistic roles in the regulation of curli expression (Kader et al. 2006; Weber et al. 2006; Simm et al. 2007). For E. coli , these are YdaM (the GGDEF protein already mentioned above) and YciR (a GGDEF + EAL protein), which control csgD transcription (Weber et al. 2006). Another EAL protein, YhjH, was shown to play a positive role in motility (Ko and Park 2000; Rychlik et al. 2002; Frye et al. 2006; Ryjenkov et al. 2006). However, the molecular details of c-di-GMP action in the control of curli expression and motility have not been characterized. The questions addressed by our study are the following: Do the FlhDC/motility and σS/curli control cascades really directly communicate to inversely coordinate their activities? And, if so, what are the factors involved, and are (some of) these factors c-di-GMP control systems; i.e., GGDEF/EAL proteins? With the present study, we identified several such factors acting at different hierarchical levels of the control network established, we provide evidence that throwing the motility-to-adhesion switch requires a precise down-regulation of motility at the transcriptional, proteolytic, and protein activity levels, and we present a framework model for the logic and the sequence of molecular events underlying this phenotypic “lifestyle” change in E. coli during entry into stationary phase.

Journal ArticleDOI
TL;DR: It is demonstrated in a group of 14 fully BCI-naive subjects that 8 out of 14 BCI novices can perform at >84% accuracy in their very first BCI session, and a further four subjects at >70%.
Abstract: The Berlin brain-computer interface (BBCI) project develops a noninvasive BCI system whose key features are: 1) the use of well-established motor competences as control paradigms; 2) high-dimensional features from multichannel EEG; and 3) advanced machine-learning techniques. Spatio-spectral changes of sensorimotor rhythms are used to discriminate imagined movements (left hand, right hand, and foot). A previous feedback study [M. Krauledat, K.-R. Muller, and G. Curio. (2007) The non-invasive Berlin brain-computer Interface: Fast acquisition of effective performance in untrained subjects. NeuroImage. [Online]. 37(2), pp. 539--550. Available: http://dx.doi.org/10.1016/j.neuroimage.2007.01.051] with ten subjects provided preliminary evidence that the BBCI system can be operated at high accuracy for subjects with less than five prior BCI exposures. Here, we demonstrate in a group of 14 fully BCI-naive subjects that 8 out of 14 BCI novices can perform at >84% accuracy in their very first BCI session, and a further four subjects at >70%. Thus, 12 out of 14 BCI-novices had significant above-chance level performances without any subject training even in the first session, as based on an optimized EEG analysis by advanced machine-learning algorithms.