Music Piracy on Peer-to-Peer Networks

Content providers from the music industry argue that peer-to-peer (P2P) networks such as KaZaA, Morpheus, iMesh, or Audiogalaxy are an enormous threat to their business. They furthermore blame these networks for their recent decline in sales figures. For this reason, an empirical investigation was conducted during a period of 6 weeks on one of the most popular files-sharing systems, in order to determine the quantity and quality of pirated music songs shared. We present empirical evidence as to what extent and in which quality music songs are being shared. A number of hypotheses are outlined and were tested. We studied, among other things, the number of users online and the number of flies accessible on such networks, the free riding problem, and the duration per search request. We further tested to see if there are any differences in the accessibility of songs based on the nationality of the artist, the language of the song, and the corresponding chart position. Finally, we outline the main hurdles users may face when downloading illegal music and the probability of obtaining high quality music tracks on such peer-to-peer networks.

The Swiss Neonatal Quality Cycle, a monitor for clinical performance and tool for quality improvement

BACKGROUND We describe the setup of a neonatal quality improvement tool and list which peer-reviewed requirements it fulfils and which it does not. We report on the so-far observed effects, how the units can identify quality improvement potential, and how they can measure the effect of changes made to improve quality. METHODS Application of a prospective longitudinal national cohort data collection that uses algorithms to ensure high data quality (i.e. checks for completeness, plausibility and reliability), and to perform data imaging (Plsek's p-charts and standardized mortality or morbidity ratio SMR charts). The collected data allows monitoring a study collective of very low birth-weight infants born from 2009 to 2011 by applying a quality cycle following the steps 'guideline - perform - falsify - reform'. RESULTS 2025 VLBW live-births from 2009 to 2011 representing 96.1% of all VLBW live-births in Switzerland display a similar mortality rate but better morbidity rates when compared to other networks. Data quality in general is high but subject to improvement in some units. Seven measurements display quality improvement potential in individual units. The methods used fulfil several international recommendations. CONCLUSIONS The Quality Cycle of the Swiss Neonatal Network is a helpful instrument to monitor and gradually help improve the quality of care in a region with high quality standards and low statistical discrimination capacity.

A Smart TCP Acknowledgment Approach for Multihop Wireless Networks

Reliable data transfer is one of the most difficult tasks to be accomplished in multihop wireless networks. Traditional transport protocols like TCP face severe performance degradation over multihop networks given the noisy nature of wireless media as well as unstable connectivity conditions in place. The success of TCP in wired networks motivates its extension to wireless networks. A crucial challenge faced by TCP over these networks is how to operate smoothly with the 802.11 wireless MAC protocol which also implements a retransmission mechanism at link level in addition to short RTS/CTS control frames for avoiding collisions. These features render TCP acknowledgments (ACK) transmission quite costly. Data and ACK packets cause similar medium access overheads despite the much smaller size of the ACKs. In this paper, we further evaluate our dynamic adaptive strategy for reducing ACK-induced overhead and consequent collisions. Our approach resembles the sender side's congestion control. The receiver is self-adaptive by delaying more ACKs under nonconstrained channels and less otherwise. This improves not only throughput but also power consumption. Simulation evaluations exhibit significant improvement in several scenarios

Increased phase synchronization during continuous face integration measured simultaneously with EEG and fMRI

Gamma zero-lag phase synchronization has been measured in the animal brain during visual binding. Human scalp EEG studies used a phase locking factor (trial-to-trial phase-shift consistency) or gamma amplitude to measure binding but did not analyze common-phase signals so far. This study introduces a method to identify networks oscillating with near zero-lag phase synchronization in human subjects.

Real-time closed-loop electrophysiology: towards new frontiers in in vitro investigations in the neurosciences

Reflected at any level of organization of the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most in vitro preparations and experimental protocols operate autonomously, and do not depend on the output of the studied system. Thanks to the progress in digital signal processing and real-time computing, it is now possible to artificially close the loop and investigate biophysical processes and mechanisms under increased realism. In this contribution, we review some of the most relevant examples of a new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to multi-electrode distributed feedback stimulation. We are convinced these represents the beginning of new frontiers for the in vitro investigation of the brain, promising to open the still existing borders between theoretical and experimental approaches while taking advantage of cutting edge technologies.

