3,420 research outputs found
Validation of nonlinear PCA
Linear principal component analysis (PCA) can be extended to a nonlinear PCA
by using artificial neural networks. But the benefit of curved components
requires a careful control of the model complexity. Moreover, standard
techniques for model selection, including cross-validation and more generally
the use of an independent test set, fail when applied to nonlinear PCA because
of its inherent unsupervised characteristics. This paper presents a new
approach for validating the complexity of nonlinear PCA models by using the
error in missing data estimation as a criterion for model selection. It is
motivated by the idea that only the model of optimal complexity is able to
predict missing values with the highest accuracy. While standard test set
validation usually favours over-fitted nonlinear PCA models, the proposed model
validation approach correctly selects the optimal model complexity.Comment: 12 pages, 5 figure
Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record
Medvedev and Melott (2007) have suggested that periodicity in fossil
biodiversity may be induced by cosmic rays which vary as the Solar System
oscillates normal to the galactic disk. We re-examine the evidence for a 62
million year (Myr) periodicity in biodiversity throughout the Phanerozoic
history of animal life reported by Rohde & Mueller (2005), as well as related
questions of periodicity in origination and extinction. We find that the signal
is robust against variations in methods of analysis, and is based on
fluctuations in the Paleozoic and a substantial part of the Mesozoic.
Examination of origination and extinction is somewhat ambiguous, with results
depending upon procedure. Origination and extinction intensity as defined by RM
may be affected by an artifact at 27 Myr in the duration of stratigraphic
intervals. Nevertheless, when a procedure free of this artifact is implemented,
the 27 Myr periodicity appears in origination, suggesting that the artifact may
ultimately be based on a signal in the data. A 62 Myr feature appears in
extinction, when this same procedure is used. We conclude that evidence for a
periodicity at 62 Myr is robust, and evidence for periodicity at approximately
27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio
Spatially-resolved electronic and vibronic properties of single diamondoid molecules
Diamondoids are a unique form of carbon nanostructure best described as
hydrogen-terminated diamond molecules. Their diamond-cage structures and
tetrahedral sp3 hybrid bonding create new possibilities for tuning electronic
band gaps, optical properties, thermal transport, and mechanical strength at
the nanoscale. The recently-discovered higher diamondoids (each containing more
than three diamond cells) have thus generated much excitement in regards to
their potential versatility as nanoscale devices. Despite this excitement,
however, very little is known about the properties of isolated diamondoids on
metal surfaces, a very relevant system for molecular electronics. Here we
report the first molecular scale study of individual tetramantane diamondoids
on Au(111) using scanning tunneling microscopy and spectroscopy. We find that
both the diamondoid electronic structure and electron-vibrational coupling
exhibit unique spatial distributions characterized by pronounced line nodes
across the molecular surfaces. Ab-initio pseudopotential density functional
calculations reveal that the observed dominant electronic and vibronic
properties of diamondoids are determined by surface hydrogen terminations, a
feature having important implications for designing diamondoid-based molecular
devices.Comment: 16 pages, 4 figures. to appear in Nature Material
Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65.
Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α-mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn't interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis
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The polygenic nature of telomere length and the anti-ageing properties of lithium
Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p 0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy
Accommodating individual travel history and unsampled diversity in Bayesian phylogeographic inference of SARS-CoV-2
Spatiotemporal bias in genome sampling can severely confound discrete trait phylogeographic inference. This has impeded our ability to accurately track the spread of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, despite the availability of unprecedented numbers of SARS-CoV-2 genomes. Here, we present an approach to integrate individual travel history data in Bayesian phylogeographic inference and apply it to the early spread of SARS-CoV-2. We demonstrate that including travel history data yields i) more realistic hypotheses of virus spread and ii) higher posterior predictive accuracy compared to including only sampling location. We further explore methods to ameliorate the impact of sampling bias by augmenting the phylogeographic analysis with lineages from undersampled locations. Our reconstructions reinforce specific transmission hypotheses suggested by the inclusion of travel history data, but also suggest alternative routes of virus migration that are plausible within the epidemiological context but are not apparent with current sampling efforts.status: publishe
From BIM towards digital twin: Strategy and future development for smart asset management
With the rising adoption of Building Information Model (BIM) for as-set management within architecture, engineering, construction and owner-operated (AECO) sector, BIM-enabled asset management has been increasingly attracting more attentions in both research and practice. This study provides a comprehensive review and analysis of the state-of-the-art latest research and industry standards development that impact upon BIM and asset management within the operations and maintenance (O&M) phase. However, BIM is not always enough in whole-life cycle asset management, especially in the O&M phase. Therefore, a framework for future development of smart asset management are proposed, integrating the concept of Digital Twin (DT). DT integrates artificial intelligence, machine learning and data analytics to create dynamic digital models that are able to learn and update the status of the physical counterpart from multiple sources. The findings will contribute to inspiring novel research ideas and promote wide-spread adoption of smart DT-enabled asset management within the O&M phaseCentre for Digital Built Britain, Innovate U
Towards cloud based big data analytics for smart future cities
© 2015, Khan et al.; licensee Springer. A large amount of land-use, environment, socio-economic, energy and transport data is generated in cities. An integrated perspective of managing and analysing such big data can answer a number of science, policy, planning, governance and business questions and support decision making in enabling a smarter environment. This paper presents a theoretical and experimental perspective on the smart cities focused big data management and analysis by proposing a cloud-based analytics service. A prototype has been designed and developed to demonstrate the effectiveness of the analytics service for big data analysis. The prototype has been implemented using Hadoop and Spark and the results are compared. The service analyses the Bristol Open data by identifying correlations between selected urban environment indicators. Experiments are performed using Hadoop and Spark and results are presented in this paper. The data pertaining to quality of life mainly crime and safety & economy and employment was analysed from the data catalogue to measure the indicators spread over years to assess positive and negative trends
Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome
Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE
playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes
A precision study of the fine tuning in the DiracNMSSM
Recently the DiracNMSSM has been proposed as a possible solution to reduce
the fine tuning in supersymmetry. We determine the degree of fine tuning needed
in the DiracNMSSM with and without non-universal gaugino masses and compare it
with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed
parameter regions we perform a precise calculation of the Higgs mass. In
addition, we include the limits from direct SUSY searches and dark matter
abundance. We find that both models are comparable in terms of fine tuning,
with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure
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