1,112 research outputs found
Forecasting and Granger Modelling with Non-linear Dynamical Dependencies
Traditional linear methods for forecasting multivariate time series are not
able to satisfactorily model the non-linear dependencies that may exist in
non-Gaussian series. We build on the theory of learning vector-valued functions
in the reproducing kernel Hilbert space and develop a method for learning
prediction functions that accommodate such non-linearities. The method not only
learns the predictive function but also the matrix-valued kernel underlying the
function search space directly from the data. Our approach is based on learning
multiple matrix-valued kernels, each of those composed of a set of input
kernels and a set of output kernels learned in the cone of positive
semi-definite matrices. In addition to superior predictive performance in the
presence of strong non-linearities, our method also recovers the hidden dynamic
relationships between the series and thus is a new alternative to existing
graphical Granger techniques.Comment: Accepted for ECML-PKDD 201
Towards the practical design of performance-aware resilient wireless NoC architectures
Recently, an improved surface wave-enabled communication fabric has been proposed to solve the reliability issues of emerging hybrid wired-wireless Network-on-Chip (WiNoC) architectures. Thus, providing a promising solution to the performance and scalability demands of the fast-paced technological growth towards exascale and Big-Data processing on future System-on-Chip (SoC) design. However, WiNoCs tradeoff optimized performance for cost by restricting the number of area and power hungry wireless nodes. Consequently, in this paper, we propose a low-latency adaptive router with a low-complexity single-cycle bypassing mechanism to alleviate the performance degradation due to the slow wired routers in such emerging hybrid NoCs. The proposed router is able to redistribute traffic in the network to alleviate average packet latency at both low and high traffic conditions. As a second contribution the paper presents an experimental evaluation of a practically implemented surface wave communication fabric. By reducing the latency between the wired nodes and wireless nodes the proposed router can improve performance efficiency in terms of average packet delay by an average of 50% in WiNoCs
Adjuvant S-1 chemotherapy after curative resection of gastric cancer in Chinese patients: assessment of treatment tolerability and associated risk factors
published_or_final_versio
Macroscopic nucleation phenomena in continuum media with long-range interactions
Nucleation, commonly associated with discontinuous transformations between
metastable and stable phases, is crucial in fields as diverse as atmospheric
science and nanoscale electronics. Traditionally, it is considered a
microscopic process (at most nano-meter), implying the formation of a
microscopic nucleus of the stable phase. Here we show for the first time, that
considering long-range interactions mediated by elastic distortions, nucleation
can be a macroscopic process, with the size of the critical nucleus
proportional to the total system size. This provides a new concept of
"macroscopic barrier-crossing nucleation". We demonstrate the effect in
molecular dynamics simulations of a model spin-crossover system with two
molecular states of different sizes, causing elastic distortions.Comment: 12 pages, 4 figures. Supplementary information accompanies this paper
at http://www.nature.com/scientificreport
Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial
Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160âmg/ sulfamethoxazole 800âmg twice a day plus folic acid 5âmg daily or doxycycline 100âmg once daily if body weight is <â50âkg or 100âmg twice daily if â„50âkg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24âmonths of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120
P120-Catenin Isoforms 1 and 3 Regulate Proliferation and Cell Cycle of Lung Cancer Cells via ÎČ-Catenin and Kaiso Respectively
<div><h3>Background</h3><p>The different mechanisms involved in p120-catenin (p120ctn) isoforms' 1/3 regulation of cell cycle progression are still not elucidated to date.</p> <h3>Methods and Findings</h3><p>We found that both cyclin D1 and cyclin E could be effectively restored by restitution of p120ctn-1A or p120ctn-3A in p120ctn depleted lung cancer cells. When the expression of cyclin D1 was blocked by co-transfection with siRNA-cyclin D1 in p120ctn depleted cells restoring p120ctn-1A or 3A, the expression of cyclin E was slightly decreased, not increased, implying that p120ctn isoforms 1 and 3 cannot up-regulate cyclin E directly but may do so through up-regulation of cyclin D1. Interestingly, overexpression of p120ctn-1A increased ÎČ-catenin and cyclin D1 expression, while co-transfection with siRNA targeting ÎČ-catenin abolishes the effect of p120ctn-1A on up-regulation of cyclin D1, suggesting a role of ÎČ-catenin in mediating p120ctn-1A's regulatory function on cyclin D1 expression. On the other hand, overexpression of p120ctn isoform 3A reduced nuclear Kaiso localization, thus decreasing the binding of Kaiso to KBS on the cyclin D1 promoter and thereby enhancing the expression of cyclin D1 gene by relieving the repressor effect of Kaiso. Because overexpressing NLS-p120ctn-3A (p120ctn-3A nuclear target localization plasmids) or inhibiting nuclear export of p120ctn-3 by Leptomycin B (LMB) caused translocation of Kaiso to the nucleus, it is plausible that the nuclear export of Kaiso is p120ctn-3-dependent.</p> <h3>Conclusions</h3><p>Our results suggest that p120ctn isoforms 1 and 3 up-regulate cyclin D1, and thereby cyclin E, resulting in the promotion of cell proliferation and cell cycle progression in lung cancer cells probably via different protein mediators, namely, ÎČ-catenin for isoform 1 and Kaiso, a negative transcriptional factor of cyclin D1, for isoform 3.</p> </div