Engineered fibrin matrices for functional display of cell membrane-bound growth factor-like activities: study of angiogenic signaling by ephrin-B2

With the rapid increase in approaches to pro- or anti-angiogenic therapy, new and effective methodologies for administration of cell-bound growth factors will be required. We sought to develop the natural hydrogel matrix fibrin as platform for extensive interactions and continuous signaling by the vascular morphogen ephrin-B2 that normally resides in the plasma membrane and requires multivalent presentation for ligation and activation of Eph receptors on apposing endothelial cell surfaces. Using fibrin and protein engineering technology to induce multivalent ligand presentation, a recombinant mutant ephrin-B2 receptor binding domain was covalently coupled to fibrin networks at variably high densities. The ability of fibrin-bound ephrin-B2 to act as ligand for endothelial cells was preserved, as demonstrated by a concomitant, dose-dependent increase of endothelial cell binding to engineered ephrin-B2-fibrin substrates in vitro. The therapeutic relevance of ephrin-B2-fibrin implant matrices was demonstrated by a local angiogenic response in the chick embryo chorioallontoic membrane evoked by the local and prolonged presentation of matrix-bound ephrin-B2 to tissue adjacing the implant. This new knowledge on biomimetic fibrin vehicles for precise local delivery of membrane-bound growth factor signals may help to elucidate specific biological growth factor function, and serve as starting point for development of new treatment strategies.

Unmet needs of young interventional cardiologists: the EAPCI Young survey

Aims: As part of the EAPCI Young Initiative, the European Association of Percutaneous Cardiovascular Interventions (EAPCI) conducted a survey to address the educational needs of young interventional cardiologists. Methods and results: A questionnaire was distributed to all individuals registered in the ESC database aged <36 years with an interest in interventional cardiology. Nearly two-thirds of participants (60%) indicated that they had difficulty in finding a fellowship training position. The desire for a fellow's course at European level was expressed by 95%, while 94% were in favour of developing a network of young interventional cardiologists in Europe. More than three-quarters of respondents (79%) said they had had difficulty in obtaining funding to attend EuroPCR. Multiple difficulties were identified in setting up a research programme, two of the more frequent being problematic access to research networks and the difficulties of finding a mentor. Career orientation was identified as another issue, with more than half of respondents (59%) declaring they followed career options by chance. Conclusions: The survey underlines the need to fill a gap in order to address the needs of young interventional cardiologists. It may serve as a starting point for developing educational initiatives targeted at young interventional cardiologists.

The ribosome as novel target for small regulatory RNAs

Small non-protein-coding RNA (ncRNA) molecules have been recognized recently as major contributors to regulatory networks in controlling gene expression in a highly efficient manner. While the list of validated ncRNAs that regulate crucial cellular processes grows steadily, not a single ncRNA has been identified that directly interacts and regulates the ribosome during protein biosynthesis (with the notable exceptions of 7SL RNA and tmRNA). All of the recently discovered regulatory ncRNAs that act on translation (e.g. microRNAs, siRNAs or antisense RNAs) target the mRNA rather than the ribosome. This is unexpected, given the central position the ribosome plays during gene expression. Furthermore it is strongly assumed that the primordial translation system in the ‘RNA world’ most likely received direct regulatory input from ncRNA-like cofactors. The fundamental question that we would like to ask is: Does the ‘RNA world still communicate’ with the ribosome? To address this question, we have analyzed the small ncRNA interactomes of ribosomes of prokaryotic (H. volcanii, S. aureus) and unicellular eukaryotic model organisms. Deep-sequencing and subsequent bioinformatic analyses revealed thousands of putative ribosome-associated ncRNAs. For a subset of these ncRNA candidates we have gathered experimental evidence that they are expressed in a stress-dependent manner and indeed directly target the ribosome. In the archaeon H. volcanii a tRNA-derived fragment was identified to target the small ribosomal subunit upon alkaline stress in vitro and in vivo. As a consequence of ribosome binding, this tRNA-fragment reduces protein synthesis by interfering with the peptidyl transferase activity. Our data reveal the ribosome as a novel target for small regulatory ncRNAs in all domains of life. Ribosome-bound ncRNAs are capable of fine tuning translation and might represent a so far largely unexplored class of regulatory sRNAs.

The ribosome as novel target for small regulatory RNAs

Small non-protein-coding RNA (ncRNA) molecules have been recognized recently as major contributors to regulatory networks in controlling gene expression in a highly efficient manner. While the list of validated ncRNAs that regulate crucial cellular processes grows steadily, not a single ncRNA has been identified that directly interacts and regulates the ribosome during protein biosynthesis (with the notable exceptions of 7SL RNA and tmRNA). All of the recently discovered regulatory ncRNAs that act on translation (e.g. microRNAs, siRNAs or antisense RNAs) target the mRNA rather than the ribosome. This is unexpected, given the central position the ribosome plays during gene expression. Furthermore it is strongly assumed that the primordial translation system in the ‘RNA world’ most likely received direct regulatory input from ncRNA-like cofactors. The fundamental question that we would like to ask is: Does the ‘RNA world still communicate’ with the ribosome? To address this question, we have analyzed the small ncRNA interactomes of ribosomes of organisms from all three domains of life. Deep-sequencing and subsequent bioinformatic analyses revealed thousands of putative ribosome-associated ncRNAs.1,2 For a subset of these ncRNA candidates we have gathered experimental evidence that they are expressed in a stress-dependent manner and indeed directly target the ribosome. We show that some of these ribosome-bound small ncRNAs are capable of fine tuning protein synthesis in vitro and in vivo. Our data therefore reveal the ribosome as a novel target for small regulatory ncRNAs in all domains of life and suggest the existence of a so far largely unexplored mechanism of translation regulation.

An mRNA-derived ncRNA targets and regulates the ribosome

Small non-protein-coding RNA (ncRNA) molecules have been recognized recently as major contributors to regulatory networks in controlling gene expression in a highly efficient manner. While the list of validated ncRNAs that regulate crucial cellular processes grows steadily, not a single ncRNA has been identified that directly interacts and regulates the ribosome during protein biosynthesis (with the notable exceptions of 7SL RNA and tmRNA). All of the recently discovered regulatory ncRNAs that act on translation (e.g. microRNAs, siRNAs or antisense RNAs) target the mRNA rather than the ribosome. This is unexpected, given the central position the ribosome plays during gene expression. To investigate whether such a class of regulatory ncRNAs does exist we performed genomic screens for small ribosome-associated RNAs in various model organisms of all three domains [1,2]. Here we focus on the functional characterisation of an 18 nucleotide long ncRNA candidate derived from an open reading frame (ORF) of an annotated S. cerevisiae gene, which encodes a tRNA methyltransferase. Yeast cells lacking this tRNA methyltransferase showed clear growth defects in high salt containing media. Genetic analysis showed that the absence of the mRNA-derived ncRNA rather than the absence of the tRNA methyltransferase activity is responsible for the observed phenotype. Since we performed a screen for small ribosome-associated RNAs we examined the regulatory potential of the synthetic 18mer during translation in vitro and in vivo. Metabolic labeling experiments in the presence of the synthetic 18mer RNA revealed an inhibitory potential on the global protein biosynthesis rate. In vitro translation and northern blot analysis further strengthen the hypothesis, that this RNA is a ribosome-associated regulatory ncRNA. Our studies in pro- and eukaryotic model organisms reveal the ribosome as a novel target for small regulatory ncRNAs in all domains of life. Ribosome-bound ncRNAs are capable of fine tuning translation and might represent a so far largely unexplored class of regulatory ncRNAs.

The ribosome as novel target for stress-induced small regulatory RNAs

Small non-protein-coding RNA (ncRNA) molecules represent major contributors to regulatory networks in controlling gene expression in a highly efficient manner. All of the recently discovered regulatory ncRNAs that act on translation (e.g. microRNAs, siRNAs or antisense RNAs) target the mRNA rather than the ribosome. To address the question, whether small ncRNA regulators exist that are capable of modulating the rate of protein production by directly interacting with the ribosome, we have analyzed the small ncRNA interactomes of ribosomes Deep-sequencing and subsequent bioinformatic analyses revealed thousands of putative ribosome-associated ncRNAs in various model organisms (1,2). For a subset of these ncRNA candidates we have gathered experimental evidence that they associate with ribosomes in a stress-dependent manner and are capable of regulating gene expression by fine-tuning the rate of protein biosynthesis (3,4). Many of the investigated ribosome-bound small ncRNA appear to be processing products from larger functional RNAs, such as tRNAs (2,3) or mRNAs (3). Post-transcriptional cleavage of RNA molecules to generate smaller fragments is a widespread mechanism that enlarges the structural and functional complexity of cellular RNomes. Our data reveal the ribosome as a target for small regulatory ncRNAs and demonstrate the existence of a yet unknown mechanism of translation regulation. Ribosome-associated ncRNAs (rancRNAs) are found in all domains of life and represent a prevalent but so far largely unexplored class of regulatory molecules (5). Future work on the small ncRNA interactomes of ribosomes in a variety of model systems will allow deeper insight into the conservation and functional repertoire of this emerging class of regulatory ncRNA molecules.