A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola
<p>Abstract</p> <p>Background</p> <p><it>In silico </it>analyses provide valuable insight into the biology of obligately intracellular pathogens and symbionts with small genomes. There is a particular opportunity to apply systems-level tools developed for the model bacterium <it>Escherichia coli </it>to study the evolution and function of symbiotic bacteria which are metabolically specialised to overproduce specific nutrients for their host and, remarkably, have a gene complement that is a subset of the <it>E. coli </it>genome.</p> <p>Results</p> <p>We have reconstructed and analysed the metabolic network of the Îł-proteobacterium <it>Buchnera aphidicola </it>(symbiont of the pea aphid) as a model for using systems-level approaches to discover key traits of symbionts with small genomes. The metabolic network is extremely fragile with > 90% of the reactions essential for viability <it>in silico</it>; and it is structured so that the bacterium cannot grow without producing the essential amino acid, histidine, which is released to the insect host. Further, the amount of essential amino acid produced by the bacterium <it>in silico </it>can be controlled by host supply of carbon and nitrogen substrates.</p> <p>Conclusion</p> <p>This systems-level analysis predicts that the fragility of the bacterial metabolic network renders the symbiotic bacterium intolerant of drastic environmental fluctuations, whilst the coupling of histidine production to growth prevents the bacterium from exploiting host nutrients without reciprocating. These metabolic traits underpin the sustained nutritional contribution of <it>B. aphidicola </it>to the host and, together with the impact of host-derived substrates on the profile of nutrients released from the bacteria, point to a dominant role of the host in controlling the symbiosis.</p
Dynamic anoxic ferruginous conditions during the end-Permian mass extinction and recovery
The end-Permian mass extinction, ~252 million years ago, is notable for a complex recovery period of ~5 Myr. Widespread euxinic (anoxic and sulfidic) oceanic conditions have been proposed as both extinction mechanism and explanation for the protracted recovery period, yet the vertical distribution of anoxia in the water column and its temporal dynamics through this time period are poorly constrained. Here we utilize FeâSâC systematics integrated with palaeontological observations to reconstruct a complete ocean redox history for the Late Permian to Early Triassic, using multiple sections across a shelf-to-basin transect on the Arabian Margin (Neo-Tethyan Ocean). In contrast to elsewhere, we show that anoxic non-sulfidic (ferruginous), rather than euxinic, conditions were prevalent in the Neo-Tethys. The Arabian Margin record demonstrates the repeated expansion of ferruginous conditions with the distal slope being the focus of anoxia at these times, as well as short-lived episodes of oxia that supported diverse biota
Strong interface-induced spin-orbit coupling in graphene on WS2
Interfacial interactions allow the electronic properties of graphene to be
modified, as recently demonstrated by the appearance of satellite Dirac cones
in the band structure of graphene on hexagonal boron nitride (hBN) substrates.
Ongoing research strives to explore interfacial interactions in a broader class
of materials in order to engineer targeted electronic properties. Here we show
that at an interface with a tungsten disulfide (WS2) substrate, the strength of
the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The
induced SOI leads to a pronounced low-temperature weak anti-localization (WAL)
effect, from which we determine the spin-relaxation time. We find that
spin-relaxation time in graphene is two-to-three orders of magnitude smaller on
WS2 than on SiO2 or hBN, and that it is comparable to the intervalley
scattering time. To interpret our findings we have performed first-principle
electronic structure calculations, which both confirm that carriers in
graphene-on-WS2 experience a strong SOI and allow us to extract a
spin-dependent low-energy effective Hamiltonian. Our analysis further shows
that the use of WS2 substrates opens a possible new route to access topological
states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines.
Final version with expanded discussion of the relation between theory and
experiments to be published in Nature Communication
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