Ribosome-associated ncRNAs (rancRNAs) An emerging class of translation regulators

Small non-protein-coding RNA (ncRNA) molecules represent major contributors to regulatory networks in controlling gene expression in a highly efficient manner. Most of the recently discovered regulatory ncRNAs acting on translation target the mRNA rather than the ribosome (e.g.: miRNAs, siRNAs, antisense RNAs). To address the question, whether ncRNA regulators exist that are capable of modulating the rate of protein production by directly interacting with the ribosome, we have analyzed the small ncRNA interactomes of ribosomes. Deep-sequencing analyses revealed thousands of putative rancRNAs in various model organisms (1,2). For a subset of these ncRNA candidates we have gathered experimental evidence that they associate with ribosomes in a stress-dependent manner and fine-tune the rate of protein biosynthesis (3,4). Many of the investigated rancRNAs appear to be processing products of larger functional RNAs, such as tRNAs (2,3), mRNAs (3), or snoRNAs (2). Post-transcriptional cleavage of RNA to generate smaller fragments is a widespread mechanism that enlarges the structural and functional complexity of cellular RNomes. Our data disclose the ribosome as target for small regulatory RNAs. rancRNAs are found in all domains of life and represent a prevalent but so far largely unexplored class of regulatory molecules (5). Ongoing work in our lab revealed first insight into rancRNA processing and mechanism of this emerging class of translation regulators.

Bringing results to fruition through publication: An analysis of a peer-reviewed, open access and context-focused journal's editorial practice

When it comes to helping to shape sustainable development, research is most useful when it bridges the science–implementation/management gap and when it brings development specialists and researchers into a dialogue (Hurni et al. 2004); can a peer-reviewed journal contribute to this aim? In the classical system for validation and dissemination of scientific knowledge, journals focus on knowledge exchange within the academic community and do not specifically address a ‘life-world audience’. Within a North-South context, another knowledge divide is added: the peer review process excludes a large proportion of scientists from the South from participating in the production of scientific knowledge (Karlsson et al. 2007). Mountain Research and Development (MRD) is a journal whose mission is based on an editorial strategy to build the bridge between research and development and ensure that authors from the global South have access to knowledge production, ultimately with a view to supporting sustainable development in mountains. In doing so, MRD faces a number of challenges that we would like to discuss with the td-net community, after having presented our experience and strategy as editors of this journal. MRD was launched in 1981 by mountain researchers who wanted mountains to be included in the 1992 Rio process. In the late 1990s, MRD realized that the journal needed to go beyond addressing only the scientific community. It therefore launched a new section addressing a broader audience in 2000, with the aim of disseminating insights into, and recommendations for, the implementation of sustainable development in mountains. In 2006, we conducted a survey among MRD’s authors, reviewers, and readers (Wymann et al. 2007): respondents confirmed that MRD had succeeded in bridging the gap between research and development. But we realized that MRD could become an even more efficient tool for sustainability if development knowledge were validated: in 2009, we began submitting ‘development’ papers (‘transformation knowledge’) to external peer review of a kind different from the scientific-only peer review (for ‘systems knowledge’). At the same time, the journal became open access in order to increase the permeability between science and society, and ensure greater access for readers and authors in the South. We are currently rethinking our review process for development papers, with a view to creating more space for communication between science and society, and enhancing the co-production of knowledge (Roux 2008). Hopefully, these efforts will also contribute to the urgent debate on the ‘publication culture’ needed in transdisciplinary research (Kueffer et al. 2007).